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PubMedDate not supplied

A pooled-data analysis of three randomized, double-masked, six-month clinical studies comparing the intraocular pressure reducing effect of latanoprost and timolol.

PURPOSE: To compare the intraocular pressure (IOP) reduction by latanoprost and timolol, and to study factors of prognostic value for assessing this reduction. METHODS: We analyzed 829 patients included in three phase 111 studies comparing six months' treatment with 0.005% latanoprost once daily and 0.5% timolol twice daily in patients with open-angle glaucoma or ocular hypertension. Analysis of covariance controlled for differences in baseline IOP and sex was used to assess the IOP reduction. RESULTS: Latanoprost reduced diurnal IOP (average of morning, noon and afternoon assessments) by 7.7 mmHg (31%) and timolol by 6.5 mmHg (26%) after six months of treatment. Thus the diurnal IOP was reduced 1.2 mmHg (18%) more with latanoprost than with timolol (p<0.001). Latanoprost-treated patients showed a further decrease in morning IOP of 0.7 mmHg (9%, p<0.001) from the initial morning IOP reduction obtained at two weeks. No such further decrease in IOP was seen with timolol. Higher baseline diurnal IOP resulted in a larger diurnal reduction during treatment with both drugs (p<0.001). Diurnal IOP in women was reduced 0.7 mmHg (11%) less than males with both drugs (p<0.001). CONCLUSIONS: Latanoprost was more effective than timolol in reducing mean diurnal IOP. The effect after two weeks was maintained for timolol while with latanoprost there was a further, significant IOP reduction from two weeks to six months. Baseline IOP was the only factor of clinical importance found to be of prognostic value for assessing the IOP reduction.

Aged↗
PubMed1978

Rapid hypotonic method for flow cytofluorometry of monolayer cell cultures. Some pitfalls in staining and data analysis.

The rapid hypotonic staining procedure developed by Krishan for DNA determinations by flow cytofluorometry has been proven accurate for in vivo cell samples and for cell lines growing in suspension culture. We show that the unmodified procedure may produce distorted DNA histograms when used for staining cells growing in monolayer cultures, however. To eliminate these distortions, it was necessary to avoid the use of trypsin by staining the attached cells directly, using a hypotonic fluorochrome solution to which nonionic detergent was added. Two sublines of HeLa S3 cells are shown to exhibit major differences in their staining characteristics. By using our revised staining procedure, the two sublines appear to produce very satisfactory DNA histograms. However, in only one subline does the S phase fraction calculated from the histograms agree with the autoradiographical labeling index. Mitotic cells remain intact under these staining conditions, and the principal observed effect of nonionic detergents in this case is to decrease the coefficient of variation of fluorescence intensity.

Cells, Cultured↗
PubMed2005

Anticoagulation therapy in patients with chronic atrial fibrillation: a retrospective claims data analysis.

OBJECTIVES: This study assessed the risk of thrombo embolic events and bleeding complications among atrial fibrillation patients. METHODS: A cohort of patients with chronic non-valvular atrial fibrillation were identified from medical claims (diagnosis codes 427.31 and 427.32). Subjects were identified from 1 January 1998-31 December 2000 and were continuously enrolled for 6 months prior to the first occurring atrial fibrillation medical claim. Cox proportional hazards analysis with time varying covariates was used for the event analysis. RESULTS: Of 6764 subjects retained for analysis, 3541 (52.4%) were exposed to warfarin. Adjusting for baseline characteristics, warfarin exposure was associated with lower likelihood of an arterial thromboembolic event compared to no exposure (HR: 0.710, CI: 0.540-0.934). No benefit was found in the use of warfarin in the prevention of intracranial events (HR: 1.119, CI: 0.929-1.349). Use of warfarin increased the risk of minor bleeding events (HR: 3.600, CI: 2.537-5.109), and all bleeding events (HR: 1.502, CI: 1.289-1.749). CONCLUSIONS: The risk of arterial thromboembolic events was associated with warfarin exposure as expected. An increase in the risk of minor and total bleeding events among patients treated with warfarin was observed. The results of this study suggest that there may be a gap between the clinical trial and coagulation clinic performance of warfarin in reducing the risk of thromboembolic events versus what is achievable in general practice.

Atrial Fibrillation↗
PubMed2004

Healthcare costs and prescription adherence with introduction of thiazolidinedione therapy in Medicaid type 2 diabetic patients: a retrospective data analysis.

