Category: Statistics

Pain Physician. 2026 Jul;29(5):E407-E416.

ABSTRACT

BACKGROUND: Fibromyalgia (FM) has been increasingly studied in the context of gut-brain-immune interactions, and several reports have suggested an association between FM and alterations in gut or oral microbial communities. However, prior studies have often suffered from heterogeneous comorbidities, inconsistent sampling procedures, and limited control for environmental factors, making it unclear whether FM is associated with a reproducible, site-independent microbial signature.

OBJECTIVES: To determine whether women with FM exhibit consistent alterations in gut or oral microbiota when evaluated under strictly standardized physiological, clinical, and environmental conditions.

STUDY DESIGN: A prospective, observational, case-control study.

SETTING: The Department of Pain Medicine and Department of Medical Microbiology at Gazi University, Türkiye.

METHODS: The patient selection comprised 31 women (16 with FM; 15 healthy controls) who met rigorous inclusion and exclusion criteria, minimizing confounding from diet, metabolic disease, medications, hormonal status, and recent infections. No therapeutic intervention was performed; all patients provided paired oral mucosal and fecal samples during the follicular phase of the menstrual cycle. Sequencing of 16S rRNA V3-V4was performed on DNA extracted from all samples. Alpha and beta diversity metrics, taxonomic profiles, and differential abundance analyses (including LEfSe with FDR correction) were compared between groups. The clinical severity of FM was assessed using scores on the visual analog scale (VAS), Widespread Pain Index (WPI), and Symptom Severity Scale (SSS).

RESULTS: No statistically significant differences were observed between FM patients and controls in fecal or oral alpha diversity (Shannon, Simpson, Chao1, Observed OTU indices, all P > 0.05). Beta diversity analyses (Bray-Curtis PERMANOVA) revealed no between-group separation in either compartment (fecal R² = 0.032, P = 0.529; oral R² = 0.032, P = 0.464). Both groups displayed preserved core microbial communities in the gut, dominated by Firmicutes and Bacteroidota and, in the oral cavity, Streptococcus-enriched profiles. Minor genus-level variations were detected, but none remained significant after FDR correction. Cross-site analyses confirmed the expected ecological divergence between oral and fecal habitats but identified no FM-specific microbial pattern. Post hoc sensitivity analysis indicated that the study was powered to detect only moderate effect sizes (R² ≥ 0.11), suggesting that subtle differences might have remained undetected.

LIMITATIONS: A modest sample size, a lack of quantitative dietary assessment, and reliance on 16S rRNA sequencing limited the detection of subtle or functional microbial alterations. Additionally, the cross-sectional design precludes causal inference.

CONCLUSIONS: Under highly controlled sampling and exclusion conditions, FM was not associated with detectable alterations in the diversity or composition of gut or oral microbes. These findings suggest that previously reported dysbiosis may reflect comorbidity-driven or phenotype-specific variation rather than a universal microbial hallmark. Larger, multi-omic and phenotype-stratified studies are needed to clarify functional host-microbiome interactions in FM.

PMID:42550534

Pain Physician. 2026 Jul;29(5):335-343.

ABSTRACT

BACKGROUND: Fibromyalgia (FM) is a chronic condition characterized by widespread pain and a range of somatic and psychological symptoms that impose a substantial burden on patients. While pregabalin is an approved and effective monotherapy for many individuals with FM, the efficacy of this medication is often incomplete, particularly for symptoms like fatigue and anxiety. Combination therapy incorporating selective serotonin and norepinephrine reuptake inhibitors (SNRIs), such as duloxetine, has shown promise for enhancing therapeutic outcomes. Venlafaxine, an SNRI with demonstrated efficacy as an FM treatment, has a distinct pharmacological mechanism from pregabalin. However, the synergistic potential of pregabalin and venlafaxine in combination has not been formally evaluated.

OBJECTIVES: This study protocol describes a trial designed to test the hypothesis that the combination of pregabalin and venlafaxine is superior to pregabalin monotherapy in providing pain relief to patients with FM.

STUDY DESIGN: This is a multicenter, prospective, randomized, open-label, blinded-endpoint study.

