Severe Illness Research Articles

Systematic Review and Meta-Analysis of Individual Participant Data: Randomized, Placebo-Controlled Trials of Selective Serotonin Reuptake Inhibitors for Pediatric Obsessive-Compulsive Disorder.

Selective serotonin reuptake inhibitors (SSRIs) are the first choice in pharmacotherapy for children and adolescents with obsessive-compulsive disorder (OCD). SSRI-trials for pediatric OCD have never been investigated using individual participant data (IPD), which is crucial for detecting patient-level effect modifiers. Here, we performed an IPD meta-analysis on the efficacy of SSRIs compared to placebo, and a meta-regression on baseline patient characteristics which might modify efficacy. We used crude participant data from short-term, randomized, placebo-controlled SSRI trials for pediatric OCD, available from the registry of the Dutch regulatory authority. We also performed a systematic literature search and approached the authors to provide IPD. We performed a one- and two-stage analysis, with change on the Children's Yale Brown Obsessive-Compulsive Scale (CY-BOCS) as the primary outcome. We used Odds Ratio (OR) with ≥ 35% CY-BOCS-reduction as the responder outcome measure. We examined modifying effect of age, sex, weight, duration of illness, family history and baseline symptom severity. We used the Cochrane Risk of Bias 2.0 tool to examine methodological rigor, and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach in order to examine certainty of evidence. We obtained data from 4 studies with a total of 614 patients. Our sample represented 86% of all participants ever included in double blind placebo controlled SSRI trials for pediatric OCD. Meta-analysis showed a reduction of 3.0 CY-BOCS points compared to placebo (95% CI 2.5 - 3.5), corresponding to a small effect size (0.38 Hedges' g). Analysis of response showed an OR of 1.89 (95% CI 1.45 - 2.45). Of all possible modifiers, severity was correlated negatively with OR for response (beta -0.92, p 0.0074). Risk of bias was generally low. All studies were performed on the North American continent with an overrepresentation of White participants. Our findings were limited by the inability to include data on additional variables such as socio-economic status and comorbidities. Our IPD meta-analysis showed a small effect size of SSRIs in pediatric OCD, with baseline severity as a negative modifier of response. Generalizability of findings might be limited by selective inclusion of White, North American participants.

Effect of healthy lifestyle score trajectory on all-cause mortality in the late middle-aged and older population: Finding from 17-year retrospective cohort study.

Recently, the World Health Organization has emphasized the importance of a healthy lifestyle in reducing severe illnesses and premature mortality. To evaluate this, the Healthy Lifestyle Score (HLS), which focuses on health protecting behaviors (e.g., smoking, alcohol consumption, physical activity, body mass index), is widely used. However, as HLS may fluctuate over time, there is increasing focus on monitoring HLS trends. Accordingly, this study aims to track HLS trajectories (HLST) and examine their association with mortality among middle-aged and older Koreans. After excluding missing values, data from 6249 participants were analyzed using the group-based trajectory model (GBTM) to classify HLST, based on the first to fourth waves of the Korean Longitudinal Study of Aging (KLoSA). The chi-square test and Cox proportional hazards model were employed to examine the association between HLST and all-cause mortality over a 10-year follow-up period (December 31, 2012, to December 31, 2022; 3650 days). Three HLST groups were identified in the GBTM analysis. These were the Poor HLST (17.8 %), Average HLST (42.9 %), and Good HLST (39.4 %) groups. Compared to the good HLST, the poor HLST had higher mortality at 1 year (hazard ratio [HR]: 1.98, p: 0.029), 3 years (HR: 1.78, p: 0.001), 5 years (HR: 1.52, p: 0.002), 7 years (HR: 1.39, p: 0.002), and 10 years (HR: 1.40, p: 0.000). Furthermore, stratified analysis by sex, age, marital status and residential region showed that male, ≥65 years, single and urban area groups had a strong association between HLST and all-cause mortality. The findings of this study underscore the necessity of policies and institutional measures grounded in community networks to mitigate the risk of all-cause mortality among vulnerable groups with persistently poor HLST.

Unveiling the Silent Pandemic: Impact of Severe Mental Illness on Cardiovascular Health in the United States.

