Tag: nevin manimala

J Am Geriatr Soc. 2022 Nov 1. doi: 10.1111/jgs.18107. Online ahead of print.

ABSTRACT

BACKGROUND: Treatment effect is typically summarized in terms of relative risk reduction or number needed to treat (“conventional effect summary”). Restricted mean survival time (RMST) summarizes treatment effect in terms of a gain or loss in event-free days. Older adults’ preference between the two effect summary measures has not been studied.

METHODS: We conducted a mixed methods study using a quantitative survey and qualitative semi-structured interviews. For the survey, we enrolled 102 residents with hypertension at five senior housing facilities (mean age 81.3 years, 82 female, 95 white race). We randomly assigned respondents to either RMST-based (n = 49) or conventional decision aid (n = 53) about the benefits and harms of intensive versus standard blood pressure-lowering strategies and compared decision conflict scale (DCS) responses (range: 0 [no conflict] to 100 [maximum conflict]; <25 is associated with implementing decisions). We used a purposive sample of 23 survey respondents stratified by both their random assignment and DCS from the survey. Inductive qualitative thematic analysis explored complementary perspectives on preferred ways of summarizing treatment effects.

RESULTS: The mean (standard deviation) total DCS was 22.0 (14.3) for the conventional decision aid group and 16.7 (14.1) for the RMST-based decision aid group (p = 0.06), but the proportion of participants with a DCS <25 was higher in the RMST-based group (26 [49.1%] vs 34 [69.4%]; p = 0.04). Qualitative interviews suggested that, regardless of effect summary measure, older individuals’ preference depended on their ability to clearly comprehend quantitative information, clarity of presentation in the visual aid, and inclusion of desired information.

CONCLUSIONS: When choosing a blood pressure-lowering strategy, older adults’ perceived uncertainty may be reduced with a time-based effect summary, although our study was underpowered to detect a statistically significant difference. Given highly variable individual preferences, it may be useful to present both conventional and RMST-based information in decision aids.

PMID:36318788 | DOI:10.1111/jgs.18107

J Laparoendosc Adv Surg Tech A. 2022 Nov 1. doi: 10.1089/lap.2022.0426. Online ahead of print.

ABSTRACT

Background: Advancement in surgery has shifted numerous procedures to a same-day discharge (SDD) setting. In this study, we evaluated factors related to SDD after robotic transversus abdominis release (rTAR). Materials and Methods: A retrospective analysis of a prospectively maintained hernia databank was performed. Patients who underwent rTAR for incisional hernias were assigned to either the SDD group (length of stay [LOS] <1) or the inpatient group (LOS ≥1 day). Pre-, intra-, and postoperative variables were compared. Predictors of SDD were explored through a logistic regression, and a mediation analysis was performed to assess their effect on the LOS. Results: Out of the 167 patients included, 53 patients were discharged the same day. Age, American Society of Anesthesiologists score, history of coronary artery disease, and wound infection were significantly higher in the inpatient group. Overall, median LOS was 1 (0-2). Postoperative complications did not differ between SDD and inpatient groups except for Clavien-Dindo Grade-II (1 versus 14, respectively; P = .039). Thirty-day readmission rates were comparable (P = .229). A binary logistic regression to predict factors associated with SDD rTAR showed statistical significance in age, operative time, mesh area, and history of wound infection. Mediation analysis showed that mesh size indirectly affected the LOS through the operative time (a = 0.54; b = 0.46; P < .001). An age >46-year-old, an operative time beyond 217 minutes, and a mesh size >475 cm² increased the probability of an inpatient stay (area-under-the-receiver operating characteristic curves: 0.69, 0.81, and 0.82, respectively). Conclusion: The pre- and intraoperative factors associated with SDD rTAR were age, history of wound infection, operative time, and mesh area. Further studies are needed to investigate the appropriateness of discharge decisions while balancing patients’ benefits, resource utilization, and costs.

PMID:36318786 | DOI:10.1089/lap.2022.0426

J Phys Chem B. 2022 Nov 1. doi: 10.1021/acs.jpcb.2c04600. Online ahead of print.