SETTING: This study will be conducted at 7 different hospitals.

METHODS: We will recruit 750 adults with a diagnosis of FM and moderate-to-severe pain. Patients will be randomly assigned in a one-to-one ratio to receive either pregabalin monotherapy or combination therapy consisting of pregabalin and venlafaxine for 12 weeks. Both groups will follow a flexible, forced-titration schedule to achieve the maximum tolerated dose. While the patients and treating physicians will be aware of the treatment allocation, the outcome assessors will remain blinded.

RESULTS: The primary outcome is the mean daily pain intensity at week 4, measured on an 11-point numeric rating scale. Secondary outcomes will be evaluated at baseline and at weeks one, 2, 4, 8, and 12 after the treatment initiation. Secondary outcomes include the worst pain intensity, the responder rates (≥ 30% and ≥ 50% pain reduction), the dose of pregabalin and/or venlafaxine, the Revised FM Impact Questionnaire, the Brief Pain Inventory severity and interference subscales, the 36-Item Short Form Survey (SF-36), the Medical Outcomes Study Sleep Scale, the Beck Depression Inventory-II, and adverse events (AEs) occuring throughout the study. Statistical analyses will be performed on the modified intention-to-treat population.

LIMITATIONS: An open-label design will be employed, with patient follow-up limited to 12 weeks.

CONCLUSION: If the combination of pregabalin and venlafaxine proves to be more effective and better tolerated than pregabalin monotherapy, the combination therapy could establish a new standard of care for FM patients who struggle to achieve sufficient pain relief through nonpharmacological therapies.

PMID:42550524

Pain Physician. 2026 Jul;29(5):E325-E336.

ABSTRACT

BACKGROUND: Postoperative sleep disturbance (PSD) is a complication that often follows surgery. The condition is closely associated with impaired recovery, heightened pain sensitivity, and increased risk of chronic postsurgical pain. While pharmacological interventions like dexmedetomidine and esketamine have been reported to improve perioperative sleep quality, their comparative efficacy-particularly in the realm of analgesia-remains uncertain.

OBJECTIVES: This review aimed to evaluate the efficacy of dexmedetomidine and esketamine in treating PSDs and providing analgesia.

STUDY DESIGN: We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) that compared the effects of dexmedetomidine, esketamine, and control interventions on adult surgical patients.

SETTING: Comprehensive literature searches were performed in 4 electronic databases from their inception to August 1st, 2025. The protocol was previously registered in the PROSPERO database under the registration number CRD420251126227.

METHODS: The primary outcomes were postoperative pain scores assessed using the Visual Analog Scale (VAS) at 24 and 48 hours. Secondary outcomes included the incidence of PSD, Athens Insomnia Scale (AIS) scores, and sleep quality measured on the Numerical Rating Scale (NRS). Subjective sleep outcomes were synthesized using a Bayesian network meta-analysis. Additionally, a supplementary traditional meta-analysis was performed on studies that used polysomnography (PSG) to evaluate objective sleep architecture.

RESULTS: Ten RCTs involving 645 patients were included in the study. Esketamine demonstrated significantly superior analgesic efficacy, substantially reducing VAS pain scores both at rest and during movement at 24 and 48 hours postoperatively. Compared to the control, both esketamine and dexmedetomidine showed a tendency to reduce the incidence of PSD on the first postoperative day (esketamine: risk ratio [RR] = 0.655, 95% credible interval [CrI]: 0.517-0.798; dexmedetomidine: RR = 0.773, 95% CrI: 0.434-1.23) and improved AIS and NRS scores. A supplementary meta-analysis of 4 PSG studies (n = 182 patients) indicated that dexmedetomidine increased the percentage of stage N2 sleep (mean difference [MD] = 13.0%, 95% confidence interval [CI]: -5.2 to 31.2) and the odds of experiencing stage N3 sleep, although the latter finding was not statistically significant (odds ratio [OR] = 2.99, 95% CI: 0.61 to 14.66).

LIMITATIONS: The primary limitation on this study is that the trials included were all conducted in China.

