Tag: statistics

Environ Int. 2023 Jun 24;178:108064. doi: 10.1016/j.envint.2023.108064. Online ahead of print.

ABSTRACT

INTRODUCTION: Native American communities suffer disproportionately from elevated metal exposures and increased risk for cardiovascular diseases and diabetes. DNA methylation is a sensitive biomarker of aging-related processes and novel epigenetic-based “clocks” can be used to estimate accelerated biological aging that may underlie increased risk. Metals alter DNA methylation, yet little is known about their individual and combined impact on epigenetic age acceleration. Our objective was to investigate the associations of metals on several DNA methylation-based aging measures in the Strong Heart Study (SHS) cohort.

METHODS: Blood DNA methylation data from 2,301 SHS participants was used to calculate age acceleration of epigenetic clocks (PhenoAge, GrimAge, DunedinPACE, Hannum, Horvath). Urinary metals [arsenic (As), cadmium (Cd), tungsten (W), zinc (Zn), selenium (Se), molybdenum (Mo)] were creatinine-adjusted and categorized into quartiles. We examined associations of individual metals through linear regression models and used Bayesian Kernel Machine Regression (BKMR) for the impact of the total metal mixture on epigenetic age acceleration.

RESULTS: The mixture of nonessential metals (W, As, Cd) was associated with greater GrimAge acceleration and DunedinPACE, while the essential metal mixture (Se, Zn, Mo) was associated with lower epigenetic age acceleration. Cd was associated with increased epigenetic age acceleration across all clocks and BKMR analysis suggested nonlinear associations between Se and DunedinPACE, GrimAge, and PhenoAge acceleration. No interactions between individual metals were observed. The associations between Cd, Zn, and epigenetic age acceleration were greater in never smokers in comparison to current/former smokers.

CONCLUSION: Nonessential metals were positively associated with greater epigenetic age acceleration, with strongest associations observed between Cd and DunedinPACE and GrimAge acceleration. In contrast, essential metals were associated with lower epigenetic aging. Examining the influence of metal mixtures on epigenetic age acceleration can provide insight into metals and aging-related diseases.

PMID:37364305 | DOI:10.1016/j.envint.2023.108064

Anesthesiology. 2023 Jun 26. doi: 10.1097/ALN.0000000000004667. Online ahead of print.

ABSTRACT

BACKGROUND: The analgesic effectiveness of contemporary motor-sparing nerve blocks used in combination for analgesia in total knee arthroplasty (TKA) is unclear. We conducted this network meta-analysis to evaluate the analgesic effectiveness of adding single-injection or continuous adductor canal block (ACB) with or without infiltration of the interspace between the popliteal artery and the capsule of the posterior knee (iPACK) to intraoperative local infiltration analgesia (LIA), compared to LIA alone, following TKA.

METHODS: Randomized trials examining the addition of single-injection or continuous ACB with or without single-injection iPACK to LIA for TKA were considered. The two primary outcomes were area under the curve (AUC) pain scores and postoperative function over 24-48 hours. Secondary outcomes included rest pain scores at 0, 6, 12, and 24 hours, opioid consumption (0-24- and 25-48-hours), and incidence of nausea/vomiting. Network meta-analysis was conducted using a frequentist approach.

RESULTS: Twenty-seven studies (2,317 patients) investigating the addition of i) single-injection ACB, ii) continuous ACB, iii) single-injection ACB and single-injection iPACK, and iv) continuous ACB and single-injection iPACK to LIA, compared to LIA alone, were included. For AUC 24-48-hour pain, the addition of continuous ACB with single-injection iPACK displayed the highest p-score probability (89%) of being most effective for pain control. The addition of continuous ACB without single-injection iPACK displayed the highest p-score probability (87%) of being most effective for postoperative function.

CONCLUSIONS: Our results suggest that continuous ACB, but not single-injection ACB and/or single-injection iPACK, can provide statistically superior analgesia when added to LIA for TKA compared to LIA alone. However, the magnitude of these additional analgesic benefits is clinically questionable.

PMID:37364292 | DOI:10.1097/ALN.0000000000004667

Am J Respir Crit Care Med. 2023 Jun 26. doi: 10.1164/rccm.202301-0034OC. Online ahead of print.

ABSTRACT

RATIONALE: Kidney injury is common and associated with worse outcomes in patient with septic shock. Mitochondrial resuscitation with thiamine (vitamin B1) may attenuate septic kidney injury.

OBJECTIVES: To assess whether thiamine supplementation attenuates kidney injury in septic shock.

METHODS: The Thiamine for Renal Protection in Septic Shock (TRPSS) trial was a multicenter, randomized, placebo-controlled trial of thiamine vs. placebo in septic shock. The primary outcome was change in serum creatinine between enrollment and 72 hours after enrollment.