ABSTRACT

Predicting the absorption of gases and liquids in semicrystalline polymers is of critical importance for numerous applications; the mechanical and transport properties of these materials are highly dependent on the amount of solutes dissolved in their bulk. For most semicrystalline polymers which are in contact with an external fluid, the observed uptake of the solute is found to be lower than that predicted by treating the amorphous domains of the polymer as subcooled polymer melts at the same thermodynamic state. This observation has recently led to the hypothesis that the amorphous domains effectively behave as polymer liquids subject to an additional “constraint pressure” which reduces the equilibrium solubility in the domains. We present a new statistical mechanical model of semicrystalline polymers. The constraint pressure emerges naturally from our treatment, as a property of the interlamellar amorphous domains caused by the stretching and localization in space of the tie-molecules (polymer chains linking different lamellae). By assuming that the interlamellar domains exchange monomers reversibly with the lamellae, the model allows one to simultaneously predict the increase of constraint pressure at low temperatures and the variation of the lamellar thickness as a function of temperature─a phenomenon known as premelting. The sorption isotherms of a range of fluids in different polyethylene and polypropylene samples are determined experimentally and the data is compared with calculations of the new model using the SAFT-VR Mie EoS. In order to accurately predict the absorption close to the vapor pressure of the penetrant, we find that it is essential to include the “free”, unconstrained amorphous domains in the description, resulting in a multiscale model with two adjustable parameters (the fractions of tie-molecules and free amorphous domains) that characterize the morphology of a given semicrystalline polymer sample. The trends observed for the adjusted parameters qualitatively match other estimates reported in the literature.

PMID:36318751 | DOI:10.1021/acs.jpcb.2c04600

J Manag Care Spec Pharm. 2022 Nov 1:1-12. doi: 10.18553/jmcp.2022.22144. Online ahead of print.

ABSTRACT

BACKGROUND: Much of the current research on treatment patterns and use of adjunctive pain and anti-inflammatory medications among patients living with psoriatic arthritis (PsA) predates the approval and uptake of IL (interleukin)-17A inhibitors. OBJECTIVE: To compare real-world treatment patterns and use of adjunctive pain and antiinflammatory medications between patients with PsA initiating the IL-17A inhibitors, ixekizumab and secukinumab, in a US-managed care population. METHODS: We conducted a retrospective cohort study using the HealthCore Integrated Research Database. Patients with a PsA diagnosis who initiated ixekizumab or secukinumab treatment between December 1, 2017, and November 30, 2019, were identified. Two cohorts were created based on which of the 2 medications was initiated (index date), and patients with prior use of either drug were excluded, as were patients with ankylosing spondylitis. Patients had to be continuously enrolled in the health plan for 6 months prior to (baseline) and 12 months after the index date (post-index). Inverse probability of treatment weighting was used to minimize confounding from baseline demographic and clinical differences between cohorts. Treatment patterns (dosing, persistence, discontinuation, and switching) and use of adjunctive pain/anti-inflammatory medications were assessed and compared between weighted cohorts using chi-square and t-tests. RESULTS: In total, 407 patients were identified in the ixekizumab cohort (mean age 51.6 years; 54% female) and 1,508 patients were identified in the secukinumab cohort (mean age 50.1 years; 59% female). Prior to weighting, presence of a psoriasis diagnosis code (ixekizumab: 60% vs secukinumab: 45%; standardized difference [std diff] = -0.30), specialty of the index prescriber (std diff = 0.38), and mean number of prior advanced therapies (2.0 vs 1.5; std diff = -0.33) were different between cohorts. Cohorts were well balanced after weighting. The majority of secukinumab patients (71%) received an index dose of 300 mg. Rates of persistence (ixekizumab: 40% vs secukinumab: 43%; P = 0.411) and switching (25% vs 20%; P = 0.072) were not statistically different between cohorts. Use of new adjunctive pain and anti-inflammatory medications was not statistically different between cohorts either (ixekizumab: 63% vs secukinumab: 58%; P = 0.187). CONCLUSIONS: Real-world treatment patterns and use of adjunctive pain and anti-inflammatory medications were similar in patients with PsA initiating ixekizumab and secukinumab in this US-managed care population. Further research examining reasons for discontinuation, switching, and use of adjunctive medications may help inform treatment decisions for patients living with PsA. DISCLOSURES: Ms Pizzicato, Ms Ketkar, and Dr Grabner are employees of HealthCore, Inc, which received funding from Eli Lilly and Company for the conduct of the study on which this manuscript is based. Ms Pepe was an employee of HealthCore, Inc., during the time the study was conducted. Dr Grabner is a shareholder of Elevance Health (legacy Anthem, Inc.). Dr Vadhariya, Dr Birt, and Ms Bolce are employees of Eli Lilly and Company, the manufacturer of ixekizumab (Taltz). Dr Birt and Ms Bolce are shareholders of Eli Lilly and Company. Dr Walsh is a paid consultant to Eli Lilly and Company and Novartis, the manufacturers of ixekizumab (Taltz) and secukinumab (Cosentyx), respectively. Additionally, Dr Walsh is a paid consultant for Pfizer, Janssen, AbbVie, and UCB and has contracts with Pfizer, AbbVie, and Merck.

