Category: Statistics

JAMA Netw Open. 2023 Jun 1;6(6):e2320035. doi: 10.1001/jamanetworkopen.2023.20035.

ABSTRACT

IMPORTANCE: While the incidence of early-onset metastatic colorectal cancer (mCRC) has been increasing, studies on the age-related disparity in this group of patients are limited.

OBJECTIVE: To evaluate the association of age with treatment-related adverse events and survival in patients with mCRC and explore the potential underlying factors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 1959 individuals. Individual data on 1223 patients with mCRC who received first-line fluorouracil and oxaliplatin therapy in 3 clinical trials, and clinical and genomic data of 736 patients with mCRC from Moffitt Cancer Center were used to assess genomic alterations and serve as an external validation cohort. All statistical analyses were conducted from October 1, 2021, through November 12, 2022.

EXPOSURES: Metastatic colorectal cancer.

MAIN OUTCOMES AND MEASURES: Survival outcomes and treatment-related adverse events were compared among patients in 3 age groups: younger than 50 (early onset), 50 to 65, and older than 65 years.

RESULTS: In the total population of 1959 individuals, 1145 (58.4%) were men. Among 1223 patients from previous clinical trials, 179 (14.6%) in the younger than 50 years group, 582 (47.6%) in the 50 to 65 years group, and 462 (37.8%) in the older than 65 years group had similar baseline characteristics except for sex and race. The younger than 50 years group had significantly shorter progression-free survival (PFS) (hazard ratio [HR], 1.46; 95% CI, 1.22-1.76; P < .001) and overall survival (OS) (HR, 1.48; 95% CI, 1.19-1.84; P < .001) compared with the 50 to 65 years group after adjustment for sex, race, and performance status. Significantly shorter OS in the younger than 50 years group was confirmed in the Moffitt cohort. The younger than 50 years group had a significantly higher incidence of nausea and vomiting (69.3% vs 57.6% [50-65 years] vs 60.4% [>65 years]; P = .02), severe abdominal pain (8.4% vs 3.4% vs 3.5%; P = .02), severe anemia (6.1% vs 1.0% vs 1.5%; P < .001), and severe rash (2.8% vs 1.2% vs 0.4% P = .047). The younger than 50 years group also had earlier onset of nausea and vomiting (1.0 vs 2.1 vs 2.6 weeks; P = .01), mucositis (3.6 vs 5.1 vs 5.7 weeks; P = .05), and neutropenia (8.0 vs 9.4 vs 8.4 weeks; P = .04), and shorter duration of mucositis (0.6 vs 0.9 vs 1.0 weeks; P = .006). In the younger than 50 years group, severe abdominal pain and severe liver toxic effects were associated with shorter survival. The Moffitt genomic data showed that the younger than 50 years group had a higher prevalence of CTNNB1 mutation (6.6% vs 3.1% vs 2.3%; P = .047), ERBB2 amplification (5.1% vs 0.6% vs 2.3%; P = .005), and CREBBP mutation (3.1% vs 0.9% vs 0.5%; P = .05), but lower prevalence of BRAF mutation (7.7% vs 8.5% vs 16.7%; P = .002).

CONCLUSIONS AND RELEVANCE: In this cohort study of 1959 patients, those with early-onset mCRC showed worse survival outcomes and unique adverse event patterns, which could be partially attributed to distinct genomic profiles. These findings may inform individualized management approaches in patients with early-onset mCRC.

PMID:37358854 | DOI:10.1001/jamanetworkopen.2023.20035

Appl Immunohistochem Mol Morphol. 2023 Jun 27. doi: 10.1097/PAI.0000000000001140. Online ahead of print.

