Tag: pubmed

Br J Clin Pharmacol. 2024 May 1. doi: 10.1111/bcp.16082. Online ahead of print.

ABSTRACT

AIMS: Corticosteroids are the treatment of choice for many inflammatory diseases but often lead to adverse effects, including hyperglycaemia. This study investigated the mechanisms driving differential effects on glucose control for AZD9567, an oral nonsteroidal selective glucocorticoid receptor modulator vs. prednisolone in 46 patients with type 2 diabetes mellitus.

METHODS: In this randomized, double-blind, 2-way cross-over study (NCT04556760), participants received either AZD9567 72 mg and prednisolone 40 mg daily (cohort 1); AZD9567 40 mg and prednisolone 20 mg daily (cohort 2); or placebo and prednisolone 5 mg daily (cohort 3). Treatment duration was 3 days with a 3-week washout between treatment periods. Glycaemic control was assessed after a standardized meal and with continuous glucose monitoring.

RESULTS: A significant difference between AZD9567 and prednisolone in favour of AZD9567 was observed for the change from baseline to Day 4 glucose excursions postmeal in cohort 1 (glucose area under the curve from 0 to 4 h -4.54%; 95% confidence interval [CI]: -8.88, -0.01; P = .049), but not in cohort 2 (-5.77%; 95% CI: -20.92, 12.29; P = .435). In cohort 1, significant differences between AZD9567 and prednisolone were also seen for the change from baseline to day 4 in insulin and glucagon secretion postmeal (P < .001 and P = .005, respectively) and change from baseline to Day 4 in GLP-1 response (P = .022). Significant differences between AZD9567 and prednisolone for 24-h glucose control were observed for both cohort 1 (-1.507 mmol/L; 95% CI: -2.0820, -0.9314; P < .001) and cohort 2 (-1.110 mmol/L; 95% CI -1.7257, -0.4941; P < .001).

CONCLUSION: AZD9567 significantly reduced treatment-induced hyperglycaemia compared with prednisolone.

PMID:38690606 | DOI:10.1111/bcp.16082

Front Pediatr. 2024 Apr 16;12:1333652. doi: 10.3389/fped.2024.1333652. eCollection 2024.

ABSTRACT

OBJECTIVE: Elastic stable intramedullary nail (ESIN) is a commonly used method for treating diaphyseal fractures of the tibia, but its application in Distal Tibial Diaphyseal Metaphyseal Junction (DTDMJ) fractures has been a subject of controversy. This study aims to evaluate the clinical efficacy of the Elastic stable intramedullary nail-Kirschner wire (E-K) technique in treating pediatric DTDMJ fractures, providing better clinical decision-making for clinicians in diagnosing and treating such fractures.

METHODS: We conducted a retrospective analysis of patients aged 3-9 years who received treatment at our hospital from January 2019-January 2021 for distal tibial diaphyseal metaphyseal junction (DTDMJ) fractures. Based on their surgical procedures, they were categorized into the Elastic Stable Intramedullary Nail-Kirschner wire group (E-K) and the ESIN group. Demographic data, surgical duration, clinical outcomes, complications, and imaging data were recorded.

RESULTS: The study included a total of 57 patients, with 24 cases in the E-K group and 33 cases in the ESIN group. There were 30 males and 27 females. The average age was (6.25 ± 1.59) years in the E-K group and (6.27 ± 1.48) years in the ESIN group. There were no significant differences between the two groups in terms of gender, age, weight, time from injury to surgery, follow-up time, side of injury, associated injuries, nail site infection, deep infection, and nail removal time (P > 0.05). Neither group experienced nonunion or refracture. The E-K group exhibited significantly lower coronal and sagittal plane angular values at the final follow-up compared to the ESIN group (P < 0.001). In the E-K group, the final follow-up coronal plane angle was 2.67 (1.09)°, while in the ESIN group, it was 6.55 (2.05)°. The final follow-up sagittal plane angle was 3.12 (1.54)° in the E-K group and 7.58 (1.48)° in the ESIN group. Both groups showed good alignment in the initial postoperative x-rays, with no statistically significant differences. However, during clinical healing, the ESIN group exhibited significant displacement, whereas the E-K group had minimal displacement, demonstrating a significant statistical difference (P < 0.001). There was a statistically significant difference in the AOFAS joint function assessment between the two groups (P = 0.027).

