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PubMed2001

Determination of indomethacin crystallinity in the presence of excipients using diffuse reflectance near-infrared spectroscopy.

Studies were conducted to investigate the use of near-infrared spectroscopy for determining the crystallinity of indomethacin in multi-component physical mixtures. Three calibration sets of amorphous/crystalline indomethacin physical mixtures were prepared over the composition range of 0-100% crystallinity. Each of the three calibration sets was diluted step-wise with increasing amounts of a single excipient (Avicel, alpha-lactose monohydrate, or sodium chloride). Near-infrared spectra were obtained after each round of dilutions using diffuse reflectance sampling on samples contained in glass vials. After a second derivative transformation, standard curves were constructed by plotting percent indomethacin crystallinity against the ratio of responses at two wavelengths. At dilution levels up to 75% Avicel or lactose, the calibration models demonstrated high coefficients of determination and low standard errors. Dilution with sodium chloride did not produce comparable results and it was necessary to use partial least-squares regression to achieve a similar level of error. These findings were confirmed with separate validation sets. An investigation of instrument error showed that the impact of instrument variability on quantification generally increased as a function of the dilution level.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

Adult blood pressure and climate conditions in infancy: a test of the hypothesis that dehydration in infancy is associated with higher adult blood pressure.

The authors hypothesized that individuals born in the early 20th century who experienced the hottest and driest summers during infancy would be more likely to have suffered severe infant diarrhea and dehydration, and consequently have had higher blood pressure in adulthood, than those who experienced cooler and wetter summers. In this context, these climate data act as an instrumental variable for the association of early-life dehydration with later blood pressure. For 3,964 randomly selected British women born between 1919 and 1940 and whose blood pressure was measured at age 60-79 years, a one standard deviation (1.3 degrees C) higher mean summer temperature in the first year of life was associated with a 1.12-mmHg (95% confidence interval: 0.33, 1.91) higher adult systolic blood pressure, and a one standard deviation higher mean summer rainfall (33.9 mm) was associated with lower systolic blood pressure (-1.65 mmHg, 95% confidence interval: -2.44, -0.85). Equivalent results for diastolic blood pressure were 0.11 (95% confidence interval: -0.65, 0.86) and -0.32 (95% confidence interval: -0.71, 0.05). The climate variables were not associated with potential confounding factors such as socioeconomic position or lifestyle risk factors. These findings provide some evidence in favor of the hypothesis that dehydration in infancy is associated with higher adult blood pressure.

Aged↗

PubMed2000

Assessing the effect of an influenza vaccine in an encouragement design.

Many randomized experiments suffer from noncompliance. Some of these experiments, so-called encouragement designs, can be expected to have especially large amounts of noncompliance, because encouragement to take the treatment rather than the treatment itself is randomly assigned to individuals. We present an extended framework for the analysis of data from such experiments with a binary treatment, binary encouragement, and background covariates. There are two key features of this framework: we use an instrumental variables approach to link intention-to-treat effects to treatment effects and we adopt a Bayesian approach for inference and sensitivity analysis. This framework is illustrated in a medical example concerning the effects of inoculation for influenza. In this example, the analyses suggest that positive estimates of the intention-to-treat effect need not be due to the treatment itself, but rather to the encouragement to take the treatment: the intention-to-treat effect for the subpopulation who would be inoculated whether or not encouraged is estimated to be approximately as large as the intention-to-treat effect for the subpopulation whose inoculation status would agree with their (randomized) encouragement status whether or not encouraged. Thus, our methods suggest that global intention-to-treat estimates, although often regarded as conservative, can be too coarse and even misleading when taken as summarizing the evidence in the data for the effects of treatments.

Journal Article↗

PubMed2026

Comparing genome-wide significant and chemosensory variants as instruments for dietary patterns in Mendelian randomization.

