SEARCH · Search PubMed

Results for “Effect Modifier, Epidemiologic”

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.

SourceResearch connectionFrom yearThrough year

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

At least 865 records · Page 48Linked to original sources

PubMed1991

Interpreting the literature in obstetrics and gynecology: II. Logistic regression and related issues.

The goal of epidemiology is accurate measure of the relationship between an exposure and a disease of interest. The control of covariates of the exposure-disease relationship is required to obtain a valid measure. Two types of covariates, confounders and effect modifiers, must be considered. Investigators can design studies to measure and control for the impact of both types of covariates. Design strategies for dealing with covariates include randomization, restriction, and matching. If the impact of a covariate is not eliminated by study design, it must be controlled for during study analysis by use of either stratification or mathematical modeling. Stratified analysis permits an assessment of the exposure-disease relationship for each category of relevant covariates. Although stratification is the best initial approach for controlling covariates, it is often impractical, particularly if more than one or two covariates must be controlled. Multivariate mathematical models are required if multiple covariates are to be controlled. Logistic regression is the mathematical modeling procedure most often used to analyze studies in obstetrics and gynecology. Although there are no uniform rules for building a proper model for regression analysis, useful general strategies are available. It must be emphasized that, though the use of mathematical modeling can control for multiple covariates and thereby improve the chance of obtaining an accurate measure of the exposure-disease relationship, it cannot "fix" data that result from a poorly designed or improperly conducted study.

Gynecology↗

PubMed1989

Human exposure to endogenous N-nitroso compounds: quantitative estimates in subjects at high risk for cancer of the oral cavity, oesophagus, stomach and urinary bladder.

A sensitive procedure to quantitate human exposure to endogenous N-nitroso compounds (NOC) has been developed. It is based on the excretion of N-nitrosoproline (NPRO) and other N-nitrosamino acids in the urine, which are measured as an index of endogenous nitrosation, following ingestion of precursors. The NPRO test has been applied to human subjects in clinical and epidemiological studies, and the kinetics and dietary modifiers of endogenous nitrosation have been investigated. Results obtained after application of the NPRO test to subjects at high risk for cancers of the stomach, oesophagus, oral cavity and urinary bladder are summarized. In most instances, higher exposures to endogenous NOC were found in high-risk subjects, but individual exposure was greatly affected by dietary modifiers or disease state. Vitamin C efficiently lowered the body burden of intragastrically formed NOC. The results point to an aetiological role of NOC in these human cancers and provide an interpretation of epidemiological findings that have shown protective effects of fruits and vegetables against several malignancies.

China↗

PubMed1985

The role of bile acids in colonic carcinogenesis.

Several line of evidence suggest that bile acids may be implicated in the pathogenesis of colonic cancer. A high consumption of fat and animal protein and a low dietary intake of fiber have been shown to be related to the incidence of colonic cancer. From these epidemiologic observations the hypothesis was proposed that the correlation between diet and colon cancer might be explained by the involvement of bile acids. Populations at a high risk of developing cancer were shown to have an increased excretion both of total and bacterially modified bile acids in their feces. Animal studies demonstrated a cocarcinogenic effect of bile acids and experimental diets containing large amounts of fat did not only induce an increased bile acid excretion but also an enhanced tumor formation in the colon. Furthermore, microbial in vitro tests showed a comutagenic activity of secondary bile acids. However, case control studies comparing the fecal bile acid excretion pattern in colonic cancer patients and control subjects failed to show such a clear relationship, which might be explained by rather similar dietary habits within one population and individual differences in sensitivity to environmental factors contributing to the tumor development. Cholecystectomy, leading to an increased exposure of bile acids to the intestinal microflora, has been suggested as a predisposing factor for the development of colonic cancer, but the results of experimental and epidemiologic studies so far are rather inconsistent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Disinfection of drinking water, disinfection by-products and cancer: what about Australia?

Chlorine, commonly used to disinfect drinking water, produces by-products known from animal studies to be carcinogenic and mutagenic. Most epidemiological studies into the possible association between chlorination by-products in drinking water and cancer have been ecological in nature, or have relied on case-control designs based on death certificates. Interpretation of results arising from these studies is limited. Individual levels of toxicant exposure and many potential confounders and effect modifiers are unable to be accounted for in the analyses. At best, these studies generate hypotheses that require more definitive investigation. Misclassification of individuals based on inaccurate assessment of the level of exposure is probable. The few analytic studies able to overcome or minimise these problems suggest a clear link between exposure to chlorinated drinking water and the development of urinary bladder cancer. They also suggest a possible link with rectal cancer. However, these studies have classified subjects by exposure to chlorinated drinking water, rather than to levels of chlorine and its by-products in drinking water. To date, the link between levels of chlorine and its by-products in water, levels of consumption and cancer has not been made. Information on the levels of chlorine and some by-products is available in many water jurisdictions in Australia. Further, epidemiological methods can be employed to quantify water consumption. Case-control studies linking these parameters would help us to understand the magnitude of the risk to human populations and provide a basis to investigate mechanisms for risk reduction.