ABSTRACT

PD-L1 IHC 22C3 pharmDx is an FDA-approved companion test to select patients for anti-PD-L1 immunotherapy. In head and neck squamous cell carcinoma PD-L1 expression is determined using a Combined Positive Score (CPS), which evaluates expression in tumor cells and tumor-associated leukocytes. We hypothesized that in nodal metastasis, the CPS should be higher given their inherent higher proportion of leukocytes. A significant difference in CPS between sites would mean that the tissue chosen for PD-L1 testing would impact patient eligibility for therapy. Currently, guidelines about which tissue should be tested do not exist. PD-L1 22C3 IHC was performed in the primary and nodal metastases of 35 head and neck squamous cell carcinoma, and a CPS was generated by 3 pathologists. Mean CPS was higher at the primary than the nodal metastasis: 47.2 versus 42.2; however, the difference was not statistically significant: P=0.259. By therapeutic groups: negative (CPS <1), low (CPS 1-19) and high (CPS≥20), low-expression was more common in the primary: 40 vs. 26%, and high-expression in the nodal metastasis: 74 vs. 60% but this difference was not statistically significant: P=0.180. Stratified by positive versus negative (CPS <1 vs. ≥1), there were no differences between sites. Interobserver agreement for CPS among the 3 raters was slight for both sites: ƙ=0.117 and 0.025, fair if stratified by therapeutic group: ƙ=0.371 and 0.318, and near perfect if stratified as negative versus positive: ƙ=0.652 and 1. There were no statistically significant differences in CPS between primary and nodal metastases independent of how the CPS was stratified.

PMID:37358840 | DOI:10.1097/PAI.0000000000001140

Phys Eng Sci Med. 2023 Jun 26. doi: 10.1007/s13246-023-01287-8. Online ahead of print.

ABSTRACT

High-density catheters combined with Orientation Independent Sensing (OIS) methods have emerged as a groundbreaking technology for cardiac substrate characterisation. In this study, we aim to assess the arrangements and constraints to reliably estimate the so-called omnipolar electrogram (oEGM). Performance was evaluated using an experimental animal model. Thirty-eight recordings from nine retrospective experiments on isolated perfused rabbit hearts with an epicardial HD multielectrode were used. We estimated oEGMs according to the classic triangular clique (4 possible orientations) and a novel cross-orientation clique arrangement. Furthermore, we tested the effects of interelectrode spacing from 1 to 4 mm. Performance was evaluated by means of several parameters that measured amplitude rejection ratios, electric field loop area, activation pulse width and morphology distortion. Most reliable oEGM estimations were obtained with cross-configurations and interelectrode spacings [Formula: see text] mm. Estimations from triangular cliques resulted in wider electric field loops and unreliable detection of the direction of the propagation wavefront. Moreover, increasing interelectrode distance resulted in increased pulse width and morphology distortion. The results prove that current oEGM estimation techniques are insufficiently accurate. This study opens a new standpoint for the design of new-generation HD catheters and mapping software.

PMID:37358782 | DOI:10.1007/s13246-023-01287-8

Matern Child Health J. 2023 Jun 26. doi: 10.1007/s10995-023-03704-6. Online ahead of print.

ABSTRACT

OBJECTIVES: Technology-based outreach offers promise for providing support to a broad population of postpartum mothers while keeping costs low. However, research on the efficacy of this approach is scarce. We conducted a pre-registered randomized pilot trial of the effects of a novel technology-based approach for supporting postpartum mothers – via text-based mentoring – from infant’s birth through 18 months.

METHODS: Mothers (n = 201) were recruited at West Penn Hospital in Pittsburgh, PA in the days immediately following delivery. Treatment mothers were matched with volunteer mentors who communicated with them entirely via text messages. Control mothers received monthly one-way texts on basic safety topics. Measures were collected via hospital records and mother surveys. We estimated treatment effects on mothers’ parenting stress, mental health, knowledge of child development, engagement in language and literacy activities, and child milestones at 4- and 18-months postpartum. We used a systematic coding approach and simple descriptive statistics to analyze the treatment mother-mentor texting transcripts.

RESULTS: We found no statistically significant impacts on targeted outcomes. However, impacts for some outcomes were meaningfully large (> 0.2 SDs). Analyses of texting transcripts showed that most mothers stayed engaged for the full 18-month study period and that mother-mentor pairs primarily discussed maternal wellbeing and child-focused topics.

CONCLUSIONS FOR PRACTICE: Postpartum mothers will engage with mentors in a text-based mentoring program around important maternal and child health topics. More research and development on technology-based supports for parents in the early childhood years is needed.