BACKGROUND: Diet is a modifiable risk factor for cardiometabolic disease, yet establishing causality remains challenging. Mendelian randomization (MR) leverages genetic variants as instrumental variables (IVs) to enable causal inference. METHOD: Using two-sample MR, we assessed the causal effects of four principal component-derived dietary patterns (DPs)-Unhealthy, Healthy, Meat-based, Pescatarian-on cardiometabolic outcomes including body mass index, coronary artery disease, blood lipids, blood pressures, type 2 diabetes, fasting glucose and insulin, and glycated haemoglobin. Two sets of IVs were employed: conventional genome-wide significant variants associated with each DP, filtered for pleiotropy and directionality; and biologically informed variants in chemosensory receptor genes, given the role of taste and smell perception in food choice. RESULTS: Using conventional IVs, the Pescatarian DP was associated with reduced fasting insulin (βIVW = -0.10 pmol/L per SD increase in the Pescatarian DP score, 95% confidence interval -0.15, -0.04; P = 1.19 × 10-3), surviving multiple sensitivity analyses. Associations between the Unhealthy DP and elevated blood pressure and glycated haemoglobin should be interpreted cautiously; one of the two filtered IVs was strongly associated with caffeine intake, limiting the attribution of these findings to the DP itself. Chemosensory Receptor IVs yielded null findings, reflecting insufficient power. CONCLUSION: Evidence for causal effects of DPs on cardiometabolic traits was limited, with the strongest support for a protective effect of the Pescatarian DP on fasting insulin. Chemosensory IVs demonstrated limited utility for DPs, likely reflecting the heterogeneous and complex sensory profiles of overall diets. Future efforts should consider guideline-based dietary indices to facilitate interpretability and translation.

Humans↗

PubMed1992

Volume-outcome relationships and in-hospital mortality: the effect of changes in volume over time.

This study examines whether patient outcomes are affected by changes in volume over time within hospitals and whether such effects are consistent with cross-sectional results previously reported in the literature. Investigating the existence of volume-outcome relationships longitudinally for specific groups of patients relates directly to the policy issue of whether, and how, specific inpatient services should be regionalized. The analysis uses up to 8 years of observations from a national sample of nearly 500 community hospitals. Outcomes are measured as inhospital mortality adjusted for case severity. Instrumental variables techniques are used to test and control for the possibility of selective referral. The results suggest that higher volume leads to better outcomes for certain groups of patients. Among the groups studied here, increases in volume lowered adjusted mortality rates for acute myocardial infarction, hernia repair, and respiratory distress syndrome in neonates; correlations were observed between volume and outcome for coronary artery bypass grafts, which seemed to be due primarily to referral patterns; and, no significant findings were found for hip replacements. In general, the effects of volume on outcome appear to be larger when estimated from longitudinal, rather than cross-sectional, data.

Adult↗

PubMed1996

Labor force participation, income, and the use of short-term hospitals by the elderly.

OBJECTIVES: Between 1970 and 1983, the rate at which the elderly were hospitalized grew by more than 40%, whereas the rate of hospitalization for the younger population was fairly stable. Past attempts to explain the different patterns among the young and the old have focused on technology, insurance, health status, and the supply of hospital services. These attempts mostly have been unsuccessful. In this article, the author examines other possible explanations, namely, that the elderly, who experienced a decline in the rate of participation in the labor force and an increase in income over this period, used increases in available time (i.e., nonwork time) and increases in income to seek out and receive greater amounts of health care. METHODS: Using small-area data from the state of North Carolina and using the method of instrumental variables estimation, the author measures the effects of labor force participation and income on the use of short-term hospitals by the elderly. RESULTS: Areas where the elderly have high income and areas where the elderly are less likely to participate in the labor force are areas where the elderly have high rates of hospital use. CONCLUSIONS: The cross-sectional results of this study are consistent with recent labor force participation, income, and hospital-use trends associated with the elderly. The negative relation between hospital use and labor force participation suggests that public policies encouraging work at late ages, such as the scheduled increase in the normal retirement age of Social Security, may lead to a modest dampening of the demand for hospital care among the elderly.

