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Nevin Manimala Statistics

Are We in Control? How Best to Include a Control Group in Interrupted Time Series Designs: A Simulation Study

J Eval Clin Pract. 2026 Jun;32(4):e70466. doi: 10.1111/jep.70466.

ABSTRACT

BACKGROUND: While controlled interrupted time series (CITS) are commonly used to evaluate public health policies, how to incorporate control(s) into their statistical modelling has received limited attention. We aimed to compare the statistical performance of different model formulations for including control groups in various segmented regression model specifications (with a particular focus on CITS and Difference-in-Difference [DiD] designs) under conditions where their assumptions are met, as well as when they are violated.

METHODS: Based on a real-world dataset, we simulated and compared the statistical performance of four model formulations grounded on segmented regressions for including control groups in a pre- and post-evaluation. The compared model formulations were: (1) CITS segmented regression, (2) DiD segmented regression, (3) single ITS of the difference between control and intervention series, and (4) incorporating the control as a covariate in a single ITS. Models were tested across scenarios challenging assumptions around the control group (e.g., non-parallel trends -challenging DiD assumptions-, or inconsistent trend difference over time between groups -challenging CITS assumption-) or regression errors (e.g., heteroscedasticity or autocorrelation). We also included models, including restricted cubic splines of time, which may mitigate distortions from assumption violations. Additionally, we tested for detecting non-parallel trends.

RESULTS: Standard DiD, CITS, and the ITS of the difference between series yielded the lowest bias whenever their design assumptions were satisfied. Overall, including time splines as covariates into ITS of the difference between series achieved the lowest bias and highest coverage also when design assumptions were violated. This makes it a valuable tool for causal inference in settings with parallel, non-parallel or inconsistent trend patterns between groups. Since violations of the trends assumption are often undetectable, methods robust to such violations are extremely valuable.

CONCLUSIONS: Modelling CITS as an ITS of the difference between series is among the most robust methods to embed control series into model specifications. Incorporating time splines as model covariates within an ITS of the difference has the potential of reducing bias from assumption violations (including parallel trends) without negative impacts when assumptions hold.

PMID:42143773 | DOI:10.1111/jep.70466

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Nevin Manimala Statistics

Predictors of Medication Cessation After Benign Prostatic Hyperplasia Procedures

J Urol. 2026 May 17:101097JU0000000000005091. doi: 10.1097/JU.0000000000005091. Online ahead of print.

ABSTRACT

PURPOSE: Medication cessation is an important motivator for patients undergoing benign prostatic hyperplasia (BPH) surgery; however, evidence on this topic remains limited. We evaluated rates and probabilities of BPH and overactive bladder (OAB) medication cessation in a statewide cohort.

MATERIALS AND METHODS: Using Michigan statewide claims data (2017-2022) from the Michigan Value Collaborative, patients who underwent BPH surgery with pre-existing BPH or OAB medications were identified. Procedures were categorized as (1) transurethral surgery, including transurethral resection of the prostate (TURP), laser photovaporization (PVP), robotic waterjet therapy (RWJT), and laser enucleation of the prostate (LEP); (2) minimally invasive surgical therapies (MISTs), including water vapor thermal therapy (WVTT), prostatic urethral lift (PUL), prostatic artery embolization (PAE), and transurethral microwave thermotherapy (TUMT); and (3) simple prostatectomy (SP). Medication cessation was defined as no refills between 181 and 365 days postoperatively. Multivariable logistic regression estimated procedure-specific probabilities of cessation.

RESULTS: Among 12,633 patients with continuous pharmacy enrollment, 8628 (68%) were prescribed BPH medications and 933 (7%) were prescribed OAB medications preoperatively. Medication cessation occurred in 61% and 62% of the BPH and OAB cohort, respectively. Predicted probabilities of BPH medication cessation were highest for LEP and SP (≥ 84%) and lowest for MISTs (< 60%). No statistically significant differences in OAB medication cessation were found across procedures.

