3 research outputs found
Contributions of Higher Resolution Observational Evidence from Electronic Health Records to Understand the Causal Relevance of Blood Lipids to Heart Failure and Atrial Fibrillation
Heart failure (HF) and atrial fibrillation (AF) are increasingly prevalent due to aging populations, and both diseases have a big economic and healthcare burden globally. To date, there is no primary prevention specific to healthy populations. Blood lipids (i.e., LDL-C, HDL-C, and TG), which are involved with pathophysiological mechanisms of HF and AF, might play a role in the origin of both diseases. Therefore, the potential causal relevance of blood lipids to HF and AF should be investigated. Linkage electronic health records (EHRs) provide an opportunity to investigate the association between blood lipids and the incidence of HF and AF, as these records contain large sample sizes (e.g., n>1 million) with a wide range of diseases and biomarkers routinely recorded in clinical practice. Challenges include structuring the data into a research-ready format, accurately defining outcomes, and handling missing data. The data used in this thesis is from the CALIBER platform, which links routinely collected EHRs from general practices, hospital admission, and the death registries of 3 million patients in England from 1997 to 2016. In this thesis, I (1) constructed cohorts from EHRs and ensured the validity of the cohorts and (2) examined the association between blood lipids and the incidence of HF and AF using the EHR population-based cohort design. The observed findings were then compared to the results from meta-regression of trials on lipid-lowering drugs and those from a Mendelian randomisation approach, and then I (3) assessed the predictive value of adding blood lipids in the risk prediction of incident HF and AF. Additionally, I developed the model for the prediction of 10-year risk of newly occurring HF and AF. Taken together, these findings have a valuable implementation. For future research, my findings can be a basis for developing a new drug to fight against HF and AF. For clinical application, my findings can inform clinicians whether blood lipids should be targeted and what levels are needed to protect people from HF and AF. Besides, my results can inform clinicians to monitor their patients for the developing of HF and AF
The Effect of Hyperoxemia on Neurological Outcomes of Adult Patients: A Systematic Review and Meta-Analysis
Hyperoxemia commonly occurs in clinical practice and is often left untreated. Many studies have shown increased mortality in patients with hyperoxemia, but data on neurological outcome in these patients are conflicting, despite worsened neurological outcome found in preclinical studies. To investigate the association between hyperoxemia and neurological outcome in adult patients, we performed a systematic review and meta-analysis of observational studies. We searched MEDLINE, Embase, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature, and ClinicalTrials.gov from inception to May 2020 for observational studies correlating arterial oxygen partial pressure (PaO2) with neurological status in adults hospitalized with acute conditions. Studies of chronic pulmonary disease or hyperbaric oxygenation