Australia↗

PubMedDate not supplied

Progress and prospects in youth violence-prevention evaluation.

The evaluation of youth violence-prevention projects using sound methods is very important. Up to now, the evaluation literature has (1) inadequately heeded known epidemiologic patterns of violence, (2) failed to differentiate types of violence, and (3) failed to differentiate the levels of risk-influence addressed by the intervention. The reports in this supplement have considered these past deficiencies. These reports also make some notable advances, such as illustrating the role that efficacy trials can and should play in violence prevention, demonstrating that programs can and should be evaluated and that design characteristics such as random assignment are plausible, balancing the practical and theoretical aspects of violence prevention, and reflecting the importance of the setting on the style and scope of the intervention. The reports and projects also have remaining limitations. Length of planned follow-up is generally quite brief. In some cases the rationale for the intervention is not adequately explained. Some reports do not clarify whether the intervention is intended for all youths or selected high-risk youth. The next steps for these and similar projects are to determine the program impact and implementation, strive for longer follow-up, document conditions that interact with proximal impact on distal outcomes, and further broaden evaluation efforts into modifying situations instead of modifying only individuals. Finally, we must recognize that the goal of evaluation is not to declare all earnest efforts effective, but to determine which efforts merit further consideration.

Adolescent↗

PubMed2002

Association between asbestos exposure, cigarette smoking, myeloperoxidase (MPO) genotypes, and lung cancer risk.

BACKGROUND: As observed in tobacco-associated carcinogenesis, genetic factors such as the polymorphic metabolic/oxidative enzyme myeloperoxidase (MPO) could modulate individual susceptibility to asbestos-associated carcinogenesis. METHODS: RFLP-PCR analysis identified the MPO genotypes in 375 Caucasian lung cancer cases and 378 matched controls. An epidemiological interview elicited detailed information regarding smoking history and occupational history and exposures. RESULTS: Asbestos exposure was associated with a significantly elevated risk estimate (OR = 1.45; 95% CI 1.04-2.02). On stratified analysis, we found the MPO genotypes modified the effect of asbestos exposure on lung cancer risk. Specifically, G/G carriers who were exposed to asbestos had an odds ratio (OR) of 1.72 (95% CI; 1.09-2.66), while A-allele carriers (G/A + A/A) exposed to asbestos exhibited a reduced OR of 0.89 (95% CI; 0.56-1.44). The OR was further reduced to 0.73 (0.49-1.06) for A-allele carriers not exposed to asbestos. A similar trend was observed for the joint effects between the MPO genotypes and pack-years smoking. Next, all three risk factors (MPO genotypes, asbestos exposure, and smoking) were analyzed simultaneously for joint effects. Heavy smokers with the G/G genotype and a history of asbestos exposure demonstrated a statistically significant elevated risk estimate (OR = 2.19; 95% CI 1.16-4.11), while the A-allele carriers with the same exposure profile were at a lower risk for lung cancer (OR = 1.18; 95% CI 0.58-2.38). The A-allele genotypes demonstrated similar protective effects for the other three exposure profiles. CONCLUSIONS: For a similar level of exposure to established carcinogens, individuals with the MPO A-allele genotypes appear to have a reduced risk of lung cancer.

Aged↗

PubMed2002

Chlamydophila pneumoniae infection of human aortic endothelial cells induces the expression of FC gamma receptor II (FcgammaRII).

