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Nevin Manimala Statistics

Beyond Only Statistical Significance: Understanding and Applying the Minimal Clinically Important Difference in Clinical Research – A Review

Am J Phys Med Rehabil. 2026 Jun 22. doi: 10.1097/PHM.0000000000003068. Online ahead of print.

ABSTRACT

Clinically meaningful outcomes require more than statistical significance; they must also represent an actual benefit to patients. The minimum clinically important difference (MCID) is the smallest change in a patient-reported outcome measure (PROM) that is clinically significant to the patient. Despite the growing use of PROMs in clinical research, considerable variability exists in how MCID is defined, calculated, and interpreted across populations and clinical contexts. The objective of this review is to provide a comprehensive summary of the various methods for estimating and interpreting MCID, including distribution-based, anchor-based, and Delphi approaches, and to discuss their relationship with statistical significance in clinical practice. A literature search was conducted using Web of Science, MEDLINE, Embase, PubMed, and Google Scholar. MCID values may vary depending on the patient population, clinical context, and the PROM administered. Each calculation methodology has its strengths and limitations in evaluating clinically meaningful change from baseline to post-treatment. It is recommended to report both a statistically significant difference, defined as P < 0.05, or equivalently a 95% confidence interval (CI) that excludes the null value (i.e., does not include 0 for mean differences or 1 for odds ratios), and a clinically meaningful difference, defined as an effect size meeting or exceeding the established MCID for the outcome measure. Reporting the effect estimate alongside its 95% CI is encouraged as the primary approach, as this conveys both the magnitude and precision of the finding.

PMID:42322131 | DOI:10.1097/PHM.0000000000003068

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Nevin Manimala Statistics

Customized three dimensionally printed palatal stents: A randomized controlled clinical trial

Clin Adv Periodontics. 2026 Jun 20. doi: 10.1002/cap.70075. Online ahead of print.

ABSTRACT

BACKGROUND: Soft tissue grafts are commonly used in periodontal surgery around teeth and implants. However, few studies have examined donor-site pain through patient-reported outcomes following soft tissue grafting. This study aimed to minimize donor-site pain during autologous gingival grafting using a three-dimensionally (3D)-printed stent and evaluate its effectiveness from a patient-centered perspective.

METHODS: In this randomized controlled trial, 32 patients requiring autogenous gingival grafts were equally allocated to the control group (Omnivac stent) or the test group (3D-printed stent). Patient-reported outcomes were assessed using a visual analog scale (VAS) and the Oral Health Impact Profile-14 (OHIP-14) questionnaire on the day of surgery and at 1, 7, and 14 days postoperatively.

RESULTS: Data from 16 control and 14 test patients were analyzed (two patients were lost to follow-up). The test group reported significantly lower VAS scores than the control group. Despite a lack of statistically significant temporal differences, marked reduction was observed on the day of surgery and on postoperative day 7. OHIP-14 scores were significantly lower in the test group than in the control group across all time points. Analysis of the individual OHIP-14 items at different intervals revealed significant reductions in discomfort-specifically in pronunciation, taste, mastication, and daily activities-when using 3D-printed stents.

CONCLUSIONS: This study applied 3D-printed stents to reduce donor-site discomfort after autogenous soft tissue grafting and evaluated their effectiveness using patient-reported outcomes. Although 3D-printed stents may not directly reduce postoperative pain, they help alleviate discomfort during routine oral functions and daily activities.

KEY POINTS: This study focuses on the free gingival graft, one of the most frequently employed soft tissue grafts in periodontal practice. While autogenous gingival grafting on the palatal side is currently considered the gold standard, it causes additional pain and discomfort in patients. This study demonstrates that three-dimensional technology can be used to improve stent design to reduce patient pain and discomfort.

PLAIN LANGUAGE SUMMARY: This randomized controlled trial demonstrates that compared with a conventional stent, a customized 3D-printed palatal stent significantly improves patient-reported comfort and oral function after autologous gingival grafting, thereby enhancing postoperative quality of life.