CONCLUSIONS: Both dexmedetomidine and esketamine improve postoperative sleep quality effectively. Esketamine demonstrates superior analgesic efficacy and has the higher probability being the optimal treatment for reducing early PSD incidence. In contrast, dexmedetomidine appears to objectively improve sleep architecture by promoting N2 sleep. The superior analgesic profile of esketamine likely underpins its enhanced subjective sleep benefits.

PMID:42550519

JAMA Netw Open. 2026 Aug 3;9(8):e2626901. doi: 10.1001/jamanetworkopen.2026.26901.

ABSTRACT

IMPORTANCE: Health systems increasingly screen for health-related social needs (HRSNs), which are modifiable social factors associated with health outcomes. However, screening selection biases and HRSN burdens are poorly characterized.

OBJECTIVE: To evaluate patient characteristics associated with HRSN screening completion, positivity, and assistance requests.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of adults with screening-eligible outpatient or inpatient encounters in a 22-state, 92-hospital system was performed from January 1, 2020, to November 30, 2024. Data were analyzed from June 7, 2025, to February 4, 2026.

EXPOSURE: Patient sociodemographic characteristics.

MAIN OUTCOMES AND MEASURES: Unadjusted standardized mean differences and adjusted logistic regression were used to identify characteristics associated with screening completion. Multivariable regression and marginal standardization were used to identify characteristics associated with positivity for any HRSN, total HRSN burden, and assistance requests.

RESULTS: Among 1 893 331 eligible adults, 696 925 (36.8%) were 65 years or older (median age, 57 [IQR, 38-71] years), 1 138 792 (60.1%) were female, 8437 (0.4%) were American Indian or Alaska Native, 60 884 (3.2%) were Asian, 257 391 (13.6%) were Black, 4193 (0.2%) were Native Hawaiian or Other Pacific Islander, and 1 561 702 (82.5%) were White; 87 641 (4.6%) were of Hispanic or Latino ethnicity, and 916 449 (48.4%) had Medicare or Medicaid coverage. A total of 1 135 136 participants (60.0%) completed screening and 334 399 (29.5%) reported at least 1 HRSN. Unadjusted differences between screened and unscreened patients were not significant (standardized mean difference, ≤0.20). In adjusted analyses, Black patients (odds ratio [OR], 0.85; 95% CI, 0.79-0.91) and Medicaid beneficiaries (OR, 0.87; 95% CI, 0.80-0.95) had lower odds of being screened, and Hispanic or Latino patients had higher odds (OR, 1.11; 95% CI, 1.01-1.23). Outpatient underscreening was attenuated in inpatient settings for Black patients and Medicaid beneficiaries. The adjusted probabilities of any positive screen were higher among Black (absolute risk difference [ARD], 12.6%; 95% CI, 9.5%-15.7%), American Indian or Alaska Native (ARD, 10.6%; 95% CI, 9.2%-11.9%), and Native Hawaiian or Other Pacific Islander (ARD, 7.2%; 95% CI, 2.1%-12.2%) patients and among Medicare (ARD, 13.1%; 95% CI, 9.7%-16.5%) and Medicaid (ARD, 18.7%; 95% CI, 16.1%-21.2%) beneficiaries compared with White and commercially insured patients. Black patients (ARD, 9.4%; 95% CI, 6.5%-12.3%) and Medicaid beneficiaries (ARD, 16.9%; 95% CI, 16.0%-17.9%) had higher adjusted probabilities of at least 3 positive domains. Among those with at least 3 positive domains, Black patients (ARD, 21.9%; 95% CI, 16.5%-27.2%), Medicare (ARD, 7.0%; 95% CI, 5.1%-8.8%), and Medicaid (ARD, 12.2%; 95% CI, 10.9%-13.6%) beneficiaries had higher assistance requests.

CONCLUSIONS AND RELEVANCE: In this cohort study across inpatient and outpatient settings, HRSN screening had a substantial reach largely free of selection. Nearly 30% of screened patients demonstrated needs, with higher rates among patients who were members of racial and ethnic minority groups and publicly insured. This study provides support for inpatient HRSN screening workflows, even as policy mandates evolve, to preserve equitable reach for patient groups with disproportionately high social needs.

