Category: Statistics

Addiction. 2026 Jun 12. doi: 10.1111/add.70502. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Naltrexone is a pharmacotherapeutic option for relapse prevention in opioid use disorder (OUD); however, studies highlight low rates of initiation and high rates of discontinuation as limiting its effectiveness. We aimed to (1) estimate the percentage of individuals with OUD who (having undergone withdrawal and wish to remain abstinent) initiate and discontinue naltrexone and (2) examine participant- and study-level factors that contribute to variation in initiation and discontinuation rates.

METHODS: We undertook a systematic review, random-effects meta-analysis and meta-regression searching Medline, Embase, PsychINFO and CENTRAL from database inception to 19 February 2025 for studies of any design from any geographical region involving individuals with OUD eligible to receive naltrexone as a relapse prevention pharmacotherapy (i.e. those completing opioid withdrawal and wishing to remain abstinent). Measurements included the percentage of individuals who initiate or discontinue oral, long-acting injectable depot or implantable formulations of naltrexone at 1, 3 or 6 months. Certainty was assessed using the GRADE framework.

RESULTS: Twenty-two studies, including 124 016 individuals, reported initiation and 95 studies, including 16 969 individuals, reported discontinuation. The pooled percentage initiating oral naltrexone among those eligible was 60.3% [95% confidence interval (CI) = 38.9%-80.0%, 2014 participants, 15 studies] and depot was 18.2% (95% CI = 2.7%-42.5%, 57 383 participants, 4 studies). The pooled percentage discontinuing oral was 50.0% (95% CI = 41.9%-58.1%, 7340 participants, 34 studies) at 1 month, 61.3% (95% CI = 50.9%-71.2%, 2347 participants, 29 studies) at 3 months and 71.0% (95% CI = 57.3%-83.0%, 1889 participants, 19 studies) at 6 months. The pooled percentage discontinuing depot was 26.1% (95% CI = 19.5%-33.3%, 3589 participants, 33 studies) at 1 month, 46.7% (95% CI = 38.4%-55.1%, 3302 participants, 33 studies) at 3 months and 60.0% (95% CI = 43.2%-75.8%, 3071 participants, 22 studies) at 6 months. Statistically significantly higher percentages initiated oral naltrexone if it was the only offered pharmacotherapy (meta-regression coefficient 33.6%, 95% CI = 8.1%-59.2%, P = 0.014) and statistically significantly lower percentages discontinued oral naltrexone at 3 and 6 months if administration was supervised (meta-regression coefficient -18.6%, 95% CI = -36.6% to -1.0%, P = 0.043 and -27.3%, 95% CI = -50.1% to -4.4%, P = 0.022, respectively). There was no clear evidence that study setting (i.e. if the study was conducted in routine clinical care or an investigational setting) substantially explained or contributed to the variation in any estimates. All outcomes were very low certainty.

CONCLUSIONS: Very low certainty evidence suggests that, among people with opioid use disorder who have undergone withdrawal and wish to remain abstinent, a substantial percentage are willing to initiate naltrexone with marked early discontinuation.

PMID:42286437 | DOI:10.1111/add.70502

Addiction. 2026 Jun 12. doi: 10.1111/add.70503. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Individuals with opioid use disorder (OUD) frequently present with co-occurring mental health conditions such as depression and posttraumatic stress disorder (PTSD), along with other mental health substance use disorders, physical health conditions and social determinants that together comprise ‘clinical complexity.’ Collaborative care (CC), a primary care-based behavioral health integration model, aims to improve outcomes through coordinated, patient-centered treatment. This study examined heterogeneity in baseline clinical complexity among participants in the CLARO (Collaboration Leading to Addiction Treatment and Recovery from Other Stresses) trial and assessed whether the effects of CC versus enhanced usual care (EUC) differed across clinical complexity groups.

