Tag: pubmed

N Engl J Med. 2022 Nov 3;387(18):1649-1660. doi: 10.1056/NEJMoa2206660.

ABSTRACT

BACKGROUND: In adults with advanced-stage Hodgkin’s lymphoma, the CD30-directed antibody-drug conjugate brentuximab vedotin combined with multiagent chemotherapy has been shown to have greater efficacy, but also more toxic effects, than chemotherapy alone. The efficacy of this targeted therapy approach in children and adolescents with Hodgkin’s lymphoma is unclear.

METHODS: We conducted an open-label, multicenter, randomized, phase 3 trial involving patients 2 to 21 years of age with previously untreated Hodgkin’s lymphoma of stage IIB with bulk tumor or stage IIIB, IVA, or IVB. Patients were assigned to receive five 21-day cycles of brentuximab vedotin with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (brentuximab vedotin group) or the standard pediatric regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (standard-care group). Slow-responding lesions, defined by a score of 4 or 5 (on a 5-point scale, with scores of 1 to 3 indicating rapid-responding lesions), were identified on centrally reviewed positron-emission tomography-computed tomography after two cycles. Involved-site radiation therapy was administered after the fifth cycle of therapy to slow-responding lesions and to large mediastinal adenopathy that was present at diagnosis. The primary end point was event-free survival, defined as the time until disease progression occurred, relapse occurred, a second malignant neoplasm developed, or the patient died. Safety and overall survival were assessed.

RESULTS: Of 600 patients who were enrolled across 153 institutions, 587 were eligible. At a median follow-up of 42.1 months (range, 0.1 to 80.9), the 3-year event-free survival was 92.1% (95% confidence interval [CI], 88.4 to 94.7) in the brentuximab vedotin group, as compared with 82.5% (95% CI, 77.4 to 86.5) in the standard-care group (hazard ratio for event or death, 0.41; 95% CI, 0.25 to 0.67; P<0.001). The percentage of patients who received involved-site radiation therapy did not differ substantially between the brentuximab vedotin group and the standard-care group (53.4% and 56.8%, respectively). Toxic effects were similar in the two groups. Overall survival at 3 years was 99.3% (95% CI, 97.3 to 99.8) in the brentuximab vedotin group and 98.5% (95% CI, 96.0 to 99.4) in the standard-care group.

CONCLUSIONS: The addition of brentuximab vedotin to standard chemotherapy resulted in superior efficacy, with a 59% lower risk of an event or death, and no increase in the incidence of toxic effects at 3 years. (Funded by the National Institutes of Health and others; AHOD1331 ClinicalTrials.gov number, NCT02166463.).

PMID:36322844 | DOI:10.1056/NEJMoa2206660

N Engl J Med. 2022 Nov 2. doi: 10.1056/NEJMoa2210058. Online ahead of print.

ABSTRACT

BACKGROUND: The BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) has been authorized for use in children 5 to 11 years of age and adolescents 12 to 17 years of age but in different antigen doses.

METHODS: We assessed the real-world effectiveness of the BNT162b2 vaccine against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children and adolescents in Qatar. To compare the incidence of SARS-CoV-2 infection in the national cohort of vaccinated participants with the incidence in the national cohort of unvaccinated participants, we conducted three matched, retrospective, target-trial, cohort studies – one assessing data obtained from children 5 to 11 years of age after the B.1.1.529 (omicron) variant became prevalent and two assessing data from adolescents 12 to 17 years of age before the emergence of the omicron variant (pre-omicron study) and after the omicron variant became prevalent. Associations were estimated with the use of Cox proportional-hazards regression models.

