Category: Nevin Manimala

Arch Orthop Trauma Surg. 2022 Jun 2. doi: 10.1007/s00402-022-04481-7. Online ahead of print.

ABSTRACT

INTRODUCTION: Contemporary studies evaluating utilization and trends of total ankle arthroplasty (TAA) and ankle fusion (AF) for tibiotalar osteoarthritis are sparse. Therefore, the purpose of this study was to utilize a nationwide administrative claims database from 2010 to 2019 to compare: (1) baseline demographics; (2) utilization, (3) in-hospital length of stay (LOS), and (4) costs of care.

METHODS: Using the PearlDiver database, a retrospective query from January 1st, 2010 to December 31st, 2019 was performed for all patients who underwent TAA and AF for tibiotalar osteoarthritis. Baseline demographics, comorbidities, and geographic utilization were compared using Pearson Chi-square analyses. Linear regression was used to compare differences in procedure utilization and in-hospital LOS during the study interval. Reimbursements between the two cohorts during the study interval were compared. A p value less than 0.05 was statistically significant.

RESULTS: In total, 14,248 patients underwent primary TAA (n = 5544) or AF (n = 8704). Patients undergoing AF were generally younger (< 60) with greater comorbidity burden driven by hypertension, diabetes mellitus, obesity, and tobacco use compared to TAA patients (p < 0.0001). Over the study interval, TAA utilization remained constant (912 vs 909 procedures; p = 0.807), whereas AF utilization decreased by 42.5% (1737 vs 998 procedures; p = 0.0001). Mean in-hospital LOS for patients undergoing TAA decreased (2.5 days vs. 2.0 days, p = 0.0004), while AF LOS increased (2.6 days vs. 3.5 days, p = 0.0003). Reimbursements for both procedures significantly declined over the study interval (TAA: $4559-$2156, AF: $4729-$1721; p < 0.013).

CONCLUSION: TAA utilization remained constant, while AF utilization declined by 42.5% from 2010 to 2019. There was divergence in the LOS for TAA versus AF patients. Both procedures significantly declined by over 50% in reimbursements over the study interval.

PMID:35652950 | DOI:10.1007/s00402-022-04481-7

Int Urogynecol J. 2022 Jun 2. doi: 10.1007/s00192-022-05240-3. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: The objective of this study was to compare the long-term outcome between vaginal hysterectomy with low uterosacral ligament suspension (VH) and the modified Manchester Fothergill procedure (MF) as surgical treatment in patients with pelvic organ prolapse (POP). We hypothesize that MF is non-inferior to VH in the long term.

METHODS: In this single-center retrospective cohort study patients who underwent MF or VH for primary apical compartment prolapse between 2003 and 2009 were eligible for inclusion. The primary outcome was subjective recurrence of POP. Secondary outcomes included number and type of reinterventions, time to reintervention and the degree of complaints.

RESULTS: One hundred sixty of 398 patients (53 MF, 107 VH) returned the questionnaires (40%). The mean follow-up was 12.97 years for MF and 13.24 years for VH (p = 0.38). There were similar rates of subjective POP recurrence (51% in both groups). The reintervention rate in the MF group was higher but reached no statistical significance [19/53 (36%) versus 29/107 (27%), p = 0.26]. Kaplan-Meier curve showed no statistically significant difference in risk of reintervention after MF at the maximum follow-up of 16.5 years [HR 1.830 (95% CI 0.934-3.586), p = 0.08]. The mean time to reintervention was 3 years shorter in the MF group (p = 0.03).

CONCLUSIONS: The subjective recurrence after MF is similar to VH in treatment of POP at the long term. MF appears to be non-inferior to VH when comparing the risk of reintervention. However, the small sample size precludes a definitive conclusion of non-inferiority, and future studies are needed.

PMID:35652948 | DOI:10.1007/s00192-022-05240-3

Arch Gynecol Obstet. 2022 Jun 2. doi: 10.1007/s00404-022-06633-x. Online ahead of print.

ABSTRACT

PURPOSE: To assess the quantitative and qualitative components of in-person focus groups as a potential intervention for female patients with urinary incontinence.

METHODS: Women over the age of 18 seeking treatment for UI were randomized to standard care with focus group participation or to standard care alone. All participants completed validated questionnaires: MESA, UDI-6, OAB-SAT-q, PGI-S, PGI-I, SQoL-F, PHQ-9, IPAQ at the beginning and conclusion of the study. Questionnaires were analyzed with repeated measures of ANOVA models in an intention-to-treat manner. Three moderated focus group sessions were held and audio recorded. Recordings were transcribed and categorized by frequency into themes using grounded theory methodology.