MEASUREMENT AND MAIN RESULTS: Eighty-eight patients were enrolled (42 patients received the intervention and 46 received placebo). There was no significant between-group difference in creatinine at 72-hours (mean difference -0.57, mg/dL, 95% CI -1.18, 0.04, p=0.07). There was no difference in receipt of kidney replacement therapy (14.3% vs. 21.7%, p=0.34), KDIGO-3 acute kidney injury (54.7% vs. 73.9%, p=0.07), or mortality (35.7% vs. 54.3%, p=0.14) between thiamine vs. placebo groups. Patients who received thiamine had more intensive care unit-free days (median 22.5 [IQR 0.0, 25.0] vs. 0.0 [IQR 0.0, 23.0], p<0.01). In the thiamine deficient cohort (27.4% of patients), there was no difference in rates of kidney failure (57.1% thiamine vs. 81.5% placebo) or in-hospital mortality (28.6% vs. 68.8%) between groups.

CONCLUSIONS: In the TRPSS trial there was no statistically significant difference in the primary outcome of change in creatinine over time. Patients receiving thiamine had more intensive care unit-free days, but no difference in other secondary outcomes. Clinical trial registration available at www.

CLINICALTRIALS: gov, ID: NCT03550794.

PMID:37364280 | DOI:10.1164/rccm.202301-0034OC

Anesthesiology. 2023 Jun 26. doi: 10.1097/ALN.0000000000004666. Online ahead of print.

ABSTRACT

BACKGROUND: The pathophysiology of delirium is incompletely understood including what molecular pathways are involved in brain vulnerability to delirium. We determined whether preoperative plasma neurodegeneration markers were elevated in patients who subsequently developed postoperative delirium through a retrospective case-control study.

METHODS: Inclusion criteria were patients ≥65 years of age, undergoing elective noncardiac surgery with a hospital stay of ≥ two days. Concentrations of preoperative plasma P-tau181, neurofilament light chain (NfL), amyloid b1-42 (Ab42), and glial fibrillary acidic protein (GFAP) concentrations were measured with digital immunoassay platform. The primary outcome was postoperative delirium measured by the Confusion Assessment Method. We did a propensity score matching on age and sex with nearest neighbor such that each patient in the delirium group was matched on age and sex with a patient in the no delirium group.

RESULTS: Our initial cohort consists of 189 patients with no delirium and 102 patients who developed postoperative delirium. Of 291 patients aged 72.5 ± 5.8 years, 50.5% were women, and 102 (35%) developed postoperative delirium. The final cohort in the analysis consisted of a no delirium (n=102) and a delirium (n=102) groups matched on age and sex using the propensity score method. Of the four biomarkers assayed, the median value for NfL was 32.05 pg/ml for the delirium group vs. 23.7 pg/ml in the no delirium group. The distribution of biomarker values significantly differed between the delirium and no delirium groups (p-value =0.02 by the Kolmogorov-Smirnov test) with the largest cumulative probability difference appearing at the biomarker value of 32.05 pg/ml.

CONCLUSIONS: These results suggest that patients who subsequently developed delirium are more likely to be experiencing clinically silent neurodegenerative changes before surgery, reflected by changes in plasma NfL biomarker concentrations, which may identify individuals with a preoperative vulnerability to subsequent cognitive decline.

PMID:37364279 | DOI:10.1097/ALN.0000000000004666

Ann Intern Med. 2023 Jun 27. doi: 10.7326/M23-0052. Online ahead of print.

ABSTRACT

BACKGROUND: Time-restricted eating (TRE), without calorie counting, has become a popular weight loss strategy, yet long-term randomized trials evaluating its efficacy are limited.

OBJECTIVE: To determine whether TRE is more effective for weight control and cardiometabolic risk reduction compared with calorie restriction (CR) or control.

DESIGN: 12-month randomized controlled trial. (ClinicalTrials.gov: NCT04692532).

SETTING: University of Illinois Chicago from January 2021 to September 2022.

PARTICIPANTS: 90 adults with obesity.

INTERVENTION: 8-hour TRE (eating between noon and 8:00 p.m. only, without calorie counting), CR (25% energy restriction daily), or control (eating over a period of 10 or more hours per day). Participants were not blinded.

MEASUREMENTS: Change in body weight, metabolic markers, and energy intake by month 12.