METHODS: Secondary analysis of CLARO, a pragmatic randomized clinical trial (n = 797) of CC versus EUC for adults with OUD and depression and/or PTSD, conducted in 18 low-resourced primary care clinics in New Mexico and California, USA. Latent class analysis of baseline data identified subgroups defined by mental health and substance use as the main characteristics along with physical health and social challenges. Six-month treatment effects were estimated using one-step models that jointly estimated latent class membership and class-specific outcomes, incorporating class × treatment interactions. Outcomes included depression symptom severity, PTSD symptom severity, and buprenorphine utilization and prescribing duration.

RESULTS: Three subgroups were identified: (1) low complexity (43%), with relative clinical and social stability; (2) mental health complexity (34%), with high psychiatric symptoms but lower substance use and moderate social adversity; and (3) high dual complexity (23%). Compared with EUC, CC was associated with lower depression severity at follow-up for the low-complexity class, but not for other classes. CC and EUC did not differ statistically significantly with respect to PTSD outcomes in any class. Buprenorphine utilization and prescribing duration outcomes were similar across CC and EUC treatment arms.

CONCLUSIONS: The effects of collaborative care may vary according to patients’ baseline clinical complexity. Collaborative care appears to be associated with more favorable depression outcomes than enhanced usual care among participants with lower clinical complexity but not among those with higher clinical complexity.

PMID:42286436 | DOI:10.1111/add.70503

Gen Thorac Cardiovasc Surg. 2026 Jun 12. doi: 10.1007/s11748-026-02326-3. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine the surgical outcomes of surgical aortic valve replacement in the transcatheter aortic valve replacement era and propose a novel patient-specific prognostic model.

METHODS: We randomly divided 772 patients with aortic stenosis who underwent surgical aortic valve replacement in 2016-2021 into two cohorts (derivation, 515; validation, 257). In the derivation cohort, no data were missing for any patients for the candidate predictors including age, sex, body mass index, left ventricular ejection fraction, levels of albumin, hemoglobin, and serum creatinine, presence of chronic atrial fibrillation, and end-stage renal disease requiring hemodialysis. We developed possible scoring models using Cox proportional hazards regression with overall survival as the endpoint and calculated the cross-validated 5-year C-statistics to assess accuracy.

RESULTS: The mean patient age was 74.2 years, and 46.9% were female. Kaplan-Meier analysis revealed overall 1- and 5-year survival rates of 96.6 and 88.7%, respectively. The 5-year C-statistic of the derivation cohort was 0.785 (95% confidence interval: 0.716-0.853), while the estimated 1-, 3-, and 5-year C-statistics of the validation cohort were 0.885 (0.806-0.965), 0.888 (0.824-0.953), and 0.801 (0.702-0.901), respectively. Calibration plots revealed good agreement between predicted and actual 5-year survival (intraclass correlation coefficient = 0.955; 95% confidence interval: 0.827-0.989).

CONCLUSIONS: This novel survival prediction model after isolated surgical aortic valve replacement in the transcatheter aortic valve replacement era showed good survival prediction, and may guide the decision-making process for surgical aortic valve replacement versus transcatheter aortic valve replacement with lifetime management.

PMID:42286392 | DOI:10.1007/s11748-026-02326-3

Breast Cancer. 2026 Jun 12. doi: 10.1007/s12282-026-01881-0. Online ahead of print.

