Tag: nevin manimala

JAMA Pediatr. 2022 May 9. doi: 10.1001/jamapediatrics.2022.1159. Online ahead of print.

NO ABSTRACT

PMID:35532906 | DOI:10.1001/jamapediatrics.2022.1159

Clin Pharmacol Drug Dev. 2022 May 9. doi: 10.1002/cpdd.1111. Online ahead of print.

ABSTRACT

Abrocitinib is a selective Janus kinase 1 inhibitor for the treatment of moderate to severe atopic dermatitis (AD). To assess the relationship between abrocitinib plasma concentrations and heart rate (HR)-corrected QT (QTc) and HR and calculate the effect of abrocitinib on these parameters at supratherapeutic concentrations, 36 healthy volunteers received single doses of abrocitinib 600 mg, placebo, and moxifloxacin 400 mg in a 3-period crossover study. The relationship between change from baseline in Fridericia-corrected QTc (∆QTcF) values and abrocitinib plasma concentrations was modeled using a prespecified linear mixed-effects model. The 90%CIs for time-matched placebo-corrected ∆QTcF (∆∆QTcF) were calculated from model parameter estimates and assessed against the regulatory threshold (10 millisecond) at the predicted supratherapeutic concentration in patients with atopic dermatitis (2156 ng/mL). Mean (90%CI) time-matched placebo-corrected change from baseline in HR (∆∆HR) was calculated similarly. At the supratherapeutic concentration, mean (90%CI) estimates for ∆∆QTcF and ∆∆HR were 6.00 (4.52-7.49) milliseconds and 6.51 (5.23-7.80) bpm, respectively. Despite a concentration-dependent effect on ∆QTcF and ∆HR, with statistically significant slopes (90%CI) of 0.0026 (0.0018-0.0035) milliseconds/(ng/mL) and 0.0031 (0.0024-0.0038) bpm/(ng/mL), respectively, abrocitinib does not have a clinically significant effect on QTc interval or HR at supratherapeutic exposures.

PMID:35532896 | DOI:10.1002/cpdd.1111

Ann Hematol. 2022 May 9. doi: 10.1007/s00277-022-04836-5. Online ahead of print.

ABSTRACT

Immune thrombocytopenia (ITP) patients are at risk developing to systemic lupus erythematosus (SLE) in the future. Our study attempted to explore the potential risk factors for the development from ITP to SLE in Chinese children by statistical analysis. This study was a retrospective case-control study. Patients diagnosed with ITP and developed to SLE after the diagnosis of ITP were defined as the case group. The control group consisted of children with ITP but without developing to SLE was recruited with a ratio of 1:2. Besides univariable analysis, multivariable logistic regression was built to evaluate the potential risk factors. A total of 150 children was included with 50 in the case group and 100 in the control group. Median developing time from ITP to SLE was 34.5 [IQR 12.5, 58.75] months. ANA was found significantly different between the two groups in our study in the univariable analysis but not in the multivariable analysis (OR = 4.50, 95% CI 0.97 to 21.01). Age diagnosed ITP was positively associated with SLE (OR = 1.07 every 5 years, 95% CI 1.01 to 1.15) with alert point at 8 years old (sensitivity 0.82, specificity 0.60). A lower level of complement was also positively associated with SLE (OR = 8.33, 95% CI 1.62 to 42.91). A minimum 3-year of close follow-up for pediatric ITP patients was recommended to monitor the risk for developing SLE. Older age and hypocomplementemia were potential risk factors for the development from ITP to SLE.

PMID:35532821 | DOI:10.1007/s00277-022-04836-5

Hepatol Int. 2022 May 9. doi: 10.1007/s12072-022-10343-6. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: The benefits of adjuvant radiotherapy (ART) in gallbladder cancer (GBC) treatment remain inconclusive owing to the rarity of GBC and lack of randomized studies.