PMID:42550509 | DOI:10.1001/jamanetworkopen.2026.26901

JAMA Netw Open. 2026 Aug 3;9(8):e2627283. doi: 10.1001/jamanetworkopen.2026.27283.

ABSTRACT

IMPORTANCE: Black women have twice the endometrial cancer mortality of White women, and studies suggest that differences in ultrasound diagnostic accuracy partially contribute to this disparity.

OBJECTIVE: To evaluate racial and ethnic differences in the diagnostic performance of transvaginal ultrasound for detecting endometrial neoplasia.

DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of 1833 women aged 50 years or older at risk of endometrial neoplasia, conducted at a large urban academic medical center from February 2014 to August 2022, with follow-up through March 2023. The statistical analyses were conducted from March 2024 to December 2025.

INTERVENTIONS: Women underwent endometrial assessment via transvaginal ultrasound followed by sonohysterogram-directed biopsy and follow-up observation to establish final outcome.

MAIN OUTCOME AND MEASURES: Assessment of transvaginal ultrasound diagnostic performance for detecting endometrial cancer and hyperplasia across racial and ethnic groups, measured by: (1) completion rate (endometrial accessibility) and (2) accuracy of completed scans. To assess any association with fibroids, analyses were repeated after excluding women with fibroids. Subgroup analyses were conducted among women with endometrial cancer, those with postmenopausal bleeding, and those without prior exposure to estrogen or tamoxifen.

RESULTS: A total of 1833 women met inclusion criteria (mean [SD] age, 60.3 [8.1] years). Most were postmenopausal (1218 women [87.4%]), and 832 (45.4%) were Black, 705 (38.5%) were Hispanic, and 253 (13.8%) were White. Black women had significantly lower completion rates (adequate endometrial visibility) for transvaginal ultrasound compared with White women (75.7% vs 88.9%; relative risk, 0.85; 95% CI, 0.80-0.90; P < .001). Accuracy of completed transvaginal ultrasound was slightly lower among Black women compared with White women (sensitivity, 96.3%; 95% CI, 91.3%-100% vs 100%; negative predictive value, 97.9%; 95% CI, 95.0%-100% vs 100%). After excluding women with fibroids, differences in completion and accuracy between Black and White women disappeared. Similar findings were observed in subgroup analyses of women with a final diagnosis of endometrial cancer, those presenting with postmenopausal bleeding, and those without prior exposure to estrogen or tamoxifen.

CONCLUSIONS AND RELEVANCE: In this cohort study of a diverse population of women, ultrasound completion rates were lower among Black women, primarily due to fibroids impairing endometrial visibility. Nevertheless, transvaginal sonography demonstrated a 76% completion rate and retained excellent ability to exclude cancer in Black women, regardless of fibroid presence.

PMID:42550505 | DOI:10.1001/jamanetworkopen.2026.27283

Phys Ther. 2026 Aug 4:pzag081. doi: 10.1093/ptj/pzag081. Online ahead of print.

ABSTRACT

IMPORTANCE: Musculoskeletal (MSK) pain is common during pregnancy but referral rates to physical therapy and the influence of MSK pain management on satisfaction with prenatal care are unknown.

OBJECTIVE: The objective was to obtain patient reports of pain during pregnancy, its impact on biopsychosocial wellbeing, health care management of pain (including referral to physical therapy), and the influence of pain management on satisfaction with prenatal care.

DESIGN: The study design was an internet survey.

SETTING: An e-survey was distributed internationally via social media, word-of-mouth, and flyers.

PARTICIPANTS: Six hundred seventy-one female respondents from 6 continents who had given birth <25 months before survey completion participated in the study.

INTERVENTIONS OR EXPOSURES: No interventions or exposures were included in this study.

MAIN OUTCOMES & MEASURES: Presence and description of pain, influence of pain on daily life, pain management, birth experiences, and patient satisfaction were reported. Descriptive statistics were used to report frequencies. Comparisons between care provider types were made using non-parametric statistics (Fisher Exact Test, 2-tailed; or Fisher-Freedman-Halton Exact Test, 2-tailed).