Age Factors↗

PubMed1999

HMO penetration and physicians' earnings.

OBJECTIVES: The goal of this study is to estimate whether cross-sectional variations in enrollment in health maintenance organizations (HMOs) affected physicians' earnings and hourly income in 1990. METHODS: Using data from a nationally representative sample of 4,577 younger physicians (<45 years) conducted in 1991, we estimated a partial reduced-form model of physicians annual income and per hour income. We tested whether HMO penetration is endogenous and used the instrumental variables approach to obtain unbiased estimates. RESULTS: HMO penetration had a negative and statistically significant impact on physicians earnings in 1990. A doubling of the average level of HMO penetration in the market is estimated to reduce annual earnings by 7% to 10.7%, and hourly earnings by approximately 6% to 9%. CONCLUSIONS: It appears that HMOs were successful in reducing physicians' annual and per hour earnings in 1990, presumably through a combination of fewer visits and lower payment rates for people covered by HMOs. Although these results cannot be generalized to all physicians, the experience of a younger cohort of physicians may still be a good indicator of the future effects of HMOs because younger physicians may be more susceptible to market forces than older and more established physicians. Moreover, these results may be somewhat conservative because they reflect market behavior in 1990, several years before the rapid growth and more aggressive market behavior of HMOs in recent years.

Cross-Sectional Studies↗

PubMed1998

Central nervous system infections after military missile head wounds.

OBJECTIVES: To evaluate variables instrumental in central nervous system infections after military missile head wounds, using uni- and multivariate analysis in 964 patients during the 8-year Iran-Iraq War. METHODS: Factors considered in this retrospective study were: the types of projectile, mode of injury, paranasal sinus involvement, number of lobes involved, transventricular injuries, place of exploration (base hospital or Nemazee Hospital), cerebrospinal fluid (CSF) fistulas, Glasgow Coma Scale (GCS) score, retained bone, and retained shell fragments. RESULTS: During the study period, 105 patients (11%) developed central nervous system infections, including 20 abscesses, 1 case of cerebritis, 2 cases of fungus cerebri, and 82 cases of meningitis. gram-negative organisms, especially Klebsiella pneumoniae, were the most frequent offending organisms. Forty-one percent of the 133 deaths were due to infections, but the death rate from infection was only 4.4%. Univariate analysis showed mode of injury, number of lobes involved, ventricular penetration, paranasal sinus involvement, CSF fistulas, place of exploration, GCS score, and retained bone fragments to have significant bearing on the incidence of central nervous system infections. On the other hand, multivariate regression analysis disclosed the following factors each enhancing infection: CSF fistulas (chi2 = 46.526), transventricular injuries (chi2 = 13.4790), and paranasal petrous sinuses involvement (chi2 = 4.2221). When compared with primary exploration at the Nemazee Hospital, both exploration at a base hospital and no exploration at all were associated with increased chances of infection (chi2 = 4.7629 and 8.3220, respectively). Additionally, when tangential, crossed penetrating, and uncrossed penetrating injuries were compared with through-and-through injuries, the uncrossed penetrating mode was associated with less infection (chi2 = 0.1652, 2.6353, and 5.0817, respectively). Only two patients were readmitted for new evidence of infection 3 and 5 months after missile head wounds, one definitely due to and the other on suspicion of CSF fistulas. One hundred and thirty-seven of 587 patients with retained bone fragments were followed a mean of 42 months with no evidence of delayed infection. CONCLUSION: In this study, CSF fistulas and transventricular and paranasal sinus injuries all were associated with increased chances of central nervous system infections after military missile head wounds. Infection rate was lower in penetrating injuries not crossing into another dural compartment. Exploration at the Nemazee Hospital, despite delays in evacuation, had less incidence of infection than surgery at a base hospital within the first 24 hours of injury. Retained bone and metal fragments, a lower GCS score at the time of admission, secondary exploration at the Nemazee Hospital, and number of lobes involved were less important when evaluated in a multivariate regression model.

