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RMD Open Jun 2024To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and... (Randomized Controlled Trial)
Randomized Controlled Trial
Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study.
OBJECTIVES
To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumour necrosis factor agent.
METHODS
In this phase 2a study, participants with RA seropositive for anticitrullinated protein antibodies (ACPA) or rheumatoid factors were randomised 3:2 to nipocalimab (15 mg/kg intravenously every 2 weeks) or placebo from Weeks 0 to 10. Efficacy endpoints (primary endpoint: change from baseline in Disease Activity Score 28 using C reactive protein (DAS28-CRP) at Week 12) and patient-reported outcomes (PROs) were assessed through Week 12. Safety, pharmacokinetics and pharmacodynamics were assessed through Week 18.
RESULTS
53 participants were enrolled (nipocalimab/placebo, n=33/20). Although the primary endpoint did not reach statistical significance for nipocalimab versus placebo, a numerically higher change from baseline in DAS28-CRP at Week 12 was observed (least squares mean (95% CI): -1.03 (-1.66 to -0.40) vs -0.58 (-1.24 to 0.07)), with numerically higher improvements in all secondary efficacy outcomes and PROs. Serious adverse events were reported in three participants (burn infection, infusion-related reaction and deep vein thrombosis). Nipocalimab significantly and reversibly reduced serum immunoglobulin G, ACPA and circulating immune complex levels but not serum inflammatory markers, including CRP. ACPA reduction was associated with DAS28-CRP remission and 50% response rate in American College of Rheumatology (ACR) criteria; participants with a higher baseline ACPA had greater clinical improvement.
CONCLUSIONS
Despite not achieving statistical significance in the primary endpoint, nipocalimab showed consistent, numerical efficacy benefits in participants with moderate to severe active RA, with greater benefit observed for participants with a higher baseline ACPA.
TRIAL REGISTRATION NUMBER
NCT04991753.
Topics: Humans; Arthritis, Rheumatoid; Male; Female; Middle Aged; Treatment Outcome; Antirheumatic Agents; Severity of Illness Index; Antibodies, Monoclonal, Humanized; Aged; Adult; Tumor Necrosis Factor-alpha; Double-Blind Method; Patient Reported Outcome Measures; Anti-Citrullinated Protein Antibodies
PubMed: 38942592
DOI: 10.1136/rmdopen-2024-004278 -
BMJ Paediatrics Open Jun 2024To determine the prevalence and associated factors of scabies among the children living in the Madrasahs (Islamic religious educational institution) of Bangladesh was...
INTRODUCTION
To determine the prevalence and associated factors of scabies among the children living in the Madrasahs (Islamic religious educational institution) of Bangladesh was the objective of the study.
METHODS
This cross-sectional study was conducted in eight selected Madrasahs from May to October 2023 among male and female children aged between 3 and 18 years. Children were screened for scabies according to criteria developed by the International Alliance for the Control of Scabies.
RESULTS
It was found that overall prevalence of scabies among the children living in Madrasahs was almost 34% (mild 73.5%, moderate 24.9% and severe 1.6%). Prevalence of scabies among male was higher than female (39.4% vs 28.4%). Male gender (aOR 2.09, 95% CI 1.27 to 3.47, p=0.004) and age (aOR 0.95, 95% CI 0.91 to 0.99, p=0.017) were two significant predictors of scabies among children. Besides, living in Madrasahs having more boarders (aOR 1.37, 95% CI 1.06 to 1.69, p=0.025), shared bedding, clothes or toilet stuffs with other children (aOR 1.46, 95% CI 1.03 to 2.09, p=0.036) and history of pruritus in the close entourage (aOR 4.19, 95% CI 3.07 to 5.73, p<0.001) were associated with a higher chance of being infected by scabies.
CONCLUSION
Almost one-third of the children living in the Islamic boarding schools in Bangladesh are suffering from scabies, more prevalence in male and younger children. Accommodation of higher number of boarders, sharing personal staffs and pruritus in close contacts increase the risk of scabies in these children.
