Tag: nevin manimala

Geroscience. 2023 Jun 1. doi: 10.1007/s11357-023-00825-2. Online ahead of print.

ABSTRACT

Balancing stroke prevention and risk of bleeding in patients with atrial fibrillation (AF) is challenging. Direct oral anticoagulants (DOACs) are by now considered standard of care for treating patients with AF in international guidelines. Our objective was to assess the safety of long-term intake of DOACs in older adults with AF. We included RCTs in elderly (≥ 65 years) patients with AF. A systematic search in MEDLINE and EMBASE was performed on 19 April 2022. For determination of risk of bias, the RoB 2 tool was applied. We pooled outcomes using random-effects meta-analyses. The quality of evidence was assessed using GRADE. Eleven RCTs with a total of 63,374 patients were identified. Two RCTs compared apixaban with either warfarin or aspirin, four edoxaban with either placebo, aspirin, or vitamin K antagonists (VKAs), two dabigatran with warfarin and three rivaroxaban with warfarin. DOACs probably reduce mortality in elderly patients with AF (HR 0.89 95%CI 0.77 to 1.02). Low-dose DOACs likely reduce bleeding compared to VKAs (HR ranged from 0.47 to 1.01). For high-dose DOACS the risk of bleeding varied widely (HR ranged from 0.80 to 1.40). We found that low-dose DOACs probably decrease mortality in AF patients. Moreover, apixaban and probably edoxaban are associated with fewer major or clinically relevant bleeding (MCRB) events compared to VKAs. For dabigatran and rivaroxaban, the risk of MCRB varies depending on dose. Moreover, subgroup analyses indicate that in the very old (≥ 85) the risk for MCRB events might be increased when using DOACs.Registration: PROSPERO: CRD42020187876.

PMID:37261677 | DOI:10.1007/s11357-023-00825-2

Clin Pharmacokinet. 2023 Jun 1. doi: 10.1007/s40262-023-01248-0. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: An important barrier to HIV prevention among transgender women (TGW) is the concern that oral pre-exposure prophylaxis (PrEP) negatively affects the efficacy of feminizing hormone therapy (FHT). We aimed to assess the impact of PrEP on FHT pharmacokinetics (PK) among TGW from Brazil.

METHODS: We performed a drug-drug interaction sub-study among TGW enrolled in a daily oral PrEP demonstration study (PrEParadas, NCT03220152). Participants had a first PK assessment (PK1) 15 days after FHT (estradiol valerate 2-6 mg plus spironolactone 100-200 mg) initiation and then started PrEP (tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg). A second PK evaluation was performed 12 weeks later (PK2). Blood samples were collected prior and after the directly observed dosing (0, 0.5, 1, 2, 4, 6, 8, and 24 hours). Pharmacokinetic parameters of estradiol, spironolactone, and metabolites were estimated by non-compartmental analysis (Monolix 2021R2, Lixoft^®) and compared as geometric mean ratios (GMRs, 90% confidence interval [CI]).

RESULTS: Among 19 TGW who completed the substudy, median age was 26 years (interquartile range: 23-27.5). Estradiol area under the plasma concentration-time curve (AUC_τ) and trough concentrations did not differ between PK1 and PK2 evaluations (GMR [90% CI]: 0.89 [0.76-1.04] and 1.06 [0.94-1.20], respectively). Spironolactone and canrenone AUC_τ were statistically lower at PK2 than PK1 (0.76 [0.65-0.89] and 0.85 [0.78-0.94], respectively). Canrenone maximum concentration was also lower at PK2 than PK1 (0.82 [0.74-0.91]).

CONCLUSION: Estradiol PK was not influenced by PrEP concomitant use. The small differences observed in some spironolactone and canrenone PK parameters should not prevent the concomitant use of estradiol-based FHT and PrEP.

TRIAL REGISTRATION: This trial (NCT03220152) was registered on July 18, 2017.

PMID:37261664 | DOI:10.1007/s40262-023-01248-0

J Cancer Surviv. 2023 Jun 1. doi: 10.1007/s11764-023-01408-y. Online ahead of print.

ABSTRACT

PURPOSE: Weight gain after breast cancer poses health risks. We aimed to identify factors associated with weight gain during adjuvant endocrine therapy (AET).

METHODS: Women initiating AET enrolled in a prospective cohort. Participants completed FACT-ES plus PROMIS pain interference, depression, anxiety, fatigue, sleep disturbance and physical function measures at baseline, 3, 6, 12, 24, 36, 48 and 60 months. Treatment-emergent symptoms were defined as changes in scores in the direction indicative of worsening symptoms that exceeded the minimal important difference at 3 and/or 6 months compared to baseline. We used logistic regression to evaluate associations of clinicodemographic features and treatment-emergent symptoms with clinically significant weight gain over 60 months (defined as ≥ 5% compared to baseline) in pre- and post-menopausal participants.