Adult↗

PubMed2005

Proximal junctional kyphosis in adult spinal deformity following long instrumented posterior spinal fusion: incidence, outcomes, and risk factor analysis.

STUDY DESIGN: To analyze patient outcomes and risk factors associated with proximal junctional kyphosis (PJK) in adults undergoing long posterior spinal fusion. OBJECTIVES: To determine the incidence of PJK and its effect on patient outcomes and to identify any risk factors associated with developing PJK. SUMMARY OF BACKGROUND DATA: The incidence of PJK and its affect on outcomes in adult deformity patients is unknown. No study has concentrated on outcomes of patients with PJK. Risk factors for developing PJK are unknown. METHODS: Radiographic data on 81 consecutive adult deformity patients with minimum 2-year follow-up (average 5.3 years, range 2-16 years) treated with long instrumented segmental posterior spinal fusion was collected. Preoperative diagnosis was adult scoliosis, sagittal imbalance or both. Radiographic measurements analyzed included the sagittal Cobb angle at the proximal junction on preoperative, early postoperative, and final follow-up standing long cassette radiographs. Additional measurements used for analysis included the C7-Sacrum sagittal plumb and the T5-T12 sagittal Cobb. Postoperative SRS-24 scores were available on 73 patients. RESULTS: Incidence of PJK as defined was 26%. Patients with PJK did not have lower outcomes scores. PJK did not produce a more positive sagittal C7 plumb. PJK was more common at T3 in the upper thoracic spine. CONCLUSIONS: Incidence of proximal junctional kyphosis was high, but SRS-24 scores were not significantly affected in patients with PJK. The sagittal C7 plumb was not significantly more positive in PJK patients. No patient, radiographic, or instrumentation variables were identified as risk factors for developing PJK.

Adult↗

PubMed2005

Multilevel spinal growth modulation with an anterolateral flexible tether in an immature bovine model.

STUDY DESIGN: A bovine model was used to evaluate the effects of a multilevel anterolateral flexible tether in a growing spine. OBJECTIVE: To evaluate the radiographic changes in a growing spine with a multilevel anterolateral tether. SUMMARY OF BACKGROUND DATA: Spinal growth modulation has long been considered as a conceptually attractive and elegant possible alternative to arthrodesis in the treatment of idiopathic scoliosis. Although some experimental studies have described spinal growth modulation, few have described a purely mechanical tether. Clinical studies of spinal epiphysiodesis have described inconsistent curve stabilization and/or correction. METHODS: A total of 33 one-month-old male calves underwent a single thoracotomy and placement of vertebral screws at T6-T9. In 11 animals, one screw per level was connected by a 3/16 in. stainless steel cable (single tether). In 11 animals, two screws per level were connected by two cables (double tether). In the remaining 11 animals, single screws in each level were left unconnected (control). After 6 months, the spines were harvested and underwent radiographic analysis. RESULTS: In the control group, there was little change in the coronal and sagittal measurements during the survival period. In the single tether group, there was variable instrumentation fixation and inconsistent creation of coronal deformity, which ranged from 0 degrees to 31 degrees. The double-tether group had more consistent creation of deformity, ranging from 23 degrees to 57 degrees. CONCLUSIONS: Given adequate bony fixation, a flexible lateral spinal tether can affect growth modulation. This technique of growth modulation may serve as a future fusionless method of correction in a growing patient with scoliosis.

Animals↗

PubMed2004

Outcome of patients with cardiac diseases admitted to coronary care units: a report from Lazio, Italy.