RESULTS: Among children, the overall effectiveness of the 10-μg primary vaccine series against infection with the omicron variant was 25.7% (95% confidence interval [CI], 10.0 to 38.6). Effectiveness was highest (49.6%; 95% CI, 28.5 to 64.5) right after receipt of the second dose but waned rapidly thereafter and was negligible after 3 months. Effectiveness was 46.3% (95% CI, 21.5 to 63.3) among children 5 to 7 years of age and 16.6% (95% CI, -4.2 to 33.2) among those 8 to 11 years of age. Among adolescents, the overall effectiveness of the 30-μg primary vaccine series against infection with the omicron variant was 30.6% (95% CI, 26.9 to 34.1), but many adolescents had been vaccinated months earlier. Effectiveness waned over time since receipt of the second dose. Effectiveness was 35.6% (95% CI, 31.2 to 39.6) among adolescents 12 to 14 years of age and 20.9% (95% CI, 13.8 to 27.4) among those 15 to 17 years of age. In the pre-omicron study, the overall effectiveness of the 30-μg primary vaccine series against SARS-CoV-2 infection among adolescents was 87.6% (95% CI, 84.0 to 90.4) and waned relatively slowly after receipt of the second dose.

CONCLUSIONS: Vaccination in children was associated with modest, rapidly waning protection against omicron infection. Vaccination in adolescents was associated with stronger, more durable protection, perhaps because of the larger antigen dose. (Funded by Weill Cornell Medicine-Qatar and others.).

PMID:36322837 | DOI:10.1056/NEJMoa2210058

J Am Chem Soc. 2022 Nov 2. doi: 10.1021/jacs.2c08770. Online ahead of print.

ABSTRACT

RNA is challenging to target with bioactive small molecules, particularly those of low molecular weight that bind with sufficient affinity and specificity. In this report, we developed a platform to address this challenge, affording a novel bioactive interaction. An RNA-focused small-molecule fragment collection (n = 2500) was constructed by analyzing features in all publicly reported compounds that bind RNA, the largest collection of RNA-focused fragments to date. The RNA-binding landscape for each fragment was studied by using a library-versus-library selection with an RNA library displaying a discrete structural element, probing over 12.8 million interactions, the greatest number of interactions between fragments and biomolecules probed experimentally. Mining of this dataset across the human transcriptome defined a drug-like fragment that potently and specifically targeted the microRNA-372 hairpin precursor, inhibiting its processing into the mature, functional microRNA and alleviating invasive and proliferative oncogenic phenotypes in gastric cancer cells. Importantly, this fragment has favorable properties, including an affinity for the RNA target of 300 ± 130 nM, a molecular weight of 273 Da, and quantitative estimate of drug-likeness (QED) score of 0.8. (For comparison, the mean QED of oral medicines is 0.6 ± 0.2). Thus, these studies demonstrate that a low-molecular weight, fragment-like compound can specifically and potently modulate RNA targets.

PMID:36322830 | DOI:10.1021/jacs.2c08770

Geriatr Psychol Neuropsychiatr Vieil. 2022 Sep 1;20(3):293-302. doi: 10.1684/pnv.2022.1058.

ABSTRACT

INTRODUCTION: Giant cell arteritis (GCA) or Horton’s disease is a segmental and focal inflammation of large and medium-sized arteries mostly seen in patients of 50 years and older. There is also a peak frequency in individuals between the ages of 70 and 80. However, clinical data is scarce in this age group and especially in patients over 80.

METHODS: A retrospective study comprised of patients diagnosed with Horton’s arteritis between 2012 and 2017, according to the American Society of Rheumatology, was conducted at Reims University Hospital. Patients were assigned to two groups according to age (≤ 75 and < 75) in order to evaluate and compare the impact of age on diagnosis, treatment and prognosis.

RESULTS: A total of 67 patients were studied. The mean age upon diagnosis was 75,85 ±8.5 years; 36 patients (53.7%) 75 years or younger and 31 patients older than 75. There was a female predominance (43 patients), 22 patients aged 75 years or younger and 21 older than 75. The mean follow up duration was 43.02 months in patients aged 75 years or younger and 30.99 in patients older than 75. This represents a difference of more than one year in terms of follow up, but is not statistically significant (p = 0.620). Eleven patients (16.4%) died during follow up: 5 patients (13.9%) aged 75 years or younger and 6 patients (19.4%) older than 75 (p = 0.547). Aortitis was significantly less seen in patients older than 75 (p = 0.0410).