CONCLUSION: The E-K technique is a viable option for treating DTDMJ fractures in pediatric patients, with well-established clinical efficacy. Its advantages include a straightforward surgical procedure, safety, and a low incidence of severe complications.

PMID:38690522 | PMC:PMC11058844 | DOI:10.3389/fped.2024.1333652

Cureus. 2024 Mar 31;16(3):e57300. doi: 10.7759/cureus.57300. eCollection 2024 Mar.

ABSTRACT

Background Temporomandibular joint disorders (TMD) represent a prevalent group of conditions impacting the temporomandibular joint. Among the therapeutic interventions, occlusal splint therapy has gained recognition for its potential to address TMD symptoms, particularly in cases involving joint displacement. Objective This study aims to investigate the effectiveness of occlusal splint therapy in cases of moderate TMD with joint displacement, focusing on changes in condylar position, joint morphology, and patient-reported outcomes. Methods A retrospective analysis was conducted involving 148 participants who underwent occlusal splint therapy between January 2018 and December 2020. Data were collected through cone beam computed tomography (CBCT) imaging for precise assessments of condylar position and joint morphology. Ethical approval was obtained, and participants provided informed consent. Baseline characteristics, medical history, and TMD severity were recorded. Occlusal splint therapy included individualized fabrication, occlusal analysis, adjustments for optimal fit, and prescribed wear schedules. Follow-up included CBCT scans at specified intervals (three months and six months), with participant-reported outcomes collected. The data analysis was conducted using IBM SPSS Statistics for Windows, Version 22.0 (Released 2013; IBM Corp., Armonk, NY, USA). Paired t-tests or nonparametric equivalents were employed to assess changes in condylar position and joint morphology. Subgroup analyses were conducted to explore potential factors influencing treatment outcomes. The significance level was set at p < 0.05 for all statistical tests. Results The entire cohort (n = 148) had a mean age of 32.5 years (± 8.1), with a balanced gender distribution. Changes in condylar position revealed a statistically significant improvement (p = 0.03), with a mean decrease of 0.2 mm posttreatment. Joint morphology changes indicated increased joint space width (p = 0.01), improved disc position (p = 0.02), and nonsignificant alterations in bony structures (p = 0.10). Patient-reported outcomes demonstrated significant improvements in pain levels, jaw functionality, and satisfaction (all p < 0.001). Age and gender subgroup analyses showed consistent improvements in condylar position, joint morphology, and patient-reported outcomes across different groups. Conclusion Occlusal splint therapy demonstrated effectiveness in improving condylar position, joint morphology, and patient-reported outcomes in cases of moderate TMD with joint displacement. The findings underscore the potential of occlusal splint therapy as a viable intervention for managing TMD, providing valuable insights for clinicians and researchers.

PMID:38690507 | PMC:PMC11059150 | DOI:10.7759/cureus.57300

BMJ Open Gastroenterol. 2024 Apr 30;11(1):e001311. doi: 10.1136/bmjgast-2023-001311.

ABSTRACT

BACKGROUND: The updated Shape of Training curriculum has shortened the duration of specialty training. We present the potential role of out of programme clinical fellowships.

METHOD: An electronic online survey was sent to all current fellows to understand their experiences, training opportunities and motivations.Data were collected on fellows’ endoscopic experiences and publications using PubMed for all previous doctors who have completed the Sheffield Fellowship Programme.