METHODS: PubMed, Medline, Embase, and Cochrane Library were systematically searched until March 2021. The primary endpoint was overall survival (OS). Comparative clinical studies that reported survival outcomes in GBC patients treated with or without ART were included. The comparability of each study was assessed by considering all possible clinical indicators (group 2: ART arm with poor clinical profile; group 1: ART arm with statistically similar profile or no evidence of having inferior clinical factors compared to non-ART arm).

RESULTS: Twenty-one studies involving 6876 GBC patients were reviewed. In pooled analyses of OS, the odds ratio (OR) was 1.26 (p = 0.111) neither favoring ART or non-ART arms. In subgroup analyses considering comparability, the OR significantly favored the ART arm (1.92, p = 0.008) among comparability group 1 studies, whereas it was 1.03 (p = 0.865) in comparability group 2 studies. The pooled rate of 5-year OS in the ART vs. non-ART arms was 44.9% vs. 20.9% in group 1 and 34.1% vs. 40.0% in group 2. With ART, significant reduction in locoregional recurrence (OR 0.21, p = 0.001) but not in distant metastasis (OR 1.32, p = 0.332) was noted.

CONCLUSION: ART not only showed benefits in patients with a similar clinical profile to those treated without ART but also yielded comparable survival in patients with an inferior clinical profile. Our results suggest the more active application of ART in GBC treatment.

PROTOCOL REGISTRATION: This study is registered in PROSPERO (CRD42021240624, available at: https://www.crd.york.ac.uk/ ).

PMID:35532861 | DOI:10.1007/s12072-022-10343-6

Arch Orthop Trauma Surg. 2022 May 9. doi: 10.1007/s00402-022-04460-y. Online ahead of print.

ABSTRACT

INTRODUCTION: This study investigated the anatomic feasibility of a new surgical therapy option for radial head arthrosis using an autologous vascularized bone graft of the second metatarsal and proximal fibula to recreate the proximal radiohumeral joint.

MATERIALS AND METHODS: Upper and lower extremities of eleven body donors were evaluated using CT prior to anatomic dissection. Several distinct anatomic parameters were measured on the ipsi- and contralateral radial and fibular head and the second metatarsal base: bone diameter, articular surface diameter, head height, metaphyseal (neck) diameter, articular surface radius, total articular surface area, and angulation of the articular surfaces (facet). Each dissection phase was photographed in a standardized fashion and all measurements were repeated by direct caliper-measurements.

RESULTS: When comparing the proximal radius and fibula to search for anatomic similarities, similar values were found in the maximum articular surface diameter and minimum and maximum measures of the neck diameter. Comparing the proximal radius and the second metatarsal, statistically similar values were found in the maximum neck diameter performing direct measurements and CT evaluation, the maximum head diameter in CT evaluation and the articular facet angulation.

CONCLUSIONS: Neither the proximal fibula nor the base of the second metatarsal are ideal bone grafts for replacement of the head of the radius. The base of the second metatarsal might be a bit more suitable as a potential donor since the angulation of the proximal articular facet is similar to that of the radius.

LEVEL OF EVIDENCE: Level IV, anatomic study.

PMID:35532813 | DOI:10.1007/s00402-022-04460-y

Z Rheumatol. 2022 May 9. doi: 10.1007/s00393-022-01209-1. Online ahead of print.

ABSTRACT

INTRODUCTION: The concept of complex multimodal rheumatologic treatment (CMRT) has been established for several years in German rheumatologic departments and aims at a multifaceted therapeutic approach to patients with rheumatic diseases. Objective of this study was to examine the therapeutic effect of CMRT in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in an acute rheumatology center.

METHODS: The treatment success of CMRT was evaluated by epidemiologic data, patient questionnaires on visual analog scales (VAS) regarding morning stiffness, pain and disease activity (DA), as well as clinical scores (Disease Activity Score 28 [DAS28], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Bath Ankylosing Spondylitis Functional Index [BASFI]), laboratory inflammation markers (CRP, erythrocyte sedimentation rate) and medication in three visits: visit 1 = begin of CMRT; visit 2 = end of CMRT; visit 3 = 3 months after CMRT.