ABSTRACT

This annual report of the National Clinical Database-Breast Cancer Registry (NCD-BCR) by the Japanese Breast Cancer Society presents nationwide breast cancer statistics for patients registered in Japan in 2023. Among 107,372 patients with breast cancer at 1317 institutions, 99.3% were females with a median age of 62 years. The distribution of the clinical stages was as follows: stage 0 (15.5%); stage I (42.1%); stage II (31.1%); stage III (7.0%); and stage IV (2.1%). Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) positivity was observed in 78.9%, 70.0%, and 13.3% of patients, respectively. Among 102,717 patients without distant metastases, 41.2% underwent breast-conserving surgery, 76.5% underwent sentinel lymph node biopsy, and 6.0% underwent breast reconstruction. The distribution of radiotherapy was as follows: 75.2% received whole-breast irradiation, 15.7% chest-wall irradiation, and 20.7% regional irradiation. Among the 13,061 patients with pT1abN0M0 breast cancer, comprising 10,819 hormone receptor [HR]-positive/HER2-negative, 1479 HER2-positive and 763 HR-negative/HER2-negative individuals, 92.4% of HR-positive/HER2-negative patients received endocrine therapy, 46.9% of HER2-positive patients received chemotherapy and/or anti-HER2 therapy, and 31.2% of HR-negative/HER2-negative patients received chemotherapy. This annual report provides a nationwide overview of contemporary systemic therapy patterns in small breast cancer and highlights size‑dependent and subtype‑specific use of systemic therapy in Japan, reflecting a risk‑adapted treatment strategy.

PMID:42286387 | DOI:10.1007/s12282-026-01881-0

Breast Cancer. 2026 Jun 12. doi: 10.1007/s12282-026-01869-w. Online ahead of print.

ABSTRACT

BACKGROUND: Bevacizumab is an anti-angiogenic agent that inhibits tumor vascularization and thereby suppresses tumor growth. Tumor-infiltrating lymphocytes (TILs), particularly CD8-positive TILs, play a critical role in the antitumor immune response. However, little is known about the effect of bevacizumab-containing chemotherapy on CD8-positive TIL dynamics. This study aimed to evaluate changes in CD8-positive TILs before and after treatment in patients with advanced breast cancer receiving bevacizumab in combination with chemotherapy.

METHODS: Thirty patients with initially inoperable advanced breast cancer who responded to first-line bevacizumab-containing chemotherapy and subsequently became eligible for surgery were included. CD8-positive TILs were assessed by immunohistochemistry in biopsy samples obtained before treatment and in surgical specimens collected after treatment. Stromal CD8-positive TILs were classified as low, intermediate, or high, based on their proportion among total stromal TILs.

RESULTS: Of the 30 patients, 20 had luminal-like breast cancer and 10 had triple-negative breast cancer. Before treatment, CD8-positive TIL expression was low in 16 patients (64.0%), intermediate in 6 (24.0%), and high in 3 (12.0%). After treatment, 10 patients (33.3%) showed low expression, 11 (36.7%) had intermediate expression, and 9 (30.0%) had high expression, indicating an increase in CD8-positive TIL levels. The high pathological response (a pathological response grade of 2 or higher) rate was 36.7%, and patients with increased CD8-positive TILs tended to show higher pathological response and better overall survival, although these differences did not reach statistical significance. In contrast, the ypT stage was significantly lower in cases with high post-treatment CD8-positive TIL expression, suggesting that immune activation after bevacizumab may contribute to local tumor regression.

CONCLUSIONS: Bevacizumab-containing chemotherapy appears to enhance CD8-positive TIL infiltration in primary breast tumors, which may contribute to improved local tumor regression and better therapeutic outcomes.

PMID:42286385 | DOI:10.1007/s12282-026-01869-w

Eur Spine J. 2026 Jun 12. doi: 10.1007/s00586-026-10072-6. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to characterize biochemical and microenvironmental changes within the Disc Vertebra Complex (DVC) in non-specific low back pain (NSLBP) patients using non-fat-saturation Multi-slices CEST MRI. By performing intra-group comparisons, we assessed associations between disc degeneration and vertebral biochemical variations.

METHODS: Ninety-nine NSLBP patients (62 males, 37 females; median age 45) underwent lumbar spine MRI. Non-fat-saturation Multi-slices CEST imaging was used to assess fat fraction (FF), fat /water content and magnetization transfer contrast in vertebrates, and water content, glycosaminoglycan (GAG), amide proton transfer (APT), nuclear overhauser enhancement (NOE) and magnetization transfer contrast in discs. Metabolic and microenvironmental changes across vertebrae (L2-S1) and intervertebral discs (L2/3-L5/S1) were analyzed. Statistical comparisons were conducted across disc grades, weight categories, and disc abnormalities.