RESULTS: Since 2004, 39 doctors have completed the Sheffield Fellowship.Endoscopic experience: current fellows completed a median average of 350 (IQR 150-500) gastroscopies and 150 (IQR 106-251) colonoscopies per year. Fellows with special interests completed either 428 hepato-pancreato-biliary procedures or 70 endoscopic mucosal resections per year.Medline publications: Median average 9 publications(IQR 4-17). They have also received multiple national or international awards and 91% achieved a doctoral degree.The seven current fellows in the new Shape of Training era (57% male, 29% Caucasian, aged 31-40 years) report high levels of enjoyment due to their research projects, supervisory teams and social aspects. The most cited reasons for undertaking the fellowship were to develop a subspecialty interest, take time off the on-call rota and develop endoscopic skills. The most reported drawback was a reduced income.All current fellows feel that the fellowship has enhanced their clinical confidence and prepared them to become consultants.

CONCLUSION: Out of programme clinical fellowships offer the opportunity to develop the required training competencies, subspecialty expertise and research skills in a supportive environment.

PMID:38688716 | DOI:10.1136/bmjgast-2023-001311

Lupus Sci Med. 2024 Apr 30;11(1):e001090. doi: 10.1136/lupus-2023-001090.

ABSTRACT

OBJECTIVE: Characterise the relationship between hydroxychloroquine (HCQ) blood levels and the number of missed doses, accounting for dosage, dose timing and the large variability in pharmacokinetics (PK) between patients.

METHODS: We externally validated a published PK model and then conducted dosing simulations. We developed a virtual population of 1000 patients for each dosage across a range of body weights and PK variability. Using the model, 10 Monte Carlo simulations for each patient were conducted to derive predicted whole blood concentrations every hour over 24 hours (240 000 HCQ levels at steady state). To determine the impact of missed doses on levels, we randomly deleted a fixed proportion of doses.

RESULTS: For patients receiving HCQ 400 mg daily, simulated random blood levels <200 ng/mL were exceedingly uncommon in fully adherent patients (<0.1%). In comparison, with 80% of doses missed, approximately 60% of concentrations were <200 ng/mL. However, this cut-off was highly insensitive and would miss many instances of severe non-adherence. Average levels quickly dropped to <200 ng/mL after 2-4 days of missed doses. Additionally, mean levels decreased by 29.9% between peak and trough measurements.

CONCLUSIONS: We propose an algorithm to optimally interpret HCQ blood levels and approximate the number of missed doses, incorporating the impact of dosage, dose timing and pharmacokinetic variability. No single cut-off has adequate combinations of both sensitivity and specificity, and cut-offs are dependent on the degree of targeted non-adherence. Future studies should measure trough concentrations to better identify target HCQ levels for non-adherence and efficacy.

PMID:38688714 | DOI:10.1136/lupus-2023-001090

BMJ Qual Saf. 2024 Apr 30:bmjqs-2024-017072. doi: 10.1136/bmjqs-2024-017072. Online ahead of print.

ABSTRACT

Direct-to-onsumer telemedicine (DTCT) has become popular as an alternative to traditional care. However, uncertainties about the potential risks associated with the lack of comprehensive quality evaluation could influence its long-term development. This study aimed to assess the quality of care provided by DTCT platforms in China using unannounced standardised patients (USP) between July 2021 and January 2022. The study assessed consultation services on both hospital and enterprise-sponsored platforms using the Institute of Medicine quality framework. It employed 10 USP cases, covering conditions such as diabetes, asthma, common cold, gastritis, angina, low back pain, child diarrhoea, child dermatitis, stress urinary incontinence and postpartum depression. Descriptive and regression analyses were employed to examine platform characteristics and compare quality across platform types. The results showed that of 170 USP visits across 107 different telemedicine platforms, enterprise-sponsored platforms achieved a 100% success in access, while hospital-sponsored platforms had a success rate of only 47.5% (56/118). Analysis highlighted a low overall correct diagnosis rate of 45% and inadequate adherence to clinical guidelines across all platforms. Notably, enterprise-sponsored platforms outperformed in accessibility, response time and case management compared with hospital-sponsored platforms. This study highlights the suboptimal quality of DTCT platforms in China, particularly for hospital-sponsored platforms. To further enhance DTCT services, future studies should compare DTCT and in-person care, aiming to identify gaps and potential risks associated with using DTCT as alternatives or supplements to traditional care. The potential of future development in enhancing DTCT services may involve exploring the integration of hospital resources with the technology and market capabilities of enterprise-sponsored platforms.