CONCLUSIONS: In this real-world, statewide cohort, BPH medication cessation varied by procedure type. Transurethral surgeries and SP were associated with higher BPH medication cessation rates, while minimally invasive surgical therapies had lower rates. These findings provide practical estimates to inform shared decision-making and counseling when considering BPH interventions.

PMID:42143772 | DOI:10.1097/JU.0000000000005091

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Evaluation of Osteoprotegerin (OPG) and Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) Biomarker Concentrations in the Saliva of Patients with Periodontitis and Depression

Clin Exp Dent Res. 2026 Jun;12(3):e70379. doi: 10.1002/cre2.70379.

ABSTRACT

BACKGROUND AND OBJECTIVES: Periodontitis is a chronic inflammatory disease affecting tooth-supporting structures, while depression is a common mental disorder with emotional and behavioral disturbances. Previous studies suggest a potential association between the two conditions. This study aimed to evaluate salivary concentrations of Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) and Osteoprotegerin (OPG)-key regulators of osteoclast activity and periodontal bone resorption-in patients with periodontitis and depression.

MATERIALS AND METHODS: In this cross-sectional study, 80 patients from Shahid Beheshti University Dental School were categorized into four groups based on the presence or absence of periodontitis and depression. Periodontitis was defined as having ≥ 2 teeth in ≥ 2 quadrants with bleeding on probing, pocket depth > 3 mm, and interdental clinical attachment loss ≥ 1 mm. Depression was assessed using the Persian PHQ-9, and individuals meeting criteria for major depressive disorder(MDD) were classified as depressed. Unstimulated saliva samples (1 mL) were collected, stored at -20°C, and analyzed for OPG and RANKL using ELISA kits. Statistical analyses included two-way ANOVA (SPSS v27; p < 0.05 significant).

RESULTS: Among 80 participants (43 females, 37 males; mean age 45.3 years), RANKL, OPG, and the RANKL/OPG ratio were higher in depressed individuals, but differences were not statistically significant (p > 0.05). RANKL levels and the RANKL/OPG ratio were significantly higher in patients with periodontitis and increased with disease severity (p ≤ 0.05), while OPG showed no significant change.

CONCLUSION: Periodontitis and its severity significantly influence salivary RANKL and the RANKL/OPG ratio, while depression does not. Within the limits of this cross-sectional design, no evidence was found that RANKL and OPG act as intermediary biomarkers linking depression and periodontitis.

PMID:42143768 | DOI:10.1002/cre2.70379

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Tooth Loss and Uncontrolled Diabetes Among Korean Adults With Type 2 Diabetes: Insights From the Korea National Health and Nutrition Examination Survey (KNHANES) 2014-2018

Clin Exp Dent Res. 2026 Jun;12(3):e70371. doi: 10.1002/cre2.70371.

ABSTRACT

OBJECTIVES: The relationship between tooth loss and glycemic control status in diabetes is inconclusive.

MATERIAL AND METHODS: Using data from the 2014-2018 Korean National Health and Nutrition Examination Survey (KNHANES), 2146 adults with diabetes aged ≥ 40 years were categorized by number of remaining teeth (0-19, 20-27, and ≥ 28). Uncontrolled diabetes and poorer glycemic control were defined as HbA1c ≥ 6.5% and ≥ 7.0%, respectively. Multivariable logistic regression models calculated the odds ratio (OR) for uncontrolled diabetes and poorer glycemic control according to the number of remaining teeth.

RESULTS: No significant association was observed in men. In women, fewer remaining teeth were associated with higher odds of uncontrolled diabetes (per 1-tooth increase OR 0.961, 95% CI 0.937-0.986; p = 0.002), and compared with ≥ 28 teeth, OR were higher in the 0-19 teeth (OR 2.500, 95% CI 1.535-4.074) and the 20-27 teeth (OR 1.679, 95% CI 1.073-2.629) (all p = 0.002). Furthermore, among women, the associations persisted in both 40-59 years (per 1-tooth increase OR 0.878, 95% CI 0.780-0.988; p = 0.030) and ≥ 60 years (per 1-tooth increase OR 0.965, 95% CI 0.939-0.992; p = 0.011). Among women aged ≥ 60 years, those with 0-19 teeth had higher odds of uncontrolled diabetes (OR 1.994, 95% CI 1.041-3.818; p = 0.029) and poorer glycemic control (OR 2.498, 95% CI 1.321-4.723; p = 0.008) compared with those with ≥ 28 teeth.

