Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “instrumental variable”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources

Genetic Association Between Sleep Traits and Vertigo Risk: A Two-sample Bidirectional Mendelian Randomization Study.

BACKGROUND: Observational studies suggest the potential association between sleep traits and vertigo; however, causal evidence remains limited. OBJECTIVE: This study aimed to explore the relationship between genetically predicted sleep traits and vertigo with the Mendelian randomization (MR) method. METHODS: Instrumental variables for sleep traits (snoring, sleep duration, insomnia, daytime sleepiness, daytime napping, and chronotype) were adopted from genomewide association studies (GWAS) data of European ancestry from UK Biobank. The summary-level datasets of vertigo were retrieved from the GWAS of FinnGen. Inversevariance weighted (IVW) method was adopted as the main analysis. RESULTS: IVW analysis revealed a significant association between genetically predicted daytime napping (OR = 1.51, 95% CI =1.08-2.12, P = 0.016) and chronotype (OR = 1.13, 95% CI =1.01-1.26, P = 0.033), both of which were associated with an increased risk of vertigo. However, we did not find evidence for a causal effect of snoring, overall sleep duration, long sleep duration, short sleep duration, insomnia, and excessive daytime sleepiness on vertigo. No reverse causality was detected. CONCLUSION: Our findings suggest that abnormal sleep patterns may serve as risk factors for vertigo disorders and offer opportunities for the prevention and management of vertigo disorders.

Humans↗

Mendelian Randomization Using a Japanese GWAS Identifies an HLA-Linked Causal Effect of Chronic Hepatitis B on Cholangiocarcinoma Risk.

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant cancer that develops in the bile ducts. Its incidence is particularly high in East Asian populations, but the underlying genetic factors remain unclear. To investigate potential risk factors for CCA, we conducted a Mendelian randomization study to infer causality. METHODS: Using large-scale genome-wide association study data from the BioBank Japan resource, we systematically investigated the causal effects of genetic predisposition to seven conditions, chronic hepatitis B (CHB), chronic hepatitis C, autoimmune hepatitis, type 1 diabetes, type 2 diabetes, chronic gastritis, and chronic pancreatitis, on CCA risk. RESULTS: Our analysis reveals a significant association between genetic susceptibility to CHB with a 24% higher likelihood of developing CCA than non-susceptible individuals (Inverse-Variance Weighted Odds Ratio = 1.24, 95% Confidence Interval: 1.08-1.42; p = 0.002). This genetic association is significantly driven by instrumental variables enriched in the immune-regulatory HLA class II region (6p21), suggesting a plausible biological mechanism. For the primary outcome (CCA), statistical significance was assessed across seven exposures at a Bonferroni-corrected threshold (two-sided p<0.0071). Notably, the CHB-CCA association remains significant after correction. This primary finding is strongly supported by comprehensive sensitivity analyses that showed no evidence of confounding by horizontal pleiotropy or heterogeneity. Conversely, no significant causal effects on CCA were identified for the other six conditions. CONCLUSIONS: Our MR analysis supports a causal role of HBV infection in CCA development, highlighting the importance of targeted HBV screening and surveillance.

Female↗

Effect of inflammatory cytokines and plasma metabolome on OSA: a bidirectional two- sample Mendelian randomization study and mediation analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep disorder. Inflammatory factors and plasma metabolites are important in assessing its progression. However, the causal relationship between them and OSA remains unclear, hampering early clinical diagnosis and treatment decisions. METHODS: We conducted a large-scale study using data from the FinnGen database, with 43,901 cases and 366,484 controls for our discovery MR analysis. We employed 91 plasma proteins from 11 cohorts (totaling 14,824 participants of European descent) as instrumental variables (IVs). Additionally, we conducted a GWAS involving 13,818 cases and 463,035 controls to replicate the MR analysis. We primarily used the IVW method, supplemented by MR Egger, weighted median, simple mode, and weighted mode methods. Meta-analysis was used to synthesize MR findings, followed by tests for heterogeneity, pleiotropy, and sensitivity analysis (LOO). Reverse MR analysis was also performed to explore causal relationships. RESULTS: The meta-analysis showed a correlation between elevated Eotaxin levels and an increased risk of OSA (OR=1.050, 95% CI: 1.008-1.096; p < 0.05). Furthermore, we found that the increased risk of OSA could be attributed to reduced levels of X-11849 and X-24978 (decreases of 7.1% and 8.4%, respectively). Sensitivity analysis results supported the reliability of these findings. CONCLUSIONS: In this study, we uncovered a novel biomarker and identified two previously unknown metabolites strongly linked to OSA. These findings underscore the potential significance of inflammatory factors and metabolites in the genetic underpinnings of OSA development and prognosis.