PMID:37358777 | DOI:10.1007/s10995-023-03704-6

Mov Disord. 2023 Jun 26. doi: 10.1002/mds.29516. Online ahead of print.

ABSTRACT

BACKGROUND: Deep brain stimulation (DBS) has been increasingly used in the management of dyskinetic cerebral palsy (DCP). Data on long-term effects and the safety profile are rare.

OBJECTIVES: We assessed the efficacy and safety of pallidal DBS in pediatric patients with DCP.

METHODS: The STIM-CP trial was a prospective, single-arm, multicenter study in which patients from the parental trial agreed to be followed-up for up to 36 months. Assessments included motor and non-motor domains.

RESULTS: Of the 16 patients included initially, 14 (mean inclusion age 14 years) were assessed. There was a significant change in the (blinded) ratings of the total Dyskinesia Impairment Scale at 36 months. Twelve serious adverse events (possibly) related to treatment were documented.

CONCLUSION: DBS significantly improved dyskinesia, but other outcome parameters did not change significantly. Investigations of larger homogeneous cohorts are needed to further ascertain the impact of DBS and guide treatment decisions in DCP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PMID:37358761 | DOI:10.1002/mds.29516

Hepatol Int. 2023 Jun 26. doi: 10.1007/s12072-023-10564-3. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Liver fibrosis predicts adverse clinical outcomes, such as liver-related death (LRD) and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the accuracy of semi-automated quantification of collagen proportionate area (CPA) as an objective new method for predicting clinical outcomes.

METHOD: Liver biopsies from patients with NAFLD underwent computerized image morphometry of Sirius Red staining with CPA quantification performed by ImageScope. Clinical outcomes, including total mortality, LRD, and combined liver outcomes (liver decompensation, HCC, or LRD), were determined by medical records and population-based data-linkage. The accuracy of CPA for predicting outcomes was compared with non-invasive fibrosis tests (Hepascore, FIB-4, APRI).

RESULTS: A total of 295 patients (mean age 50 years) were followed for a median (range) of 9 (0.2-25) years totalling 3253 person-years. Patients with CPA ≥ 10% had significantly higher risks for total death [hazard ratio (HR): 5.0 (1.9-13.2)], LRD [19.0 (2.0-182.0)], and combined liver outcomes [15.6 (3.1-78.6)]. CPA and pathologist fibrosis staging (FS) showed similar accuracy (AUROC) for the prediction of total death (0.68 vs. 0.70), LRD (0.72 vs. 0.77) and combined liver outcomes (0.75 vs. 0.78). Non-invasive serum markers Hepascore, APRI, and FIB-4 reached higher AUROC; however, they were not statistically significant compared to that of CPA except for Hepascore in predicting total mortality (0.86 vs. 0.68, p = 0.009).

CONCLUSION: Liver fibrosis quantified by CPA analysis was significantly associated with clinical outcomes including total mortality, LRD, and HCC. CPA achieved similar accuracy in predicting outcomes compared to pathologist fibrosis staging and non-invasive serum markers.

PMID:37358741 | DOI:10.1007/s12072-023-10564-3

Breast Cancer. 2023 Jun 26. doi: 10.1007/s12282-023-01474-1. Online ahead of print.

ABSTRACT

INTRODUCTION: The oncoplastic conservative surgery was developed as a natural evolution of traditional surgery, attempting to improve the therapeutic and aesthetic outcomes where tumor resection could be followed by not-adequate results. Our primary aim is to evaluate how patient satisfaction and quality-of-life after conservative oncoplastic surgery, using BREAST-Q (BCT Module), change pre- and post-operatively. The secondary aim is to compare patient-reported outcome after oncoplastic or traditional conservative surgery.

PATIENTS AND METHODS: We enrolled 647 patients who underwent traditional conservative surgery or oncoplastic surgery from January 2020 to December 2022. Only 232 women (35.9%) completed the BREAST-Q questionnaire on a web-based platform, at the preoperative phase and 3 months after treatment.

RESULTS: The average score of “Psychosocial well-being” and “Satisfaction with Breasts” 3 months after surgery showed a statistically significant improvement, while the average score for “Physical well-being: Chest” at 3 months showed a worsening compared to the baseline. “Sexual well-being” did not show statistically significant change. A significant difference between the post-operative outcome of oncoplastic surgery and traditional surgery was observed only for Physical well-being (better for traditional surgery).