Severe mental illness (SMI) encompasses depression, bipolar disorder, and schizophrenia which affect the daily quality of life. While it has a significant impact on their social life, it is also supposedly linked with various comorbidities, of which, cardiovascular disease (CVD) is the most frequently reported. Various biological, behavioral, and genetic mechanisms are thought to play a role: hypothalamic-pituitary-adrenal axis, autonomic nervous system dysregulation, inflammation, and psychotropic medications. Lack of exercise, low-fiber diet, smoking, substance abuse, and failure of medicine compliance also strongly contribute to the increased risk for CVD-related death. The understanding of the complex relationship between CVD and SMI would thus play a significant role in decreasing the incidence of CVD-related morbidity and mortality. This article aims to review and explain the hypothesized increased risk of CVD events in patients with SMI.

“Who am I?” The HiddenAspects of Dissociative Identity Disorder

Dissociative identity disorder (DID) is a persistent posttraumatic condition marked by impaired memory and selfidentity functions resulting from childhood trauma. It is a severe chronic psychiatric illness characterized by neurobiological, cognitive, and interpersonal disintegration in reaction to intolerable stress. Dissociative Identity Disorder (DID) remains inadequately researched; nevertheless, more investigation may elucidate neurobiological and cognitive characteristics, as well as the interplay between individuals and environmental stressors

Characteristics of Patients Experiencing Opioid Overdose and Eligibility for Prehospital Treatment with Buprenorphine

ABSTRACT OBJECTIVES Opioids kill tens of thousands of patients each year. While only a fraction of people with opioid use disorder (OUD) have accessed treatment in the last year, 30% of people who died from an overdose had an Emergency Medical Services (EMS) encounter within a year of their death. Prehospital buprenorphine represents an important emerging OUD treatment, yet limited data describe barriers to this treatment. Our objectives were to quantify the number of patients encountered by EMS who were eligible for prehospital buprenorphine, and to examine characteristics of patients who did or did not receive treatment. METHODS In this retrospective observational study, we analyzed EMS patient records from Contra Costa County, CA, where paramedics were trained to identify patients experiencing opioid withdrawal and administer buprenorphine. Patient records were selected for review based on “buprenorphine patient triggers,” which were keywords within the charts that identified patients with potential overdose or symptoms that could indicate withdrawal or naloxone administration. We describe proportion of eligible patients and the characteristics of those who did and did not receive prehospital buprenorphine. RESULTS We reviewed 1,159 records from September 2020 to July 2022. Of included patients, 984 (85%) were not eligible for buprenorphine. Nearly half (482, 49%,) of patients ineligible for buprenorphine fell into 2 primary categories: 331 (33%) had altered mental status (326 of 331 received naloxone), and 151 (15%) had no active withdrawal symptoms documented. Additional exclusions included other intoxicants, severe medical illness, or the patient denied having an OUD. Of those eligible for buprenorphine, 67 (38%) received buprenorphine. Of the 108 patients who did not receive buprenorphine, 69 (64%) had protocol deviation, 24 (22%) declined treatment, and 15 (14%) were in a non-enabled zone. Of all buprenorphine administrations, 19 (28%) were post-opioid overdose and 48 (72%) were for abstinence withdrawal. CONCLUSIONS One-in-three EMS patients with suspected opioid use disorder were ineligible for treatment with buprenorphine due to altered mental status. The second largest group consisted of patients who were eligible but not offered buprenorphine, highlighting potential gaps in paramedic training, logistical challenges in field administrations, and other factors that warrant further exploration.

Cost-effectiveness of the SMILE intervention compared with usual care for people with severe mental illness: A randomized clinical trial

Objectives Only studying effectiveness of lifestyle interventions for people with severe mental illness (SMI) is insufficient for policy making. As budgets for healthcare are limited, policy makers face the problem of allocating scarce healthcare resources. Cost-effectiveness studies are needed, but currently cost-effectiveness studies of lifestyle interventions for people with SMI delivered in ambulatory care are limited. The aim of this current study was to evaluate the cost-effectiveness of a lifestyle intervention for people with SMI living in the Dutch community in comparison with usual care. Methods and findings An economic evaluation was performed using a societal perspective alongside the Severe Mental Illness Lifestyle Evaluation (SMILE) pragmatic cluster randomized controlled trial. The SMILE lifestyle intervention is a one-year, group-based intervention delivered by trained mental healthcare workers. Costs, body weight change and quality of life were assessed at baseline, 6 and 12 months. Mixed models were used to estimate incremental costs and effects between the treatment group and the usual care group. Overall, the SMILE intervention resulted in lower total costs compared to the usual care group (-€719, 95% CI -7133; 3897). The effect difference between the intervention and usual care groups was -3.76 (95% CI -6.30; -1.23) kilograms for body weight and -0.037 (95% CI -0.083; 0.010) for QALYs. Conclusions Overall, the SMILE intervention resulted in lower total costs compared to the usual care group and was cost-effective for body weight change. However, the SMILE intervention does not seem cost-effective with regards to QALYs. More cost-effectiveness studies in other countries and other settings are needed to gain further insight into the cost-effectiveness of lifestyle interventions for people with SMI.

