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Nevin Manimala Statistics

The antigenic landscape of human influenza N2 neuraminidases from 2009 until 2017

Elife. 2024 May 28;12:RP90782. doi: 10.7554/eLife.90782.

ABSTRACT

Human H3N2 influenza viruses are subject to rapid antigenic evolution which translates into frequent updates of the composition of seasonal influenza vaccines. Despite these updates, the effectiveness of influenza vaccines against H3N2-associated disease is suboptimal. Seasonal influenza vaccines primarily induce hemagglutinin-specific antibody responses. However, antibodies directed against influenza neuraminidase (NA) also contribute to protection. Here, we analysed the antigenic diversity of a panel of N2 NAs derived from human H3N2 viruses that circulated between 2009 and 2017. The antigenic breadth of these NAs was determined based on the NA inhibition (NAI) of a broad panel of ferret and mouse immune sera that were raised by infection and recombinant N2 NA immunisation. This assessment allowed us to distinguish at least four antigenic groups in the N2 NAs derived from human H3N2 viruses that circulated between 2009 and 2017. Computational analysis further revealed that the amino acid residues in N2 NA that have a major impact on susceptibility to NAI by immune sera are in proximity of the catalytic site. Finally, a machine learning method was developed that allowed to accurately predict the impact of mutations that are present in our N2 NA panel on NAI. These findings have important implications for the renewed interest to develop improved influenza vaccines based on the inclusion of a protective NA antigen formulation.

PMID:38805550 | DOI:10.7554/eLife.90782

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Effectiveness of Radiofrequency Ablation of the Genicular Nerves of the Knee for the Management of Intractable Pain from Knee Osteoarthritis

Pain Physician. 2024 May;27(4):E419-E429.

ABSTRACT

BACKGROUND: The knee joint is one of the most common diseases in elderly individuals. This is a progressive and debilitating condition. The purpose of knee osteoarthritis treatment is to manage pain, increase mobility, and improve the quality of life.

OBJECTIVES: This study evaluated the therapeutic effect of radiofrequency thermocoagulation (RFTC) on the genicular nerves in patients with intractable pain due to knee osteoarthritis, as well as its effects on pain severity and magnetic resonance imaging (MRI) findings.

STUDY DESIGN: A prospective outcome study.

SETTING: The outpatient clinic of a single academic medical center.

METHODS: We conducted a prospective study. Fifty consecutive patients with intractable knee pain due to osteoarthritis were enrolled and underwent ultrasound (US)-guided RFTC of the genicular nerves (medial superior genicular nerve, medial inferior genicular nerve, and lateral superior genicular nerve). Pain severity was measured using the Numeric Rating Scale (NRS), and knee osteoarthritis-associated symptoms were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at pretreatment and one, 3, and 6 months after RFTC treatment. We also analyzed the relationship between therapeutic outcomes and pain severity based on pre-treatment and knee MRI findings.

RESULTS: No dropouts were observed. The most significant reduction in knee symptoms associated with knee osteoarthritis was observed after one month of treatment; however, at 3 and 6 months, there was a rebound effect, leading to a decrease in therapeutic efficacy. Nonetheless, there was still a noticeable decrease in symptoms due to knee osteoarthritis compared to those prior to RFTC treatment. The effect of RFTC treatment was better when pre-treatment pain was relatively less severe, knee effusion was not severe, there were no meniscal tears in the middle or posterior zones, no bone marrow edema in the middle and posterior zones of the femur and tibia, and no severe cartilage defects in the posterior femur and middle and posterior tibia.

LIMITATIONS: We conducted our study without a control or a placebo group.

CONCLUSION: RFTC of the genicular nerve is a good therapeutic option for controlling intractable pain following knee osteoarthritis. In addition, we found that a lower level of pain prior to treatment, along with the absence or lesser degree of knee joint effusion, as well as an absence or less severe middle or posterior knee pathologies associated with knee osteoarthritis, can predict a more favorable therapeutic outcome.

PMID:38805537

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Computed Tomography-Guided Radiofrequency Ablation for Glossopharyngeal Neuralgia: Comparison of Cervical Computed Tomography Angiography, Transverse Process of Atlas, and Styloid Process Localization to Styloid Process Localization Alone

Pain Physician. 2024 May;27(4):E395-E406.