Female↗

Exploring the causal relationship between plasma proteins and postherpetic neuralgia: a Mendelian randomization study.

BACKGROUND: The proteome represents a valuable resource for identifying therapeutic targets and clarifying disease mechanisms in neurological disorders. This study investigated potential causal relationships between plasma proteins and postherpetic neuralgia (PHN). METHODS: We conducted a two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary statistics from the Decode Genetics dataset (4,907 plasma proteins) and the FinnGen database (490 PHN cases and 435,371 controls). Instrumental variables (IVs) were selected based on relevance, independence, and exclusivity. Causal associations were assessed using inverse-variance weighted (IVW), MR-Egger regression, simple mode, weighted mode, and weighted median methods. Sensitivity analyses, including leave-one-out tests, evaluated result robustness, while colocalization analysis examined shared causal variants between traits. RESULTS: Eight plasma proteins showed significant associations with PHN (PFDR < 0.05). Higher levels of ATRN, PIANP, and CD48 correlated with increased PHN risk, whereas elevated KIR2DL5A, GPI, SEMG2, EIF4B, and HFE2 levels were associated with reduced risk. Sensitivity analyses supported these findings and excluded genetic pleiotropy as a major confounding factor. Colocalization analysis did not detect shared causal variants (PPH4 < 0.8). CONCLUSION: These results suggest a potential causal role for eight plasma proteins in PHN pathogenesis. While these proteins may serve as biomarkers or therapeutic candidates, further validation is required. This study advances understanding of PHN pathophysiology and supports future investigations into diagnostic and therapeutic strategies.

Mendelian randomization↗

Home and community-based waivers for disabled adults: program versus selection effects.

This paper addresses whether changes in expenditures from participation in a Medicaid home and community-based waiver are due to selection effects or true program effects. We examined North Carolina Medicaid claims data (FY1998 to FY2000) for disabled or blind adults likely to need facility-based care using two-part expenditure models for nursing home, inpatient, and total expenditures. Instrumental variables estimation controlled for selection into the program. Although no savings in total costs were found in this sample, significant decreases were found in the level of nursing home and hospital inpatient expenditures for waiver participants, achieving the goals of the home and community-based waiver program.

Adult↗

The impact of SCHIP on insurance coverage of children.

In this paper we use the Medical Expenditure Panel Survey between 1996 and 2002 to investigate the impact of the State Children's Health Insurance Program (SCHIP) on insurance coverage for children. We explore a range of alternative estimation strategies, including instrumental variables and difference-in-trends models. We find that SCHIP had a significant impact in decreasing uninsurance and increasing public insurance for both children targeted by SCHIP and those eligible for Medicaid. With respect to changes in private coverage our results are less conclusive: some specifications resulted in no significant effect of SCHIP on private insurance coverage, while others showed significant decreases in private insurance. Associated estimates of SCHIP crowd-out had wide confidence intervals and were sensitive to estimation strategy.

Adult↗

Medicaid and service use among homeless adults.

This paper examines the effect of Medicaid recipiency on the level and site of medical service use among homeless single men and women in New York City. Simple regressions of Medicaid on service use indicate that Medicaid significantly increases the likelihood that homeless individuals receive services, especially emergency and inpatient hospital services. In further analyses that control for health status, use instrumental variables procedures, and examine differences between a similar population in 1985 and 1987, we find that Medicaid neither increases nor diminishes access to emergency rooms. We find some evidence suggesting that Medicaid does improve access to nonhospital medical care.

Adult↗

How hospital ownership affects access to care for the uninsured.

This article addresses the effect of hospital ownership on the delivery of service to uninsured patients. It compares the volume of uninsured patients treated in for-profit and nonprofit hospitals by regarding hospital ownership and service as endogenous. Instrumental variable estimates are used to predict the percentage of patients who are uninsured, controlling for hospital ownership and service. The study shows that when for-profit and nonprofit hospitals are located in the same area, they serve an equivalent number of uninsured patients, but for-profit hospitals indirectly avoid the uninsured by locating more often in better-insured areas.

Chi-Square Distribution↗

[A mobile reanimation model (reanimationmobile) for initial newborn infant care].

A mobile unit for reanimation of the newborn is reported to be used alternatively in the deliveryroom or in the surgical tract. The following adventages are achieved: a large working plate easily accessible from three sides, a complete and variable instrumentation, an efficent warmth supply and the possibility for easy cleaning and desinfection.

Disinfection↗

Differences between generalists and mental health specialists in the psychiatric treatment of Medicare beneficiaries.