Outcome of a semi-closed mixed intensive care unit in a medical college: A prospective observational study

Background and aims: The patients with the most severe illnesses are admitted in intensive care unit (ICU). This study was conducted to explore the outcome of patients admitted to the intensivist led semi-closed mixed ICU of a medical college in Nepal. Methods: Five hundred and forty-two patients with age 18 years or above, admitted to the level three ICU of National Medical College over one year period was included in the study. The outcome of the patient was defined as discharge to ward, death, leave against medical advice, or do not resuscitate. Results: Out of 542 patients admitted in the ICU during the study period, 444 (82%) patients were discharged to the ward, 63 (12%) died, 24 (4%) left against medical advice and 11 (2%) gave do not resuscitate orders. Mortality in intubated and trauma patients was 25.0% and 4.7% respectively. Conclusion: This study shows favourable results in terms of patient outcome in an intensivist led semi-closed mixed ICU of a medical college in Nepal.

Preterm Birth Frequency and Associated Outcomes From the MATISSE (Maternal Immunization Study for Safety and Efficacy) Maternal Trial of the Bivalent Respiratory Syncytial Virus Prefusion F Protein Vaccine.

To describe preterm birth frequency and newborn and infant outcomes overall and among preterm children in the MATISSE (Maternal Immunization Study for Safety and Efficacy) trial of maternal vaccination with bivalent respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVpreF) to protect infants against severe RSV-associated illness. MATISSE was a global, phase 3, randomized, double-blind trial. Pregnant individuals received single injections of RSVpreF or placebo. Adverse events of special interest, including preterm birth (gestational age less than 37 weeks) and low birth weight (2,500 g or less), were collected through 6 months after delivery (pregnant participants) and from birth through age 12 or 24 months (pediatric participants). Overall, 7,386 pregnant participants received RSVpreF (n=3,698) or placebo (n=3,688); 7,305 newborns and infants were included in the analysis. Most children in both groups were born full term (more than 93%) with normal birth weight (95% or higher). Newborn and infant outcomes, including rates of low birth weight and neonatal hospitalization, were favorable and comparable between groups. Preterm birth rates were 5.7% in the RSVpreF arm and 4.7% in the placebo arm (relative risk [RR] 1.20, 95% CI, 0.98-1.46); most were late preterm. Newborn and infant outcomes, including rates of low birth weight and neonatal hospitalization, were comparable between groups. Twenty-two newborn or infant deaths occurred during the study (RSVpreF n=8, placebo n=14). When stratified by income region, preterm birth rates in RSVpreF and placebo recipients were both 5.0% in high-income countries. Rates in non-high-income countries were 7.0% and 4.0% in the RSVpreF and placebo groups, respectively, and 8.3% and 4.0% in South Africa (RR 2.06, 95% CI, 1.21-3.51). In this study of maternal RSVpreF vaccination, no clinically significant increase in adverse events of special interest, including preterm birth, low birth weight, or neonatal hospitalization, was observed among pregnant people in the overall analysis. In subgroup analysis of non-high-income countries, an elevated risk of preterm birth was observed. More research is needed to better ascertain preterm delivery risk factors, particularly aimed at minimizing disparities among geographic regions. This study was sponsored by Pfizer. ClinicalTrials.gov, NCT04424316.