Topics: Humans; Scabies; Male; Bangladesh; Female; Cross-Sectional Studies; Child; Prevalence; Adolescent; Risk Factors; Child, Preschool; Islam; Schools
PubMed: 38942588
DOI: 10.1136/bmjpo-2023-002421 -
Methods in Enzymology 2024Structural biology research of terpene synthases (TSs) has provided a useful basis to understand their catalytic mechanisms in producing diverse terpene products with...
Structural biology research of terpene synthases (TSs) has provided a useful basis to understand their catalytic mechanisms in producing diverse terpene products with polycyclic ring systems and multiple chiral centers. However, compared to the large numbers of>95,000 terpenoids discovered to date, few structures of TSs have been solved and the understanding of their catalytic mechanisms is lagging. We here (i) introduce the basic catalytic logic, the structural architectures, and the metal-binding conserved motifs of TSs; (ii) provide detailed experimental procedures, in gene cloning and plasmid construction, protein purification, crystallization, X-ray diffraction data collection and structural elucidation, for structural biology research of TSs; and (iii) discuss the prospects of structure-based engineering and de novo design of TSs in generating valuable terpene molecules, which cannot be easily achieved by chemical synthesis.
Topics: Alkyl and Aryl Transferases; Crystallography, X-Ray; Terpenes; Cloning, Molecular; Models, Molecular; Protein Conformation
PubMed: 38942516
DOI: 10.1016/bs.mie.2024.03.012 -
Methods in Enzymology 2024Terpenes comprise the largest class of natural products and are used in applications spanning the areas of medicine, cosmetics, fuels, flavorings, and more. Copalyl...
Terpenes comprise the largest class of natural products and are used in applications spanning the areas of medicine, cosmetics, fuels, flavorings, and more. Copalyl diphosphate synthase from the Penicillium genus is the first bifunctional terpene synthase identified to have both prenyltransferase and class II cyclase activities within the same polypeptide chain. Prior studies of bifunctional terpene synthases reveal that these systems achieve greater catalytic efficiency by channeling geranylgeranyl diphosphate between the prenyltransferase and cyclase domains. A molecular-level understanding of substrate transit phenomena in these systems is highly desirable, but a long disordered polypeptide segment connecting the prenyltranferase and cyclase domains thwarts the crystallization of full-length enzymes. Accordingly, these systems are excellent candidates for structural analysis using cryo-electron microscopy (cryo-EM). Notably, these systems form hexameric or octameric oligomers, so the quaternary structure of the full-length enzyme may influence substrate transit between catalytic domains. Here, we describe methods for the preparation of bifunctional hexameric copalyl diphosphate synthase from Penicillium fellutanum (PfCPS). We also outline approaches for the preparation of cryo-EM grids, data collection, and data processing to yield two-dimensional and three-dimensional reconstructions.
Topics: Penicillium; Alkyl and Aryl Transferases; Cryoelectron Microscopy; Diterpenes; Fungal Proteins; Dimethylallyltranstransferase
PubMed: 38942500
DOI: 10.1016/bs.mie.2023.11.002 -
Journal of the American Board of Family... Jun 2024Social risk data collection is expanding in community health centers (CHCs). We explored clinicians' practices of adjusting medical care based on their awareness of...
BACKGROUND
Social risk data collection is expanding in community health centers (CHCs). We explored clinicians' practices of adjusting medical care based on their awareness of patients' social risk factors-that is, changes they make to care plans to mitigate the potential impacts of social risk factors on their patients' care and health outcomes-in a set of Texas CHCs.
METHODS
Convergent mixed methods. Surveys/interviews explored clinician perspectives on adjusting medical care based on patient social risk factors. Survey data were analyzed with descriptive statistics; interviews were analyzed using thematic analysis and inductive coding.