PMID:36318701 | DOI:10.18553/jmcp.2022.22144

Chirurgia (Bucur). 2022 Oct;117(5):579-584. doi: 10.21614/chirurgia.2766.

ABSTRACT

PURPOSE: To determine how individual vascular road-mapping impacts the surgeonsâ?? expectations in difficulty in D3 right colectomy for cancer, and compare these expectations to the results previously published. Aim/summary background data:Literature still lacks data on surgeons expectations using preoperative 3D roadmap of the vascular system.

METHOD: Surgeons filled out a survey asking expectations about operation time, estimated blood loss, amount of lymph nodes harvested and difficulty. The patients were classified into 4 groups and 2 subgroups according to the crossing pattern of the ileocolic artery and the jejunal veins. SPSS was used for statistical analysis. Results: Twelve surgeons were included. Eight of them expected type 2 anatomy to be least time consuming while 11/12 indicated anatomy group 4 to be the most. Five surgeons expected low blood loss in group 2 anatomy patients while 10/12 expected higher blood loss in group 4 anatomy patients. Three anticipated that group 2 would generate the highest lymph node yield and while 2/12 surgeons expected the lowest in anatomy group 4. Eight surgeons perceived group 2 as the least challenging while 10/12 experienced group 4 as the most difficult. Compared to previously published results only group 4b operating time met surgeons expectations.

CONCLUSION: Using a vascular roadmap at surgery evens out surgeons expectations in operation time, blood loss, lymph node harvested and difficulty. Comparing expectations to previously published data shows operating time in one anatomy group as the only factor where these expectations were met.

PMID:36318688 | DOI:10.21614/chirurgia.2766

Cancer Epidemiol Biomarkers Prev. 2022 Nov 1:EPI-22-0877. doi: 10.1158/1055-9965.EPI-22-0877. Online ahead of print.

ABSTRACT

BACKGROUND: Exposure to cigarette smoke, particularly in early life, is modestly associated with ovarian cancer risk and may impact systemic immunity and the tumor immune response. However, no studies have evaluated whether cigarette smoke exposure impacts the ovarian tumor immune microenvironment.

METHODS: Participants in the Nurses’ Health Study (NHS) and NHSII reported on early life exposure to cigarette smoke and personal smoking history on questionnaires (n=165,760). Multiplex immunofluorescence assays were used to measure markers of T cells and immune checkpoints in tumor tissue from 385 incident ovarian cancer cases. We used Cox proportional hazards models to evaluate hazard ratios (HR) and 95% confidence intervals (CI) for developing ovarian tumors with a low (<median) or high (≥median) immune cell percentage by cigarette exposure categories.