RESULTS: Significant biochemical variations were observed across vertebral levels, with decreasing water content and increasing FF from L2 to S1. The pH-sensitive markers (APT) showed caudal trends, indicating relative changes in proton environment. Protruding discs and discs with high-intensity zones (HIZ) showed reduced pH and hydration, alongside altered macromolecular structures. Adjacent vertebrae of protruding discs exhibited decreased water content, indicative of early bone marrow edema.

CONCLUSIONS: Non-fat-saturation Multi-slices CEST MRI enables holistic profiling of the disc-vertebra complex (DVC) and detects localized, grade-dependent biochemical heterogeneity. Notably, differences emerged between vertebrae and discs with and without protrusion / HIZ, alongside grade-dependent variations.

PMID:42286353 | DOI:10.1007/s00586-026-10072-6

Eur Spine J. 2026 Jun 12. doi: 10.1007/s00586-026-10079-z. Online ahead of print.

ABSTRACT

PURPOSE: Postoperative pain after lumbar microdiscectomy (MD) can be significant. While both the lumbar erector spinae plane block (L-ESPB) and the posterior quadratus lumborum block (P-QLB) are used for analgesia, they have not been directly compared. We hypothesized that L-ESPB and P-QLB would provide different levels of analgesia after MD.

METHODS: This single-center, prospective, randomized controlled trial included 60 adult patients (ASA I-II) undergoing unilateral single-level lumbar MD. Patients were randomized to receive a bilateral, postoperative L-ESPB (n = 30) or P-QLB (n = 30) with 30 mL of 0.25% bupivacaine per side. The primary outcome was the Numerical Rating Scale (NRS) pain score at 2 h postoperatively. Secondary outcomes included NRS pain scores over 24 h, rescue analgesia requirements, and adverse events.

RESULTS: Patients in the L-ESPB group had statistically lower static and dynamic NRS pain scores at all measured time points (1, 2, 4, 8, 16, and 24 h) compared to the P-QLB group (p = 0.001). The number of patients requiring rescue analgesia was lower in the L-ESPB group (1 vs. 9 patients, p = 0.012), and the total tramadol consumption was also lower (p = 0.005). The incidence of nausea and itching was significantly lower in the L-ESPB group. One patient in the L-ESPB group experienced a temporary motor block.

CONCLUSION: In patients undergoing lumbar MD, L-ESPB provided superior analgesia and resulted in lower opioid consumption and fewer opioid-related side effects compared to P-QLB over the first 24 postoperative hours.

PMID:42286352 | DOI:10.1007/s00586-026-10079-z

Am J Respir Crit Care Med. 2026 Jun 12:aamag276. doi: 10.1093/ajrccm/aamag276. Online ahead of print.

ABSTRACT

RATIONALE: Physician Orders for Life-Sustaining Treatment (POLST) and Advance Directives (AD) aim to honor patient autonomy. However, the impact of the signatory’s identity-whether the patient or a surrogate-on clinical trajectories in the intensive care unit (ICU) remains poorly characterized.

OBJECTIVES: To evaluate the association between signatory identity and terminal care intensity and hospitalization costs among adult patients in the ICU.

METHODS: This nationwide population-based cohort study utilized the South Korean National Health Insurance Service database, including 1,189,042 adult ICU admissions between 2020 and 2023. Statistical analyses employed high-dimensional fixed-effects models to account for institutional variability across 417 hospitals.