Comparison of Serum Vitamin D Status in Critically ill and Non-critically ill Children and its Relationship with Illness Severity and Clinical Outcomes: A Case–Control Study

Abstract Background: The role of vitamin D in immune function is well-established in adults, but remains unclear in children. Objectives: We aimed to determine the prevalence of vitamin D deficiency in critically ill versus non-critically ill children and the correlation between vitamin D level with illness severity and clinical outcomes. Materials and Methods: This was a hospital-based, case–control study involving 35 critically ill and 35 non-critically ill children aged 1 month to 18 years. Serum Vitamin D levels were determined and categorized. Severity of illness of the critically ill group was classified based on calculated modified Sequential Organ Failure Assessment scores, and participants were followed-up until discharge or demise. Results: Median values of vitamin D levels in the critically ill (78.2 ng/mL) and the non-critically ill (60.3 ng/mL) were significantly different (P = 0.003). None of the children in both groups were found to be vitamin D–deficient. There was no significant correlation between vitamin D levels and severity of illness (P = 0.69). Children with overdose, non-toxic levels were less likely to die when compared with those in the optimal range of vitamin D, with odds ratio (95%CI) 0.05 (0.004–0.65). Conclusion: Serum vitamin D deficiency was uncommon in our cohort of critically ill children and was not related to severity of illness, mortality, or length of hospital stay. Although routine vitamin D assessment and supplementation has been proposed to boost the immune system of critically ill adults to help them recover faster, it may not be of added benefit in children.

Binding Antibodies Responses to SARS-COV-2 Infection in Hospitalized Patients and Vaccinated Subjects: A Longitudinal Prospective Observational Study

Abstract Background: Prevalence of seropositivity following SARS-CoV-2 infection is vital in evaluating herd immunity. However, depending on illness severity, it remains unclear whether the breadth and magnitude of immune response to SARS-CoV-2 infection is for short or long term. Objective: To test the persistence of humoral antibody responses after SARS-CoV-2 exposure in patients with different illness severity and among volunteers who had been vaccinated. Methods: This study was conducted in two Saudi Arabian tertiary hospitals. Participants were categorized as critically ill COVID-19 patients, non-critically ill COVID-19 patients, or vaccinated volunteers. We collected demographic data, COVID-19 exposure history, symptoms, vaccination details, and serum samples to analyze antibody persistence. We evaluated SARS-CoV-2 antibody concentrations in COVID-19 patients with varying disease severity and age groups, as well as in BNT162b2-vaccinated individuals, focusing on IgG levels against the S.FL and S1 domains of the spike protein. Results: The study included 172 adults: 92 unvaccinated hospitalized COVID-19 patients and 80 vaccinated volunteers. All vaccinated subjects demonstrated seropositivity to the SARS-CoV-2 spike protein, with nearly 80% having a median antibody titer of 13,500 AU/mL. Notably, vaccinated subjects exhibited significantly higher IgG levels than naturally infected patients (P < 0.001), including higher S.FL and S1 titers, regardless of severity. Age, comorbidities, and previous infections influenced S-specific antibody levels. Among hospitalized patients, 58% required intensive care, with 28- and 90-day mortality rates of 23% and 43%, respectively. Conclusion: These findings shed light on the immune response dynamics following SARS-CoV-2 infection compared to vaccinated individuals, where the latter showed significantly higher level of antibodies response, providing crucial insights for evaluating short-term herd immunity and the effectiveness of natural infection-induced immunity.

Correlation of the cycle threshold value of SARS-CoV-2 by RT-PCR with biomarker levels in the prognosis of patients hospitalized with COVID-19

ABSTRACT Background and Objective: The COVID-19 disease caused by SARS-CoV-2 was declared as pandemic by WHO soon after its emergence in 2019. This virus was known to cause serious clinical symptoms and severe illness. By using RT-PCR, which reports the cycle threshold value, the disease is diagnosed, whereas for the severity of the disease, biomarker levels, like IL-6, CRP, D-dimer, serum ferritin and serum procalcitonin, can be measured. We, thus, aimed to explore any potential correlation of the cycle threshold value and biomarker level with the outcome of COVID-19-positive hospitalized patients. Method: Patients with the cycle threshold (Ct) value <35 were included in the study and their initial Ct values were noted. Different biochemical parameters, such as C-reactive protein (CRP), serum ferritin, D-dimer, Interleukin-6 and serum procalcitonin, were assessed for severity. They were classified according to Ct value into three groups: Group 1 >30.0, Group 2 20.0–30.0 and Group 3 <20.0. Results: The study included 370 hospitalized COVID-19 patients with a mean age (mean ± SD) of 51.08 (16.58%) years and 250 (67.5%) males and 120 (32.4%) females. Comparison of data with outcome shows that IL-6, CRP amongst the biomarker and Ct value (deduced by RT-PCR test) were significantly correlated with the mortality (P value < 0.05). The ROC curve was also plotted for these parameters, which shows that IL-6, CRP, PCT and Ct value were better prognostic marker. Poor prognosis was found in Group 2 (Ct value 20.0–30.0) patients compared to Group 1 and Group 3. There was significant correlation (P value < 0.05) between Ct value and outcome of the patient. Interpretation and Conclusion: This study depicts that low Ct value and elevated levels of IL-6 and CRP can be used as a screening tool to detect the mortality in COVID-19 patients as they are significantly correlated with the mortality.