RESULTS: Women exposed versus not to cigarette smoke early in life had a higher risk of developing ovarian cancer with low levels of T cells overall (CD3+: HR: 1.54, 95%CI: 1.08, 2.20) and recently activated cytotoxic T cells (CD3+CD8+CD69+: HR: 1.45, 95%CI: 1.05, 2.00). These findings were not statistically significant at the Bonferroni corrected p-value of 0.0083. Adult smoking was not significantly associated with tumor immune markers after Bonferroni correction.

CONCLUSION: These results suggest early life cigarette smoke exposure may modestly increase risk of developing ovarian tumors with low abundance of total T cells and recently activated cytotoxic T cells.

IMPACT: Future research should focus on understanding the impact of exposures throughout the life course on the ovarian tumor immune microenvironment.

PMID:36318652 | DOI:10.1158/1055-9965.EPI-22-0877

Ultrasound Obstet Gynecol. 2022 Nov;60(5):673-680. doi: 10.1002/uog.26050.

ABSTRACT

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with increased risk of adverse maternal and perinatal outcomes. Vaccines are highly effective at preventing severe coronavirus disease 2019 (COVID-19), but there are limited data on COVID-19 vaccines in pregnancy. This study aimed to investigate the reactogenicity and immunogenicity of COVID-19 vaccines in pregnant women when administered according to the 12-week-interval dosing schedule recommended in the UK.

METHODS: This was a cohort study of pregnant women receiving COVID-19 vaccination between April and September 2021. The outcomes were immunogenicity and reactogenicity after COVID-19 vaccination. Pregnant women were recruited by phone, e-mail and/or text and were vaccinated according to vaccine availability at their local vaccination center. For immunogenicity assessment, blood samples were taken at specific timepoints after each dose to evaluate nucleocapsid protein (N) and spike protein (S) antibody titers. The comparator group comprised non-pregnant female healthcare workers in the same age group who were vaccinated as part of the national immunization program in a contemporaneous longitudinal cohort study. Longitudinal changes in serum antibody titers and association with pregnancy status were assessed using a two-step regression approach. Reactogenicity assessment in pregnant women was undertaken using an online questionnaire. The comparator group comprised non-pregnant women aged 18-49 years who had received two vaccine doses in primary care. The association of pregnancy status with reactogenicity was assessed using logistic regression analysis.

RESULTS: Overall, 67 pregnant women, of whom 66 had received a mRNA vaccine, and 79 non-pregnant women, of whom 50 had received a mRNA vaccine, were included in the immunogenicity study. Most (61.2%) pregnant women received their first vaccine dose in the third trimester, while 3.0% received it in the first trimester and 35.8% in the second trimester. SARS-CoV-2 S-antibody geometric mean concentrations after mRNA vaccination were not significantly different at 2-6 weeks after the first dose but were significantly lower at 2-6 weeks after the second dose in infection-naïve pregnant compared with non-pregnant women. In pregnant women, prior infection was associated with higher antibody levels at 2-6 weeks after the second vaccine dose. Reactogenicity analysis included 108 pregnant women and 116 non-pregnant women. After the first dose, tiredness and chills were reported less commonly in pregnant compared with non-pregnant women (P = 0.043 and P = 0.029, respectively). After the second dose, feeling generally unwell was reported less commonly (P = 0.046) in pregnant compared with non-pregnant women.

CONCLUSIONS: Using an extended 12-week interval between vaccine doses, antibody responses after two doses of mRNA COVID-19 vaccine were found to be lower in pregnant compared with non-pregnant women. Strong antibody responses were achieved after one dose in previously infected women, regardless of pregnancy status. Pregnant women reported fewer adverse events after both the first and second dose of vaccine. These findings should now be addressed in larger controlled studies. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

PMID:36318630 | DOI:10.1002/uog.26050

Gut Microbes. 2022 Jan-Dec;14(1):2138672. doi: 10.1080/19490976.2022.2138672.