RESULTS
Across 4 CHCs, we conducted 15 clinician interviews and collected 97 surveys. Interviews and surveys overall indicated support for adjustment activities. Two main themes emerged: 1) clinicians reported making frequent adjustments to patient care plans based on their awareness of patients' social contexts, while simultaneously expressing concerns about adjustment; and 2) awareness of patients' social risk factors, and clinician time, training, and experience all influenced clinician adjustments.
CONCLUSIONS
Clinicians at participating CHCs described routinely adjusting patient care plans based on their patients' social contexts. These adjustments were being made without specific guidelines or training. Standardization of adjustments may facilitate the contextualization of patient care through shared decision making to improve outcomes.
PubMed: 38942447
DOI: 10.3122/jabfm.2023.230289R1 -
BMJ Open Quality Jun 2024Intravenous medication errors continue to significantly impact patient safety and outcomes. This study sought to clarify the complexity and risks of the intravenous...
OBJECTIVES
Intravenous medication errors continue to significantly impact patient safety and outcomes. This study sought to clarify the complexity and risks of the intravenous administration process.
DESIGN
A qualitative focus group interview study.
SETTING
Focused interviews were conducted using process mapping with frontline nurses responsible for medication administration in September 2020.
PARTICIPANTS
Front line experiened nurses from a Japanese tertiary teaching hospital.
PRIMARY AND SECONDARY OUTCOME MEASURES
The primary outcome measure was to identify the mental models frontline nurses used during intravenous medication administration, which influence their interactions with patients, and secondarily, to examine the medication process gaps between the mental models nurses perceive and the actual defined medication administration process.
RESULTS
We found gaps between the perceived clinical administration process and the real process challenges with an emphasis on the importance of verifying to see if the drug was ordered for the patient immediately before its administration.
CONCLUSIONS
This novel and applied improvement approach can help nurses and managers better understand the process vulnerability of the infusion process and develop a deeper understanding of the administration steps useful for reliably improving the safety of intravenous medications.
Topics: Humans; Qualitative Research; Medication Errors; Focus Groups; Patient Safety; Infusions, Intravenous; Perception; Female; Administration, Intravenous; Adult; Nursing Staff, Hospital; Male; Japan; Interviews as Topic; Attitude of Health Personnel
PubMed: 38942437
DOI: 10.1136/bmjoq-2024-002809 -
BMJ Open Quality Jun 2024WHO reported that neonatal hypothermia accounts for about 27% of newborn deaths worldwide. It is a serious concern in Ethiopia and other parts of sub-Saharan Africa; it...
BACKGROUND
WHO reported that neonatal hypothermia accounts for about 27% of newborn deaths worldwide. It is a serious concern in Ethiopia and other parts of sub-Saharan Africa; it poses a serious threat to global health, increasing morbidity and mortality. Hypothermic neonates are more likely to experience respiratory distress, infections and other issues that could result in longer hospital stays and delayed development. The objective of this quality improvement project was to minimise intensive medical treatments, maximise resource usage and enhance overall health outcomes for newborns at Gandhi Memorial Hospital by reducing neonatal hypothermia.
METHODS
Over 10 months (from 1 March 2021 to 30 January 2022), neonatal hypothermia incidence was assessed using Quality Supervision Mentoring Team and Health Management Information System data. Root cause analysis and literature review led to evidence-based interventions in a change bundle. After team training and neonatal intensive care unit (NICU) relocation, Plan-Do-Study-Act cycles tested the bundle. Close temperature monitoring and data collection occurred. Run charts evaluated intervention success against baseline data, informing conclusions about effectiveness.
RESULT
The quality improvement project reduced neonatal hypothermia in NICU admissions from a baseline median of 80.6% to a performance median of 30%.