RESULTS: MSK pain was reported by 90% of participants, with more than 50% reporting pain in multiple body regions. Those who saw an Obstetrician-gynecologist were more likely to report pain, though both provider groups had high pain rates (92.7% vs 85%). Thermal therapy was the most common pain management recommendation (33.7%); physical therapy was recommended to only 29.4% of individuals with pregnancy-related musculoskeletal pain. Pain caused negative feelings/emotions in 77.2% of respondents and difficulty with performance of physical activity, household, and childcare tasks in approximately 50% of respondents. Care providers’ response to pain influenced patient satisfaction in 49% of respondents.

CONCLUSIONS AND RELEVANCE: Pregnancy MSK pain influences physical functioning, psychosocial wellbeing, and satisfaction with prenatal care. Patients report poor pain management by perinatal care providers, highlighting needs for better education, more pain management options, and multidisciplinary care. Physical therapists need to develop working relationships with prenatal care providers to improve care during pregnancy.

PMID:42550503 | DOI:10.1093/ptj/pzag081

J Burn Care Res. 2026 Aug 4:irag130. doi: 10.1093/jbcr/irag130. Online ahead of print.

ABSTRACT

INTRODUCTION: Preoperative communication checklists are used to improve surgical safety and team coordination. We evaluated whether introduction of a preoperative communication checklist was associated with reduced operative duration in a burn operating room.

METHODS: We conducted a quality improvement study comparing operative outcomes before and after introduction of a preoperative communication checklist in a burn unit. Cases from August 19, 2020, to August 20, 2022, were included, with checklist introduction occurring in August 20, 2021. Adult patients undergoing excisional debridement procedures were analyzed. The primary outcome was operative duration. Mixed-effects models were used to assess the association between checklist use and operative duration while adjusting for surgeon, procedure type, and square area excised.

RESULTS: A total of 139 patients undergoing 281 operations were included (143 pre-checklist, 138 post-checklist). Mean operative duration decreased from 107.8 minutes pre-checklist to 96.0 minutes post-checklist. In adjusted analysis, checklist use was associated with a 17.99-minute reduction in operative duration (p<0.001). Procedures involving autograft, ReCell, and biodegradable temporizing matrix were associated with increased operative time, as was greater square area excised. In interaction models, the overall reduction was not statistically significant; however, ReCell procedures demonstrated a significant reduction of 30.49 minutes (p=0.003) following checklist introduction.

CONCLUSION: Introduction of a preoperative communication checklist was associated with decreased operative duration. The greatest effect was observed in ReCell procedures, suggesting that improved preoperative coordination may enhance efficiency in complex workflows. Preoperative checklists represent a scalable quality improvement strategy to optimize operative efficiency and resource utilization in burn care.

PMID:42550498 | DOI:10.1093/jbcr/irag130

Pain Med. 2026 Aug 4:pnag100. doi: 10.1093/pm/pnag100. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the incidence and risk factors of chronic opioid use following head and neck adenoid cystic carcinoma (HNACC) surgery and explore the association between postoperative opioid use and survival outcomes.

DESIGN: Observational retrospective cohort study.

SETTINGS: Perioperative care of cancer patients at the UT – MD Anderson Cancer Center.

SUBJECTS: Adults (≥18 years) who underwent HNACC surgery with curative intent were included; while those with recurrent or metastatic disease at the time of surgery or who received palliative treatment were excluded.

METHODS: Multivariable logistics and Cox regression analyses were performed to identify predictors of chronic opioid use and explore associations with recurrence-free survival (RFS) and overall survival (OS). Chronic opioid use was defined as an active opioid prescription documented and reconciled by a clinician on postoperative day 90 (POD90).

RESULTS: Among 102 subjects included in the study, 47.1% were taking opioids chronically after surgery. Preoperative opioid use was associated with more than double the odds of chronic postoperative opioid use, whereas older age and ASA class 1-2 were associated with reduced odds. Positive surgical margins, bone graft procedures, and neck dissection were independently associated with poorer prognosis. No statistically significant association between opioid use an RFS and OS was observed.