ABSTRACT

We enrolled consecutive IBS-M patients (n = 25) according to Rome IV criteria. Fecal samples were obtained from all patients twice (pre-and post-intervention) and high-throughput 16S rRNA sequencing was performed. Six weeks of personalized nutrition diet (n = 14) for group 1 and a standard IBS diet (n = 11) for group 2 were followed. AI-based diet was designed based on optimizing a personalized nutritional strategy by an algorithm regarding individual gut microbiome features. The IBS-SSS evaluation for pre- and post-intervention exhibited significant improvement (p < .02 and p < .001 for the standard IBS diet and personalized nutrition groups, respectively). While the IBS-SSS evaluation changed to moderate from severe in 78% (11 out of 14) of the personalized nutrition group, no such change was observed in the standard IBS diet group. A statistically significant increase in the Faecalibacterium genus was observed in the personalized nutrition group (p = .04). Bacteroides and putatively probiotic genus Propionibacterium were increased in the personalized nutrition group. The change (delta) values in IBS-SSS scores (before-after) in personalized nutrition and standard IBS diet groups are significantly higher in the personalized nutrition group. AI-based personalized microbiome modulation through diet significantly improves IBS-related symptoms in patients with IBS-M. Further large-scale, randomized placebo-controlled trials with long-term follow-up (durability) are needed.

PMID:36318623 | DOI:10.1080/19490976.2022.2138672

J Am Chem Soc. 2022 Nov 1. doi: 10.1021/jacs.2c07918. Online ahead of print.

ABSTRACT

Amidines are a ubiquitous class of bioactive compounds found in a wide variety of natural products; thus, efficient strategies for their preparation are in great demand. Specifically, their common structural core decorated with three substituents sets amidines as perfect candidates for multicomponent synthesis. Herein, we present a highly modular metal-free multicomponent strategy for the synthesis of sulfonyl amidines. This work was focused on selecting readily accessible reagents to facilitate the in situ formation of enamines by the addition of amines to ketones. These components were coupled with azides to provide a broad reaction scope with respect to all three coupling partners. Aromatic and aliphatic amines and ketones were tolerated under our reaction conditions. Likewise, the presence of a methyl group on the ketone was critical to reactivity, which was leveraged for the design of a highly regioselective reaction with aliphatic ketones. A biologically active compound was successfully synthesized in one step, demonstrating the practical utility of our methodology. Finally, the postulated mechanism was investigated and supported both experimentally and by means of a multivariate statistical model.

PMID:36318611 | DOI:10.1021/jacs.2c07918

PLoS Genet. 2022 Nov 1;18(11):e1010474. doi: 10.1371/journal.pgen.1010474. eCollection 2022 Nov.

ABSTRACT

Insular organisms often evolve predictable phenotypes, like flightlessness, extreme body sizes, or increased melanin deposition. The evolutionary forces and molecular targets mediating these patterns remain mostly unknown. Here we study the Chestnut-bellied Monarch (Monarcha castaneiventris) from the Solomon Islands, a complex of closely related subspecies in the early stages of speciation. On the large island of Makira M. c. megarhynchus has a chestnut belly, whereas on the small satellite islands of Ugi, and Santa Ana and Santa Catalina (SA/SC) M. c. ugiensis is entirely iridescent blue-black (i.e., melanic). Melanism has likely evolved twice, as the Ugi and SA/SC populations were established independently. To investigate the genetic basis of melanism on each island we generated whole genome sequence data from all three populations. Non-synonymous mutations at the MC1R pigmentation gene are associated with melanism on SA/SC, while ASIP, an antagonistic ligand of MC1R, is associated with melanism on Ugi. Both genes show evidence of selective sweeps in traditional summary statistics and statistics derived from the ancestral recombination graph (ARG). Using the ARG in combination with machine learning, we inferred selection strength, timing of onset and allele frequency trajectories. MC1R shows evidence of a recent, strong, soft selective sweep. The region including ASIP shows more complex signatures; however, we find evidence for sweeps in mutations near ASIP, which are comparatively older than those on MC1R and have been under relatively strong selection. Overall, our study shows convergent melanism results from selective sweeps at independent molecular targets, evolving in taxa where coloration likely mediates reproductive isolation with the neighboring chestnut-bellied subspecies.

PMID:36318577 | DOI:10.1371/journal.pgen.1010474