CONCLUSION AND RECOMMENDATION
The quality improvement project at Gandhi Memorial Hospital effectively reduced neonatal hypothermia through interventions such as the temperature management bundle and NICU relocation, leading to improved patient care, fewer hypothermic neonates and enhanced body temperature management. Continuous monitoring, adherence to best practices, sharing success and outcome assessment are crucial for enhancing the project's effectiveness and sustaining positive impacts on neonatal hypothermia reduction and patient outcomes.
Topics: Humans; Ethiopia; Infant, Newborn; Quality Improvement; Hypothermia; Incidence; Intensive Care Units, Neonatal; Female; Male
PubMed: 38942436
DOI: 10.1136/bmjoq-2023-002656 -
BMJ (Clinical Research Ed.) Jun 2024
Topics: Humans; Female; Pregnancy; Texas; Infant Mortality; Infant, Newborn; Infant; Abortion, Induced; Abortion, Legal
PubMed: 38942430
DOI: 10.1136/bmj.q1447 -
The Journal of Investigative Dermatology Jun 2024Early detection of melanoma is a major determinant in disease outcome and drives the number of (over)excised naevi in clinical practice. This study aimed to evaluate...
Early detection of melanoma is a major determinant in disease outcome and drives the number of (over)excised naevi in clinical practice. This study aimed to evaluate demographic features and melanoma risk of clinically suspicious, mainly flat naevus subtypes. Based on the methodology of ex vivo dermoscopy and derm dotting, the 12 most prevalent naevus subtypes were identified in a collection of over 7000 naevi excised for medical reason. Dermoscopical, histopathological and clinical features of these subtypes were described. In addition, the association with melanoma history, histopathological atypia and melanoma occurrence within naevi was compared. Nearly half of the naevi removed for medical reasons were of the hypermelanotic subtype with no or mild histopathological atypia and low melanoma association, suggesting overtreatment in daily practice. Contrarily, the subtypes atypical lentiginous naevus and orange pulverocytic flat naevus were associated with higher proportions of (severe) atypia and melanoma (history). We believe these subtypes may reflect different tumoural and/or (germline) genetic entities with different melanoma risk. The data from this study may direct further prospective research on specific naevus subtypes in order to obtain better insights in associated clinical/genetic factors and melanoma risk.
PubMed: 38942231
DOI: 10.1016/j.jid.2024.03.046 -
Appetite Jun 2024Zero alcohol products (ZAPs) could reduce alcohol-related harms by acting as a substitute for alcoholic beverages. However, concerns have been raised regarding the...
INTRODUCTION
Zero alcohol products (ZAPs) could reduce alcohol-related harms by acting as a substitute for alcoholic beverages. However, concerns have been raised regarding the potential for these products to expose young people to additional alcohol-related stimuli, further normalising alcohol use and acting as a gateway to underage alcohol consumption. Scarce research has examined whether these concerns are warranted.
METHOD
This project comprised two parts involving Australian adolescents aged 15-17 years. Part 1 was a series of 5 online focus groups (n=44) that provided initial insights into perceptions of and experiences with ZAPs. Part 2 was a national online survey (n=679) that assessed the generalisability of the focus group findings and identified factors associated with ZAP-related attitudinal and behavioural outcomes.
RESULTS
ZAPs were found to be salient and attractive to Australian adolescents. Over a third of surveyed adolescents (37%) had tried ZAPs. The focus group participants and survey respondents generally perceived ZAPs in a positive light, seeing them as a useful alternative to alcohol for both adolescents and adults who want to circumvent social expectations to use alcohol. Some of the study participants acknowledged the potential for ZAPs to serve as a gateway to alcohol use and recommended reducing their visibility and accessibility.
CONCLUSION
ZAPs are likely exposing minors to additional alcohol-related stimuli potentially increasing their risk of underage alcohol consumption. Regulatory responses to ZAPS need to protect young people from the potential adverse consequences of ZAPs exposure while enabling the products to be used by adults as an alcohol substitute.
PubMed: 38942148
DOI: 10.1016/j.appet.2024.107582