were excluded. Relative risks (RRs) were pooled at the study level by using a random-effects model to compare the risk of poor neurological outcome in patients with hyperoxemia and patients without hyperoxemia. Sensitivity and subgroup analyses and assessments of publication bias and risk of bias were performed. Maximum and mean PaO2 in patients with favorable and unfavorable outcomes were compared using standardized mean difference (SMD). Of 6255 records screened, 32 studies were analyzed. Overall, hyperoxemia was significantly associated with an increased risk of poor neurological outcome (RR 1.13, 95% confidence interval [CI] 1.05-1.23, statistical heterogeneity I2 58.8%, 22 studies). The results were robust across sensitivity analyses. Patients with unfavorable outcome also showed a significantly higher maximum PaO2 (SMD 0.17, 95% CI 0.04-0.30, I2 78.4%, 15 studies) and mean PaO2 (SMD 0.25, 95% CI 0.04-0.45, I2 91.0%, 13 studies). These associations were pronounced in patients with subarachnoid hemorrhage (RR 1.34, 95% CI 1.14-1.56) and ischemic stroke (RR 1.41, 95% CI 1.14-1.74), but not in patients with cardiac arrest, traumatic brain injury, or following cardiopulmonary bypass. Hyperoxemia is associated with poor neurological outcome, especially in patients with subarachnoid hemorrhage and ischemic stroke. Although our study cannot establish causality, PaO2 should be monitored closely because hyperoxemia may be associated with worsened patient outcome and consequently affect the patient's quality of life
Effectiveness of Modified Premedication Regimen on Hypersensitivity Reactions in Colorectal Cancer Patients Receiving FOLFOX Chemotherapy: A Pilot Study
āļāļāļāļąāļāļĒāđāļ āļ§āļąāļāļāļļāļāļĢāļ°āļŠāļāļāđ: āļāļēāļĢāļĻāļķāļāļĐāļēāļāļģāļĢāđāļāļāļāļĩāđāļĄāļĩāļ§āļąāļāļāļļāļāļĢāļ°āļŠāļāļāđāđāļāļ·āđāļāļĻāļķāļāļĐāļēāļāļ§āļēāļĄāļāļļāļāđāļĨāļ°āļāļąāļāļāļąāļĒāđāļŠāļĩāđāļĒāļāļāļāļāļāļēāļĢāđāļāļīāļāļāļāļīāļāļīāļĢāļīāļĒāļēāļ āļđāļĄāļīāđāļ§āđāļāļīāļ āđāļĨāļ°āđāļāļ·āđāļāđāļāļĢāļĩāļĒāļāđāļāļĩāļĒāļāļāļĢāļ°āļŠāļīāļāļāļīāļāļĨāļāļāļāļāļēāļĢāđāļŦāđāļĒāļēāļāļģāļāđāļāļāđāļŦāđāđāļāļĄāļĩāļāļģāļāļąāļāļĢāļ°āļŦāļ§āđāļēāļāļŠāļđāļāļĢāļāļąāđāļāđāļāļīāļĄāđāļĨāļ°āļŠāļđāļāļĢāļāļĩāđāļĄāļĩāļāļēāļĢāļāļĢāļąāļāļāļĢāļļāļ āļ§āļīāļāļĩāļāļēāļĢāļĻāļķāļāļĐāļē: āļāļđāđāļ§āļīāļāļąāļĒāđāļāđāļāļģāļāļēāļĢāļĻāļķāļāļĐāļēāđāļāļīāļāļŠāļąāļāđāļāļāļĒāđāļāļāļŦāļĨāļąāļ āđāļāđāļāļāđāļāļĄāļđāļĨāļāļđāđāļāđāļ§āļĒāđāļĢāļāļĄāļ°āđāļĢāđāļāļĨāđāļēāđāļŠāđāđāļŦāļāđāđāļĨāļ°āļĨāļģāđāļŠāđāļāļĢāļāļāļģāļāļ§āļ 58 āļāļ āļāļĩāđāļĄāļĩāļāļēāļĒāļļ 20 āļāļĩāļāļķāđāļāđāļāđāļĨāļ°āđāļāđāļĢāļąāļāļĒāļēāđāļāļĄāļĩāļāļģāļāļąāļāļŠāļđāļāļĢ FOLFOX-4 āļŦāļĢāļ·āļ mFOLFOX-6 āļ āđāļĢāļāļāļĒāļēāļāļēāļĨāļāļ°āđāļĒāļē āļāļąāđāļāđāļāđāđāļāļ·āļāļāļĄāļāļĢāļēāļāļĄ āļ.āļĻ. 2560 āļāļķāļ āļĄāļāļĢāļēāļāļĄ āļ.āļĻ. 2563 āļĒāļēāļāļģāļāđāļāļāđāļŦāđāđāļāļĄāļĩāļāļģāļāļąāļāļŠāļđāļāļĢāļāļąāđāļāđāļāļīāļĄ (āļŠāļđāļāļĢ 1) āļāļĢāļ°āļāļāļāļāđāļ§āļĒāļĒāļē dexamethasone 8 - 12 mg āļĒāļēāļāļģāļŠāļđāļāļĢāļāļĢāļąāļāļāļĢāļļāļ (āļŠāļđāļāļĢ 2) āļāļĢāļ°āļāļāļāļāđāļ§āļĒāļĒāļē dexamethasone 20 mg āļĢāđāļ§āļĄāļāļąāļāļĒāļē ranitidine 50 mg āđāļĨāļ° chlorpheniramine maleate 10 mg āļāļĨāļāļēāļĢāļĻāļķāļāļĐāļē: āļāļ§āļēāļĄāļāļļāļāļāļāļāļāļēāļĢāđāļāļīāļāļāļāļīāļāļīāļĢāļīāļĒāļēāļ āļđāļĄāļīāđāļ§āđāļāļīāļāđāļāļĒāļĢāļ§āļĄāļāļāļāļĒāļēāļāļąāđāļāļŠāļāļāļŠāļđāļāļĢāļĄāļĩāļāđāļēāļāļĢāļ°āļĄāļēāļ 