Chronic endothelial infection is believed to be one of the factors able to cause endothelial cell damage and trigger the onset of human atherosclerosis. Chlamydophila pneumoniae infects endothelial cells and has received special attention because of both epidemiological and experimental evidence supporting its role as a risk factor for atherosclerosis. It is also possible that otherwise independent risk factors for atherosclerosis may have synergistic effects. Immune phenomena, such as the formation of circulating immune complexes (IC) containing modified LDL and corresponding antibodies, have been linked to the development of coronary artery disease. The antibodies involved in the immune response to modified lipoproteins are predominantly of the pro-inflammatory IgG1 and IgG3 subclasses. However, it is difficult to understand how circulating IC could cause endothelial damage and initiate the atherosclerotic process, unless they were formed in the subendothelial space or immobilized by endothelial cells. The last hypothesis would be possible if endothelial cells expressed Fcgamma receptors. Healthy endothelial cells do not express Fcgamma receptors, but endothelial cells infected by a variety of infectious agents do. Thus we decided to investigate whether infection of endothelial cells with C. pneumoniae is also able to cause the expression of Fcgamma receptors. The expression of Fcgamma receptors (CD64, 32, and 16) on human aortic endothelial cells infected with C. pneumoniae for 4, 24, 36, and 48 h was studied by flow cytometry. Twenty-four hours after infection 30-40% of the endothelial cells had detectable inclusion bodies, 8-9% of the total number of cells (approximately 25% of the infected cells) expressed FcgammaRII, and about 1.5-2% (5% of infected cells) expressed FcgammaRI and FcgammaRIII. Double-staining studies confirmed that the expression of FcgammaRII was limited to C. pneumoniae-infected endothelial cells. We conclude that C. pneumoniae infection induces primarily the expression of FcgammaRII by endothelial cells and this may be a significant link between two proposed pathogenic mechanisms involved in the pathogenesis of human atherosclerosis.

Antigen-Antibody Complex↗

PubMed2002

Generation and characterization of six single VP4 gene substitution reassortant rotavirus vaccine candidates: each bears a single human rotavirus VP4 gene encoding P serotype 1A[8] or 1B[4] and the remaining 10 genes of rhesus monkey rotavirus MMU18006 or bovine rotavirus UK.

The global disease burden of rotavirus diarrhea in infants and young children has stimulated interest in the biological and clinical characteristics of these agents, leading to intensive efforts to develop a vaccine. A rhesus rotavirus (RRV)-based quadrivalent vaccine ("RotaShield") was licensed and administered to about 1 million infants and found to be highly effective. However, it was withdrawn because of a link with intussusception. This vaccine was developed according to a modified "Jennerian" approach in which one of the two major outer capsid proteins (VP7) shares neutralization specificity with one of the four epidemiologically important human rotavirus serotypes. The other outer capsid protein (VP4) is derived solely from RRV and is distinct from the VP4 of the four human rotavirus serotypes of epidemiologic importance. In an effort to further increase the immunogenicity of the existing VP7-based RRV quadrivalent vaccine, we generated three single VP4 gene substitution reassortant rotavirus candidate vaccines, each of which bears a single human rotavirus VP4 gene encoding P serotype 1A[8] or 1B[4] specificity while the remaining 10 genes are derived from the rhesus rotavirus. By incorporating one or two of these strains into the quadrivalent vaccine, a pentavalent or hexavalent RRV-based vaccine could be formulated thus providing antigenic coverage not only for VP7 serotype 1, 2, 3 and 4 but also for VP4 serotype 1A[8] or 1B[4], thus possibly augmenting its immunogenicity. Similarly, three single VP4 gene (P1A[8] or P1B[4]) substitution reassortants have also been generated in a background of 10 bovine (UK) rotavirus genes for addition to a second generation UK-based quadrivalent vaccine.

Animals↗

PubMed2004

Obstructive sleep apnoea and stroke.

Many patients with stroke have concomitant sleep apnoea, which can affect recovery potential. Although stroke can lead to the development of sleep-disordered breathing, the current evidence suggests that sleep-disordered breathing may function as a risk factor for stroke. In this review, we focus on the association between obstructive sleep apnoea and stroke reviewing both the epidemiological data with respect to causation and the biological data, which explores pathogenesis. There is convincing evidence to believe that sleep apnoea is a modifiable risk factor for stroke; however, prospective studies are needed to establish the cause-and-effect relationship.

Cardiovascular Diseases↗

PubMed2001

Influence of dietary fat type on arterial thrombosis tendency.