OBJECTIVE: To examine differences between the general medical and mental health specialty sectors in the expenditure and treatment patterns of aged and disabled Medicare beneficiaries with a physician diagnosis of psychiatric disorder. DATA SOURCES: Based on 1991-1993 Medicare Current Beneficiary Survey data, linked to the beneficiary's claims and area-level data on provider supply from the Area Resources File and the American Psychological Association. STUDY DESIGN: Outcomes examined included the number of psychiatric services received, psychiatric and total Medicare expenditures, the type of services received, whether or not the patient was hospitalized for a psychiatric disorder, the length of the psychiatric care episode, the intensity of service use, and satisfaction with care. We compared these outcomes for beneficiaries who did and did not receive mental health specialty services during the episode, using multiple regression analyses to adjust for observable population differences. We also performed sensitivity analyses using instrumental variables techniques to reduce the potential bias arising from unmeasured differences in patient case mix across sectors. PRINCIPAL FINDINGS: Relative to beneficiaries treated only in the general medical sector, those seen by a mental health specialist had longer episodes of care, were more likely to receive services specific to psychiatry, and had greater psychiatric and total expenditures. Among the elderly persons, the higher costs were due to a combination of longer episodes and greater intensity; among the persons who were disabled, they were due primarily to longer episodes. Some evidence was also found of higher satisfaction with care among the disabled individuals treated in the specialty sector. However, evidence of differences in psychiatric hospitalization rates was weaker. CONCLUSIONS: Mental health care provided to Medicare beneficiaries in the general medical sector does not appear to substitute perfectly for care provided in the specialty sector. Our study suggests that the treatment patterns in the specialty sector may be preferred by some patients; further, earlier findings indicate geographic barriers to obtaining specialty care. Thus, the matching of service use to clinical need among this vulnerable population may be inappropriate. The need for further research on outcomes is indicated.

Aged↗

Left main coronary artery disease. Clinical and angiographic features. A retrospective study regarding two groups of patients with left main coronary artery disease and three-vessel disease.

BACKGROUND: The aim of this study was to assess the ability of clinical and instrumental features to identify patients with left main coronary artery disease (LMCD) compared with a three-vessel coronary artery disease group. METHODS: A cohort of 70 patients with LMCD was matched with another one of 66 patients with three-vessel disease. A history of angina before angiography was similar in both groups; the higher degrees of stable angina and the forms of unstable angina were moderately prevalent in the group with LMCD. RESULTS: In the last subgroup a significantly reduced incidence of previous acute myocardial infarction (AMI) was observed (p < 0.05). The resting electrocardiogram (ECG) showed higher incidence of atrial fibrillation (fa) and left bundle branch block (BBS) in the subjects with LMCD, with a statistic value (p < 0.05). The exercise test performed by a lot of patients appeared equally positive for inducible ischemia in the 2 groups. Significantly higher exercise peak load was achieved by the patients with three-vessel disease (p < 0.05). The coronary angiography showed a prevalence of right dominant circulation in the 2 groups; significantly the collateral circulation was more represented in the subjects with three-vessel disease (p < 0.05). Most patients with LMCD underwent a bypass coronary artery graft surgery (CABG surgery) more frequently than the ones with three-vessel disease (p < 0.01). In the former group the cardiovascular mortality within an average 2-year follow-up proved higher as to the latter group even if without statistic significance. CONCLUSIONS: Nevertheless this retrospective study showed some limitations. Particularly the incidence of clinical and instrumental variables and their capacity to differentiate LMCD patients from those with three-vessel disease were not demonstrated.

Acute Disease↗

The effects of managed care and prospective payment on the demand for hospital nurses: evidence from California.

OBJECTIVE: To examine the effects of managed care and the prospective payment system on the hospital employment of registered nurses (RNs), licensed practical nurses (LPNs), and aides. DATA SOURCES: Hospital-level data from California's Office of Statewide Health Planning and Development (OSHPD) Hospital Disclosure Reports from 1976/1977 through 1994/1995. Additional information is extracted from OSHPD Patient Discharge Data. STUDY DESIGN: Multivariate regression equations are used to estimate demand for nurses as a function of wages, hospital output, technology level, and ownership. Separate equations are estimated for RNs, LPNs, and aides for all daily services and for medical-surgical units. Instrumental variables are used to correct for the endogeneity of wages, and fixed effects are included to control for unobserved differences across hospitals. PRINCIPAL FINDINGS: HMOs are associated with a lower use of LPNs and aides, and HMOs do not have a statistically significant effect on the demand for RNs. Managed care has a smaller effect on nurse staffing in medical-surgical units than in daily service units as a whole. The prospective payment system does not have a statistically significant effect on nurse staffing. CONCLUSIONS: HMOs have affected nursing employment both because HMOs have reduced the number of discharges and because of a direct relationship between HMO penetration and the demand for LPNs and aides. Contrary to press reports, LPNs and aides have been affected more by HMOs than have registered nurses.

