Category: Nevin Manimala

J Orthop Res. 2023 May 30. doi: 10.1002/jor.25637. Online ahead of print.

ABSTRACT

Cartilage thickness change is a well-documented biomarker of osteoarthritis pathogenesis. However, there is still much to learn about the spatial and temporal patterns of cartilage thickness change in health and disease. In this study, we develop a novel analysis method for elucidating such patterns using a functional connectivity approach. Descriptive statistics are reported for 1186 knees that did not develop osteoarthritis during the 8 years of observation, which we present as a model of cartilage thickness change related to healthy aging. Within the control population, patterns vary greatly between male and female subjects, while BMI has a more moderate impact. Finally, several differences are shown between knees that did and did not develop osteoarthritis. Some but not all significance appears to be accounted for by differences in sex, BMI, and knee alignment. With this work, we present the connectome as a novel tool for studying spatiotemporal dynamics of tissue change. This article is protected by copyright. All rights reserved.

PMID:37254620 | DOI:10.1002/jor.25637

Pain Pract. 2023 May 30. doi: 10.1111/papr.13256. Online ahead of print.

ABSTRACT

OBJECTIVE: This prospective longitudinal study compares outcomes between Medicare beneficiaries receiving percutaneous image-guided lumbar decompression (PILD) using the mild® procedure and a control group of patients receiving interspinous spacers for the treatment of lumbar spinal stenosis (LSS) with neurogenic claudication (NC).

METHODS: Patients diagnosed with LSS with NC and treated with either the mild procedure or a spacer were identified in the Medicare claims database. The incidence of harms, the rate of subsequent interventions, and the overall combined rate of harms and subsequent interventions during 2-year follow-up after the index procedure were compared between the two groups and assessed for statistical significance with p = 0.05.

RESULTS: The study included 2229 patients in the mild group and 3401 patients who were implanted with interspinous spacers. The rate of harms for those treated with the mild procedure was less than half that of patients implanted with a spacer (5.6% vs. 12.1%, respectively; p < 0.0001) during 2-year follow-up. The rate of subsequent interventions was not significantly different between the two groups (24.9% and 26.1% for the mild and spacer groups, respectively; p = 0.7679). The total rate of harms and subsequent interventions for mild was found to be noninferior to spacers (p < 0.0001).

CONCLUSIONS: This comprehensive study of real-world Medicare claims data demonstrated a significantly lower rate of harms for the mild procedure compared to interspinous spacers for patients diagnosed with LSS with NC, and a similar rate of subsequent interventions during 2-year follow-up.

PMID:37254613 | DOI:10.1111/papr.13256

Public Health Res (Southampt). 2023 Mar;11(3):1-77. doi: 10.3310/FKPY6814.

ABSTRACT

BACKGROUND: Substance use and offending are related in the context of other disinhibitory behaviours. Adolescents involved in the criminal justice system constitute a particularly vulnerable group, with a propensity to engage in risky behaviour that has long-term impact on their future health and well-being. Previous research of the RISKIT programme provided evidence of a potential effect in reducing substance use and risky behaviour in adolescents.

OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of a multicomponent psychosocial intervention compared with treatment as usual in reducing substance use for substance-using adolescents involved in the criminal justice system.

DESIGN: A mixed-methods, prospective, pragmatic, two-arm, randomised controlled trial with follow-up at 6 and 12 months post randomisation.

SETTING: The study was conducted across youth offending teams, pupil referral units and substance misuse teams across four areas of England (i.e. South East, London, North West, North East).

PARTICIPANTS: Adolescents aged between 13 and 17 years (inclusive), recruited between September 2017 and June 2020.

INTERVENTIONS: Participants were randomised to treatment as usual or to treatment as usual in addition to the RISKIT-Criminal Justice System (RISKIT-CJS) programme. The RISKIT-CJS programme was a multicomponent intervention and consisted of two individual motivational interviews with a trained youth worker (lasting 45 minutes each) and two group sessions delivered over half a day on consecutive weeks.

MAIN OUTCOME MEASURES: At 12 months, we assessed per cent days abstinent from substance use over the previous 28 days. Secondary outcome measures included well-being, motivational state, situational confidence, quality of life, resource use and fidelity of interventions delivered.