Cardiovascular disease has a multifactorial aetiology, as is illustrated by the existence of numerous risk indicators, many of which can be influenced by the dietary fat type. It should be recalled, however, that only after a cause-and-effect relationship has been established between the disease and a given risk indicator (called a risk factor in that case), modifying this factor can be expected to affect disease morbidity and mortality. In this review, effects of dietary lipids on cardiovascular risk are considered, with special emphasis on modification of arterial thrombosis and platelet thrombotic processes, coagulation and fibrinolysis. Although epidemiological studies do not give entirely consistent results, replacement of dietary saturated by unsaturated fatty acids generally lowers cardiovascular morbidity and mortality. The few (secondary) prevention studies reported so far confirmed this for fish oil or fish oil concentrates, as well as for vegetable oils rich in oleic-, linoleic- or a-linolenic acids. Animal thrombosis models demonstrated that dietary unsaturated fatty acids reduce arterial thrombosis tendency as compared to saturated fatty acids. Using restenosis after percutaneous transluminal coronary angioplasty (PTCA) and occlusion of coronary artery bypass grafts (CABG) as human models of arterial thrombosis, fish oil treatment has been shown to have an anti-thrombotic effect, but results are inconsistent (PTCA) or need confirmation (CABG). Major thrombotic and anti-thrombotic conditions and processes include endothelial integrity, thrombotic functions of blood platelet, coagulation, and fibrinolysis. The dietary fat type can affect endothelial integrity, but results are inconsistent and often difficult to interpret in terms of arterial thrombosis tendency. The same can be concluded for platelet aggregation, especially because results of dietary interventions often depend on the aggregation measuring technique. Novel well-validated methods are required to solve this problem. Dietary fats can affect certain factors involved in blood coagulation and fibrinolysis. Thus, Factor VII activity is increased by the fat content of the diet. However, the dietary fat type seems of less importance. Studies addressing the effect of specific fatty acids on extrinsic clotting and thrombin formation in vivo did not produce consistent results. The same holds for the dietary fatty acid effects on promoters and inhibitors of the plasma fibrinolytic potential. Although trans unsaturated fatty acids may increase cardiovascular risk, this is probably not mediated by effects on arterial thrombosis.

Animals↗

PubMed2006

Associations between catalase phenotype and genotype: modification by epidemiologic factors.

Catalase is an endogenous antioxidant enzyme that neutralizes hydrogen peroxide and is induced by oxidative challenge. A -262C --> T polymorphism in the promoter region of the gene (CAT) is associated with risk of several conditions related to oxidative stress. We sought to determine the functional effects of the CAT polymorphism on enzyme activity in erythrocytes and the potential modifying effects of demographic and lifestyle factors on genotype/phenotype relationships, using specimens and data from controls from breast and prostate cancer studies in Arkansas (n = 420). There was a dose-response reduction in catalase activity by genotype, with geometric means of 115.4 units/mg hemoglobin for those with CC genotypes, 82.1 units/mg for those with CT genotypes, and 73.5 units/mg for those with TT genotypes. Associations were only observed among Caucasians (P < 0.0001), with no effects among African Americans (P = 0.91), and were stronger among women than men, although numbers in stratified analyses were small. Differences in catalase activity by genotype were most pronounced among those in the highest tertiles of consumption of fruits and vegetables (-35%, P = 0.003), with weaker relationships among those who were lower consumers (-21.8%, P = 0.16). Among those with CC genotypes, there was no change in activity by consumption, but there were notable decreases in activity by tertiles of consumption for those with at least one T allele. These data indicate that the CAT -262C --> T polymorphism predicts a portion of catalase phenotype, which may be limited to Caucasians. Associations between genotype and phenotype were modified by dietary factors, illustrating the biochemical complexity of studies of genetic polymorphisms and disease risk.

Adult↗

PubMed2002

A theoretical approach to predicting the success of genetic manipulation of malaria mosquitoes in malaria control.

BACKGROUND: Mosquitoes that have been genetically modified to better encapsulate the malaria parasite Plasmodium falciparum are being considered as a possible tool in the control of malaria. Hopes for this have been raised with the identification of genes involved in the encapsulation response and with advances in the tools required to transform mosquitoes. However, we have only very little understanding of the conditions that would allow such genes to spread in natural populations. METHODS: We present here a theoretical model that combines population genetical and epidemiological processes, thereby allowing one to predict not only these conditions (intensity of transmission, evolutionary cost of resistance, tools used to drive the genes) but also the impact of the spread of refractoriness on the prevalence of the disease. RESULTS: The main conclusions are 1) that efficient transposons will generally be able to drive genes that confer refractoriness through populations even if there is a substantial (evolutionary) cost of refractoriness, but 2) that this will decrease malaria prevalence in the human population substantially only if refractoriness is close to 100% effective. CONCLUSIONS: If refractoriness is less than 100% effective (because of, for example, environmentally induced variation in the effectiveness of the mosquito's immune response), control programmes based on genetic manipulation of mosquitoes will have very little impact on the epidemiology of malaria, at least in areas with intense transmission.