Correlates of Perceived Illness Severity and Terminality in Advanced Lung and Prostate Cancer.

While prognostic awareness has been commonly assessed as perceived illness terminality in patients with advanced cancer, both perceptions of illness severity and terminality may be correlated with symptom burden and quality of life. The present study examined physical and psychological symptoms, quality of life, and smoking status in relation to perceived illness severity and terminality in patients with advanced, inoperable lung and prostate cancer. Patients (N=198) were recruited from hospitals in the midwestern U.S. to complete a one-time survey. Prognostic awareness was assessed in the following categories: "relatively healthy," "seriously ill but not terminally ill," or "seriously and terminally ill." Only 12% reported an accurate prognostic awareness ("seriously and terminally ill") and 66% perceived themselves as "relatively healthy." Higher levels of anxiety, depressive symptoms, fatigue, and pain, and worse quality of life were associated with a higher likelihood of reporting serious illness, irrespective of perceived illness terminality. Smoking status was unrelated to prognostic awareness. For patients with advanced lung cancer, greater breathlessness was associated with a higher likelihood of reporting serious or terminal illness. Our findings suggest that perceiving cancer as serious, not just terminal, is related to symptom burden and quality of life. Results point to the need for interventions to improve prognostic understanding and coping with the disease.

Characterizing the SARS-CoV-2 antibody response and associations with patient factors: Serological profiling of participants enrolled in the GENCOV study.

The GENCOV study sought to evaluate serological differences between individuals with differing COVID-19 severity and outcomes. We assessed the SARS-CoV-2 antibody response of GENCOV participants cross-sectionally 1-, 6-, and 12-months following COVID-19 diagnosis to identify patient factors associated with more robust and durable humoral immune responses. COVID-19 patients and a control cohort of vaccinated infection-naïve participants were recruited at hospital sites across the Greater Toronto Area in Ontario, Canada. Commercially available and laboratory-developed serological assays were used to characterize features of participants' antibody responses, including both binding and neutralizing antibodies. Regression analyses were performed to identify associations between participant characteristics and features of the SARS-CoV-2 antibody response. Samples were obtained from participants 1- (n=938), 6- (n=842), and 12-months (n=662) post-infection or vaccination. At all time points, vaccinees, and to a greater extent those who were both infected and vaccinated, had significantly elevated anti-spike antibody levels compared to unvaccinated participants. Increasing age and/or illness severity were associated with significantly higher antibody levels among unvaccinated participants. Among vaccines, those who were vaccinated after infection (i.e., hybrid immunity) had consistently higher antibody levels compared to participants who were infection-naïve or vaccinated before their infection (i.e., breakthrough infections). Additionally, receiving more vaccine doses and having a more recent vaccination were strongly associated with higher antibody levels across all time points. Our findings highlight various patient factors, including vaccination, which contribute to robust, durable SARS-CoV-2 antibody responses. Overall, the findings presented here may inform future vaccine development and rollout plans.

COVID-19 in patients with multiple sclerosis-A narrative review.