BACKGROUND: Coronary care units (CCUs) currently treat a variety of diseases, but little is known about the effectiveness of CCUs on heart conditions other than acute myocardial infarction. OBJECTIVES: The objectives of this study were to evaluate the association between direct admission to CCUs and the risk of inhospital death in patients with heart disease, to investigate factors affecting direct admission to a CCU, and to assess the effect of CCU admission on the use of invasive procedures in patients with arrhythmias. RESEARCH DESIGN: We conducted a retrospective analysis of discharge-abstract data from Lazio, Italy, hospitals. We used logistic regression, propensity score, and instrumental variable analysis to compare inhospital risk of death between patients admitted to CCUs and to ordinary wards in 13 different groups of heart disease. We used linear regression to study the association between the rate of CCU admission and the relative risk of death. RESULTS: The study included 181,049 heart disease admissions, of which 8620 were admitted to CCUs (4.8%). Risk of death was significantly lower in patients admitted directly to CCUs for "acute myocardial infarction" (odds ratio [OR], 0.57), "acute ischemic heart disease" (OR, 0.55), and "other arrhythmias" (OR, 0.56). Mortality ORs were inversely related to the rate of CCU admission. CCU patients with arrhythmias received more invasive procedures (OR, 2.70) than non-CCU patients. CONCLUSION: Direct admission to a CCU is associated with a decrease in mortality for patients with "acute myocardial infarction," "acute heart ischemia," and "other arrhythmias." Patients most likely to benefit from CCU care are preferentially admitted to CCUs. CCUs make larger use of invasive procedures than ordinary wards.

Aged↗

PubMed2006

Access to care and utilization among children: estimating the effects of public and private coverage.

OBJECTIVES: We examine the relationship between health insurance coverage and children's access to and utilization of medical care. Access measures we study are having a usual source of care (USC) and lacking a USC for financial or insurance reasons. We also examine indicators for ambulatory visits, well-child visits, dental visits, emergency room use, and inpatient hospital stays. METHODS: We pool data from the first 7 years of the Medical Expenditure Panel Survey (MEPS), 1996 to 2002. Pooling yields a large sample of children, enabling us to analyze access and utilization using simple descriptive statistics, multivariate analysis, and instrumental variables estimation (IV). IV estimation is of particular interest given the possibility of bias caused by confounding factors (such as child health or parent attitudes) and measurement error in insurance coverage. We also compare estimates from IV linear probability models to estimates from IV probit with residual inclusion. RESULTS: As previous studies have found, public and private coverage are both associated with large increases in access and utilization. Simple mean comparisons suggest that private coverage has a larger effect than does public coverage. Differences between public and private coverage are reduced (and often reversed) when we control for other characteristics of children and their families. IV coverage effect estimates from both linear probability and residual inclusion probit models are substantially greater than conventional estimates across a wide range of access and utilization measures. CONCLUSIONS: Despite concerns that conventional estimates overstate the impact of coverage on access and use, our results suggest that the reverse may be true. One explanation may be that conventional estimates are biased toward zero due to error in the reporting of insurance coverage. The magnitude of the coverage effects we find highlights the importance of reducing uninsurance among children.

Aid to Families with Dependent Children↗

PubMed2006

Evaluation of a mature trauma system.

INTRODUCTION: An effective trauma system should offer patients triaged to a trauma center (TC) a survival advantage and cost-effective treatment. Three questions were asked: 1) Does treatment at a TC versus a nontrauma center (NTC) improve survival? 2) Is the system cost-effective? 3) Is access to the system equitable? METHODS: The 2003 Florida discharge database identified patients with ICD9 codes 800 to 959. Survival risk ratios (SRR) were calculated using 1999-2000 data and ICISS were produced for each code. Using 2003 data, mortality rates were calculated for matched patients at TCs and NTCs. Instrumental variables methodology was used to account for differences in mortality risks of patients triaged to TCs versus NTCs. Logistic regression analysis was used to determine differences in mortality. Charge/cost ratios were analyzed to compute the cost care and cost/life saved. Accessibility to a TC within 85 minutes of injury was assessed. RESULTS: Treatment at a TC was associated with an 18% reduction in mortality. Mean costs of care in TCs and NTCs were $11,910 and $6019, respectively. Dividing the mean cost difference by the reduction in mortality yields a cost of $34,887/life saved. A total of 42% of patients returned to work within 24 months of injury. Using an expected median of 19 years of employment for a 33-year-old individual and proposed state funding figures for the trauma system, a life saved results in an approximate annual cost to the state of between $100 and $500. Currently, 95% of citizens of the state have access to the trauma system within 85 minutes of injury; however, only 38% of trauma patients are triaged to a TC. Addition of 3 TCs would increase these percentages to 99% and 65%. CONCLUSIONS: Triage to a Florida TC is associated with a decreased risk of death. Moreover, cost/life year saved is favorable when compared with societal expenditures for other health problems. Improved deployment of TCs is necessary to optimize access. This assessment methodology is a useful model for evaluation of mature trauma systems.