Animals↗

PubMed1995

Optimal case-control matching in practice.

We illustrate modern matching techniques and discuss practical issues in defining the closeness of matching for retrospective case-control designs (in which the pool of subjects already exists when the study commences). We empirically compare matching on a balancing score, analogous to the propensity score for treated/control matching, with matching on a weighted distance measure. Although both methods in principle produce balance between cases and controls in the marginal distributions of the matching covariates, the weighted distance measure provides better balance in practice because the balancing score can be poorly estimated. We emphasize the use of optimal matching based on efficient network algorithms. An illustration is based on the design of a case-control study of hepatitis B virus infection as a possible confounder and/or effect modifier of radiation-related primary liver cancer in atomic bomb survivors.

Adult↗

PubMed2004

Role of Primary Care Clinicians in the Diagnosis and Treatment of LUTS and BPH.

Primary care clinicians are often responsible for the treatment of lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). The combination of the compelling epidemiologic presence of BPH, compromised quality of life due to LUTS, and the availability of highly effective oral therapeutic agents, offers an opportunity for substantial clinical impact in the primary care setting. Evolving management pathways include utilization of both symptom-modifying treatment and disease-modifying treatment. Alpha blockers are excellent to provide symptomatic treatment, but do not alter long-term disease progression. Alpha reductase inhibitors provide therapy by reducing the need for surgical intervention and the incidence of acute urinary retention. The combination of alpha blockers and alpha reductase inhibitors will be best for some patients, typically those with large prostate glands in whom disease progression is most likely. Primary care clinicians will want to become more familiar with recent clinical trails that are shaping emerging therapeutic practice.

Journal Article↗

PubMed2006

MDR1 gene polymorphisms and risk of gingival hyperplasia induced by calcium antagonists.

BACKGROUND: Gingival overgrowth is a common side effect of calcium antagonists. Although the pathogenesis is unknown, several lines of evidence point to a modulation of inflammatory processes. Because the calcium antagonists, albeit to a variable degree, act as inhibitors of P-glycoprotein (P-gp), the gene product of multidrug resistance 1 (MDR1), and inflammation may modify P-gp expression, we analyzed the MDR1 polymorphisms as risk factors for gingival overgrowth induced by calcium antagonists. METHODS: Clinical, laboratory, and anamnestic data including periodontal parameters and use of calcium antagonists were assessed in a cross-sectional epidemiologic investigation (N = 1484). MDR1 polymorphisms in exon 21 G2677T/A and exon 26 C3435T were determined. P-gp expression was detected in gingival tissues. In a matched-pair analysis, 93 subjects using calcium antagonists and 186 not using them were compared. RESULTS: P-gp is expressed in the endothelial layers of blood vessels obtained from healthy or inflamed gingiva. Subjects treated with calcium antagonists had significantly deeper gingival pockets than their drug-free counterparts (P <.0001). This drug-related side effect was associated with the MDR1 2677G/G or G/TA genotype (P <.001) but not with the variant genotype T/TA. This drug effect was proved by multiple regression analysis with adjustment for the risk factors of periodontitis (age, sex, smoking, and education) (P <.0001) and was associated with elevated C-reactive protein levels. The association of probing depth with the MDR1 polymorphism was confirmed in the matched-pair analysis (P <.0001). CONCLUSION: Treatment with calcium antagonists leads to gingival hyperplasia, which is associated with the MDR1 G2677T/A polymorphism. The MDR1 genotype may modify the inflammatory response to the drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects.

The purpose of this double-blind study was to investigate the influence of adding a quercetin-containing supplement to the diet on plasma quercetin status, serum/platelet fatty acid levels and risk factors for heart disease. Healthy men and women with cholesterol levels of 4.0-7.2 mmol/L, consumed four capsules daily of either a quercetin-containing supplement (1.0 g quercetin/d) or rice flour placebo for 28 d. Quercetin intakes were approximately 50-fold greater than the dietary intakes associated with lower coronary heart disease mortality on the basis of epidemiologic studies. Subjects consuming quercetin-containing capsules had plasma quercetin concentrations approximately 23-fold higher than those of subjects consuming the control capsules. Quercetin supplementation did not modify serum total, LDL or HDL cholesterol or triglyceride levels. There were also no alterations of other cardiovascular disease or thrombogenic risk factors, including platelet aggregation, platelet thromboxane B2 production, blood pressure or resting heart rate. Furthermore, there was no effect on the levels of (n-6) or (n-3) polyunsaturated fatty acids in serum or platelet phospholipids. In conclusion, supplementation with quercetin-containing capsules markedly enhanced the plasma quercetin concentration but had no effect on other cardiovascular or thrombogenic risk factors.