RESULTS: Of 309 participants, 99 (32%) were pre-menopausal. The 60 months cumulative incidence of clinically significant weight gain was greater in pre- than post-menopausal participants (67% vs 43%, p < 0.001). Among pre-menopausal participants, treatment-emergent pain interference (OR 2.49), aromatase inhibitor receipt (OR 2.8), mastectomy, (OR 2.06) and White race (OR 7.13) were associated with weight gain. Among post-menopausal participants, treatment-emergent endocrine symptoms (OR 2.86), higher stage (OR 2.25) and White race (OR 2.29) were associated with weight gain while treatment-emergent physical function decline (OR 0.30) was associated with lower likelihood of weight gain.

CONCLUSIONS: Weight gain during AET is common, especially for pre-menopausal women. Clinicodemographic features and early treatment-emergent symptoms may identify at risk individuals.

IMPLICATIONS FOR CANCER SURVIVORS: Patients at risk for weight gain can be identified early during AET.

GOV IDENTIFIER: NCT01937052, registered September 3, 2013.

PMID:37261654 | DOI:10.1007/s11764-023-01408-y

Hernia. 2023 Jun 1. doi: 10.1007/s10029-023-02813-z. Online ahead of print.

ABSTRACT

PURPOSE: There is a growing trend to expand Ambulatory Surgery (AS) criteria in abdominal wall surgery. No Admission (NOADS) circuit. The present study aimed to assess the impact of classification criteria on postoperative results and hospital stays in a NOADS versus a conventional admission circuit to throw some light on surgical circuit inclusion.

METHODS: A retrospective analysis of a prospective;y maintained database was performed comparing groin hernia’s interventions in a NOADS vs Admission circuit in our center in 2018-2021. A multiple regression predictive model followed by a retrospective retest were dessigned to assess the impact of each criterion on hospital stay. In total, 743 patients were included, 399 in the Admission circuit (ADC) and 344 in NOADS circuit (NOADS).

RESULTS: There were no statistical differences in complication or readmission rates (p = 0.343 and p = 0.563), nevertheless, a shorter hospital stay was observed in NOADS (p = 0.000). A hierarchical multiple regression predictive model proposed two opposite scenarios. The best scenario, not likely to need admission, was a female patient operated via the laparoscopic approach of a unilateral primary hernia (Estimated Postoperative Stay: 0.049 days). The worst scenario, likely to need admission, was a male patient operated via the open approach of a bilateral and recurrent hernia (Estimated Postoperative Stay: 1.505 Days).

CONCLUSION: Groin hernia patients could safely benefit from a No Admission (NOADS) circuit. Our model could be useful for surgical circuit decision-making, especially for best/worst scenarios.

PMID:37261641 | DOI:10.1007/s10029-023-02813-z

J Magn Reson Imaging. 2023 Jun 1. doi: 10.1002/jmri.28839. Online ahead of print.

ABSTRACT

BACKGROUND: Lenticulostriate artery (LSA) obstruction is a potential cause of subcortical infarcts. However, MRI LSA evaluation at 3T is challenging.

PURPOSE: To investigate middle cerebral artery (MCA) plaque characteristics and LSA morphology associated with subcortical infarctions in LSA territories using 7-T vessel wall MRI (VW-MRI) and time-of-flight MR angiography (TOF-MRA).

STUDY TYPE: Prospective.

POPULATION: Sixty patients with 80 MCA atherosclerotic plaques (37 culprit and 43 non-culprit).

FIELD STRENGTH/SEQUENCE: 7-T with 3D TOF-MRA and T1-weighted 3D sampling perfection with application-optimized contrast using different flip angle evolutions (SPACE) sequences.

ASSESSMENT: Plaque distribution (superior, inferior, ventral, or dorsal walls), LSA origin involvement, LSA morphology (numbers of stems, branches, and length), and plaque characteristics (normalized wall index, maximal wall thickness, plaque length, remodeling index, intraplaque hemorrhage, and plaque surface morphology (regular or irregular)) were assessed.

STATISTICAL TESTS: Least absolute shrinkage and selection operator regression, generalized estimating equations regression, receiver operating characteristic curve, independent t-test, Mann-Whitney U test, Chi-square test, Fisher’s exact test, and intra-class coefficient. A P value <0.05 was considered statistically significant.