CONCLUSIONS: Fewer remaining teeth were associated with poorer glycemic control among women with diabetes, independent of periodontitis. This association was most pronounced in women aged ≥ 60 years. Large cohort studies are warranted to clarify causality and to evaluate the roles of periodontitis and dental caries in this relationship.

PMID:42143765 | DOI:10.1002/cre2.70371

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Salivary Bicarbonate Fails to Mirror Systemic Acid-Base Balance in Pediatric Patients at Risk of Metabolic Disturbances

G Ital Nefrol. 2026 Apr 30;43(2):2026-vol2. doi: 10.69097/43-02-2026-05.

ABSTRACT

Introduction. The utility of salivary bicarbonate as a non-invasive marker of systemic acid-base status in pediatric patients remains unclear. This study investigated the possible correlation between salivary and blood gas analysis at risk for acid-base disturbances, including those with chronic kidney disease (CKD) or receiving acetazolamide. Methods. In a single-center cross-sectional study (July 2024-March 2025), 94 pediatric patients (6-18 years) underwent simultaneous blood and saliva sampling for gas analysis. Patients were stratified into metabolic acidosis (<22 mmol/L), normal (22-26 mmol/L), or metabolic alkalosis (>26 mmol/L) groups based on serum bicarbonate. Results. No relationship was observed between salivary and serum bicarbonate (r = 0.112, p = 0.281), pH, or base excess. However, strong correlations emerged within salivary parameters: bicarbonate was positively associated with salivary pH (r = 0.682, p < 0.001) and base excess (r = 0.865, p < 0.001). Patients with eGFR <30 ml/min/1.73m² had significantly higher salivary bicarbonate (13.6 mmol/L vs 6.8 mmol/L, p = 0.004), independently of bicarbonate supplementation. This was also negatively associated with calcium (β = -8.67, p = 0.004) and lactate (β = -0.82, p = 0.008). Dialysis status and underlying diagnosis were additional independent predictors. While patients with metabolic acidosis showed higher median salivary bicarbonate than those with normal or alkalotic profiles, this difference was not statistically significant (p = 0.545). Conclusions. Salivary bicarbonate does not reflect systemic acid-base balance but is elevated in advanced CKD, suggesting a local regulatory phenomenon worthy of further exploration.

PMID:42143748 | DOI:10.69097/43-02-2026-05

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Nevin Manimala Statistics

Effects of Statistical Learning on Stimulus Detection Speed Reflect Attention Rather Than Representational Changes

Cogn Sci. 2026 May;50(5):e70226. doi: 10.1111/cogs.70226.

ABSTRACT

Statistical learning (SL) is believed to enable humans to assimilate a range of statistical structures, and thus plays a role in many cognitive functions. There is also a growing interest in how SL interacts with basic cognitive processes, including perception and attention. Here, we ask how the extent to which stimuli predict, and are predicted by, other elements in a continuous stream affects their perception (i.e., encoding and representation) and the attention they attract. In two experiments, participants were first exposed to a stream of structured pairs of visual shapes (e.g., AB and CD). Then, they completed a target detection task to test if stimulus detection speed is influenced by a target’s predictability during exposure (indexing representation) or by whether the shape preceding the target reliably predicted elements in the input (indexing attention). In Experiment 1 (N = 86), Reaction Times (RTs) were faster for second elements from structured pairs (i.e., cued elements) than first elements (i.e., cue elements), even when they appeared in new configurations (e.g., AD and CB). However, in Experiment 2 (N = 89), which orthogonally manipulated the target and the preceding shape properties, RTs were influenced solely by whether the preceding element was a cue for other elements, but not by the target’s predictability. Thus, in contrast to previous studies using the same paradigm, our results do not provide evidence for an effect of SL on representation. Instead, our findings highlight how attention is guided by knowledge of statistical regularities, pointing to SL as a system that helps minimize uncertainty in structured environments.