RESULTS: In this study 162 patients from the Rheumatology Center, Rhineland-Palatinate, Germany (96 (59.3%) RA, 30 (18.8%) AS, 36 (22.2%) PsA) were recruited. Statistical examinations revealed a significant improvement of VAS(DA) (visit 2 versus visit 1: RA: p = 0.02, AS: p < 0.001, PsA: p < 0.001), morning stiffness (RA: p < 0.001, AS: p = 0.03, PsA: p < 0.001) and patient reported pain (all; p < 0.001) in the context of CMRT. In the RA and AS subgroups improvements of DAS28 and BASDAI could also be observed (visit 2 versus visit 1: both; p < 0.001). Moreover, significant improvement of patient reported outcomes could be observed 3 months after CMRT regarding VAS(DA) (RA: p = 0.02 und AS: p = 0.03, morning stiffness (PsA: p = 0.02) and patient reported pain (RA: p = 0.01)). Interestingly, subgroup analyses showed that the therapeutic benefit was independent of the concomitant pharmacotherapy.

CONCLUSION: The results of this study suggest a therapeutic benefit for patients being treated by CMRT and highlight the high value of this therapeutic concept in patients with systemic-inflammatory rheumatic diseases.

PMID:35532799 | DOI:10.1007/s00393-022-01209-1

J Neurol. 2022 May 9. doi: 10.1007/s00415-022-11161-4. Online ahead of print.

ABSTRACT

OBJECTIVE: Higher body mass index (BMI) during early life is thought to be a causal risk factor for multiple sclerosis (MS). We used longitudinal Mendelian randomisation (MR) to determine whether there is a critical window during which BMI influences MS risk.

METHODS: Summary statistics for childhood BMI (n ~ 28,000 children) and for MS susceptibility were obtained from recent large genome-wide association studies (GWAS) (n = 14,802 MS, 26,703 controls). We generated exposure instruments for BMI during four non-overlapping age epochs (< 3 months, 3 months-1.5 years, 2-5 years, and 7-8 years) and performed MR using the inverse variance weighted method with standard sensitivity analyses. Multivariable MR was used to account for effects mediated via later-life BMI.

RESULTS: For all age epochs other than birth, genetically determined higher BMI was associated with an increased liability to MS: Birth [Odds Ratio (OR) 0.81, 95% Confidence Interval (CI) 0.50-1.31, Number of Single-Nucleotide Polymorphisms (N_SNPs) = 7, p = 0.39], Infancy (OR 1.18, 95% CI 1.04-1.33, N_SNPs = 18, p = 0.01), Early childhood (OR 1.31, 95% CI 1.03-1.66, N_SNPs = 4, p = 0.03), Later childhood (OR 1.34, 95% CI 1.08-1.66, N_SNPs = 4, p = 0.01). Multivariable MR suggested that these effects may be mediated by effects on adult BMI.

CONCLUSION: We provide evidence using MR that genetically determined higher BMI during early life is associated with increased MS risk. This effect may be driven by shared genetic architecture with later-life BMI.

PMID:35532785 | DOI:10.1007/s00415-022-11161-4

Arch Dermatol Res. 2022 May 9. doi: 10.1007/s00403-022-02356-w. Online ahead of print.