CONCLUSION: Our study showed no significant difference in either age group. However, aortitis was less seen in patients older than 75 years. Patients aged 75 or younger seemed more prone to relapses, but their follow up periods were shorter.

PMID:36322811 | DOI:10.1684/pnv.2022.1058

Proc Natl Acad Sci U S A. 2022 Nov 16;119(46):e2202538119. doi: 10.1073/pnas.2202538119. Epub 2022 Nov 2.

ABSTRACT

Understanding community-level selection using Lewontin’s criteria requires both community-level inheritance and community-level heritability, and in the discipline of community and ecosystem genetics, these are often conflated. While there are existing studies that show the possibility of both, these studies impose community-level inheritance as a product of the experimental design. For this reason, these experiments provide only weak support for the existence of community-level selection in nature. By contrast, treating communities as interactors (in line with Hull’s replicator-interactor framework or Dawkins’s idea of the “extended phenotype”) provides a more plausible and empirically supportable model for the role of ecological communities in the evolutionary process.

PMID:36322791 | DOI:10.1073/pnas.2202538119

Sci Adv. 2022 Nov 4;8(44):eabq4415. doi: 10.1126/sciadv.abq4415. Epub 2022 Nov 2.

ABSTRACT

Volcanic activity typically switches between high-activity states with many eruptions and low-activity states with few or no eruptions. We present a simple two-regime physics-informed statistical model that allows interpreting temporal modulations in eruptive activity. The model enhances comprehension and comparison of different volcanic systems and enables homogeneous integration into multivolcano hazard assessments that account for potential changes in volcanic regimes. The model satisfactorily fits the eruptive history of the three active volcanoes in the Neapolitan area, Italy (Mt. Vesuvius, Campi Flegrei, and Ischia) which encompass a wide range of volcanic behaviors. We find that these volcanoes have appreciably different processes for triggering and ending high-activity periods connected to different dominant volcanic processes controlling their eruptive activity, with different characteristic times and activity rates (expressed as number of eruptions per time interval). Presently, all three volcanoes are judged to be in a low-activity state, with decreasing probability of eruptions for Mt. Vesuvius, Ischia, and Campi Flegrei, respectively.

PMID:36322667 | DOI:10.1126/sciadv.abq4415

Logoped Phoniatr Vocol. 2022 Nov 2:1-13. doi: 10.1080/14015439.2022.2140455. Online ahead of print.

ABSTRACT

Background and Aim: To date, little research is available that objectively quantifies female adolescent singing-voice characteristics in light of the physiological and functional developments that occur from puberty to adulthood. This exploratory study sought to augment the pool of data available that offers objective voice analysis of female singers in late adolescence.Methods: Using long-term average spectra (LTAS) and inverse filtering techniques, dynamic range and voice-source characteristics were determined in a cohort of vocally healthy cis-gender female adolescent singers (17 to 19 years) from high-school choirs in Aotearoa New Zealand. Non-parametric statistics were used to determine associations and significant differences.Results: Wide intersubject variation was seen between dynamic range, spectral measures of harmonic organisation (formant cluster prominence, FCP), noise components in the spectrum (high-frequency energy ratio, HFER), and the normalised amplitude quotient (NAQ) suggesting great variability in ability to control phonatory mechanisms such as subglottal pressure (P_sub), glottal configuration and adduction, and vocal tract shaping. A strong association between the HFER and NAQ suggest that these non-invasive measures may offer complimentary insights into vocal function, specifically with regard to glottal adduction and turbulent noise in the voice signal.Conclusion: Knowledge of the range of variation within healthy adolescent singers is necessary for the development of effective and inclusive pedagogical practices, and for vocal-health professionals working with singers of this age. LTAS and inverse filtering are useful non-invasive tools for determining such characteristics.