RESULTS: A total of ten control and eight intervention participants agreed to participate. Seven women attended all three focus group sessions and were included in the final analysis. Transcripts from focus group sessions observed women identified most with (1) urinary incontinence (UI) as a chronic disease, (2) shame managing UI, and (3) social constraints of toileting. Participants self-reported appreciation of focus group participation and desire for on-going sessions. Analysis of the questionnaires did not demonstrate statistically significant differences.

CONCLUSION: Data ascertained from questionnaires were unable to demonstrate a meaningful effect in improved treatment outcomes for control and intervention participants. Grounded theory analysis of transcripts identified four primary themes: (1) appreciation of the focus group, (2) UI as a gendered issue, (3) lack of public awareness, and (4) history of negative provider interactions. All focus group participants self-reported interest in attending future focus group sessions.

PMID:35652933 | DOI:10.1007/s00404-022-06633-x

J Mol Evol. 2022 Jun 2. doi: 10.1007/s00239-022-10058-0. Online ahead of print.

ABSTRACT

We draw attention to an under-appreciated simulation method for generating artificial data in a phylogenetic context. The approach, which we refer to as jump-chain simulation, can invoke rich models of molecular evolution having intractable likelihood functions. As an example, we simulate data under a context-dependent model allowing for CpG hypermutability and show how such a feature can mislead common codon models used for detecting positive selection. We discuss more generally how this method can serve to elucidate the ways by which currently used models for inference are susceptible to violations of their underlying assumptions. Finally, we show how the method could serve as an inference engine in the Approximate Bayesian Computation framework.

PMID:35652926 | DOI:10.1007/s00239-022-10058-0

Acta Obstet Gynecol Scand. 2022 Jun 2. doi: 10.1111/aogs.14386. Online ahead of print.

ABSTRACT

INTRODUCTION: Glucocorticoid (GC) -induced fetal programming of the activity of the hypothalamus-pituitary-adrenal axis (HPAA) and its associated cognitive and behavioral consequences in later life have been well characterized in several animal species. However, information on humans is scarce. In this study, we examined HPAA activity markers and associated outcomes at 8 to 9 years of age among children prenatally exposed to GC for suspected preterm birth. Our hypothesis was that antenatal exposure to the betamethasone (BM) is associated with exacerbation of HPAA activity in childhood.

MATERIAL AND METHODS: Prospective observational study in 31 children whose mothers received single (n = 19) or multiple (n = 12) courses of BM for threatened preterm birth but born with normal weight appropriate for the gestational age (median 37+⁶ weeks of gestation) compared with 38 non-exposed, age-matched children. Primary end point was the activity of the HPAA in response to the Trier Social Stress Test. Secondary end points were changes in autonomic nervous system (ANS) activity, cognitive performance (IQ), attention-deficit/hyperactivity disorder (ADHD) symptoms, and electrocortical activity (EEG).

RESULTS: There was no statistically significant difference in HPAA activity markers between antenatal BM exposed and unexposed groups. ANS activity in BM-exposed children shifted towards a higher parasympathetic tone reflected by a higher overall high-frequency band power of heart rate variability. IQ scores were within normal limits for both groups; however, BM-exposed children had lower IQ scores than the unexposed group. BM-exposed group had marginally more ADHD core symptoms and increased electrocortical activity in the occipital brain region compared with controls. A monotonic dose-response relationship between BM exposure and activity of the ANS and IQ was estimated in post-hoc analyses.

CONCLUSIONS: Antenatal exposure to BM in the context of threatened preterm birth was not associated with changes in HPAA activity in childhood. However, BM exposure may be associated with changes in ANS activity. Antenatal GC prophylaxis is a valuable and often life-saving therapy, but its prescription may warrant a well-balanced risk-benefit assessment.

PMID:35652410 | DOI:10.1111/aogs.14386

Anticancer Agents Med Chem. 2022 Jun 1. doi: 10.2174/1871520622666220601115458. Online ahead of print.