Adult↗

PubMed2025

The relationship between major depression, attention-deficit hyperactivity disorder and coronary artery disease: A two-sample Mendelian randomization analysis.

Coronary artery disease (CAD) constitutes a principal cause of global morbidity and mortality. Studies imply a connection between mental health disorders, especially major depression (MD) and attention-deficit hyperactivity disorder (ADHD), and the risk of CAD. To investigate the causal influence of genetic susceptibility to MD and attention-deficit/hyperactivity disorder (ADHD) on the risk of CAD, summary-level data from genome-wide association studies involving individuals of European descent were utilized. This analysis identified 11 single-nucleotide polymorphisms (SNPs) associated with MD, 60 SNPs linked to ADHD, and 10 SNPs related to CAD as instrumental variables. The inverse variance weighted method was employed for causal estimation, complemented by sensitivity analyses using MR-Egger regression and the weighted median estimator. A positive causal relationship was identified between MD, attention-deficit/hyperactivity disorder (ADHD), and the risk of CAD [MD: Odds Ratio (OR): 42.66, 95% Confidence Interval (CI): 7.55-241.2; ADHD: OR: 1.055, 95% CI: 1.006-1.106]. No significant causal association was observed between obesity and ADHD. In the multivariable Mendelian randomization (MVMR) analysis, the causal effect of ADHD on CAD was found to be diminished (OR: 1.005, 95% CI: 0.998-1.020), while the impact of body mass index on CAD remained stable (OR: 1.557, 95% CI: 1.459-1.661). This Mendelian randomization study reveals the lack of a consistent association among MD, ADHD, and CAD, suggesting a causal relationship and bidirectional effects between ADHD and obesity.

Humans↗

PubMed2025

Is there a genetic correlation between tinnitus and temporomandibular joint disorder?: A two-sample Mendelian randomization study.

Tinnitus and temporomandibular disorder (TMD) are frequent coexistence of clinical symptoms caused by some systemic diseases in all humans. The observational research results on the correlation between tinnitus and TMD are inconsistent with the reported findings. The purpose of the study was to explore the bidirectional causal relationship between tinnitus and TMD. This study adopts a two-sample Mendelian randomization (MR) methodology. Single-nucleotide polymorphisms from the genome-wide association study were used as instrumental variables to elucidate the bidirectional causal relationship between tinnitus and TMD. The quality of our study was evaluated in accordance with the STROBE-MR guidelines. The MR analysis results showed that tinnitus (yes, most or all of the time now) could be significantly reduced TMD muscular pain linked with fibromyalgia (OR = 0.239, 95% CI: 0.087-0.66, P = .0057), but there was no correlation between other frequencies of tinnitus and the increased risk of TMD in genetic predisposition (all P > .05). The reverse MR analysis revealed no causal relationship and correlation between TMD exposure and increased risk of tinnitus. Sensitivity analysis indicated no horizontal pleiotropy and insignificant heterogeneity. This MR study supports evidence of a correlation between high-frequency tinnitus and reduced risk of TMD muscle pain associated with fibromyalgia. Further research on disease mechanisms are needed to explore the correlation between tinnitus and TMD.

Humans↗

PubMed2025

The causal relationship between antihypertensive drugs and knee osteoarthritis: A drug target Mendelian randomization study.