RESULTS: Seventy-seven persons completed the study. Mean age was 40 years (SD, 11), 33% were Black, and 46% were Hispanic. Mean reduction in energy intake was -425 kcal/d (SD, 531) for TRE and -405 kcal/d (SD, 712) for CR. Compared with the control group, weight loss by month 12 was -4.61 kg (95% CI, -7.37 to -1.85 kg; P ≤ 0.01) (-4.87% [CI, -7.61% to -2.13%]) for the TRE group and -5.42 kg (CI, -9.13 to -1.71 kg; P ≤ 0.01) (-5.30% [CI, -9.06% to -1.54%]) for the CR group, with no statistically significant difference between TRE and CR (0.81 kg [CI, -3.07 to 4.69 kg; P = 0.68]) (0.43% [CI, -3.48% to 4.34%]).

LIMITATION: Not blinded, not powered to detect relatively large differences in weight loss, and lack of adjustment for multiple comparisons.

CONCLUSION: Time-restricted eating is more effective in producing weight loss when compared with control but not more effective than CR in a racially diverse population.

PRIMARY FUNDING SOURCE: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.

PMID:37364268 | DOI:10.7326/M23-0052

J Neuroophthalmol. 2023 Jun 26. doi: 10.1097/WNO.0000000000001908. Online ahead of print.

ABSTRACT

BACKGROUND: Prospective evaluation of optical coherence tomography (OCT) and OCT angiography (OCT-A) characteristics in different stages of papilledema in idiopathic intracranial hypertension (IIH).

METHODS: In this prospective, observational study patients of IIH with papilledema were recruited and divided into 3 groups-early/established (Group 1), chronic (Group 2), and atrophic papilledema (Group 3). Peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell inner plexiform layer (GC-IPL) were recorded on OCT. Peripapillary and macular perfusion was documented at superficial retinal, deep retinal, and choriocapillary level using OCT-A. The investigations were repeated at 3 months.

RESULTS: RNFL showed significant thinning in all groups on follow-up with the atrophic group showing maximum thinning (P = 0.01-Group 3). GC-IPL was significantly reduced in all stages of papilledema at baseline compared with the controls. Thinnest GC-IPL was noted in the atrophic group (52.75 ± 7.44 μm; P = 0.00 in Group 3 vs controls) that showed further deterioration on follow-up. On Image J analysis, significant decrease was noted at various levels in the peripapillary and macular perfusion at baseline especially in the atrophic group which showed further deterioration noted on follow-up. The final visual acuity showed a statistically significant weak negative correlation with baseline RNFL (r = -0.306) and GC-IPL (r = -0.384) and moderately negative correlation with baseline superficial peripapillary retinal perfusion (r = -0.553). A significant negative correlation was seen between increasing grade of papilledema and superficial peripapillary retinal perfusion with both Image J and automated indices (r = -0.46; r = -0.61), respectively.

CONCLUSIONS: GC-IPL may help identify early damage in papilledema even in the presence of thicker RNFL. Significant vascular changes can be observed on OCT-A that may help predict the final visual outcome in papilledema due to IIH.

PMID:37364246 | DOI:10.1097/WNO.0000000000001908

Rev Esc Enferm USP. 2023 Jun 26;57(spe):e20230030. doi: 10.1590/1980-220X-REEUSP-2023-0030en. eCollection 2023.

ABSTRACT

OBJECTIVE: To analyze the migratory process, ways of living, and working conditions of Haitians residing in the municipality of Cascavel, Paraná, as well as their impact on health conditions, consumption patterns, and political and ideological life.

METHOD: cross-sectional observational design. Data was collected through semi-structured interviews conducted from December 2019 to December 2020 with 128 participants who were Haitian immigrants residing in the municipality. Simple descriptive statistics were used for the data analysis, and the findings were discussed in conjunction with relevant literature, with the social determination theory serving as a reference.

RESULTS: The majority of participants were male 75.0% (n = 96), young adults 71.0% (n = 91), speakers of two or more languages 87.5% (n = 112), catholic 61.7% (n = 79), high school education or higher 57.0% (n = 73). They consider their life and health conditions good but are unsatisfied with the working conditions and salary.

CONCLUSION: Haitian immigrants’ arrival facilitation to work in cold stores may indicate labor exploitation of economically and socially vulnerable groups. Immigration policies and the recognition of the educational level of their country of origin may contribute to improving the living condition of this population.

PMID:37364238 | DOI:10.1590/1980-220X-REEUSP-2023-0030en

J Phys Chem Lett. 2023 Jun 26:6119-6126. doi: 10.1021/acs.jpclett.3c01504. Online ahead of print.