CONCLUSIONS: The study showed significant improvement in patient-reported outcomes 3 months after the surgery, except for physical discomfort that increases especially after oncoplastic surgery. Furthermore, our data, as well as many others, point to the appropriateness of using OCS where there is an effective indication, while the perspective of patients cannot find significant superiority over TCS in any of the areas analyzed.

PMID:37358721 | DOI:10.1007/s12282-023-01474-1

Drugs. 2023 Jun 26. doi: 10.1007/s40265-023-01914-4. Online ahead of print.

ABSTRACT

BACKGROUND: Budesonide is accepted as first-choice therapy for microscopic colitis (MC); however, symptoms often recur and some patients may be dependent, intolerant, or even fail budesonide. We performed a systematic review and meta-analysis to determine the effectiveness of non-budesonide therapies (thiopurines, bismuth subsalicylate [BSS], bile acid sequestrants [BAS], loperamide and biologics) for MC suggested by international guidelines.

METHODS: We searched the CENTRAL, MEDLINE, and EMBASE databases from their inception to 18 April 2023 for the above-mentioned therapeutics in MC. We pooled the response and remission rates by medication using a random-effects model.

RESULTS: Twenty-five studies comprising 1475 patients were included in the meta-analysis. Treatment with BSS showed the highest response rate of 75% (95% confidence interval [CI] 0.65-0.83; I² = 70.12%), with 50% achieving remission of symptoms (95% CI 0.35-0.65; I² = 71.06%). Treatment with tumor necrosis factor (TNF) inhibitors (infliximab and adalimumab) demonstrated a response rate of 73% (95% CI 0.63-0.83; I² = 0.00%), with a remission rate of 44% (95% CI 0.32-0.56; I² = 0.00%). The response rate for those treated with vedolizumab was similar; 73% responded to treatment (95% CI 0.57-0.87; I² = 35.93%), with a remission rate of 56% (95% CI 0.36-0.75; I² = 46.30%). Loperamide was associated with response and remission rates of 62% (95% CI 0.43-0.80; I² = 92.99%) and 14% (95% CI 0.07-0.25), respectively, whereas BAS use was associated with response and remission rates of 60% (95% CI 0.51-0.68; I² = 61.65%) and 29% (95% CI 0.12-0.55), respectively. Finally, the outcomes for thiopurine use were 49% (95% CI 0.27-0.71; I² = 81.45%) and 38% (95% CI 0.23-0.54; I² = 50.05%), respectively DISCUSSION: The present systematic review and meta-analysis provides rates of effectiveness of non-budesonide therapies for MC based on available data in the field. Studies in the meta-analysis showed a large amount of heterogeneity due to the variability in assessing the clinical effects of intervention between the studies caused by differences in the definitions of response or remission rates between the studies included. This may likely result in overestimating the benefit of a treatment. Furthermore, the number of participants and drug dosages varied, and only a few studies applied disease-specific activity indices. Only one randomized controlled trial (RCT) was identified. All other 24 included studies were either case series or (retrospective) cohort studies, which complicated efforts to perform further sensitivity analyses to adjust for potential confounders and risk of bias. In addition, the overall evidence on the effect of these treatment options was judged as low, mostly due to comparability bias and the observational nature of the available studies, which limited statistically robust comparisons of rates of effectiveness of the different non-budesonide agents ranked against each other. However, our observational findings may inform clinicians regarding the most rational selection of non-budesonide therapies to patients with MC.

CLINICAL TRIALS REGISTRATION: PROSPERO protocol #CRD42020218649.

PMID:37358712 | DOI:10.1007/s40265-023-01914-4

Neurosurg Rev. 2023 Jun 26;46(1):150. doi: 10.1007/s10143-023-02050-z.