California↗

The optimal outcomes of post-hospital care under medicare.

OBJECTIVE: To estimate the differences in functional outcomes attributable to discharge to one of four different venues for post-hospital care for each of five different types of illness associated with post-hospital care: stroke, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), hip procedures, and hip fracture, and to estimate the costs and benefits associated with discharge to the type of care that was estimated to produce the greatest improvement. STUDY SETTING/DATA SOURCES: Consecutive patients with any of the target diagnoses were enrolled from 52 hospitals in three cities. Data sources included interviews with patients or their proxies, medical record reviews, and the Medicare Automated Data Retrieval System. ANALYSIS: A two-stage regression model looked first at the factors associated with discharge to each type of post-hospital care and then at the outcomes associated with each location. An instrumental variables technique was used to adjust for selection bias. A predictive model was created for each patient to estimate how that person would have fared had she or he been discharged to each type of care. The optimal discharge location was determined as that which produced the greatest improvement in function after adjusting for patients' baseline characteristics. The costs of discharge to the optimal type of care was based on the differences in mean costs for each location. DATA COLLECTION/EXTRACTION METHODS: Data were collected from patients or their proxies at discharge from hospital and at three post-discharge follow-up times: six weeks, six months, and one year. In addition, the medical records for each participant were abstracted by trained abstractors, using a modification of the Medisgroups method, and Medicare data were summarized for the years before and after the hospitalization. PRINCIPAL FINDINGS: In general, patients discharged to nursing homes fared worst and those sent home with home health care or to rehabilitation did best. Because the cost of rehabilitation is high, greater use of home care could result in improved outcomes at modest or no additional cost. CONCLUSIONS: Better decisions about where to discharge patients could improve the course of many patients. It is possible to save money by making wiser discharge planning decisions. Nursing homes are generally associated with poorer outcomes and higher costs than the other post-hospital care modalities.

Activities of Daily Living↗

Uninsured status and out-of-pocket costs at midlife.

OBJECTIVE: To investigate how baseline health insurance coverage affects subsequent out-of-pocket costs and utilization of health services over a two-year period. DATA SOURCE: The first two waves of the Health and Retirement Study, a nationally representative survey of the noninstitutionalized population, ages 51 to 61 at baseline. Interviews were conducted in 1992 and 1994. Our sample consisted of 7,018 respondents who did not report public insurance as their sole source of coverage at baseline. STUDY DESIGN: We compared self-reports of physician visits, hospitalizations, and out-of-pocket health care costs, measured as payments to physicians, hospitals, and nursing homes, by type of insurance coverage at the beginning of the period. We estimated multivariate models of costs and service use to control for individual health, demographic, and economic characteristics and employed instrumental variable techniques to account for the endogeneity of insurance coverage. PRINCIPAL FINDINGS: Controlling for personal characteristics and accounting for the endogeneity of insurance coverage, persons at midlife with job-related health benefits went on to spend only about $50 per year less in out-of-pocket payments for health services than persons who lacked health insurance at the beginning of the period. However, they spent about $650 more per year in insurance premiums than the uninsured. The uninsured used relatively few health services, except when they were seriously ill, in which case they were likely to acquire public insurance. CONCLUSIONS: The medically uninsured appear to avoid substantial out-of-pocket health care costs by using relatively few health services when they are not seriously ill, and then relying upon health care safety nets when they experience medical problems. These results suggest that the main impact of non-insurance at midlife is not to place the locus of responsibility for costly health care upon individuals. Instead, it discourages routine care and transfers the costs of care for severe health events to other payers. Our findings on the high cost of employment-based coverage are consistent with evidence that the proportion of workers accepting health benefits from employers has been declining in recent years.

Age Factors↗

Does physician specialty affect the survival of elderly patients with myocardial infarction?