PMID:42143743 | DOI:10.1111/cogs.70226

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Nevin Manimala Statistics

The Immediate Effects of a 3D Intraoral Scanner as an Adjunctive Oral Hygiene Educational Tool: A Randomised Controlled Trial

Int J Dent Hyg. 2026 May 17. doi: 10.1111/idh.70091. Online ahead of print.

ABSTRACT

OBJECTIVES: This single-visit randomised controlled clinical trial (RCT) aimed to evaluate the immediate effects of a three-dimensional (3D) intraoral scanner as an adjunctive oral hygiene education tool compared to standard personalised oral hygiene instruction (OHI) in healthy adults.

METHODS: Fifty-two subjects were randomised into the IOS (test) or the hand mirror (control) group. Full mouth plaque score (FMPS) was measured at baseline and immediately after the intervention. Subjects also completed a questionnaire assessing their perception of plaque visualisation and the effectiveness of the intervention.

RESULTS: Both groups achieved a statistically significant reduction in FMPS post-intervention compared to baseline (p < 0.05). The test group demonstrated a statistically significant change in FMPS (p < 0.05) and a reduction in plaque on the posterior teeth compared to the control group (p < 0.05), but not on the anterior teeth (p > 0.05). The treatment effect increased towards the posterior teeth, reaching statistical significance from the third molars to the second premolars (p < 0.05). Survey results also revealed that 96.2% of the test group favoured the IOS, particularly for visualising and cleaning posterior and lingual/palatal surfaces.

CONCLUSION: The 3D intraoral scanner showed short-term benefits in plaque visualisation and removal, especially in areas with poor visibility. IOS is well-accepted by subjects and may serve as a promising adjunctive tool in OHE.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT06349330 (available at https://clinicaltrials.gov/study/NCT06349330).

PMID:42143740 | DOI:10.1111/idh.70091

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Nevin Manimala Statistics

Harnessing institutional knowledge: mixed methods evaluation of peer coaching in a multi-site EHR transition

J Am Med Inform Assoc. 2026 May 17:ocag071. doi: 10.1093/jamia/ocag071. Online ahead of print.

ABSTRACT

OBJECTIVE: Health systems undertaking electronic health record (EHR) transitions often struggle to prepare and support clinicians in learning and using the new system. We evaluated a national peer coaching program-the National EHRM Supplemental Staffing Unit (NESSU)-designed to support clinicians during the U.S. Department of Veterans Affairs’ (VA’s) transition to a new EHR. Our goal was to assess NESSU’s reach, perceived usefulness, and association with key EHR user outcomes, and to characterize how NESSU achieved its observed impacts.

MATERIALS AND METHODS: Using a convergent mixed-methods design, we surveyed EHR users at the most recent VA facility to implement the new EHR. Descriptive statistics summarized program reach and perceived helpfulness. Regression models assessed associations between NESSU participation and 3 outcomes: burnout, EHR-related stress, and EHR confidence. Qualitative data included 62 interviews with users and open-ended survey responses. We used structured coding and thematic analysis to identify themes.

RESULTS: Among 385 respondents, 58.4% reported receiving NESSU support and 83.6% of those rated it as helpful. NESSU participation was associated with lower rates of burnout (29% vs 41%, P = 0.016) but not with differences in EHR confidence or EHR-related stress. Qualitative analysis yielded 4 themes describing how NESSU functioned (filling education gaps, providing responsive support, offering expert guidance, and drawing upon notable interpersonal skills) and one theme describing its overall impact.

DISCUSSION: Findings demonstrate that peer coaching can address important support needs during EHR transitions.

CONCLUSION: Scalable, clinician-led peer coaching may represent an essential component of large-scale EHR transitions, supporting both implementation and clinician well-being.