Adult↗

PubMed2006

The effect of Ginkgo biloba on functional measures in multiple sclerosis: a pilot randomized controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating neurological disease afflicting young and middle-aged adults, resulting in problems with coordination, strength, cognition, affect, and sensation. OBJECTIVE: The objective of this study was to determine whether a ginkgo extract (EGb 761) improved functional performance in individuals with MS. DESIGN: This study used a double-blind, placebo-controlled, parallel group design. The end point was change between baseline (ie, preintervention) and follow-up evaluation following a regimen of four tablets per day at 60 mg per tablet for four weeks. SETTING: The study was conducted in academic and clinical-based settings. PATIENTS/PARTICIPANTS: Twenty-two individuals with MS were randomly assigned to either the treatment or control condition. Groups did not differ with respect to age, IQ, and education. INTERVENTION: Half of the subjects received 240 mg per day of ginkgo special extract (EGb 761), and the other half received placebo. MAIN OUTCOME MEASURE: The main outcome measures assessed depression (Center for Epidemiologic Studies of Depression Scale [CES-D]), anxiety (State-Trait Anxiety Inventory [STAI]), fatigue (Modified Fatigue Impact Scale [MFIS]); symptom severity (Symptom Inventory [SI]) and functional performance (Functional Assessment of Multiple Sclerosis [FAMS]). RESULTS: The ginkgo group had significantly more individuals showing improvement on four or more measures with improvements associated with significantly larger effect sizes on measures of fatigue, symptom severity, and functionality. The ginkgo group also exhibited less fatigue at follow-up compared with the placebo group. CONCLUSIONS: This exploratory pilot study showed that no adverse events or side effects were reported and that ginkgo exerted modest beneficial effects on select functional measures (eg, fatigue) among some individuals with MS.

Activities of Daily Living↗

PubMed2026

Performance of seven carbapenemase detection assays in Pseudomonas aeruginosa across different epidemiological settings: a multicenter cross-sectional study.

The detection of carbapenemases in Pseudomonas aeruginosa remains challenging due to a great variety of other resistance mechanisms, and most laboratories, therefore, do not test for them. This study aimed to comparatively evaluate seven phenotypic carbapenemase detection assays across three epidemiological settings. A total of 320 P. aeruginosa isolates from three German centers with varying carbapenemase prevalences (5.8%-51.4%), including 113 carbapenemase-producing isolates carrying VIM-2 (n = 58), NDM-1 (n = 19), and GIM-1 (n = 16), underwent whole-genome sequencing as reference to assess seven phenotypic carbapenemase-detection tests: modified- and modified-zinc-supplemented carbapenem inactivation method (mCIM and mzCIM), simplified carbapenem inactivation method (sCIM), Carba NP, imipenem-cloxacillin test (IC-4000), and two imipenem-EDTA disk assays. Of all confirmation assays, mzCIM and sCIM showed the best overall performance for carbapenemase detection (sensitivity/specificity: 100%/94.2% and 99.1%/92.8%), followed by mCIM (93.8%/96.1%). Carba NP achieved the highest specificity (99.0%), but the lowest sensitivity (85.8%). EDTA-based assays and IC-4000 were highly sensitive (96.5%-100%) but less specific (79.7%-87.0%). Negative predictive values were consistently high (≥98%-100%) across all assays and prevalence settings, whereas positive predictive values varied (72.5%-98.0%). Both mzCIM and sCIM exhibited robust performance for carbapenemase detection in P. aeruginosa, representing the most suitable approach across diverse epidemiological settings. Their high negative predictive values indicate that these assays are particularly effective for ruling out carbapenemase production. Furthermore, both assays are cost-effective, simple to perform, and can be readily implemented in any routine microbiology laboratory.IMPORTANCEThis study provides comparative diagnostic accuracy data for seven phenotypic carbapenemase detection assays in Pseudomonas aeruginosa (PA) across different prevalence settings. Modified-zinc-supplemented carbapenem inactivation method (mzCIM) and simplified carbapenem inactivation method (sCIM) are the most robust screening tools and show that local carbapenemase-producing P. aeruginosa (CP-PA) prevalence substantially influences the utility of all evaluated assays.

CIM↗