PMID:42322120 | DOI:10.1002/cap.70075

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Nevin Manimala Statistics

Endometriosis and cardiovascular disease risk: a meta-analysis of cohort studies

Ann Med. 2026 Dec;58(1):2534083. doi: 10.1080/07853890.2025.2534083. Epub 2026 Jun 19.

ABSTRACT

OBJECTIVES: This meta-analysis aimed to evaluate the association between endometriosis (EM) and cardiovascular disease (CVD) risk by synthesizing evidence from large-scale cohort studies, with emphasis on subtype-specific risks and geographic disparities.

METHODS: We systematically searched PubMed, Embase, and Cochrane Library for cohort studies published until December 2024. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses stratified CVD subtypes (e.g. ischemic heart disease, atrial fibrillation), continents, and country development levels. Heterogeneity and publication bias were assessed via I2 statistics, sensitivity analyses, and Egger’s test.

RESULTS: Eleven cohort studies (n = 3,100,610 participants) were included. EM was associated with a 22% increased risk of all-cause CVD (HR = 1.22; 95% CI: 1.08-1.38; I2 = 94.6%). Subgroup analyses revealed elevated risks for myocardial infarction (HR = 1.29; 95% CI: 1.10-1.50), coronary artery disease (HR = 1.47; 95% CI: 1.29-1.67), and cerebrovascular events (HR = 1.18; 95% CI: 1.12-1.25), but not heart failure. Geographic disparities were significant, with higher CVD risks in Asian (HR = 1.36; 95% CI: 1.25-1.48) and North American cohorts (HR = 1.37; 95% CI: 1.16-1.61) compared to European populations (HR = 0.93; 95% CI: 0.64-1.34).

CONCLUSIONS: EM is independently associated with an elevated risk of CVD, particularly for coronary artery disease and myocardial infarction. These findings underscore the need for targeted cardiovascular monitoring in EM patients, particularly in high-risk populations.

PMID:42322096 | DOI:10.1080/07853890.2025.2534083

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Efficacy and Safety of the C3 Inhibitor Pegcetacoplan in Paroxysmal Nocturnal Hemoglobinuria: A Systematic Review and Meta-Analysis

Eur J Haematol. 2026 Jun 19. doi: 10.1111/ejh.70247. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of the complement C3 inhibitor pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria (PNH).

METHODS: PubMed, Embase, Web of Science, and Cochrane Library were systematically searched for studies reporting pegcetacoplan use in PNH. Outcomes included transfusion-requirement, hemoglobin normalization, mean hemoglobin levels, lactate dehydrogenase normalization, reticulocyte count normalization, and safety endpoints. Pooled proportions with 95% confidence intervals were calculated using random-effects models, and heterogeneity was assessed using the I2 statistic.

RESULTS: Five studies comprising 271 patients were included. Transfusion avoidance was observed in 80.6% of patients, with a pooled transfusion-requirement rate of 19.4%. LDH normalization occurred in 68.5% of patients (I2 = 0%). Hemoglobin normalization was observed in 42.9%, while reticulocyte count normalization reached 66%. Any-grade adverse events occurred in 83.5% of patients, most commonly pyrexia, headache, and dizziness. Serious adverse events occurred in 16.6%, decreasing to 12% after sensitivity analysis. Breakthrough hemolysis was reported in 14.8%, and infections in 17%.

CONCLUSION: Pegcetacoplan demonstrates consistent efficacy signals across key hematologic endpoints and an acceptable safety profile, supporting its potential role as an important therapeutic option, particularly in patients with persistent extravascular hemolysis despite C5 inhibition.

PMID:42322093 | DOI:10.1111/ejh.70247

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Nevin Manimala Statistics

Normal standardized left ventricular longitudinal strain curves stratified by age and sex in healthy individuals: The Copenhagen City Heart Study

Eur Heart J Cardiovasc Imaging. 2026 Jun 20:jeag154. doi: 10.1093/ehjci/jeag154. Online ahead of print.