OBJECTIVES: Outcomes in patients with type 2 diabetes may vary depending on the antidiabetic medication used. Observational studies of outcomes of diabetes pharmacotherapy are needed to understand the implications of choice of controller in different populations. This study compared differences in total health care costs, medication adherence, and persistence in patients with type 2 diabetes enrolled in the North Carolina Medicaid Program that were newly started on thiazolidinedione (TZD) therapy with patients starting other oral antidiabetics during the same period. In addition differences among the TZDs with respect to these outcomes were examined. METHODS: A total of 1774 patients newly starting TZD therapy between July 2001 and June 2002 were compared to 1709 patients starting other oral antidiabetic medication (metformin or sulfonylureas) for health care costs and outcomes in the post-medication start year. In addition, a sub-group analysis of health care costs in patients starting either TZD (pioglitazone [n = 1086] versus rosiglitazone [N = 688]) was compared. All included patients had complete enrollment for the 24 months of follow-up. Multivariate techniques incorporating health care utilization in the year prior to start of new therapy were utilized to determine the cost impact of one therapy versus another. RESULTS: Results of multiple regression analyses suggest that patients starting TZD have better treatment adherence and persistence in the post-medication start year compared to patients starting other oral antidiabetics (13% increase in Medication Possession Ratios, and 10% increase in therapy persistence index, both p < 0.001). In addition, patients starting TZDs had 16.1% lower total annual health care costs (p < 0.01) compared to patients starting other oral antidiabetics. There were no differences in adherence and cost outcomes between the 2 TZDs. CONCLUSIONS: Introduction of thiazolidinedione therapy in a Medicaid-enrolled type 2 diabetic population was associated with significantly improved treatment adherence, persistence, and lower annual health care costs in the post-start year compared to patients starting other oral antidiabetics.

Administration, Oral↗
PubMed2005

Associations between diet and disease activity in ulcerative colitis patients using a novel method of data analysis.

BACKGROUND: The relapsing nature and varying geographical prevalence of ulcerative colitis (UC) implicates environmental factors such as diet in its aetiology. METHODS: In order to determine which foods might be related to disease activity in UC a new method of dietary analysis was developed and applied. Eighty-one UC patients were recruited at all stages of the disease process. Following completion of a 7 d diet diary, clinical assessment including a sigmoidoscopic examination (scale 0 (normal mucosa) to 6 (very active disease)) was conducted. Food weights for each person were adjusted (divided) by the person's calorific intake for the week. Each food consumed was given a food sigmoidoscopy score (FSS) calculated by summing the products of the (adjusted) weight of food consumed and sigmoidoscopy score for each patient and occurrence of food and dividing by the total (adjusted) weight of the food consumed by all 81 patients. Thus, foods eaten in large quantities by patients with very active disease have high FSSs and vice versa. Foods consumed by <10 people or weighing <1 kg for the whole group were excluded, leaving 75 foods. RESULTS: High FSS foods were characterized by high levels of the anti-thiamin additive sulfite (Mann-Whitney, p < 0.001), i.e. bitter, white wine, burgers, soft drinks from concentrates, sausages, lager and red wine. Caffeine also has anti-thiamin properties and decaffeinated coffee was associated with a better clinical state than the caffeine containing version. Beneficial foods (average intake per week) included pork (210 g), breakfast cereals (200 g), lettuce (110 g), apples and pears (390 g), milk (1250 ml), melon (350 g), bananas (350 g), bacon (120 g), beef and beef products (500 g), tomatoes (240 g), soup (700 g), citrus fruits (300 g), fish (290 g), yogurt (410 g), cheese (110 g), potatoes (710 g) and legumes (120 g). CONCLUSIONS: The dietary analysis method described provides a new tool for establishing relationships between diet and disease and indicates a potentially therapeutic diet for UC.

Adult↗
PubMed2001

The miracle of microarray data analysis.

A report on the tenth Annual Bioinformatics and Genome Research meeting of the Cambridge Healthtech Institute's Beyond Genome 2001 series, San Francisco, USA, 17-19 June 2001.

Humans↗
PubMed2002

Profound effect of normalization on detection of differentially expressed genes in oligonucleotide microarray data analysis.

BACKGROUND: Oligonucleotide microarrays measure the relative transcript abundance of thousands of mRNAs in parallel. A large number of procedures for normalization and detection of differentially expressed genes have been proposed. However, the relative impact of these methods on the detection of differentially expressed genes remains to be determined. RESULTS: We have employed four different normalization methods and all possible combinations with three different statistical algorithms for detection of differentially expressed genes on a prototype dataset. The number of genes detected as differentially expressed differs by a factor of about three. Analysis of lists of genes detected as differentially expressed, and rank correlation coefficients for probability of differential expression shows that a high concordance between different methods can only be achieved by using the same normalization procedure. CONCLUSIONS: Normalization has a profound influence of detection of differentially expressed genes. This influence is higher than that of three subsequent statistical analysis procedures examined. Algorithms incorporating more array-derived information than gene-expression values alone are urgently needed.

Animals↗
PubMed2006

ProCAT: a data analysis approach for protein microarrays.

Protein microarrays provide a versatile method for the analysis of many protein biochemical activities. Existing DNA microarray analytical methods do not translate to protein microarrays due to differences between the technologies. Here we report a new approach, ProCAT, which corrects for background bias and spatial artifacts, identifies significant signals, filters nonspecific spots, and normalizes the resulting signal to protein abundance. ProCAT provides a powerful and flexible new approach for analyzing many types of protein microarrays.