PMID:42143681 | DOI:10.1093/jamia/ocag071

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A SEER Registry-Based Analysis of the Management Strategies and Survival Outcomes of Colorectal Cancer With Isolated Synchronous Lung Metastases

World J Surg. 2026 May 17. doi: 10.1002/wjs.70415. Online ahead of print.

ABSTRACT

BACKGROUND: Current treatment guidelines for stage IV colorectal cancer (CRC) with isolated synchronous lung metastases are limited. This study aimed to assess the association between management strategies and cancer-specific survival (CSS).

METHODS: This study was a retrospective cohort analysis of patients with stage IV colorectal adenocarcinoma and isolated synchronous lung metastases from the SEER registry (2010-2022). Patients were grouped by treatment strategy: surgery-only, chemotherapy-only, or combined surgery and chemotherapy. The main outcome measure was 3-year CSS, assessed by Kaplan-Meier statistics and multivariable Cox regression to adjust for survival confounders.

RESULTS: 5666 (6.9%) of 82,502 patients with stage IV CRC had isolated lung metastases. 736 (13%) were treated with surgery-only, 1870 (33%) chemotherapy-only, and 1908 (33.6%) surgery and chemotherapy; no treatment was recorded in 20.3% of patients. Chemotherapy alone was increasingly used over time (from 33.8% to 51.1%), whereas combined treatment decreased. Combined surgery and chemotherapys was associated with the highest 3-year CSS (55.1%) compared with chemotherapy-only (26.1%) and surgery-only (21.7%) (p < 0.001). Resection of both primary CRC and lung metastases combined with chemotherapy conferred the best 3-year CSS (66.2%). Combined surgery for primary and metastatic tumors and chemotherapy was associated with significant mortality risk reduction (HR 0.31, p < 0.001) compared with chemotherapy-only. Older age, signet-ring cell histology, poor differentiation, N2 primary disease, elevated CEA, and perineural invasion were associated with reduced CSS.

CONCLUSIONS: Combined resection of primary CRC and synchronous lung metastases with chemotherapy was associated with the best survival outcomes. However, use of this combined strategy is employed in select patients and has decreased over time.

PMID:42143670 | DOI:10.1002/wjs.70415

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Triphala Modulates the Membrane Vesicle Transcriptome of Enterococcus durans VIT3 to Influence Antibiotic Response and Probiotic Functions

Mol Biotechnol. 2026 May 17. doi: 10.1007/s12033-026-01578-x. Online ahead of print.

ABSTRACT

Membrane vesicles (MVs) are critical mediators of bacterial communication, physiology, and host interactions. This study explores how triphala, a polyherbal formulation, modulates the RNA cargo of MVs in Enterococcus durans VIT3 isolate under varied stress conditions. The isolated MVs from all treatment conditions (triphala, antibiotics, or sequential combinations) were spherical, intact, with negative zeta potential and sizes ranging from 56.4 to 462.3 nm. Cytotoxicity assays indicated no toxicity toward CaCo2 cells under the tested conditions. Transcriptomic profiling suggested that triphala pretreatment enhanced relative expression of genes linked to oxidative stress defense (ohrB, sodA), envelope integrity (dlt operon, pbp, mprF), and CRISPR-Cas-associated genes (cas1). In contrast, antibiotic first regimens suppressed stress and defense-associated genes, underscoring treatment order effects. Notably, triphala antibiotic sequence condition showed coordinated expression patterns within ATP synthase, arginine deiminase, and CRISPR loci, suggesting operon-level transcriptional organization of metabolic and stress-response pathways. STRING network analysis further supported clustering of genes showing relatively higher expression into functionally related molecules. Collectively, these findings suggest a potential role for triphala in shaping MV RNA cargo, offering a conceptual framework for synbiotic strategies aimed at supporting microbial stress resilience. All transcriptomic observations are based on pooled MV samples, which represent exploratory expression trends rather than statistically inferred differential expression or functional outcomes.

PMID:42143634 | DOI:10.1007/s12033-026-01578-x