ABSTRACT

AIMS: To establish normal sex- and age-specific longitudinal strain curves, to quantify their morphological variation with age, and to demonstrate their utility by deriving novel measures from them with the aim of testing prognostic value.

METHODS AND RESULTS: Age- and sex-appropriate normal strain curves were derived from healthy participants of the Copenhagen City Heart Study (CCHS). Four novel measures were constructed: early (EDS) and late (LDS) diastolic strain, primarily to assess age-related variation in strain curve morphology, and mean and diastolic strain deviation. Their prognostic value was assessed using Cox proportional hazards regression and C-statistics internally in the CCHS and externally in the LOOP study against a composite endpoint of cardiovascular death and incident heart failure or atrial fibrillation.In total, 1,641 healthy subjects (mean±SD age 45.3±15.2 years, 62.3% female) from the CCHS and 1,307 (mean±SD age 74.4±4.0 years, 47.4% female) from the LOOP study were included. EDS decreased with age while LDS increased. During a median follow-up of 4.9 [IQI: 3.0, 5.6] years, 409 (31.3%) subjects met the outcome in the LOOP study. Mean strain deviation was independently associated with the outcome (adjusted HR = 1.02 (95% CI: 1.00, 1.05), p = 0.045), while diastolic strain deviation was not.

CONCLUSION: We established normal sex- and age-specific longitudinal strain curves and furthermore demonstrated their utility by deriving novel measures from these with prognostic value beyond conventional measures. While promising, further validation in external populations is warranted. The normal curves and relevant code are publicly available.

PMID:42322083 | DOI:10.1093/ehjci/jeag154

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SARS-CoV-2 Infection, Vaccination Status, and Dementia Risk: A Nested Case-Control Study

Influenza Other Respir Viruses. 2026 Jun;20(6):e70277. doi: 10.1111/irv.70277.

ABSTRACT

OBJECTIVES: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may affect cognition, but its association with incident dementia remains inconsistent. We explored the association of SARS-CoV-2 infection and its vaccination with dementia risk in a nationwide sample of middle-aged and older adults.

METHODS: This nested case-control study used electronic healthcare data from Israel’s largest health provider. Participants were dementia-free individuals aged ≥ 50 years at baseline (March 2020), followed up until May 2022. Incident dementia cases were matched to dementia-free controls using density sampling by age, sex, and date of entry to the study, with a ratio of 1:10. SARS-CoV-2 was defined by positive polymerase chain reaction (PCR) or institutional antigen tests. Multivariable conditional logistic regression models evaluated the association of SARS-CoV-2, its severity and vaccination, and pneumonia as a comparator, with dementia risk.

RESULTS: Among the 1,145,322 eligible participants, 27,280 dementia cases were matched to 272,800 controls. SARS-CoV-2 infection was associated with increased dementia risk (OR = 1.18; 95% CI 1.12-1.24; p < 0.001). This association was confined to hospitalized individuals with mild (OR = 2.39; 95% CI 2.07-2.76) and moderate-to-severe disease (OR = 1.93; 95% CI 1.70-2.20), was comparable to pneumonia (OR = 1.89; 95% CI 1.80-1.99), and was no longer evident after 6 months (OR = 1.04; 95% CI 0.96-1.12). COVID-19 vaccination was associated with 7%, 15%, and 31% lower dementia risk after two, three, and four doses, respectively. Unvaccinated individuals with prior COVID-19 had the highest dementia risk.

CONCLUSIONS: Dementia diagnoses are increased after COVID-19, especially in hospitalized patients. Risk is comparable to other respiratory infections.

PMID:42322076 | DOI:10.1111/irv.70277

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Nevin Manimala Statistics

Lower Risk of Developing Gestational Diabetes Mellitus in the Group Prenatal Care Model

Paediatr Perinat Epidemiol. 2026 Jun 19. doi: 10.1111/ppe.70167. Online ahead of print.