ABSTRACT

BACKGROUND: Glossopharyngeal neuralgia (GPN) is a condition that causes simultaneous headache and facial pain. The treatment for GPN is similar to the treatment for trigeminal neuralgia. Craniotomy microvascular decompression (MVD) or radiofrequency (RF) therapy is needed if conservative treatment with oral drugs fails. Therefore, the choice of radiofrequency therapy target is essential when treating GPN. However, finding the glossopharyngeal nerve simply by styloid process positioning is challenging.

STUDY DESIGN: Prospective, clinical research study.

SETTING: Department of Anesthesiology and Pain Medical Center, Jiaxing, China.

OBJECTIVE: To compare the clinical effects of computed tomography (CT)-guided RF treatments on GPN when the triple localization of cervical CT, the transverse process of the atlas, and the styloid process is used to those achieved when the treatments are guided by the styloid process alone.

METHODS: From August 2016 to December 2019, 19 cases of GPN neuralgia were treated by radiofrequency under the guidance of CT guided by the styloid process only. (These patients comprised the single localization (SL) of styloid process group, in whom the target of the RF treatments was the posterior medial side of half of the styloid process). From January 2020 to December 2022, 16 cases of GPN were treated by RF under the guidance of CT with cervical CTA (CT angiography), the transverse process of the atlas, and the styloid process. (These patients were placed in the TL group, in whom the target of RF therapy was the gap between the internal carotid artery and the internal jugular vein behind the horizontal styloid process at the lower edge of the transverse process of the atlas). Two percent lidocaine was injected subcutaneously at the needle insertion site, and a stylet with a 21-gauge blunt RF needle (model: 240100, manufacturer: Englander Medical Technology Co., Ltd.) was slowly advanced toward the target. After that, an RF probe was introduced, then low (2 Hz)- and high (50 Hz)-frequency currents of the RF instrument (model: PMG-230, Canada Baylis company) were applied to stimulate. A successful test was defined as a 0.5-1.0 mA current stimulation that could induce the original pain area in the pharynx, the inner ear, or both, without any abnormal irritation of the vagus or accessory nerves. If the first test was unsuccessful, then in the SL group, the needle tip’s position was adjusted to the distal end of the styloid process, and in the triple localization (TL) group, the needle tip depth’s was fine-tuned. A continuous RF treatment was given after a successful test. The RF temperature was 95ºC for 180 seconds. The time that the first puncture reached the target, the puncture paths, the success rate of the first test, the time that the glossopharyngeal nerve was found, the frequency of adjustments to the position of the RF needle, the incidence of intraoperative and postoperative complications, and the therapeutic effects were recorded.

RESULTS: There were no significant differences in demographic data such as age, medical history, lateral classification, and pain score between the groups, but the TL group had a higher proportion of women than did the SL group. All patients’ puncture targets were identified according to the designed puncture path before the operation. There was no difference between the 2 groups in the time of the first puncture to the target (5.05 ± 1.22 vs. 5.82 ± 1.51, P = 0.18), and the designed puncture depth (3.65 ± 0.39 vs. 4.04 ± 0.44). The difference in puncture angles (13.48 ± 3.56 vs. 17.84 ± 3.98, P < 0.01) was statistically significant, and in 8 cases in the SL group, the glossopharyngeal nerve could not be found after 60 minutes of testing, so the RF treatment was terminated. Meanwhile, this problem occurred in only 2 cases in the TL group. There were 3 cervical hematoma cases and 2 cases of transient hoarseness and cough in the SL group, whereas the TL group had, respectively, 0 and one cases of those issues. There was no death in either group.

LIMITATIONS: More clinical data should be collected in future studies.

CONCLUSION: When using RF as a treatment for GPN, the glossopharyngeal nerve is easier to find by using the triple positioning of the cervical CTA, the transverse process of the atlas and the styloid process as the target to determine the anterior medial edge of the internal carotid artery behind the styloid process at the level of the lower edge of the atlas transverse process. The glossopharyngeal nerve is more difficult to locate when only the posterior medial edge of the styloid process is targeted. The single-time effective rate of 180 seconds of RF ablation at 90ºC for GPN can reach 87.5% (14/16), suggesting the treatment’s potential for clinical application.