RESULTS: A total of 693 adolescents were assessed for eligibility, of whom 505 (73%) consented. Of these, 246 (49%) were allocated to the RISKIT-CJS intervention and 259 (51%) were allocated to treatment as usual only. At month 12, the overall follow-up rate was 57%: 55% in the RISKIT-CJS arm and 59% in the treatment-as-usual arm. At month 12, we observed an increase in per cent days abstinent from substances in both arms of the study, from 61% to 85%, but there was no evidence that the RISKIT-CJS intervention was superior to treatment as usual. A similar pattern was observed for secondary outcomes. The RISKIT-CJS intervention was not found to be any more cost-effective than treatment as usual. The qualitative research indicated that young people were positive about learning new skills and acquiring new knowledge. Although stakeholders considered the intervention worthwhile, they expressed concern that it came too late for the target population.

LIMITATIONS: Our original aim to collect data on offences was thwarted by the onset of the COVID-19 pandemic, and this affected both the statistical and economic analyses. Although 214 (87%) of the 246 participants allocated to the RISKIT-CJS intervention attended at least one individual face-to-face session, 98 (40%) attended a group session and only 47 (19%) attended all elements of the intervention.

CONCLUSIONS: The RISKIT-CJS intervention was no more clinically effective or cost-effective than treatment as usual in reducing substance use among adolescents involved in the criminal justice system.

FUTURE RESEARCH: The RISKIT-CJS intervention was considered more acceptable, and adherence was higher, in pupil referral units and substance misuse teams than in youth offending teams. Stakeholders in youth offending teams thought that the intervention was too late in the trajectory for their population.

TRIAL REGISTRATION: This trial is registered as ISRCTN77037777.

FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 11, No. 3. See the NIHR Journals Library website for further project information.

PMID:37254608 | DOI:10.3310/FKPY6814

Birth Defects Res. 2023 May 30. doi: 10.1002/bdr2.2206. Online ahead of print.

ABSTRACT

BACKGROUND: Building on findings that linked higher levels of sunspot (SS) activity with a range of health and adverse birth outcomes, we sought to understand how SS activity over a 17-year time period may be correlated with the occurrence of birth defects.

METHODS: Data from the Texas Birth Defects Registry, vital events from the Texas Center for Health Statistics, and mean monthly numbers of sunspots from the National Oceanic and Atmospheric Administration were utilized. Poisson regression was used to calculate crude/adjusted prevalence ratios (cPRs/aPRs) and 95% confidence intervals for three quartiles (Q) of increasing SS activity (compared to a referent of low activity) and 44 birth defects (31 non-cardiac; 13 cardiac) with estimated dates of conception from 1998 to 2016.

RESULTS: We found moderately protective aPRs (range: 0.60-0.89) in a little over half of the case groups examined in our quartiles of higher SS activity (19 non-cardiac; 6 cardiac), after adjusting for maternal age, race/ethnicity, and education. Particularly protective aPRs in the highest SS quartiles (Q3-4) were noted for: anophthalmia, cataract, gastroschisis, trisomy 18, ventricular septal defects, atrial septal defects, and pulmonary valve atresia or stenosis. Conversely, modestly elevated aPRs were noted for two defect groups (agenesis, aplasia, and hypoplasia of the lung and microcephaly [Q2-3]). Following an additional adjustment of year of conception, results remained similar although many of the estimates were attenuated.

CONCLUSION: The seemingly protective associations between increasing SS activity may be an artifact of increasing spontaneous abortions that occur following conception during these periods of heightened SS activity.

PMID:37254605 | DOI:10.1002/bdr2.2206

Psychol Med. 2023 May 31:1-10. doi: 10.1017/S0033291723001356. Online ahead of print.

ABSTRACT

BACKGROUND: Prior research has identified altered brain structure and function in individuals at risk for self-directed violence thoughts and behaviors. However, these studies have largely utilized healthy controls and findings have been inconsistent. Thus, this study examined differences in resting-state functional network connectivity among individuals with lifetime suicide attempt(s) v. lifetime self-directed violence thoughts alone.

METHODS: Using data from the UK Biobank, this study utilized a series of linear regressions to compare individuals with lifetime suicide attempt(s) (n = 566) v. lifetime self-directed violence thoughts alone (n = 3447) on within- and between- network resting-state functional connectivity subnetworks.

RESULTS: There were no significant between-group differences for between-network, within-network, or whole-brain functional connectivity after adjusting for age, sex, ethnicity, and body mass index and performing statistical corrections for multiple comparisons. Resting-state network measures may not differentiate between individuals with lifetime suicide attempt(s) and lifetime self-directed violence thoughts alone.

CONCLUSIONS: Null findings diverge from results reported in smaller neuroimaging studies of suicide risk, but are consistent with null findings in other large-scale studies and meta-analyses. Strengths of the study include its large sample size and stringent control group. Future research on a wider array of imaging, genetic, and psychosocial risk factors can clarify relative contributions of individual and combined variables to suicide risk and inform scientific understanding of ideation-to-action framework.