Recently studies have revealed a robust association between hypertension and knee osteoarthritis (KOA), with patients likely to suffer from both conditions. We employed Mendelian randomization (MR) analysis to assess the impact of antihypertensive medications on KOA, aiming to offer clinical guidance for concomitant drug therapy and identify potential therapeutic targets for KOA. We obtained exposure instruments (instrumental variables) by locating Single-nucleotide polymorphisms related to systolic blood pressure near drug target genes. We then conducted Mendelian randomization analyses between the exposure data and genome-wide association studies data on KOA to evaluate the impact of antihypertensive drugs on KOA. We observed a significant association between decreased expression of the SLC12A2 target gene and a reduced risk of KOA (odds ratio: 0.915, 95% confidence interval: 0.869-0.964, P < .001). In this study, we find that SLC12A2 inhibitors can have a beneficial effect on KOA, and that the SLC12A2 gene may be a potential therapeutic target for KOA. These findings suggest that when treating patients with both hypertension and KOA, clinicians may consider prioritizing the use of SLC12A2 inhibitors.

Humans↗

PubMed2026

Causality between genetically predicted type 2 diabetes and ankle fracture risk: A 2-sample Mendelian randomization study.

It has been proven that diabetes mellitus plays an important role in the occurrence and development of joint fractures. In this study, a 2-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationship between diabetes and ankle fractures. We pooled the data from the published genome-wide association studies. Diabetes mellitus type 2 was derived from pooled genome-wide association study data of 655,666 European individuals (61,714 patients and 1178 controls). Data on ankle fractures were derived from pooled genome-wide association study data in a total of 460,340 European individuals (6479 patients and 453,861 controls). Using diabetes-associated loci as instrumental variables, we used inverse variance weighting, MR-Egger, weighted median, simple multivariate analysis and weighted multivariate analysis to evaluate the association between diabetes and ankle fracture risk. Reverse MR analysis was performed on the Diabetes mellitus type 2 that were found to be causally associated with ankle fractures in forward MR analysis. Sensitivity analysis was used to evaluate the robustness of the results. Statistical analysis showed a significant causal relationship between diabetes and ankle fractures (inverse variance weighting: OR = 1.07, 95% CI = 1.01-1.32, P = .02). Diabetes mellitus is associated with an increased risk of ankle fracture. The results of MR analysis can be used as a guide for the screening of diabetes and ankle fractures, which is helpful to improve the awareness of screening, early diagnosis and early treatment.

Humans↗

PubMed2026

Ferroptosis as a mediator of gut microbiota-driven inflammatory bowel disease: Evidence from genetic analyses.

Gut microbiota dysbiosis is increasingly recognized as a contributor to inflammatory bowel disease (IBD), yet causal relationships and underlying mechanisms remain unclear. Ferroptosis, an iron-dependent form of regulated cell death, plays a key role in epithelial barrier damage and inflammation. This study aimed to determine whether specific gut microbial taxa are causally associated with IBD and whether ferroptosis-related genes mediate this association using Mendelian randomization (MR). Two-sample MR and mediation MR analyses were performed using genome-wide association study summary data from the FinnGen consortium (IBD), the genome-wide association study catalog (473 gut microbial taxa), and the deCODE database (ferroptosis-related genes). Instrumental variables were selected with thresholds of P < 1 × 10-6 for microbes and P < 5 × 10-8 for traits, and linkage disequilibrium clumping (r2 < 0.001) was applied. Twenty-three microbial taxa showed significant causal associations with IBD (e.g., Chromatiales, OR = 0.51; Acetobacterales, OR = 2.61). Several ferroptosis-related genes were linked to IBD risk (e.g., GPX4, STAT3, IDO1). Mediation MR revealed that genes such as MUC1, IDO1, and ADAM23 partially mediated microbial effects on IBD, with mediation proportions up to 7.6%. This study provides novel genetic evidence supporting a gut microbiota-ferroptosis-IBD axis. Ferroptosis-related pathways may partially mediate microbial effects on IBD pathogenesis and represent promising targets for future therapeutic interventions.

Ferroptosis↗