Multiple sclerosis (MS) is a complex neurodegenerative disease characterized by immune dysregulation, affecting over 2.5 million people worldwide. Interestingly, COVID-19 infection can cause neurodegeneration through demyelination similar to that of MS, and COVID-19 infection can lead to long-term neurological sequelae, post-COVID-19 neurological syndrome. These overlapping neurological mechanisms suggest that patients with MS (PwMS) may have a unique and potentially more complex relationship with COVID-19. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can enter the central nervous system via the olfactory nerve or through interactions with angiotensin-converting enzyme-2 receptors in the blood-brain barrier, potentially initiating or enhancing neurodegenerative processes through demyelination. The risk of SARS-CoV-2 infection among PwMS is similar to that of the general population; however, PwMS with higher Expanded Disability Status Scale scores, longer MS duration, or progressive forms of MS are at an increased risk for developing severe COVID-19 outcomes. Most disease-modifying therapies (DMT), such as interferon, glatiramer, teriflunomide, and cladribine, do not appear to affect the risk of COVID-19 infection, the severity of COVID-19 illness, or the response to COVID-19 vaccines. As a result, these therapies should be continued during COVID-19 infection in PwMS. Rituximab, however, has been shown to increase the risk of severe COVID-19 outcomes. For managing symptomatic COVID-19 infection in PwMS, remdesivir and neutralizing monoclonal antibodies are shown to be effective. COVID-19-associated cytokine release syndrome can be managed with corticosteroids. Importantly, COVID-19 infection does not increase susceptibility to MS relapses or exacerbate the progression of MS symptoms. Furthermore, COVID-19 vaccination is encouraged for all MS patients, particularly those at greater risk of severe outcomes, as it does not trigger relapses, exacerbate MS symptoms, or diminish the efficacy of DMT. Despite these findings, high-quality evidence remains lacking to fully establish the relationship between COVID-19 and MS, highlighting the need for further research in this area.

Refinement of post-COVID condition core symptoms, subtypes, determinants, and health impacts: A cohort study integrating real-world data and patient-reported outcomes

Post-COVID-19 condition (PCC) affects millions of people, and is an essential component of the long-term impact of COVID-19 during the post-pandemic era. Yet, consensus on clinical case definition and core components of PCC remains lacking, affecting our ability to inform research and evidence-based management. Our study aims 1) to identify the most specific symptoms for PCC, and identify clinical subtypes; 2) to evaluate both virus- and host-related determinants of PCC, and 3) assess the impact of PCC on physical and mental health. We studied participants from UK Biobank who completed a health and wellbeing survey between June and September 2022. Participants reported the current conditions of the presence, duration, and functional limitations of 45 symptoms, using an online questionnaire designed specifically for COVID-19 research. SARS-CoV-2 infection status and disease history were obtained through linkage to surveillance data and electronic medical records, respectively. Participants reporting symptoms within 30 days after infection (acute phase) were excluded. The most specific PCC symptoms were defined using two criteria: statistical significance (P<0.05 after Bonferroni correction) and clinical relevance (absolute risk increase > 5%). Propensity score weighting was used to control for confounding. Subtypes of PCC were then defined based on the specific symptoms among the COVID-19 infected individuals. A multivariable regression was used to study pathogen- and host-related risk factors for PCC, and its impact on 13 physical and 4 mental health patient-reported functional outcomes. 172,303 participants (mean age 68.9, 57.4% female) were included in the analysis, of whom 43,395 had PCR-confirmed COVID-19. We identified 10 most specific symptoms and classified four PCC subtypes: ENT subtype (30.1%), characterized by alterations in smell, taste, and hearing loss; cardiopulmonary subtype (10.4%), characterized by shortness of breath, postural tachycardia, chest tightness, and chest pressure; neurological subtype (23.5%), characterized by brain fog and difficulty speaking; and general fatigue subtype (38.0%), characterized by mild fatigue. A higher PCC risk was observed for patients with Wild-type variant, multiple infections, and severe acute COVID-19 illness, consistently across the four PCC subtypes. In addition, a range of factors, including socioeconomic deprivation, higher BMI, unhealthy lifestyle, and multiple chronic health conditions, were associated with increased PCC risk, except for age and sex. Conversely, vaccination was associated with a largely reduced PCC risk, particularly for the cardiopulmonary subtypes. Individuals with PCC experienced a much worse physical and mental health. Specifically, the cardiopulmonary subtype had the most pronounced adverse impact on function impairments, followed by neurological, mild fatigue, and ENT subtype. The most affected functions included the ability to concentrate, participate in day-to-day work, and emotional vulnerability to health problems. PCC can be categorized into four distinct subtypes based on ten core symptoms. These subtypes appeared to share a majority of pathogen and host-related risk factors, but their impact on health varied markedly by subtype. Our findings could help refine current guidelines for precise PCC diagnosis and progression, enhance the identification of PCC subgroups for targeted research, and inform evidence-based policy making to tackle this new and debilitating condition. NIHR Senior Research Fellowship (grant SRF-2018-11-ST2-004).

Incidence of Severe Illness in Pediatric Influenza Outpatients Treated with Baloxavir or Neuraminidase Inhibitors.