Cyclic AMP-Dependent Protein Kinases↗
PubMed2025

Identifying key palmitoylation-associated genes in endometriosis through genomic data analysis.

BACKGROUND: Palmitoylation, a post-translational lipid modification, has garnered increasing attention for its role in inflammatory processes and tumorigenesis. Emerging evidence suggests a potential association between palmitoylation and inflammatory responses in the pathogenesis of endometriosis. However, the precise mechanistic interplay remains elusive, necessitating further investigation. METHODS: This study integrated transcriptomic analysis and Mendelian randomization (MR) to identify a causal gene set implicated in endometriosis. Differentially expressed genes (DEGs) were first identified in the training dataset using the limma package in R. Weighted gene co-expression network analysis (WGCNA) was subsequently performed, leveraging Single Sample Gene Set Enrichment Analysis (ssGSEA)-derived scores of palmitoylation-related genes (PRGs) as phenotypic traits to identify key modular genes. The intersection of these key modular genes with DEGs yielded a refined gene set. Machine learning algorithms were then applied to further optimize gene selection, followed by external validation, immune infiltration analysis, RNA network construction, and exploration of potential targeted drug candidates. RESULTS: Through a rigorous screening process, VRK1, GALNT12, and RMI1 emerged as key genes associated with palmitoylation, exhibiting significant downregulation in endometriosis samples (P <&#x2009;0.05), indicative of a potential protective role. Immune infiltration analysis further revealed strong correlations between these genes and M2 macrophages as well as resting Natural Killer (NK) cells. Additionally, investigations into the targeted RNA network and drug association profiling provided novel insights, laying the groundwork for future high-quality validation studies. CONCLUSIONS: This study employed a comprehensive analytical framework to identify palmitoylation-associated key genes in endometriosis. The integration of immunoinfiltration analysis, RNA network construction, and drug association profiling offers valuable insights for advancing clinical diagnostics, disease monitoring, and therapeutic development in endometriosis.

Humans↗
PubMed2026

Age-related genomic characterization and therapeutic targets in Chinese breast cancer: insights from prospective targeted sequencing and clinical data analysis.

BACKGROUND: In China, breast cancer occurs at a much younger age and has a higher recurrence and mortality rate. However, with changes in lifestyle, there has been a trend towards an older age of breast cancer incidence in Chinese women. There is a paucity of large-scale next-generation sequencing cohorts for the analysis of genomic characterization in these populations and the identification of potential therapeutic targets. METHODS: To address this gap, we performed prospective targeted sequencing of tumor and blood samples from Chinese patients and collected detailed clinical information. We then categorized patients into two groups based on age (<&#x2009;40&#xa0;years, n&#x2009;=&#x2009;637;&#x2009;&#x2265;&#x2009;40&#xa0;years, n&#x2009;=&#x2009;3442) and proceeded to provide comprehensive descriptions of somatic and germline mutations in both groups. RESULTS: The somatic mutation analysis revealed that PIK3CA, FOXA1, and TBX3 mutations were more prevalent in elderly patients. By leveraging the aforementioned mutational characteristics, we employed our institution's FUTURE-SUPER clinical trial, an umbrella study targeting metastatic breast cancer, to confirm the potential benefits of PI3K-AKT-mTOR pathway inhibitors among elderly patients with breast cancer. Furthermore, TP53 and ERBB2 were more likely to be co-mutated in young women. Patients with TP53 and ERBB2 co-mutation tend to have a poorer prognosis, but through investigation of the SPARK cohort, patients carrying the TP53 and ERBB2 co-mutation are more likely to benefit from immune checkpoint inhibitor combination with tyrosine kinase inhibitor therapy. In our study, we observed a higher frequency of mutations in the DNA homology-dependent recombination pathway in young patients with breast cancer, which was associated with an elevated Ki67 index. Additionally, we confirmed a significant prevalence of germline breast cancer susceptibility gene 1 (gBRCA1) mutations in young patients, whereas germline checkpoint kinase 2 (gCHEK2) mutations are more common in elderly patients. CONCLUSIONS: Our study, which makes use of the largest Chinese breast cancer sequencing cohort, sought to characterize the age-related genomic profile of breast cancer patients and identify novel therapeutic opportunities for individuals with breast cancer.

Adult↗
PubMed2005

The relationship between service intensity and the quality of health care: an exploratory data analysis.

This paper provides an empirical check of some assumptions used to define the quality of care in the health services literature. Specifically, we test (i) whether service intensity is the only important determinant of a provider's quality and (ii) whether higher service intensity always causes higher quality. Using a panel of hospitals from Washington State, we find evidence that rejects both of these assumptions. As a result, further work is needed to postulate a more general definition that does not rely on these assumptions.

Health Services Research↗