ABSTRACT

Recurrent changes of temperature and persistence of cooling along fingers at the room temperature make hands the most frequent region of interest for thermography in systemic sclerosis (SSc). The aim of this study was to evaluate dependance of temperature in hands on a subtype of the disease, immune profile of antinuclear antibodies (ANA), and lung involvement. There were 29 patients with limited cutaneous involvement (lcSSc) and 10 patients with diffuse cutaneous disease (dcSSc) enrolled for the study. To compare measurements to normal values, there were enrolled 29 healthy volunteers (control group). All participants were submitted to thermography with handheld camera FLIR One Pro for iOS, attached to mobile phone iPhone 11, at the fixed temperature of 21 °C. Measurements included average temperature (T_avg) over nailfolds in thumbs and fingers II-V, as well as the difference in average temperatures (TΔ) between metacarpus of the hand and its thumb and fingers II-V. Both thumbs and fingers II-V remained cooler in subjects with dcSSc compared to those with lcSSc. This implicated a significantly greater TΔ along thumbs and fingers II-V in dcSSc group. Although T_avg at nailfolds in SSc patients was not lower than in healthy controls, TΔ remained significantly more pronounced in both lcSSc and dcSSc subjects. A positivity to ACA in lcSSc group was found to be associated with significantly lower T_avg and more pronounced TΔ in fingers II-V than the presence of anti-Scl70 antibodies. Temperature measurements remained statistically independent on a presence of ILD in lcSSc group, but both thumbs and fingers II-V in dcSSc group were warmer in case of lung involvement. The study showed the dcSSc subtype, the positivity of ACA in lcSSc, but not lung involvement were associated with poorer thermal control in the hands of SSc patients. A comparison to healthy controls highlighted the weakness of temperature measurements at nailfolds (T_avg) but increased the value of TΔ in thermography of hands.

PMID:35532783 | DOI:10.1007/s00403-022-02356-w

Tissue Eng Regen Med. 2022 May 9. doi: 10.1007/s13770-022-00445-5. Online ahead of print.

ABSTRACT

Bone graft materials have mixed effects of bone repair in the field of oral maxillofacial surgery. The qualitative analyses performed by previous studies imply that autogenous odontogenic materials and autogenous bone have similar effects on bone repair in clinical jaw bone transplantation. This retrospective systematic assessment and network meta-analysis aimed to analyze the best effect of clinical application of autogenous odontogenic materials and autogenous, allogeneic, and xenogeneic bone grafts in bone defect repair. A systematic review was performed by searching the PubMed, Cochrane Library, and other journal databases using selected keywords and Medical Subject Headings search terms. 10 Papers (n = 466) that met the inclusion criteria were selected. The assessment of heterogeneity did not reveal any overall statistical difference or heterogeneity (P = 0.051 > 0.05), whereas the comparison between autogenous and allogeneic bone grafts revealed local heterogeneity (P = 0.071 < 0.1). Risk of bias revealed nine unclear studies and one high-risk study. The overall consistency was good (P = 0.065 > 0.05), and the local inconsistency test did not reveal any inconsistency. The publication bias was good. The confidence regarding the ranking of bone graft materials after GRADE classification was moderate. The effects on bone repair in the descending order were as follows: autogenous odontogenic materials, xenogeneic bone, autogenous bone, and allogeneic bone. This result indicates that the autogenous odontogenic materials displayed stronger effects on bone repair compared to other bone graft materials. Autogenous odontogenic materials have broad development prospects in oral maxillofacial surgery.

PMID:35532735 | DOI:10.1007/s13770-022-00445-5

Biometrics. 2022 May 9. doi: 10.1111/biom.13692. Online ahead of print.

ABSTRACT

Pragmatic trials evaluating health care interventions often adopt cluster randomization due to scientific or logistical considerations. Systematic reviews have shown that co-primary endpoints are not uncommon in pragmatic trials but are seldom recognized in sample size or power calculations. While methods for power analysis based on K (K≥ 2) binary co-primary endpoints are available for cluster randomized trials (CRTs), to our knowledge, methods for continuous co-primary endpoints are not yet available. Assuming a multivariate linear mixed model that accounts for multiple types of intraclass correlation coefficients among the observations in each cluster, we derive the closed-form joint distribution of K treatment effect estimators to facilitate sample size and power determination with different types of null hypotheses under equal cluster sizes. We characterize the relationship between the power of each test and different types of correlation parameters. We further relax the equal cluster size assumption and approximate the joint distribution of the K treatment effect estimators through the mean and coefficient of variation of cluster sizes. Our simulation studies with a finite number of clusters indicate that the predicted power by our method agrees well with the empirical power, when the parameters in the multivariate linear mixed model are estimated via the expectation-maximization algorithm. An application to a real CRT is presented to illustrate the proposed method. This article is protected by copyright. All rights reserved.

PMID:35531926 | DOI:10.1111/biom.13692