PMID:38805535

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Percutaneous Vertebroplasty Versus Balloon Kyphoplasty in the Treatment of Osteoporotic Vertebral Compression Fractures: Evaluating the Overlapping Meta-analyses

Pain Physician. 2024 May;27(4):E383-E394.

ABSTRACT

BACKGROUND: Numerous meta-analyses and systematic reviews have explored the differences between percutaneous vertebroplasty (PVP) and percutaneous balloon kyphoplasty (PKP) for treating osteoporotic vertebral compression fractures (OVCFs), however, their final conclusions have been inconsistent. The inconsistent conclusions drawn from these meta-analyses create uncertainty among clinicians about the best treatment approach for OVCFs.

OBJECTIVE: The aim of this study was to conduct a cross-sectional analysis of overlapping meta-analyses comparing PVP and PKP treatments for OVCF in order to help clinicians have access to the best available evidence and provide treatment recommendations based on the best available evidence.

STUDY DESIGN: A cross-sectional analysis of overlapping meta-analyses.

METHODS: We conducted a comprehensive search of meta-analyses published up to February 2023 in PubMed, Embase, Cochrane Library and Web of Science databases to identify relevant studies. The methodological quality of these studies was assessed using the Assessment of Multiple Systematic Reviews tool (original AMSTAR) and the Oxford Centre for Evidence-based Medicine Levels of Evidence. Two researchers independently extracted the data and assessed the quality of these meta-analyses. To determine which meta-analyses represented the best evidence, we employed the Jadad decision algorithm.

RESULTS: Seventeen meta-analyses were included in the study, with AMSTAR scores ranging from 4 to 9, with an average of 7. After rigorous scrutiny, the Zhu et al study was determined to provide the best evidence. According to their findings, both PVP and PKP effectively alleviate pain and improve function in the treatment of OVCFs, without any statistically significant differences between them. In addition, PKP can reduce the risk of polymethylmethacrylate leakage compared to PVP.

LIMITATIONS: This study analyzed published overlapping meta-analyses, inherently confining our investigation to the meta-analysis level. Furthermore, based on the AMSTAR scores, several included studies exhibited lower methodological quality.

CONCLUSIONS: Currently, the best evidence indicates that PVP and PKP are equally effective at alleviating pain and enhancing function in the treatment of OVCFs, but PKP had a lower incidence of polymethylmethacrylate leakage. However, there is still a need for high-quality randomized controlled trials to provide higher levels of evidence regarding other aspects of the differences between the 2 procedures.

PMID:38805534

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Effectiveness and Safety of Flupentixol and Melitracen Tablets for the Treatment of Patients with Persistent Idiopathic Facial Pain: A Retrospective Observational Study

Pain Physician. 2024 May;27(4):263-272.

ABSTRACT

BACKGROUND: Flupentixol and melitracen are being investigated for their potential effectiveness in managing persistent idiopathic facial pain (PIFP), based on their mechanisms of action as dopamine receptor antagonists and noradrenaline/serotonin reuptake inhibitors, respectively. The efficacy and safety of flupentixol and melitracen (FM) tablets in treating PIFP were retrospectively analyzed at our hospital.

OBJECTIVES: The aim of this study is to determine the effectiveness and safety of FM tablets in treating PIFP.

STUDY DESIGN: Retrospective unicentric cohort design.

SETTING: An academic university hospital.

METHODS: A retrospective analysis was conducted on a cohort comprising 128 patients with a definite diagnoses of PIFP who were treated with FM tablets (flupentixol 0.5 mg and melitracen 10 mg tablet, >= 4 tablets/d) from January 2022 through May 2023 at an academic university hospital. Baseline conditions were statistically described, and Numeric Rating Scale (NRS-11) scores of pain levels before and during treatment were collected. Pain relief rates were calculated. Differences in baseline characteristics between responsive and unresponsive patients were evaluated using statistical tests. Additionally, the side effects experienced during treatment were summarized.