ABSTRACT

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication with both short- and long-term adverse outcomes for both mothers and their offspring. CenteringPregnancy group prenatal care (CPNC) model has gained popularity due to its unique design to support pregnant individuals in managing multiple risk factors during pregnancy. However, whether participation in CPNC reduces the risk of developing GDM remains uncertain.

OBJECTIVE: To compare the GDM incidence between pregnant individuals receiving CPNC and those receiving traditional individual prenatal care (IPNC).

METHODS: This retrospective cohort study included 8313 participants (CPNC: 1832; IPNC: 6481) from South Carolina. GDM was screened and diagnosed between 24 and 30 weeks of gestation with the two-step approach. We applied inverse probability of treatment weighting (IPTW) using stabilized propensity score (PS) weights. The weighted risk ratio (RR) of CPNC relative to IPNC for GDM was estimated using weighted marginal log-binomial models.

RESULTS: In the original cohort, the incidence of GDM was 4.7% in the CPNC group and 6.8% in the IPNC group. After applying stabilized IPTW, baseline characteristics were well balanced between groups. In the weighted pseudo-cohort, CPNC was associated with a lower risk of GDM compared with IPNC (RR 0.64, 95% confidence interval [CI] 0.51, 0.81). In subgroup analyses, this inverse association was observed among non-Hispanic White (RR 0.61, 95% CI 0.43, 0.86) and non-Hispanic Black participants (RR 0.69, 95% CI 0.47, 1.00), but not among Hispanic participants (RR 1.05, 95% CI 0.62, 1.77). Results from multivariable logistic regression in the original cohort were consistent in direction but less precise. There was no evidence of additive interaction by race/ethnicity.

CONCLUSIONS: Pregnant individuals receiving CPNC had a lower risk of developing GDM than those receiving IPNC.

PMID:42322067 | DOI:10.1111/ppe.70167

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Clinical accuracy and applications of large language models in pediatric orthopedics: a systematic review

J Pediatr Orthop B. 2026 Jun 23. doi: 10.1097/BPB.0000000000001368. Online ahead of print.

ABSTRACT

To systematically evaluate the accuracy, reliability, and clinical applicability of artificial intelligence and large language models (LLMs) in pediatric orthopedics, comparing their performance against established clinical guidelines and assessing their utility for patient education and clinical decision support. A search of PubMed and ScienceDirect (2020-2025) identified 2624 articles using the keywords ‘ChatGPT’, ‘Gemini’, ‘Claude’ and ‘orthopedic pediatrics’. After screening and refinement using Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, 15 studies met inclusion criteria. Studies evaluated ChatGPT, Google Gemini, Meta AI, Microsoft Copilot, and Claude across multiple pediatric orthopedic conditions across conditions like developmental dysplasia of the hip, slipped capital femoral epiphysis, and scoliosis. Heterogeneity was assessed using Cochran’s Q and I2 statistics, and publication bias was evaluated using funnel plots and Egger’s test. LLM accuracy ranged from 44.3 to 93% (pooled: 74.1%), with pooled accuracy of 74.1%. Reproducibility was moderate, with ChatGPT demonstrating a Spearman coefficient of 0.55 for complex queries. Regional expert consensus scores varied significantly (Europe: 80, North America: 65; P = 0.034; Fleisskappa = 0.113). Up to 33% of responses to guideline-based questions were rated neutral or inaccurate. Reading complexity was elevated (Flesch-Kincaid grade: 12.7), exceeding the recommended sixth-grade level. Parent surveys indicated 82% trust in artificial intelligence as supplementary tools with professional oversight. Minimal statistical heterogeneity was observed (I2 = 0.00%), though publication bias was detected (Egger’s test P = 0.0001). LLMs show potential for education and triage but lack consistency in complex scenarios, elevated reading complexity, and significant regional variability in expert assessments. These tools should be used as educational supplements under professional medical supervision rather than for independent clinical decision-making. Broader clinical application requires domain-specific tuning, standardized evaluation, and readability optimization.

LEVEL OF EVIDENCE: Level V- systematic review.