PMID:38688711 | DOI:10.1136/bmjqs-2024-017072

Thorax. 2024 Apr 30:thorax-2023-220887. doi: 10.1136/thorax-2023-220887. Online ahead of print.

ABSTRACT

BACKGROUND: Owing to discrepancies in methodologies and how idiopathic pulmonary fibrosis (IPF) is diagnosed it is challenging to establish a consistent understanding of the disease burden In the UK, over 10 years ago, the incidence and prevalence of IPF were reported as 2.8-8.7 per 100 000 person-years (from 2000 to 2012) and 39 per 100 000 persons (in 2012), respectively. Here, we estimated the incidence and prevalence of IPF in England from 2008 to 2018 and investigated IPF mortality.

METHODS: Using Clinical Practice Research Datalink Aurum and Hospital Episode Statistics (HES) linked datasets, we estimated incidence and prevalence using four validated diagnostic-code-based algorithms. Using the registered number of deaths (from Office of National Statistics) with the underlying cause being recorded as IPF, we estimated IPF mortality for the same period.

RESULTS: Using Aurum-based definitions, incidence increased over time by 100% for Aurum narrow (3-6.1 per 100 000 person-years) and by 25% for Aurum broad (22.4-28.6 per 100 000 person-years). However, using HES-based definitions showed a decrease in incidence over the same period and lay between the two extremes derived for Aurum-based definition. IPF mortality in 2018 was 7.9 per 100 000 person-years and increased by 53% between 2008 and 2018.

INTERPRETATION: When using best-case definitions, incidence rose throughout the study period. Scaling this to England’s population (2018), our best estimate would be in the range of 8000-9000 new cases per year which is higher than previously reported estimates (5000-6000). This increased burden in the new cases of IPF each year impacts future health service planning and resource allocation.

PMID:38688708 | DOI:10.1136/thorax-2023-220887

J Epidemiol Community Health. 2024 Apr 30:jech-2023-221720. doi: 10.1136/jech-2023-221720. Online ahead of print.

ABSTRACT

BACKGROUND: Growing up with parental alcohol use disorder (AUD) is a risk factor for psychiatric disorders. This study investigated the risk of mood disorders and of anxiety disorders in the adult children of parents with AUD, adjusted for sociodemographic factors.

METHODS: Individual-level register data on the total population were linked to follow children of parents with AUD from 1973 to 2018 to assess their risk of mood disorders and of anxiety disorders. AUD, mood disorders and anxiety disorders were defined with International Statistical Classification of Diseases and Related Health Problems codes from the National Patient Register. HRs of outcomes were calculated with Cox regression. Model 1 was adjusted for the child’s sex, parental education and death of a parent. Model 2 was adjusted for those factors and parental diagnosis of mood or anxiety disorder.

RESULTS: Those with ≥1 parent with AUD (99 723 of 2 421 479 children) had a higher risk of mood disorder and of anxiety disorder than those whose parents did not have AUD (HR mood 2.32, 95% CI 2.26 to 2.39; HR anxiety 2.66, 95% CI 2.60 to 2.72). The risk remained elevated after adjustment for sociodemographic factors and parental psychiatric diagnosis (HR mood 1.67, 95% CI 1.63 to 1.72; HR anxiety 1.74, 95% CI 1.69 to 1.78). The highest risks were associated with AUD in both parents, followed by AUD in mothers and then in fathers.