PMID:36322641 | DOI:10.1080/14015439.2022.2140455

J Can Dent Assoc. 2022 Aug;88:m7.

ABSTRACT

OBJECTIVE: Various teething remedies have been widely marketed to caregivers. Unsafe remedies, including teething necklaces and topical anesthetics, have been implicated in adverse events, such as suffocation injuries and death. However, little is known about the extent of their use. Our primary objective was to assess the prevalence of teething remedy use among caregivers. A secondary objective was to determine whether the use of unsafe teething remedies is related to socioeconomic status (SES) or maternal education.

METHODS: Children aged 12-18 months visiting primary care providers for routine checkups were included. Children outside that age group and those with chronic medical conditions were excluded. Caregivers completed a questionnaire about their children’s teething symptoms and remedies used to relieve them. Unsafe remedies were defined on the basis of American Academy of Pediatrics and Canadian Paediatric Society recommendations and included topical anesthetics, teething necklaces and liquid-filled teething rings.

RESULTS: Of the 130 questionnaires, 123 were complete and included in statistical analysis: 98% of families used teething remedies and 67% were unsafe. Of these families, 27% used amber teething necklaces; 28% used more than 1 unsafe remedy. Apart from topical anesthetic use, no significant correlations were found between overall unsafe remedy use and SES or maternal education.

CONCLUSION: Unsafe teething remedies are commonly used despite recommendations against them. Use of unsafe teething remedies transcends SES and education level.

PMID:36322634

J Can Dent Assoc. 2022 Jul;88:m5.

ABSTRACT

OBJECTIVES: To understand the risk factors that may be associated with the development of oral lichen planus (OLP) and its progression.

STUDY DESIGN: We conducted retrospective chart reviews of adult patients with OLP who presented to oral medicine and oral pathology clinics in 2 provinces between September 2016 and January 2020. Data regarding age, sex, disease duration, sites of involvement, comorbidities, medications, allergies, smoking, alcohol use, treatment and follow up were collected. Descriptive statistics were assessed.

RESULTS: Among the 94 patients with OLP, mean age was 62 years and most were female (73%). Mean disease duration was 3.1 years. Hypertension, thyroid disorders and diabetes were present in 32%, 28% and 17% of patients, respectively. A significant proportion of patients reported a major surgical procedure (47%) as a preceding event and an additional 7% reported a preceding stressful life event. Three OLP patients (3%) developed squamous cell carcinoma or dysplasia. The mean disease duration for these patients was 4.06 years and the frequency of biopsy in our study was approximately 14%.

CONCLUSIONS: Female sex, endocrine and immunological comorbidities, such as thyroid disease and diabetes, and psychological stress may play a role in the development of OLP in the Canadian population. A small percentage of patients may develop malignant transformation and, thus, require long-term monitoring.

PMID:36322633

Fam Community Health. 2022 Oct 31. doi: 10.1097/FCH.0000000000000350. Online ahead of print.

ABSTRACT

Congestive heart failure (CHF) readmissions are frequent and costly but preventable. The purpose of this study was to analyze socioeconomic and health-related factors of CHF readmissions by examining the relationship between 30-day readmissions of individuals with CHF and their payer status, race, ethnicity, primary language spoken, living arrangement, and comorbidities. This retrospective case-control study used secondary data from 450 CHF patients admitted to a not-for-profit Northern Virginia hospital from July 2014 to December 2017. Data were analyzed using χ2 and logistic regression. Living arrangements and comorbid chronic renal failure (CRF) were statistically significant predictors of CHF readmissions; all other factors were nonsignificant. Patients who lived with family and those in assisted living facilities were less likely to be readmitted than those who lived alone (odds ratio [OR] = 0.2 and 0.5, respectively). Patients without CRF were less likely to be readmitted than those who had CRF (OR = 0.6). This study contributes data to inform community-based health programs tailored toward frequently readmitted individuals due to CHF exacerbation.

PMID:36322616 | DOI:10.1097/FCH.0000000000000350