ABSTRACT

Purpose To investigate the safety and efficacy of lobaplatin-TACE in the treatment of primary hepatocellular carcinoma. Method The data of 536 patients who underwent TACE in the interventional department from January 2016 to January 2020 were collected. Patients were divided into two groups according to the chemotherapeutic drugs used in TACE.: epirubicin-TACE group(N = 260), lobaplatin-TACE group(N = 276). Primary study endpoint: (1) The tumor response after TACE; (2)The survival rates ; Secondary study endpoints:(1)Changes of liver function and blood routine before and after TACE;(2)Occurrence of post-embolization syndrome and infection after TACE. Results The ORR was 35.0% in epirubicin-TACE group and 51.1% in lobaplatin-TACE group(P=0.001). The DCR was 73.1% in epirubicin-TACE group and 82.2% in lobaplatin-TACE group(P=0.011). The 6-month, 9-month, 12-month, and 15-month survival rates were higher in the lobaplatin-TACE group than in the epirubicin-TACE group(P=0.029,P=0.001,P=0.005,P=0.002). mOS: Epirubicin-TACE group,14.8 months; Lobaplatin-TACE group,18.6 months (P =0.007). mPFS: Epirubicin-TACE group,9.5 months; Lobaplatin-TACE group,12.8 months (P =0.000). There was no statistical difference in ALT, AST, total bilirubin and Leucocyte after TACE between the two groups (P=0.343,P=0.368,P=0.288,P=0.359). The platelet decrease after TACE was more significant in the lobaplatin-TACE group than in the epirubicin-TACE group (P=0.046). There was no statistical difference in the incidence rate of abdominal pain, fever and infection after TACE between the two groups (P=0.502,P=0.602,P=0.726).The incidence of vomiting after TACE in the lobaplatin-TACE group was higher than that in the epirubicin-TACE group (P=0.003). Conclusion Lobaplatin-TACE has higher tumor response rate and survival rate.Lobaplatin-TACE is a safe and effective treatment strategy,it is worthy of clinical application.

PMID:35652401 | DOI:10.2174/1871520622666220601115458

Inquiry. 2022 Jan-Dec;59:469580221098755. doi: 10.1177/00469580221098755.

ABSTRACT

Courses on basic life support (BLS) and automated external defibrillator (AED) in schools lead to increase in knowledge but its retention is less well explored. We aimed to explore the long-term retention of knowledge and practical skills among schoolchildren after a BLS and AED course to be able to tailor future courses accordingly. Study was conducted in 3 parts and included 823 seventh and ninth graders from different elementary schools in Maribor, Slovenia. In Study 1 (n=611) we assessed students’ baseline knowledge and immediate knowledge gain after our BLS and AED course with a validated questionnaire; in Study 2 (n=116) we assessed retention of gained knowledge and skills after 5 months with a modified Cardiff test and Little Anne QCPR manikin; in Study 3 (n=96) we assessed retention of knowledge 2 years after the course. Mean differences in knowledge before and after the course in Study 1 and between studies were analyzed using paired t-tests and independent t-tests. Differences between individual question scores at different time points were compared using Mann – Whitney U test. A two-sided P<0,05 was considered significant. Practical skills retention was presented with descriptive statistics. Knowledge gain was significant immediately after the course with 83% correct answers compared to 60% at baseline. Scores dropped significantly after 5 months (73%) and after 2 years (75%), but remained significantly better than at baseline (P<0.001). Practical skills perfomance score as per Cardiff test after 5 months was 63%. Overall BLS performance score as per QCPR app was 59%, with an overall cardio score of 77% (average compression rate: 124/min and depth: 52 mm) and ventilation score of 44%. This study showed that long term retention of theoretical knowledge was satisfying whereas poor practical skills performance after 5 months calls for a more intense practical training on repeat courses.

PMID:35652386 | DOI:10.1177/00469580221098755

Anticancer Agents Med Chem. 2022 Jun 1. doi: 10.2174/1871520622666220601093452. Online ahead of print.

ABSTRACT

Background C-KIT is a receptor tyrosine kinase with oncogenic properties overexpressed in PCa cases. Through the use of an alternative promoter, a truncated c-KIT protein (tr-KIT) of 30-50 kDa is generated, lacking the extracellular and transmembrane domain. Tr-KIT promotes the formation of a multi-molecular complex composed by Fyn, Plcγ1 and Sam68. Imatinib blocks the activity of full-length c-KIT but has no effect on tr-KIT. LNCaP is the human PCa cell line that shows tr-KIT overexpression and PC3 does not show tr-KIT overexpression. miR-128/193a-5p/494 are miRNAs targeting FYN, PLCγ1 and SAM68 combinatorily. The question of the study is that: can miR-128/193a-5p/494 be related with imatinib resistance in PCa? Method LNCaP and PC3 cells were treated with imatinib in IC50 doses. Before and after imatinib administration, RNA was isolated and cDNA conversion was performed. By qPCR analysis, expression changes of tr-KIT specific pathway elements and miR-128/193a-5p/494 analyzed before and after imatinib administration. Results After imatinib administration, miR-128/193a-5p/494 were overexpressed statistically significantly in LNCaP cells while they were downregulated statistically significantly in PC3 cells (p<0.05). Also, FYN was upregulated in LNCaP cells (p<0.05) but there was no change in PC3 after imatinib administration. Conclusion Especially upregulation of FYN may sponge miR128/193a-5p/494 and downregulate their transcriptional activity in LNCaP cells having tr-KIT acitivity. So, miR-128/193a-5p/494 may have critical role in imatinib resistance via tr-KIT pathway.