CONCLUSION: Adult children of parents with AUD have a raised risk of mood and anxiety disorders even after adjustment for sociodemographic factors and parental mood or anxiety disorder. These population-level findings can inform future policies and interventions.

PMID:38688702 | DOI:10.1136/jech-2023-221720

RMD Open. 2024 Apr 30;10(2):e003962. doi: 10.1136/rmdopen-2023-003962.

ABSTRACT

OBJECTIVE: ANCA-associated vasculitis (AAV) is a relapsing-remitting disease, resulting in incremental tissue injury. The gold-standard relapse definition (Birmingham Vasculitis Activity Score, BVAS>0) is often missing or inaccurate in registry settings, leading to errors in ascertainment of this key outcome. We sought to create a computable phenotype (CP) to automate retrospective identification of relapse using real-world data in the research setting.

METHODS: We studied 536 patients with AAV and >6 months follow-up recruited to the Rare Kidney Disease registry (a national longitudinal, multicentre cohort study). We followed five steps: (1) independent encounter adjudication using primary medical records to assign the ground truth, (2) selection of data elements (DEs), (3) CP development using multilevel regression modelling, (4) internal validation and (5) development of additional models to handle missingness. Cut-points were determined by maximising the F1-score. We developed a web application for CP implementation, which outputs an individualised probability of relapse.

RESULTS: Development and validation datasets comprised 1209 and 377 encounters, respectively. After classifying encounters with diagnostic histopathology as relapse, we identified five key DEs; DE1: change in ANCA level, DE2: suggestive blood/urine tests, DE3: suggestive imaging, DE4: immunosuppression status, DE5: immunosuppression change. F1-score, sensitivity and specificity were 0.85 (95% CI 0.77 to 0.92), 0.89 (95% CI 0.80 to 0.99) and 0.96 (95% CI 0.93 to 0.99), respectively. Where DE5 was missing, DE2 plus either DE1/DE3 were required to match the accuracy of BVAS.

CONCLUSIONS: This CP accurately quantifies the individualised probability of relapse in AAV retrospectively, using objective, readily accessible registry data. This framework could be leveraged for other outcomes and relapsing diseases.

PMID:38688690 | DOI:10.1136/rmdopen-2023-003962

BMJ Open Respir Res. 2024 Apr 30;11(1):e002333. doi: 10.1136/bmjresp-2024-002333.

ABSTRACT

OBJECTIVES: The diagnostic process for patients with interstitial lung diseases (ILD) remains complex. The aim of this study was to characterise the diagnostic care pathway and identify barriers and potential solutions to access a timely and accurate ILD diagnosis.

DESIGN: This mixed-method study was comprised of a quantitative chart review, patient and physician surveys and focus groups.

RESULTS: Chart review was completed for 97 patients. Median time from symptom onset to ILD diagnosis was 12.0 (IQR 20.5) months, with 46% diagnosed within 1 year. Time from first computed tomography (CT) scan to respirology referral was 2.4 (IQR 21.2) months. Referrals with a prior CT were triaged sooner than referrals without (1.7±1.6 months vs 3.9±3.3 months, p=0.013, 95% CI 0.48 to 2.94). On patient surveys (n=70), 51% felt that their lung disease was not recognised early enough. Commonly reported challenges to timely diagnosis included delayed presentation to primary care, initial misdiagnoses and long wait-times for specialists. Forty-five per cent of physicians (n=20) identified diagnostic delays, attributed to delayed presentations to primary care (58%), initial misdiagnoses (67%) and delayed chest imaging (75%). Themes from patient and respirologist focus groups included patient-related, healthcare provider-related and system-related factors leading to delays in diagnosis.

CONCLUSIONS: This mixed-methods study identified patient and system-related factors that contribute to diagnostic delays for patients with ILD, with most delays occurring prior to respirology referral. ILD awareness and education, earlier presentation to primary care, expedited access to chest imaging and earlier referral to respirology may expedite diagnosis.

PMID:38688689 | DOI:10.1136/bmjresp-2024-002333