RESULTS: Among 1,189,042 patients, surrogate-determined POLST (SD-POLST) was more than three times as prevalent as patient-determined POLST (PD-POLST). Among 90-day decedents, PD-POLST was associated with significantly reduced odds of invasive terminal care (OR, 0.43; 95% CI, 0.43-0.54). Conversely, SD-POLST more than doubled the odds (OR, 2.16; 95% CI, 1.98-2.35). Notably, even patients with proactive ADs experienced increased care intensity once a surrogate signed the final order (OR, 1.69; 95% CI, 1.51-1.89), indicating a phenomenon of “AD erosion.” SD-POLST was also associated with significantly higher daily hospitalization costs (cost ratio, 1.04; 95% CI, 1.02-1.06) compared with no documentation.

CONCLUSION: The clinical efficacy of POLST in limiting non-beneficial care depends fundamentally on the signatory. Surrogate-led decisions were associated with paradoxically higher care intensity and costs, potentially overriding prior patient wishes. These findings highlight the critical importance of early, patient-led discussions to ensure goal-concordant end-of-life care in the ICU.

PMID:42286341 | DOI:10.1093/ajrccm/aamag276

Aesthetic Plast Surg. 2026 Jun 12. doi: 10.1007/s00266-026-06052-2. Online ahead of print.

ABSTRACT

BACKGROUND: This study aims to comprehensively evaluate the short-term changes in ocular surface parameters and meibomian gland function following Full-incision double-eyelid blepharoplast.

METHODS: In this observational self-controlled study, 50 patients (100 eyes) undergoing full-incision double-eyelid blepharoplasty were enrolled. Assessments were conducted preoperatively and at 1 week, 1 month, and 3 months postoperatively. These included the Ocular Surface Disease Index (OSDI) questionnaire, fluorescein tear film break-up time (FBUT), corneal fluorescein staining (CFS), Schirmer I test, meibum quality, meibomian gland expressibility, meibomian gland dropout (excluding 1-week), lipid layer thickness (LLT), and incomplete blinking rate (IBR). Statistical comparisons were performed using ANOVA with post-hoc analysis.

RESULTS: Compared to baseline, OSDI scores, meibum quality, meibomian gland expressibility, and IBR showed statistically significant deterioration at both 1 week and 1 month post-surgery (all p < 0.001). In contrast, no significant changes were observed in FBUT, CFS, Schirmer I test, LLT, or meibomian gland dropout at any time point. By the 3-month follow-up, all significantly altered parameters-OSDI, meibum quality, expressibility, and IBR-had recovered to levels that were not statistically different from preoperative baseline values.

CONCLUSIONS: Full-incision double-eyelid blepharoplasty induces a transient but significant dysfunction of the ocular surface and meibomian glands in the early postoperative period, which is closely associated with a sharp increase in incomplete blinking. These findings underscore the importance of proactive postoperative management, including dry eye counseling, artificial tears, and blink training, to enhance patient comfort during the recovery phase.

LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID:42286332 | DOI:10.1007/s00266-026-06052-2

Aesthetic Plast Surg. 2026 Jun 12. doi: 10.1007/s00266-026-06123-4. Online ahead of print.

ABSTRACT

This letter to the editor offers a constructive commentary on a recently published multivariate analysis of predictors of complications in abdominoplasty. The authors commend the original study for its rigorous surgical standardization, consecutive patient enrollment, and single‑surgeon design, and agree that high body mass index and active smoking are independent risk factors, while preservation of Scarpa’s fascia appears protective. However, three methodological limitations are identified. First, the sample size and number of events barely meet the minimum recommended events‑per‑variable ratio for multivariate regression. Second, treating seroma, necrosis, and dehiscence as independent outcomes ignores competing risks among these complications, which may bias risk estimates. Third, the single‑center, single‑surgeon design limits external validity, and the finding that diabetes is not a risk factor contradicts some existing literature. The letter suggests that future analyses adopt competing‑risk models and include multicenter external validation. It also notes that no new patient data are provided, so the proposed statistical refinements await empirical verification.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID:42286329 | DOI:10.1007/s00266-026-06123-4