PMID:37254555 | DOI:10.1017/S0033291723001356

Curr Rheumatol Rev. 2023 May 29. doi: 10.2174/1573397119666230529105122. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study was to assess the performance of computed tomography (CT) scan and magnetic resonance imaging (MRI) for detecting sacroiliitis in non-radiographic SpA (nr-SpA).

METHODS: This cross-sectional monocentric double-blind study included 63 patients consulting for symptoms suggestive of SpA between February 2014 and February 2017. Patients with conventional radiographs showing a confirmed sacroiliitis (grade 3 or 4) were not included. Eligible patients underwent CT and MRI of sacroiliac joints (SIJ). CT and MR images were interpreted by 2 experienced musculoskeletal radiologists blinded to clinical and laboratory data. Two professors in rheumatology blinded to radiologists’ conclusions analyzed clinical data, laboratory tests, HLA typing, X-rays, CT and MRI images, and divided the patients into 2 groups: confirmed nr-SpA or no SpA. This classification was considered the gold standard when analyzing the results.

RESULTS: 46 women and 17 men were included in this study. 47 patients were classified as confirmed nr-SpA (74.6%) and 16 patients as no SpA (25.4%). Sensitivity, specificity, and positive and negative predictive values of CT and MRI for detecting sacroiliitis were, respectively, estimated at 71.7%, 71.4%, 89.2%, 43.5%, and 51.2%, 100%, 100%, and 40%. CT and MRI findings were found to be statistically associated (p<0.001).

CONCLUSION: SIJ MRI is a highly specific method in the detection of sacroiliitis, but with a moderate sensitivity. SIJ CT scan, usually known as the third option after radiography and MRI, has much greater diagnostic utility than it has been documented previously.

PMID:37254543 | DOI:10.2174/1573397119666230529105122

Protein Pept Lett. 2023 May 29. doi: 10.2174/0929866530666230529143121. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma is a primary liver cancer and 6th most common cancer globally. Inefficient diagnostic strategies and the limited availability of treatments are the foremost reasons. Variable factors directly impact the disease burden, among them, molecular alterations have been found to play a significant role. In liver, arginosuccinate synthase-1 is a center of arginine metabolism and rate limiting enzyme of urea cycle. It also triggers multiple mechanisms that lead to HCC pathogenesis.

OBJECTIVES: The aim of this study is to analyze the ASS1 gene expression, its polymorphic genotype and microsatellite instability among HCC patients from our Pakistani population.

METHOD: Blood samples were collected from disease and healthy control individuals. Allele-Specific PCR was performed for SNP analysis. MSI of tri and tetra nucleotide repeats were analyzed by PCR. The differential expression of ASS1 gene was also investigated. Furthermore, the reactome database and STRING software were utilized for finding correlations between ASS1 gene with other associated gene/proteins.

RESULTS: The GG wild-type genotype was more prevailed in the disease group as compared to the control. Significant downregulation in ASS1 and NOS2 genes was observed. Bioinformatics analysis reveals the correlation between ASS1 polymorphism and HCC development appears to be linked with the EMT pathway and polyamine production. Furthermore, MSI significantly resided in the disease group. Results were analyzed statistically to calculate the significance of obtained results.

CONCLUSION: Study concludes that the insight of HCC mechanism through population-specific genetic mutations and altered gene expression of ASS1 might be helpful in early diagnostic and therapeutic purposes.

PMID:37254538 | DOI:10.2174/0929866530666230529143121

Curr Mol Med. 2023 May 29. doi: 10.2174/1566524023666230529143837. Online ahead of print.

ABSTRACT

BACKGROUND: The c-ETS-1 (ETS1) expression is high in clear cell renal cell carcinoma (ccRCC) tissues; however, how it impacts ccRCC is currently unknown.

METHOD: The online STRING web source was used to construct a protein network interacting with ETS1. The Cell Counting Kit-8 was used to detect the cell viability. A clonogenic assay, a wound-healing assay, and a Transwell assay were used to detect cell proliferation, invasion and migration abilities. Western blot was used to detect the expression of proteins.

RESULT: The data showed the expression of ETS1 in ccRCC tissues to be significantly increased compared to adjacent tissues (p<0.05). The positive expression of ETS1 in ccRCC patients aged 20-100 was statistically significant compared to adjacent normal tissues (p<0.05). The grade of ETS1 positive expression (1-4) and lymph node metastasis (N1) in ccRCC were significantly higher than those in adjacent normal tissues (p<0.05). The tumour stage (stages 1-4) in ccRCC patients with positive ETS1 expression was significantly higher than that in adjacent normal tissues (p<0.05). Knockdown of ETS1 and PERK inhibitors significantly inhibited the proliferation, migration and invasion of ccRCC cells. Knockdown of ETS1 inhibited MMP-2 expression, and an extracellular signal-related kinase (ERK) inhibitor inhibited both ETS1 and MMP-2 expression.