RESULTS: Plaque irregular surface, superior wall plaque, longer plaque length, LSA origin involvement, fewer LSA stems, and shorter total and average lengths of LSAs were significantly associated with culprit plaques. Multivariable logistic analysis confirmed that LSA origin involvement (OR, 28.51; 95% CI, 6.34-181.02) and plaque irregular surface (OR, 8.32; 95% CI, 1.41-64.73) were independent predictors in differentiating culprit from non-culprit plaques. A combination of LSA origin involvement and plaque irregular surface (area under curve = 0.92; [95% CI, 0.86-0.98]) showed good performance in identifying culprit plaques, with sensitivity and specificity of 86.5% and 86.0%, respectively.

DATA CONCLUSION: 7-T VW-MRI and TOF-MRA can demonstrate plaque involvement with LSA origins. MCA plaque characteristics derived from 7-T VW-MRI showed good diagnostic accuracy in determining the occurrence of subcortical infarctions.

EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

PMID:37259904 | DOI:10.1002/jmri.28839

J Obstet Gynaecol Res. 2023 Jun 1. doi: 10.1111/jog.15699. Online ahead of print.

ABSTRACT

AIM: To explore left ventricular structural/functional abnormalities in preeclampsia patients by using multimodal echocardiography and to analyze the cardiac impact in preeclampsia subtypes.

METHODS: A total of 103 individuals, including 64 preeclampsia patients and 39 healthy pregnant women were recruited for this study from 2019 to 2021. There were 34 patients with preeclampsia with severe features (SPE) patients and 30 with preeclampsia with nonsevere features (NSPE), including 9 with early-onset NSPE (EO-NSPE) patients, 27 early-onset SPE (EO-SPE) patients, 21 later-onset NSPE (LO-NSPE), and 7 with later-onset SPE (LO-SPE). All patients underwent multimodal echocardiography before treatment, including two-dimensional, Doppler, and speckle-tracking echocardiography, to evaluate left ventricular structure/function. Analysis of variance was used to determine statistical significance across groups.

RESULTS: EO-SPE patients showed decreased left ventricular ejection fractions, peak longitudinal systolic strain at apical four-chambers, peak circumferential, and radial systolic strain at the apical and mitral annular plane systolic excursion (MAPSE), and increased mitral regurgitation compared to other preeclampsia patients. Compared to LO-NSPE and EO-SPE patients, LO-SPE patients showed increased left ventricular mass indexed to height^2.7 and early diastolic left ventricular diastolic filling/mitral annular velocity, and decreased MAPSE and early/late diastolic mitral annular velocity.

CONCLUSION: EO-SPE patients were characterized by left ventricular injury and systolic function reduced. LO-SPE patients were characterized by left ventricular hypertrophy and reduced diastolic function. Multimodal echocardiography can detect myocardial injury in PE patients at an early stage.

PMID:37259850 | DOI:10.1111/jog.15699

Future Oncol. 2023 Jun 1. doi: 10.2217/fon-2023-0165. Online ahead of print.

ABSTRACT

Purpose: To evaluate the risk factors for young-onset advanced colorectal neoplasia. Methods: We performed a meta-analysis of 30 potential exposure risk factors from 28 original studies. Results: Several risk factors showed statistical significance, including male sex (odds ratio [OR]: 1.28; 95% CI: 1.12-1.47), metabolic syndrome (OR: 1.34; 95% CI: 1.25-1.44), hypertension (OR: 1.22; 95% CI: 1.17-1.28), diabetes (OR: 1.23; 95% CI: 1.15-1.32), inflammatory bowel disease (OR: 4.62; 95% CI: 1.12-17.54), obesity (OR: 1.23; 95% CI: 1.06-1.43), sedentary behavior (OR: 1.25; 95% CI: 1.06-1.48), smoking (OR: 1.19; 95% CI: 1.05-1.36), high alcohol consumption (OR: 1.37; 95% CI: 1.10-1.71), high intake of sugar (OR: 2.58; 95% CI: 1.61-4.13) and red meat (OR: 1.10; 95% CI: 1.04-1.16), and family history of colorectal cancer (OR: 3.14; 95% CI: 1.29-7.64). Conclusion: Our study identified potential risk factors for young-onset advanced colorectal neoplasms to help develop targeted primary prevention strategies.

PMID:37259811 | DOI:10.2217/fon-2023-0165

Stat Med. 2023 Jun 30;42(14):2311-2340. doi: 10.1002/sim.9725. Epub 2023 Apr 22.