ABSTRACT

To analyze the perioperative course and clinical outcome of patients with large (lPA) and giant (gPA) pituitary adenoma who underwent endoscopic endonasal transsphenoidal surgery (EETS) using either two-dimensional (2D-E) or three-dimensional (3D-E) endoscopic systems. Single-center retrospective study of consecutive patients with lPA and gPA who underwent EETS between November 2008 and January 2023. LPA were defined as ≥ 3 cm and < 4 cm in diameter in at least one dimension and a volume of ≥ 10ccm; gPA were defined as larger than 4 cm in diameter and with a greater volume than 10ccm. Patient data (age, sex, endocrinological and ophthalmological status) and tumor data (histology, tumor volume, size, shape, cavernous sinus invasion according to the Knosp classification) were analyzed. 62 patients underwent EETS. 43 patients were treated for lPA (69.4%) and 19 patients for gPA (30.6%). 46 patients (74.2%) underwent surgical resection using 3D-E and 16 patients 2D endoscopy (25.8%). Statistical results are referred to the comparison between 3D-E and 2D-E. Patients’ age ranged from 23-88 years (median 57), 16 patients were female (25.8%), 46 male (74.2%). Complete tumor resection was possible in 43.5% (27/62), partial resection in 56.5% (35/62). Resection rates did not differ between 3D-E (27 patients [43.5%]) and 2D-E (7 patients [43.8%], (p = 0.985). Visual acuity improved in 30 of 46 patients with preoperative deficit (65.2%). In the 3D-E group 21 of 32 patients (65.7%) improved, compared to 9 of 14 patients in the 2D-E group (64.3%). Improvement of visual field was achieved in 31 of 50 patients (62.0%; 22 of 37 patients in the 3D-E group [59.4%] and 9 of 13 patients in the 2D-E group [69.2%]). CSF leak was the most frequent complication and occurred in 9 patients (14.5%, [8 patients 17.4% 3D-E]) without statistical significance. Other surgical complications like postoperative bleeding, infection (meningitis) and deterioration of visual acuity and field were detected without statistical difference. New pituitary anterior lobe dysfunction was observed in 30 of 62 patients (48.4%, 8 patients [50.0%] in the 2D-E group and 22 patients [47.8%] in the 3D-E group). A transient deficit of posterior lobe was detected in 22.6% (14/62). No patient died within 30 days of surgery. Although 3D-E may improve surgical dexterity, in this series of lPA and gPA it was not associated with higher resection rates compared to 2D-E. However, 3D-E visualization during resection of large and giant PA is safe and feasible and patient’s clinical outcome is not different compared to 2D-E.

PMID:37358696 | DOI:10.1007/s10143-023-02050-z

Neurol Sci. 2023 Jun 26. doi: 10.1007/s10072-023-06909-3. Online ahead of print.

ABSTRACT

BACKGROUND: Pregnancy has been observed to reduce the frequency of relapses in Multiple Sclerosis (MS) patients, but the relapse risk tends to increase during the early post-partum period. Increased pre- and post-partum disease activity may predict a poor long-term prognosis. This study aimed to evaluate the correlation between magnetic resonance imaging (MRI) activity during the year before pregnancy and long-term clinically meaningful worsening in Expanded Disability Status Scale (EDSS).

METHODS: This observational, retrospective, case-control study included 141 pregnancies in 99 females with MS. Statistical analyses were used to evaluate the correlation between MRI activity during the year pre-pregnancy and post-partum clinical worsening during a 5-year follow-up. Clustered logistic regression was used to investigate the predictors of 5-year clinically meaningful worsening in EDSS (lt-EDSS).

RESULTS: We found a significant correlation between an active MRI pre-pregnancy and lt-EDSS (p = 0.0006). EDSS pre-pregnancy and lt-EDSS were also significantly correlated (p = 0.043). Using a multivariate model, we predicted which females would not experience long-term clinical deterioration by a stable MRI pre-pregnancy (92.7% specificity; p = 0.004).

CONCLUSIONS: An active MRI pre-conception is a strong predictor of lt-EDSS and a higher annual relapse rate during the follow-up period, regardless of whether the female had clinical evidence of disease activity prior to conception and delivery. Optimizing disease control and achieving imaging stability prior to conception may reduce the risk of long-term clinical deterioration.

PMID:37358691 | DOI:10.1007/s10072-023-06909-3