RESULTS: Among the included 128 patients, 105 (82.0%) patients achieved pain relief (pain NRS-11 score reduction rate >= 50%). The median treatment onset time was 3 (1-7) days. NRS-11 scores of responsive patients at week 2, week 4, week 8, and week 12 were significantly lower than the baseline NRS-11 scores (P < 0.001), regardless of their Hamilton Depression Rating Scale score. Pain duration was the only factor that related to responsiveness (Wilcoxon rank sum test, P < 0.001; logistic regression, P = 0.001). No serious side effects that could affect patients’ lives were observed during the first week of treatments.

LIMITATIONS: Due to its retrospective nature, this study is limited by its lack of a randomized control. The lack of data on nonresponders who did not achieve significant pain relief hinders assessing overall change and the placebo effects’. Patients previously treated with antidepressants were excluded, making it hard to determine if FM tablets were a better treatment for PIFP. Additionally, the small sample size in a single center may be influenced by chance variation in pain relief.

CONCLUSIONS: FM tablets showed its potential in the management of PIFP with considerable efficacy and safety. Early administration of FM tablets after a PIFP diagnosis may result in a high possibility of pain relief.

PMID:38805533

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Use of a Large Language Model to Identify and Classify Injuries With Free-Text Emergency Department Data

JAMA Netw Open. 2024 May 1;7(5):e2413208. doi: 10.1001/jamanetworkopen.2024.13208.

NO ABSTRACT

PMID:38805230 | DOI:10.1001/jamanetworkopen.2024.13208

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Air and Noise Pollution Exposure in Early Life and Mental Health From Adolescence to Young Adulthood

JAMA Netw Open. 2024 May 1;7(5):e2412169. doi: 10.1001/jamanetworkopen.2024.12169.

ABSTRACT

IMPORTANCE: Growing evidence associates air pollution exposure with various psychiatric disorders. However, the importance of early-life (eg, prenatal) air pollution exposure to mental health during youth is poorly understood, and few longitudinal studies have investigated the association of noise pollution with youth mental health.

OBJECTIVES: To examine the longitudinal associations of air and noise pollution exposure in pregnancy, childhood, and adolescence with psychotic experiences, depression, and anxiety in youths from ages 13 to 24 years.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the Avon Longitudinal Study of Parents and Children, an ongoing longitudinal birth cohort founded in 1991 through 1993 in Southwest England, United Kingdom. The cohort includes over 14 000 infants with due dates between April 1, 1991, and December 31, 1992, who were subsequently followed up into adulthood. Data were analyzed October 29, 2021, to March 11, 2024.

EXPOSURES: A novel linkage (completed in 2020) was performed to link high-resolution (100 m2) estimates of nitrogen dioxide (NO2), fine particulate matter under 2.5 μm (PM2.5), and noise pollution to home addresses from pregnancy to 12 years of age.

MAIN OUTCOMES AND MEASURES: Psychotic experiences, depression, and anxiety were measured at ages 13, 18, and 24 years. Logistic regression models controlled for key individual-, family-, and area-level confounders.

RESULTS: This cohort study included 9065 participants who had any mental health data, of whom (with sample size varying by parameter) 51.4% (4657 of 9051) were female, 19.5% (1544 of 7910) reported psychotic experiences, 11.4% (947 of 8344) reported depression, and 9.7% (811 of 8398) reported anxiety. Mean (SD) age at follow-up was 24.5 (0.8) years. After covariate adjustment, IQR increases (0.72 μg/m3) in PM2.5 levels during pregnancy (adjusted odds ratio [AOR], 1.11 [95% CI, 1.04-1.19]; P = .002) and during childhood (AOR, 1.09 [95% CI, 1.00-1.10]; P = .04) were associated with elevated odds for psychotic experiences. Pregnancy PM2.5 exposure was also associated with depression (AOR, 1.10 [95% CI, 1.02-1.18]; P = .01). Higher noise pollution exposure in childhood (AOR, 1.19 [95% CI, 1.03-1.38]; P = .02) and adolescence (AOR, 1.22 [95% CI, 1.02-1.45]; P = .03) was associated with elevated odds for anxiety.