ABSTRACT

The structural factors affecting triplet-triplet annihilation (TTA) at the molecular level are not well-understood. Here, our steady-state photoluminescence and transient absorption results demonstrate that the spin statistical factor, η, decreases from 0.60 to 0.46 and 0.14 going from 9,10-diphenylanthracene (DPA) to the 1,5-DPA and 2,6-DPA isomers, respectively, during photon upconversion with a platinum octaethylporphyrin sensitizer. Density functional theory (DFT) shows that η depends on the energetics of hot triplet states and molecular rigidity. The significantly high conical intersection energy between the S₀ and T₁ states for 9,10-DPA gives its longer triplet lifetime. Time-dependent DFT calculations show that 9,10-DPA and 1,5-DPA can undergo high-level reverse intersystem crossing from their T₂ and T₃ states, respectively, to the bright S₁ state, increasing the limit of the spin statistical factor. Both factors ultimately serve to enhance the TTA efficiency. This work provides insight into designing molecules for efficient light-emitting and photon upconversion applications.

PMID:37364235 | DOI:10.1021/acs.jpclett.3c01504

J Clin Oncol. 2023 Jun 26:JCO2202624. doi: 10.1200/JCO.22.02624. Online ahead of print.

ABSTRACT

PURPOSE: Despite therapeutic advances, outcomes for patients with platinum-resistant/refractory ovarian cancer remain poor. Selective glucocorticoid receptor modulation with relacorilant may restore chemosensitivity and enhance chemotherapy efficacy.

METHODS: This three-arm, randomized, controlled, open-label phase II study (ClinicalTrials.gov identifier: NCT03776812) enrolled women with recurrent, platinum-resistant/refractory, high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer, or ovarian carcinosarcoma treated with ≤4 prior chemotherapeutic regimens. Patients were randomly assigned 1:1:1 to (1) nab-paclitaxel (80 mg/m²) + intermittent relacorilant (150 mg the day before, of, and after nab-paclitaxel); (2) nab-paclitaxel (80 mg/m²) + continuous relacorilant (100 mg once daily); or (3) nab-paclitaxel monotherapy (100 mg/m²). Nab-paclitaxel was administered on days 1, 8, and 15 of each 28-day cycle. The primary end point was progression-free survival (PFS) by investigator assessment; objective response rate (ORR), duration of response (DOR), overall survival (OS), and safety were secondary end points.

RESULTS: A total of 178 women were randomly assigned. Intermittent relacorilant + nab-paclitaxel improved PFS (hazard ratio [HR], 0.66; log-rank test P = .038; median follow-up, 11.1 months) and DOR (HR, 0.36; P = .006) versus nab-paclitaxel monotherapy, while ORR was similar across arms. At the preplanned OS analysis (median follow-up, 22.5 months), the OS HR was 0.67 (P = .066) for the intermittent arm versus nab-paclitaxel monotherapy. Continuous relacorilant + nab-paclitaxel showed numerically improved median PFS but did not result in significant improvement over nab-paclitaxel monotherapy. Adverse events were comparable across study arms, with neutropenia, anemia, peripheral neuropathy, and fatigue/asthenia being the most common grade ≥3 adverse events.

CONCLUSION: Intermittent relacorilant + nab-paclitaxel improved PFS, DOR, and OS compared with nab-paclitaxel monotherapy. On the basis of protocol-prespecified Hochberg step-up multiplicity adjustment, the primary end point did not reach statistical significance (P < .025). A phase III evaluation of this regimen is underway (ClinicalTrials.gov identifier: NCT05257408).

PMID:37364223 | DOI:10.1200/JCO.22.02624

Am J Dent. 2023 Jun;36(3):156-1160.

ABSTRACT

PURPOSE: To evaluate the effects of toothpaste tablets on the gloss and surface roughness of resin-based composite materials and determine the relationship between gloss and roughness.

METHODS: Rectangular jigs were designed and printed. Wells (2 mm deep x 7 mm diameter) were filled with Filtek Supreme Ultra A2B, light-cured and polished. A small-area glossmeter was used for gloss (GU) measurements and a profilometer for roughness measurements (Ra) at baseline and after challenge with each toothpaste. An automated tooth-brushing machine was set at 120 strokes/minute for a total of 10,000 strokes to evaluate four test groups with 16 specimens in each group. NC: Brushing with distilled water; TABS: Colgate Anywhere Travel Tooth Tabs; CP: Colgate Cavity Protection Toothpaste and AW: Colgate Whitening Advanced Toothpaste. Kruskal-Wallis test was used to test the difference in gloss and surface roughness among the groups and Pearson correlation was used to compare the relationship between gloss and roughness.

RESULTS: There was no statistically significant difference in gloss and roughness among the four groups at baseline. At post-brushing, there was a statistically significant difference among the groups (P< 0.001) with increased roughness and decreased gloss for CP and AW when compared to TABS. There was a statistically significant correlation between post-brushing roughness and post-brushing gloss (P< 0.001, rho: -0.815). Thus, the higher the surface roughness the lower the gloss.

CLINICAL SIGNIFICANCE: Toothpaste tablets retain better gloss and roughness of resin-based composite materials when compared to conventional toothpastes.

PMID:37364194