A single oral dose of baloxavir marboxil, a cap-dependent endonuclease inhibitor, is approved for patients with influenza A or B infection; however, real-world evidence is limited. We evaluated the effectiveness of baloxavir vs neuraminidase inhibitors in reducing the incidence of severe illness in influenza outpatients aged 5-11 years. In this retrospective cohort study, we analyzed individual-level data from patients treated with these antivirals, using a large, Japanese health insurance claims database (JMDC). Patients were included at the first date of diagnosis of the influenza virus infection (Day 1) in two influenza seasons. The primary outcome was the incidence of hospitalization from Day 2-14. Of 196,749 included patients (Season 2018/2019, n=103,709; Season 2019/2020, n=93,040), 20.9% received baloxavir, 38.8% received oseltamivir, 28.7% received laninamivir, and 11.6% received zanamivir. In each treatment group, 61-70% patients had influenza A. The incidence of hospitalization from Day 2-14 was significantly lower for baloxavir than for oseltamivir, laninamivir, and zanamivir. The adjusted risk ratio (95% CI) for oseltamivir, laninamivir, and zanamivir were 1.86 (1.30-2.68), 2.11 (1.37-3.25), and 1.90 (1.31-2.77), respectively, compared with baloxavir. Comparative incidence of hospitalizations between agents were unaffected by season or virus type. Using a large, Japanese health insurance claims database, a lower rate of hospitalization was demonstrated in children aged 5-11 years with an influenza virus infection when treated with baloxavir vs neuraminidase inhibitors. Thus, single dose, oral baloxavir may reduce the incidence of severe illness in these patients.

Effectiveness of the BNT162b2 XBB.1.5-adapted vaccine against COVID-19 hospitalization related to the JN.1 variant in Europe: a test-negative case-control study using the id.DRIVE platform

Prior studies have reported lower effectiveness of XBB.1.5-adapted vaccines against hospitalization related to the Omicron JN.1 variant than the XBB variant. This study evaluated the effectiveness and durability of the BNT162b2 XBB.1.5-adapted vaccine against JN.1-related hospitalization during the 2023-2024 season in Europe. A test-negative case-control study was carried out in adults (≥18y) hospitalized between 2 October 2023 and 2 April 2024 with severe acute respiratory infection (SARI) within the id.DRIVE partnership. This study included nine sites across Belgium, Germany, Italy, and Spain. Cases had a laboratory-confirmed JN.1 infection or a positive SARS-CoV-2 test with symptom onset during JN.1 predominance; controls had a negative SARS-CoV-2 test and symptom onset during JN.1 predominance. The primary objective was to estimate BNT162b2 XBB.1.5-adapted vaccine effectiveness (VE) against COVID-19 hospitalization. One case was matched with up to four controls, according to symptom onset date and site. Multivariable analyses were adjusted for symptom onset date, age, sex, and number of chronic conditions. Among 308 test-positive cases and 1117 test-negative controls, BNT162b2 XBB.1.5-adapted VE against hospitalization compared to no vaccination this season was 53.8% (95% CI 38.4-65.4) after a median of 63 days following vaccination. Protection was sustained through five months; VE was 52.2% (95% CI 41.3-61.1) 2 to <4 weeks after vaccination, 48.9% (95% CI 17.9-68.2) at 4 to <8 weeks, and ranged from 54.6% to 59.5% at 4-week intervals from 8 to <22 weeks. BNT162b2 XBB.1.5-adapted vaccine provided protection against JN.1-related hospitalization, regardless of prior vaccination history, with no evidence of waning through five months. These data support yearly vaccination against COVID-19 to prevent severe illness during the respiratory virus season. Pfizer.

In silico antiviral effect assessment of some venom gland peptides from Odontobuthus doriae scorpion against SARS-CoV-2.