CONCLUSIONS AND RELEVANCE: In this longitudinal cohort study, early-life air and noise pollution exposure were prospectively associated with 3 common mental health problems from adolescence to young adulthood. There was a degree of specificity in terms of pollutant-timing-outcome associations. Interventions to reduce air and noise pollution exposure (eg, clean air zones) could potentially improve population mental health. Replication using quasi-experimental designs is now needed to shed further light on the underlying causes of these associations.

PMID:38805229 | DOI:10.1001/jamanetworkopen.2024.12169

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Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects: A Randomized Clinical Trial

JAMA Netw Open. 2024 May 1;7(5):e2412291. doi: 10.1001/jamanetworkopen.2024.12291.

ABSTRACT

IMPORTANCE: Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years.

OBJECTIVES: To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD.

DESIGN, SETTING, AND PARTICIPANTS: This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children’s hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks’ gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024.

INTERVENTION: Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks’ gestational age.

MAIN OUTCOMES AND MEASURES: The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment.

RESULTS: The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02133573.

PMID:38805228 | DOI:10.1001/jamanetworkopen.2024.12291

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Survival, Function, and Cognition After Hospitalization in Long-Term Acute Care Hospitals

JAMA Netw Open. 2024 May 1;7(5):e2413309. doi: 10.1001/jamanetworkopen.2024.13309.

ABSTRACT

IMPORTANCE: More than 70 000 Medicare beneficiaries receive care in long-term acute care hospitals (LTCHs) annually for prolonged acute illness. However, little is known about long-term functional and cognitive outcomes of middle-aged and older adults after hospitalization in an LTCH.

OBJECTIVE: To describe survival, functional, and cognitive status after LTCH hospitalization and to identify factors associated with an adverse outcome.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included middle-aged and older adults enrolled in the Health and Retirement Study (HRS) with linked fee-for-service Medicare claims. Included participants were aged 50 years or older with an LTCH admission between January 1, 2003, and December 31, 2016, with HRS interviews available before admission. Data were analyzed between November 1, 2021, and June 30, 2023.

MAIN OUTCOMES AND MEASURES: Function and cognition were ascertained from HRS interviews conducted every 2 years. The primary outcome was death or severe impairment in the 2.5 years after LTCH hospitalization, defined as dependencies in 2 or more activities of daily living (ADLs) or dementia. Multivariable logistic regression was performed to evaluate associations with a priori selected risk factors including pre-LTCH survival prognosis (Lee index score), pre-LTCH impairment status, and illness severity characterized by receipt of mechanical ventilation and prolonged intensive care unit stay of 3 days or longer.

RESULTS: This study included 396 participants, with a median age of 75 (IQR, 68-82) years. Of the participants, 201 (51%) were women, 125 (28%) had severe impairment, and 318 (80%) died or survived with severe impairment (functional, cognitive, or both) within 2.5 years of LTCH hospitalization. After accounting for acute illness characteristics, prehospitalization survival prognosis as determined by the Lee index score and severe baseline impairment (functional, cognitive, or both) were associated with an increased likelihood of death or severe impairment in the 2.5 years after LTCH hospitalization (adjusted odds ratio [AOR], 3.2 [95% CI, 1.7 to 6.0] for a 5-point increase in Lee index score; and AOR, 4.5 [95% CI, 1.3 to 15.4] for severe vs no impairment).

CONCLUSIONS AND RELEVANCE: In this cohort study, 4 of 5 middle-aged and older adults died or survived with severe impairment within 2.5 years of LTCH hospitalization. Better preadmission survival prognosis and functional and cognitive status were associated with lower risk of an adverse outcome, and these findings should inform decision-making for older adults with prolonged acute illness.

PMID:38805226 | DOI:10.1001/jamanetworkopen.2024.13309

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Value in Optimizing the Components of App Interventions Before Final Testing

JAMA Intern Med. 2024 May 28. doi: 10.1001/jamainternmed.2024.0833. Online ahead of print.

NO ABSTRACT

PMID:38805201 | DOI:10.1001/jamainternmed.2024.0833