31.0% āđāļāļĒāļŠāđāļ§āļāđāļŦāļāđ (38.9%) āđāļāļīāļāđāļāļĩāļĒāļāļāļĢāļąāđāļāđāļāļĩāļĒāļ§ āđāļĨāļ°āļĄāļąāļāđāļāđāļāļāļ§āļēāļĄāļĢāļļāļāđāļĢāļāđāļāļĢāļ°āļāļąāļāļāļēāļāļāļĨāļēāļ (āļĢāļ°āļāļąāļ 2) āļāļđāđāļāđāļ§āļĒāļāļĩāđāđāļāđāļĢāļąāļāļĒāļēāļāļģāđāļāļĄāļĩāļāļģāļāļąāļāļŠāļđāļāļĢ 2 āļĄāļĩāļāļąāļāļĢāļēāļāļēāļĢāđāļāļīāļāļāļāļīāļāļīāļĢāļīāļĒāļēāļ āļđāļĄāļīāđāļ§āđāļāļīāļāļāđāļāļĒāļāļ§āđāļēāļāļēāļĢāđāļāđāļĢāļąāļāļĒāļēāļāļģāļŠāļđāļāļĢ 1 āļāļķāļ 85% āļāļĒāđāļēāļāļĄāļĩāļāļąāļĒāļŠāļģāļāļąāļāļāļēāļāļŠāļāļīāļāļī (Incidence Rate Ratio 0.15; 95% CI 0.05 to 0.42; P-value <0.001) āļāļēāļĢāļĄāļĩāļāļēāļĒāļļāļāđāļāļĒāļāļ§āđāļē 60 āļāļĩ āđāļāđāļāđāļāļĻāļŦāļāļīāļ āļĄāļĩāļāļĢāļ°āļ§āļąāļāļīāđāļāđāļĢāļąāļāļĒāļēāđāļāļĄāļĩāļāļģāļāļąāļāđāļāļĨāļāļīāļāļąāļĄāļĢāļļāđāļ 3 āđāļĨāļ°āļāļēāļĢāđāļāđāļĢāļąāļāļĒāļēāđāļāļĄāļĩāļāļģāļāļąāļāļŠāļđāļāļĢ mFOLFOX-6 āļĄāļĩāđāļāļ§āđāļāđāļĄāļāļĩāđāļāļ°āļŠāļąāļĄāļāļąāļāļāđāļāļąāļāļāļēāļĢāđāļāļīāļāļāļāļīāļāļīāļĢāļīāļĒāļēāļ āļđāļĄāļīāđāļ§āđāļāļīāļāđāļāđāđāļĄāđāļĄāļĩāļāļąāļĒāļŠāļģāļāļąāļāļāļēāļāļŠāļāļīāļāļī āļŠāļĢāļļāļ: āļāļēāļĢāđāļāļīāđāļĄāļāļāļēāļāļĒāļē dexamethasone āļĢāđāļ§āļĄāļāļąāļāļāļēāļĢāđāļŦāđāļĒāļē ranitidine āđāļĨāļ° chlorpheniramine maleate āļĨāļāļāļąāļāļĢāļēāļāļēāļĢāđāļāļīāļāļāļāļīāļāļīāļĢāļīāļĒāļēāļ āļđāļĄāļīāđāļ§āđāļāļīāļ āļāļąāđāļāļāļĩāđāļāđāļ§āļĒāļāļāļēāļāļāļąāļ§āļāļĒāđāļēāļāļāļĩāđāđāļĨāđāļ āļāļķāļāļĒāļąāļāļāđāļāļāļāļģāļāļēāļāļ§āļīāļāļąāļĒāļāļĩāđāļĄāļĩāļāļāļēāļāļāļąāļ§āļāļĒāđāļēāļāđāļŦāļāđāļāļķāđāļāđāļāļ·āđāļāđāļāđāļĒāļ·āļāļĒāļąāļāļāļĨāļāļēāļĢāļĻāļķāļāļĐāļēāļāļąāļāļāļĨāđāļēāļ§āļāđāļāđāļ āļāļģāļŠāļģāļāļąāļ: āļĄāļ°āđāļĢāđāļāļĨāđāļēāđāļŠāđāđāļŦāļāđāđāļĨāļ°āļĨāļģāđāļŠāđāļāļĢāļ, āļāļāļīāļāļīāļĢāļīāļĒāļēāļ āļđāļĄāļīāđāļ§āđāļāļīāļ, āļĒāļēāđāļāļĄāļĩāļāļģāļāļąāļ, āļĒāļēāļāļģāļāđāļāļāđāļŦāđāđāļāļĄāļĩāļāļģāļāļąāļAbstract Objective: To examine the prevalence of and factors associated with hypersensitivity reactions (HSRs) and to compare the effectiveness of traditional chemotherapy premedication to a modified preventive regimen. Method: In this retrospective observational study, we used data from 58 colorectal cancer patients aged 20 years or older receiving FOLFOX-4 or mFOLFOX-6 at Phayao Hospital from January 2017 and January 2020. The traditional premedication (Regimen 1) consisted of dexamethasone 8 - 12 mg. The modified premedication (Regimen 2) consisted of dexamethasone 20 mg plus ranitidine 50 mg and chlorpheniramine maleate 10 mg. Results: The prevalence of HSR in both preventive regimens was approximately 31.0%. Most of HSR incidences (38.9%) occurred only once with moderate severity (Grade 2). Rate of HSR with Regimen 2 was 85% lower than that of Regimen 1 with statistical significance (incidence rate ratio = 0.15; 95% CI = 0.05 to 0.42; P-value < 0.001). Age less than 60 years, being female, having a history of receiving third-generation platinum chemotherapy, and receiving mFOLFOX-6 chemotherapy tended to be related to HSR. However, the associations did not reach statistical significance. Conclusion: Increasing dexamethasone dosage while adding ranitidine and chlorpheniramine maleate into the regimen may reduce the HSR rate. Due to the small sample size, a larger study is required to confirm these findings. Keywords: colorectal cancer, hypersensitivity reaction, chemotherapy, premedicatio