SARS-CoV-2 is from the enveloped virus family responsible for the COVID-19 pandemic. No efficient drugs are currently available to treat infection explicitly caused by this virus. Therefore, searching for effective treatments for severe illness caused by SARS-CoV-2 is crucial. Scorpion venoms are significant sources of peptides with pharmaceutical potential, including antivirals. Although some studies have determined the antiviral effects of some scorpion peptides on other members of the Coronaviridae family, a few anti-SARS-CoV-2 effects of these peptides have been reported until now. This study assessed the antiviral effects of five predicted antimicrobial peptides with potential for antiviral activities from the Iranian yellow scorpion "Odontobuthus doriae" by computational methods. These peptides were selected from the cDNA library that our research team constructed. A 3D model of peptides was designed with I-TASSER. The models were refined using a 200 ns Molecular Dynamics (MD) simulation using Gromacs 2021.2 software. Refined models were Docked with the RBD domain of SARS-CoV-2 spike protein using HADDOCK software. The docking of human ACE2 peptide with the RBD domain was also assessed. The docked complexes (RBD-peptide and RBD-ACE2) were refined again by a 100 ns MD simulation and then analyzed. The results from molecular docking after molecular dynamics simulation showed that ODAMP2 and ODAMP5 after stabilizing analysis and according to MMPBSA results (with -59.24 kcal/mol and -51.82 kcal/mol, respectively) have a strong binding affinity to the RBD domain of COVID-19 spike protein compared to human ACE2 and some other studied components. Therefore, this peptide can be an excellent candidate for use as an agent to inhibit the RBD domain of SARS-COV2 virus in clinical studies for medicinal purposes after in vitro and in vivo laboratory evaluations.

Raman spectroscopic fingerprinting for the identification and quantitative analysis of sports doping β-agonists based on gold nanopolyhedra.

Beta-stimulant, that is, β-adrenergic stimulant, also known as β-agonists, is bioactive catecholamine compounds naturally produced in animals' adrenal medulla glands that induce relaxation in asthmatic airway smooth muscles upon inhalation while also temporarily boosting athletic alertness and alleviating fatigue. However, their potential for dependency poses health risks including unnoticed exacerbation leading to severe illness or fatality prompting their inclusion on WADA's prohibited substances list. Surface-enhanced Raman spectroscopy (SERS) offers a rapid, sensitive, and label-free means for identifying characteristic peaks associated with β-agonist compounds. In our investigation, the utilization of seed-mediated synthesis technique facilitated production of gold polyhedral substrates serving as highly sensitive biosensors for detecting β-agonist presence. The unique geometry of these particles generates enhanced SERS signals due to their multiple corners, resulting low detection limits (9.33×10-7, 6.28×10-7, and 6.19×10-7 g·mL-1 for salbutamol, clenbuterol and higenamine respectively), with promising prospects for improving overall sensitivity in β-agonists detection.

A Retrospective Observational Cohort Analysis of Oncology Patients with Febrile Neutropenia in the Emergency Department of a Tertiary Care Hospital in Oman

Abstract Background: Febrile neutropenia, a critical concern in chemotherapy-treated oncology patients, demands swift and guideline-based management. This study evaluated guideline adherence and clinical outcomes in the management of febrile neutropenia in oncology patients in the emergency department (ED). Methods: This retrospective study was conducted over 4 years. The primary focus was the evaluation of adherence to guidelines for patient disposition and clinical outcomes. Data were retrieved from the hospital’s electronic records, systematically organized, and analyzed. Results: A total of 121 febrile neutropenic cases were included in the study. Of these, 52.9% were classified as low risk, with 44.6% having hematological malignancies and 55.4% having solid malignancies. Most patients (89.3%) presented with active cancer, and the mean neutrophil count was 0.18. High-risk patients exhibited significantly higher rates of positive blood cultures (31.6% vs. 1.6%) and positive urine cultures (20.8% vs. 7.7%). Chest X-rays were positive in 5.5% of low-risk patients and 23.2% of high-risk patients. Fungal infection rates were 1.6% in low-risk patients and 29.8% in high-risk patients. Complications were more frequent in high-risk patients, including sepsis-induced hypotension in 6.3% of low-risk patients and 43.9% of high-risk patients. Deaths occurred in 21.1% of high-risk patients, and intensive care unit (ICU) admissions were 24.6% in the high-risk group, with no ICU admissions in the low-risk group. Binary logistic regression revealed that male patients had a 60% lower risk of guideline discordance than female patients (odds ratio [OR]: 0.400, 95% confidence interval [CI]: 0.180-0.891, P = 0.025), whereas diabetic patients had a 75% lower risk than nondiabetic patients (OR: 0.254, 95% CI: 0.069–0.934, P = 0.039). Conclusion: As expected, high-risk patients demonstrated greater illness severity than low-risk patients, with higher rates of admission, sepsis-induced hypotension, and mortality.