PMID:42322047 | DOI:10.1097/BPB.0000000000001368

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Orthostatic Myoclonus-Clinical and Electrophysiological Features in a Large Retrospective Cohort

Mov Disord Clin Pract. 2026 Jun 19. doi: 10.1002/mdc3.70712. Online ahead of print.

ABSTRACT

BACKGROUND: Orthostatic myoclonus is characterized by irregular, lower limb myoclonic bursts during stance and is a major cause of postural instability and falls. However, studies are limited, and little is known about its pathophysiology.

OBJECTIVES: We sought to define the clinical and electrophysiological features of orthostatic myoclonus in a large, single-center cohort.

METHODS: We included 42 participants (24 males, 18 females) with a mean age of 74 years (range, 46-93) from Westmead Hospital presenting with orthostatic myoclonus from 2007 to 2023. Medical records were retrospectively reviewed for demographic details, symptoms, co-morbidities, and treatment. Lower limb surface electromyography (EMG) was analyzed using a custom-designed algorithm to automatically identify myoclonic bursts and measure their duration, synchronicity, and rhythmicity. Differences in burst parameters between muscles and associations between burst parameters and clinical characteristics were statistically evaluated.

RESULTS: Mean burst durations during standing were 77 to 90 ms across lower limb muscles. Maximum burst activity and bilateral synchronicity occurred in tibialis anterior. Only 12% of participants exhibited any rhythmicity. A total of 79% of participants had a coexistent neurological disorder including 26% with parkinsonism. There was no significant association between parkinsonism and burst parameters. However, there was a significant, inverse correlation between the presence of neuropathy or radiculopathy and synchronous activity (P = 0.02).

CONCLUSIONS: We provide a computationally robust clinical and electrophysiological analysis of orthostatic myoclonus in a large cohort. Our findings support the theory of a subcortical generator arising from protean secondary causes and subject to peripheral modulation. Further work is needed to clarify treatment outcomes.

PMID:42322040 | DOI:10.1002/mdc3.70712

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Longitudinal Associations Between Inflammation and Multi-Dimensional Fatigue up to 2 Years After Colorectal Cancer Diagnosis

Int J Cancer. 2026 Jun 19. doi: 10.1002/ijc.70613. Online ahead of print.

ABSTRACT

Cancer-related fatigue (CRF) is a prevalent symptom among colorectal cancer (CRC) survivors. While inflammation is a proposed underlying mechanism, longitudinal evidence including pre-treatment assessments remains scarce. Within the population-based PROCORE study, newly diagnosed CRC patients provided blood samples and completed questionnaires at diagnosis (n = 411; 60.6% male; age = 67.0 years), 12- (n = 304), and 24-month follow-up (n = 252). Eleven inflammatory biomarkers (CRP, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-17A, IL-22, sTNFRI, and sTNFRII) were assayed; CRF was measured with the Multidimensional Fatigue Inventory. Hybrid linear mixed models disentangled between- and within-subject associations, controlling for sociodemographic (e.g., age), clinical (e.g., cancer treatment), and lifestyle covariates (e.g., BMI), sleep quality, and pain. A normative age- and sex matched sample (n = 204; 52.5% male; age = 64.3 years) was included for comparison. Soluble TNF receptors (sTNFRI/II) were most robustly and positively associated with nearly all fatigue dimensions. CRP was positively associated with mental and physical fatigue; IL-8 positively associated with multiple domains including reduced motivation; and IFN-γ positively associated with general fatigue and reduced activity. Lower IL-1α was associated with more mental fatigue. Between-subject effects mirrored overall results; within-subject effects were more selective. Associations were most consistently observed for mental fatigue. In controls, less associations were significant; CRP was the most robust marker and positively associated with general fatigue, reduced activity, and reduced motivation. CRC survivors exhibited a broader, mostly TNF-α driven inflammatory signature of fatigue than controls. Findings highlight inflammation as a potential target underlying CRF, informing survivorship care strategies.

PMID:42322026 | DOI:10.1002/ijc.70613