OBJECTIVE: To determine the effect of treatment by a cardiologist on mortality of elderly patients with acute myocardial infarction (AMI, heart attack), accounting for both measured confounding using risk-adjustment techniques and residual unmeasured confounding with instrumental variables (IV) methods. DATA SOURCES/STUDY SETTING: Medical chart data and longitudinal administrative hospital records and death records were obtained for 161,558 patients aged > or =65 admitted to a nonfederal acute care hospital with AMI from April 1994 to July 1995. Our principal measure of significant cardiologist treatment was whether a patient was admitted by a cardiologist. We use supplemental data to explore whether our analysis would differ substantially using alternative definitions of significant cardiologist treatment. STUDY DESIGN: This retrospective cohort study compared results using least squares (LS) multivariate regression with results from IV methods that accounted for additional unmeasured patient characteristics. Primary outcomes were 30-day and one-year mortality, and secondary outcomes included treatment with medications and revascularization procedures. DATA COLLECTION/EXTRACTION METHODS: Medical charts for the initial hospital stay of each AMI patient underwent a comprehensive abstraction, including dates of hospitalization, admitting physician, demographic characteristics, comorbid conditions, severity of clinical presentation, electrocardiographic and other diagnostic test results, contraindications to therapy, and treatments before and after AMI. PRINCIPAL FINDINGS: Patients admitted by cardiologists had fewer comorbid conditions and less severe AMIs. These patients had a 10 percent (95 percent CI: 9.5-10.8 percent) lower absolute mortality rate at one year. After multivariate adjustment with LS regression, the adjusted mortality difference was 2 percent (95 percent CI: 1.4-2.6 percent). Using IV methods to provide additional adjustment for unmeasured differences in risk, we found an even smaller, statistically insignificant association between physician specialty and one-year mortality, relative risk (RR) 0.96 (0.88-1.04). Patients admitted by a cardiologist were also significantly more likely to have a cardiologist consultation within the first day of admission and during the initial hospital stay, and also had a significantly larger share of their physician bills for inpatient treatment from cardiologists. IV analysis of treatments showed that patients treated by cardiologists were more likely to undergo revascularization procedures and to receive thrombolytic therapy, aspirin, and calcium channel-blockers, but less likely to receive beta-blockers. CONCLUSIONS: In a large population of elderly patients with AMI, we found significant treatment differences but no significant incremental mortality benefit associated with treatment by cardiologists.

Age Factors↗

Expectations among the elderly about nursing home entry.

OBJECTIVE: To assess whether the covariates that explain expectations of nursing home entry are consistent with the characteristics of those who enter nursing homes. DATA SOURCES: Waves 1 and 2 of the Assets and Health Dynamics Among the Oldest Old (AHEAD) survey. STUDY DESIGN: We model expectations about nursing home entry as a function of expectations about leaving a bequest, living at least ten years, health condition, and other observed characteristics. We use an instrumental variables and generalized least squares (IV-GLS) method based on Hausman and Taylor (1981) to obtain more efficient estimates than fixed effects, without the restrictive assumptions of random effects. PRINCIPAL FINDINGS: Expectations about nursing home entry are reasonably close to the actual probability of nursing home entry. Most of the variables that affect actual entry also have significant effects on expectations about entry. Medicaid subsidies for nursing home care may have little effect on expectations about nursing home entry; individuals in the lowest asset quartile, who are most likely to receive these subsidies, report probabilities not significantly different from those in other quartiles. Application of the IV-GLS approach is supported by a series of specification tests. CONCLUSIONS: We find that expectations about future nursing home entry are consistent with the characteristics of actual entrants. Underestimation of risk of nursing home entry as a reason for low levels of long-term care insurance is not supported by this analysis.

Activities of Daily Living↗

Data-based modelling and proportional-integral-plus (pip) control of nitrate in an activated sludge benchmark.

This paper presents the result of an investigation into the Proportional Integral Plus (PIP) control of nitrate in the second zone of an activated sludge benchmark. A data-based reduced order model is used as the control model and identified using the Simplified Refined Instrumental Variable (SRIV) identification and estimation algorithm. The PIP control design is based on the Non Minimum State Space (NMSS) form and State Variable Feedback (SVF) methodology. The PIP controller is tested against dynamic load disturbances and compared with the response of a well tuned PI controller.

Benchmarking↗

Impregnated nets or ddt residual spraying? Field effectiveness of malaria prevention techniques in solomon islands, 1993-1999.

The incidence of malaria in Solomon Islands has been decreasing since 1992. The control program used a combination of methods including DDT residual house spraying and insecticide-treated mosquito nets. To determine how much each method contributed to malaria control, data were analyzed on monthly incidence and on control activities for 41 of 110 malaria zones over the same time period (January 1993 to August 1999). After correction for endogeneity, then spraying, insecticide treatment of nets, and education about malaria are all independently associated with reduction in incident cases of malaria or fever, while larviciding with temephos is not. The evidence suggests that although impregnated bed nets cannot entirely replace DDT spraying without substantial increase in incidence, their use permits reduced DDT spraying. The paper shows that non-experimental data can be used to infer causal links in epidemiology, provided that instrumental variables are available to correct for endogeneity.

Bedding and Linens↗