ABSTRACT

We propose a permutation-based method for testing a large collection of hypotheses simultaneously. Our method provides lower bounds for the number of true discoveries in any selected subset of hypotheses. These bounds are simultaneously valid with high confidence. The methodology is particularly useful in functional Magnetic Resonance Imaging cluster analysis, where it provides a confidence statement on the percentage of truly activated voxels within clusters of voxels, avoiding the well-known spatial specificity paradox. We offer a user-friendly tool to estimate the percentage of true discoveries for each cluster while controlling the family-wise error rate for multiple testing and taking into account that the cluster was chosen in a data-driven way. The method adapts to the spatial correlation structure that characterizes functional Magnetic Resonance Imaging data, gaining power over parametric approaches.

PMID:37259808 | DOI:10.1002/sim.9725

Cancer Prev Res (Phila). 2023 Jun 1;16(6):333-341. doi: 10.1158/1940-6207.CAPR-22-0388.

ABSTRACT

NeuVax is a vaccine comprised of the HER2-derived MHC class I peptide E75 (nelipepimut-S, NPS) combined with GM-CSF. We completed a randomized trial of preoperative vaccination with NeuVax versus GM-CSF alone in patients with ductal carcinoma in situ (DCIS). The primary objective was to evaluate for NPS-specific cytotoxic T lymphocyte (CTL) responses. Patients with human leukocyte antigen (HLA)-A2-positive DCIS were enrolled and randomized 2:1 to NeuVax versus GM-CSF alone and received two inoculations prior to surgery. The number of NPS-specific CTL was measured pre-vaccination, at surgery, and 1 and 3 to 6 months post-operation by dextramer assay. Differences in CTL responses between groups and between pre-vaccination and 1-month post-operation were analyzed using a two-sample t test or Wilcoxon rank sum test. The incidence and severity of adverse events were compared between groups. Overall, 45 patients were registered; 20 patients were HLA-A2 negative, 7 declined participation, 1 withdrew, and 4 failed screening for other reasons. The remaining 13 were randomized to NeuVax (n = 9) or GM-CSF alone (n = 4). Vaccination was well-tolerated with similar treatment-related toxicity between groups with the majority (>89%) of adverse events being grade 1. The percentage of NPS-specific CTLs increased in both arms between baseline (pre-vaccination) and 1-month post-operation. The increase was numerically greater in the NPS+GM-CSF arm, but the difference was not statistically significant. NPS+GM-CSF is safe and well-tolerated when given preoperatively to patients with DCIS. In patients with HLA-A2-positive DCIS, two inoculations with NPS+GM-CSF can induce in vivo immunity and a continued antigen-specific T-cell response 1-month postsurgery.

PREVENTION RELEVANCE: This trial showed that vaccination of patients with HLA-A2-positive DCIS with NeuVax in the preoperative setting can induce a sustained antigen-specific T-cell response. This provides proof of principle that vaccination in the preoperative or adjuvant setting may stimulate an adaptive immune response that could potentially prevent disease recurrence.

PMID:37259799 | DOI:10.1158/1940-6207.CAPR-22-0388

Clin Implant Dent Relat Res. 2023 Jun 1. doi: 10.1111/cid.13230. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate the peri-implant soft tissue and marginal bone loss (MBL) around implants with platform-switching and internal conical connection placed at crestal and subcrestal levels in posterior areas.

MATERIALS AND METHODS: Nineteen partially edentulous patients with at least two adjacent missing teeth in posterior areas unilaterally or bilaterally were included. Forty-two implants were placed randomly at the crestal or subcrestal (1 mm) level in a split-mouth design. Implant-supported fixed dental prostheses with screw retention were delivered after 4 months of healing. Clinical and radiological measurements were performed at implant placement (T0), restoration delivery (T1), and 1-year follow-up after loading (T2). MBL was calculated as the change in distance from the implant-abutment interface to the first radiographically visible bone-implant contact. A repeated-measures mixed ANOVA followed by a paired Student’s t-test with the Bonferroni correction was used for statistical analysis. p < 0.05 was considered statistically significant.

RESULTS: Eighteen patients with thirty-eight implants completed the study at T2. The MBL was lower in the subcrestal group than in the crestal group (0.04 ± 0.08 vs. 0.17 ± 0.17 mm, p = 0.004). The peri-implant probing depth (PD) was 2.31 ± 0.48 mm in the subcrestal group and 1.92 ± 0.43 mm in the crestal group; this difference was statistically significant (p = 0.002). Intragroup comparison showed no significant differences in MBL, or PD around the crestal group and subcrestal group from T1 to T2.

CONCLUSION: After 1 year of functional loading, subcrestal placement of implants with platform-switching and internal conical connection showed lower MBL and was associated with greater PD and peri-implant soft tissue height than implants placed at the crestal level.

PMID:37259774 | DOI:10.1111/cid.13230