CONCLUSION: A high expression of ETS1 is associated with the progression of ccRCC. This study suggests that ETS1 promotes proliferation by increasing MMP2 expression in ccRCC, and combined knockdown of ETS1 and inhibition of ERK can significantly inhibit the proliferation, migration and invasion of ccRCC. ETS1 may be a therapeutic and prognostic target for renal cell carcinoma.

PMID:37254537 | DOI:10.2174/1566524023666230529143837

J Telemed Telecare. 2023 May 30:1357633X231174933. doi: 10.1177/1357633X231174933. Online ahead of print.

ABSTRACT

INTRODUCTION: The prevalence of non-adherence to antidiabetic treatment remains high despite various efforts. Thus, the positive effects of the antidiabetic treatment cannot be optimised and the disease progresses to complications. This present systematic review and meta-analysis aimed to evaluate the effects of mobile applications (apps) intervention on medication adherence and type 2 diabetes mellitus (T2DM) control.

METHODS: This research was conducted following the PRISMA guidelines. The databases that had been searched included Web of Science, PubMed, Scopus, Cochrane Library and Ovid from 2017 to 2022. Study characteristics were retrieved and study outcomes such as adherence status and diabetes control were extracted and quantitatively analysed through meta-analysis.

RESULTS: Eight studies met the final inclusion criteria and were included in the analysis, contributing to a total of 884 subjects. The methodological quality of the included studies was variable. Three studies reported statistically significant improvement in medication adherence through mobile apps intervention. Additionally, the mobile apps intervention proved effective in reducing glycaemic outcomes. As compared to non-mobile apps users, glycated haemoglobin (HbA1c) significantly decreased by 0.36% (95% CI -0.47% to -0.25%), whereas fasting plasma glucose (FPG) significantly decreased by 16.75 mg/dL (95% CI -17.60 mg/dL to -15.80 mg/dL).

CONCLUSION: Mobile apps intervention had beneficial impacts on medication adherence and glycaemic parameters. Future research should explore the best practical approach for real-world settings.

PMID:37254516 | DOI:10.1177/1357633X231174933

BMC Health Serv Res. 2023 May 30;23(1):556. doi: 10.1186/s12913-023-09544-y.

ABSTRACT

OBJECTIVE: In addition to the common difficulties of ongoing trials, the COVID-19 pandemic posed several challenges to scientists worldwide and created an additional burden for vulnerable patient groups. In the nFC-isPO of individualised treatment for anxiety and depression in newly diagnosed patients with cancer caregivers (e.g. psycho-oncologists) reported elevated HADS scores in newly enrolled patients after the outbreak of the COVID-19 pandemic. Accordingly, the question arises whether the pandemic affected HADS scores. Therefore, stratified analyses by the time of enrolment (T1) were performed for patients with 12 months of care (T3).

METHODS: Patients with 12 months of care (N = 1,140) were analysed. A comparison within the regression discontinuity design according to the time points at which patients completed the baseline (T1) HADS questionnaire was conducted to examine differences between patients recruited before Q2/2020 (pre-pandemic) and after the coronavirus outbreak. Furthermore, mean HADS scores at T1 and T3 for all quarters during the study were compared.

RESULTS: Mean T1 and T3 HADS scores of patients with cancer during the pandemic are only slightly higher than those of the pre-pandemic group. No significant treatment effect was observed in either the pre-pandemic (p = 0.5495, Late = 1.7711) or the post-pandemic group (p = 0.9098, LATE=-0.2933). In contrast, the average local treatment effect in the post-pandemic group suggests a minimal decrease in HADS score in the predefined range and thus a positive treatment effect for isPO. Comparison of mean HADS scores at T1 and T3 did not show a large increase by pandemic-related timepoints, however, a decrease of approximately 2-3 points over each quarter at 12 months compared to baseline is observed.

CONCLUSION: The existing nFC-isPO care is resilient to crisis and may counteract external influences such as the Corona pandemic. Accordingly, the pandemic had little influence on the fears of patients with cancer in the nFC-isPO. This emphasises that psycho-oncology is vital for the reduction of stress, anxiety and depression in patients with cancer.

TRIAL REGISTRATION: The study was registered in the German Clinical Trials Registry on 30 October 2018 under the ID “DRKS00015326”.

PMID:37254172 | DOI:10.1186/s12913-023-09544-y