CONCLUSIONS: These findings suggest that patients with HNACC exhibit several risk factors for chronic opioid use, underscoring the importance of careful opioid prescribing and monitoring in this population.

PMID:42550492 | DOI:10.1093/pm/pnag100

J Natl Cancer Inst. 2026 Aug 4:djag268. doi: 10.1093/jnci/djag268. Online ahead of print.

ABSTRACT

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) and biological aging have been individually associated with increased cancer risks. However, their joint effect on cancer risks remains unknown.

METHODS: We analyzed data from 332,911 participants at baseline in the UK Biobank. We defined CHIP as a pathogenic variant with variant allele fractions ≥2%. Biological aging was assessed by the phenotypic age acceleration (PhenoAgeAccel) and categorized as biologically younger and older. Associations of CHIP and biological aging with 25 cancers were assessed by Cox proportional hazard models. Interactions between CHIP and biological aging were tested on additive and multiplicative scales.

RESULTS: CHIP was associated with higher risks of myeloid malignancies (HR 9.56, 95%CI 8.28-11.03), lung cancer (HR 1.61, 95%CI 1.42-1.82) and oesophageal cancer (HR 1.54, 95%CI 1.18-2.01). Biologically older participants had higher risks of hematologic neoplasms (HR 1.42, 95%CI 1.30-1.55) and various solid tumors compared with biologically younger participants. CHIP carriers who were biologically older had increased risks of hematologic neoplasms (HR 6.56, 95%CI 5.67-7.59) and various solid tumors compared with biologically younger participants without CHIP. The proportion of excess risk attributable to additive interaction was 40% for hematologic neoplasms and 27% for lung cancer. A significant multiplicative interaction was also observed for hematologic neoplasms (P interaction<0.001).

CONCLUSION: CHIP confers substantial cancer risk, amplified when participants are biologically older. Assessing CHIP and biological aging may serve as an effective strategy for early screening and risk stratification for hematologic neoplasms and lung cancer.

PMID:42550479 | DOI:10.1093/jnci/djag268

J Natl Cancer Inst. 2026 Aug 4:djag265. doi: 10.1093/jnci/djag265. Online ahead of print.

ABSTRACT

BACKGROUND: Acute chemotherapy-related gastrointestinal symptoms can limit colorectal cancer treatment. We evaluated electroacupuncture as adjunctive care for acute gastrointestinal symptom burden during chemotherapy.

METHODS: This multicenter, randomized, patient- and assessor-blinded, sham-controlled trial was conducted at 6 tertiary hospitals in China from July 2022 to August 2025. Adults with colorectal cancer and chemotherapy-related gastrointestinal symptoms were randomly assigned 1 1:1 to electroacupuncture, nonpenetrating sham acupuncture, or usual care. Treatments were given once daily for 3 days during chemotherapy. The primary outcome was change in Gastrointestinal Symptom Rating Scale (GSRS) total score from baseline to day 3. Secondary outcomes included rescue medication use and adverse events.

RESULTS: Among 230 randomized patients (mean age, 60.1 years; 54.3% men), 211 (91.7%) completed the 3-day intervention. At day 3, electroacupuncture reduced GSRS total scores more than sham acupuncture (mean difference [MD], -1.54; 95% CI, -2.35 to -0.74; P < .001) and usual care (MD, -1.30; 95% CI, -2.09 to -0.50; P = .001). These differences did not exceed the prespecified minimal clinically important difference of 2.15 points. Electroacupuncture was associated with higher odds of remaining rescue-free than sham acupuncture (adjusted OR, 2.86; 95% CI, 1.23 to 6.63; P = .015) and usual care (adjusted OR, 2.64; 95% CI, 1.16 to 6.01; P = .021). No serious adverse events occurred.

CONCLUSIONS: Electroacupuncture was associated with statistically significant but modest short-term reductions in acute gastrointestinal symptom burden. The between-group differences did not exceed the prespecified clinical-importance threshold and should be interpreted cautiously.

TRIAL REGISTRATION: Chinese Clinical Trials Register identifier ChiCTR2200062317.

PMID:42550476 | DOI:10.1093/jnci/djag265