PMID:35652400 | DOI:10.2174/1871520622666220601093452

Stroke. 2022 Jun 2:101161STROKEAHA121038035. doi: 10.1161/STROKEAHA.121.038035. Online ahead of print.

ABSTRACT

BACKGROUND: The risk of aneurysmal subarachnoid hemorrhage (aSAH) is increased in postmenopausal women compared with men of similar age, suggesting a role for sex hormones. We aimed to explore whether sex hormones, and age at menarche/menopause have a causal effect on aSAH risk by conducting a 2-sample MR study (Mendelian randomization).

METHODS: We obtained sex-specific genetic instruments for serum estradiol, bioavailable testosterone (BioT), SHBG (sex hormone-binding globulin), and age at menarche/menopause from genome-wide association studies. The associated sex-specific aSAH risk was estimated with inverse-variance weighted MR analyses with various statistical sensitivity analyses. Multivariable and cluster MR analyses were performed for BioT and SHBG to account for a genetic and phenotypic correlation between the 2 exposures. The clusters represented (1) single-nucleotide polymorphisms primarily increasing SHBG, with secondary decreasing effects on BioT, and (2) single-nucleotide polymorphisms affecting BioT without affecting SHBG.

RESULTS: Univariable MR analyses showed an 18% increased aSAH risk among women per 1-SD increase in genetically determined SHBG levels (odds ratio, 1.18 [95% CI, 1.05-1.34]; P=0.007). Suggestive evidence was identified for a 27% decreased risk of aSAH among women per 1-SD increase in BioT (odds ratio, 0.73 [95% CI, 0.55-0.95]; P=0.02). The latter association disappeared in cluster analysis when only using SHBG-independent variants. MR analyses with variants from the cluster with primary SHBG effects and secondary (opposite) BioT-effects yielded a statistically significant association (odds ratio, 1.21 [95% CI, 1.05-1.40]; P=0.008). No other causal associations were identified.

CONCLUSIONS: Genetic predisposition to elevated serum levels of SHBG, with secondary lower serum BioT levels, is associated with an increased aSAH risk among women, suggesting that SHBG and BioT causally elevate aSAH risk. Further studies are required to elucidate the underlying mechanisms and their potential as an interventional target to lower aSAH incidence.

PMID:35652345 | DOI:10.1161/STROKEAHA.121.038035

Circulation. 2022 Jun 2:101161CIRCULATIONAHA121055484. doi: 10.1161/CIRCULATIONAHA.121.055484. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiovascular health (CVH) from young adulthood is strongly associated with an individual’s future risk of cardiovascular disease (CVD) and total mortality. Defining epigenomic biomarkers of lifelong CVH exposure and understanding their roles in CVD development may help develop preventive and therapeutic strategies for CVD.

METHODS: In 1085 CARDIA study (Coronary Artery Risk Development in Young Adults) participants, we defined a clinical cumulative CVH score that combines body mass index, blood pressure, total cholesterol, and fasting glucose measured longitudinally from young adulthood through middle age over 20 years (mean age, 25-45). Blood DNA methylation at >840 000 methylation markers was measured twice over 5 years (mean age, 40 and 45). Epigenome-wide association analyses on the cumulative CVH score were performed in CARDIA and compared in the FHS (Framingham Heart Study). We used penalized regression to build a methylation-based risk score to evaluate the risk of incident coronary artery calcification and clinical CVD events.

RESULTS: We identified 45 methylation markers associated with cumulative CVH at false discovery rate <0.01 (P=4.7E-7-5.8E-17) in CARDIA and replicated in FHS. These associations were more pronounced with methylation measured at an older age. CPT1A, ABCG1, and SREBF1 appeared as the most prominent genes. The 45 methylation markers were mostly located in transcriptionally active chromatin and involved lipid metabolism, insulin secretion, and cytokine production pathways. Three methylation markers located in genes SARS1, SOCS3, and LINC-PINT statistically mediated 20.4% of the total effect between CVH and risk of incident coronary artery calcification. The methylation risk score added information and significantly (P=0.004) improved the discrimination capacity of coronary artery calcification status versus CVH score alone and showed association with risk of incident coronary artery calcification 5 to 10 years later independent of cumulative CVH score (odds ratio, 1.87; P=9.66E-09). The methylation risk score was also associated with incident clinical CVD in FHS (hazard ratio, 1.28; P=1.22E-05).

CONCLUSIONS: Cumulative CVH from young adulthood contributes to midlife epigenetic programming over time. Our findings demonstrate the role of epigenetic markers in response to CVH changes and highlight the potential of epigenomic markers for precision CVD prevention, and earlier detection of subclinical CVD, as well.

PMID:35652342 | DOI:10.1161/CIRCULATIONAHA.121.055484