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Validity of using prescription medications to classify disease – a retrospective observational study using routinely collected electronic health records from the UK
No full textBackground: Epidemiological studies rely on valid classifications of patients’ disease status. However, in the absence of perfect information on every patients’ health status, researchers use proxy information with variable and often unknown validity.Methods: To investigate the validity of using prescription records for disease classification, we conducted a retrospective observational study on a UK-wide database of medical prescriptions and clinical records (Optimum Patient Care Research Database). We used electronic health records of 25,000 randomly selected patients for each year between 2004 and 2020 (total N=425,000) and compared disease classification of 18 different chronic conditions based on clinical records for a period of three years (gold standard) with disease classification based on prescription records for the same period. We then used logistic regression to analyse if positive and negative predicted values (PPV and NPV) were associated with known predictors of disease.Results: Results showed large variations in PPV ranging from 8% (heart failure) to 94% (all type diabetes) and smaller variations in NPV ranging from 96% (anxiety) to 100% (Type 1 diabetes). Age, sex, ethnicity, and year but not socio-economic status were associated with variations in validity, especially in classifying dementia, diabetes, and depression.Discussion: Varying validity can partly be explained by different (stratum-specific) prevalence of disease. Additionally, conditions like heart failure can be treated with medication that can also be prescribed for other conditions or can be treated without medication. However, varying validity can also be attributed to imperfect clinical records, which we used as gold standard. As a consequence of low validity, the apparent prevalence based on using prescription records was between 1.3 times lower (all-type diabetes) and up-to 11 times higher (heart failure) than the true prevalence based on the clinical records.Conclusion: Studies using prescription data to classify disease status run a substantial risk of misclassification bias.<br/
Incidence and prognosis of apparent-treatment resistant hypertension: a multi-state analysis using real world evidence
No full textBackgroundThere is limited evidence regarding the incidence and prognosis of apparent resistant hypertension (aRHT) in hypertensive patients. This study aimed to estimate the incidence of aRHT and assess the risk of cardiovascular and kidney complications in patients with aRHT compared to those without aRHT, using a multi-state analysis.MethodsThis retrospective cohort study utilized real-world data from hypertensive patients treated at Ramathibodi Hospital, Bangkok, Thailand, between January 2010 and June 2024. aRHT was defined as having uncontrolled blood pressure (BP), while using ≥ 3 antihypertensive medications or having controlled BP with using ≥ 4 antihypertensive medications. The outcomes of interest were cardiovascular and kidney complications including coronary artery disease (CAD), stroke, heart failure (HF), and chronic kidney disease (CKD), and all-cause mortality. A multi-state analysis was applied to estimate the risk of disease progression from hypertension without complications to aRHT, CAD, stroke, HF, CKD, and all-cause death. Kaplan-Meier estimates with a clock-reset approach were used to calculate transition probabilities for each progression. Multivariate Cox regression analysis was applied to assess the risk factors of aRHT and assess the prognosis of aRHT.ResultsAmong 114,364 hypertensive patients, the incidence of aRHT was 2.61 per 100 person-years (95% confidence interval [CI], 2.56–2.65). Results from multivariate Cox regression analysis found that the independent risk factors of aRHT were increasing age, males, obesity, type 2 diabetes mellitus, dyslipidemia, and having cardiovascular and kidney complications including CAD, stroke, CKD, and HF. Regarding the prognosis of aRHT, compared to non-aRHT patients, those with aRHT had significant higher risk of CAD, CKD, HF, and all-cause mortality with hazard ratios (95% CI) of 1.80 (1.56–2.08), 1.93 (1.79–2.08), 4.24 (3.54–5.08), and 2.84 (1.89–4.27), respectively.ConclusionsThe risk of aRHT was higher in hypertensive patients with cardiovascular and kidney complications compared to those without. Patients with aRHT had a worse prognosis than hypertensive patients without aRHT, as evidenced by higher risks of CAD, CKD, HF, and all-cause death
Time-restricted eating to improve metabolic abnormalities in polycystic ovarian syndrome (TimeMAP)
No full textOBJECTIVE: Time-restricted eating (TRE) represents a novel intervention that may improve hyperinsulinaemia and reduce weight, but has not been studied in polycystic ovarian syndrome (PCOS). In a randomised interventional study (NCT05126199 [1]), we investigated the feasibility of TRE in PCOS including recruitment, compliance, safety, drop-out rate, and effect on insulin-related parameters, anthropometrics, nutritional intake and metabolic indices.METHODS: Participants were randomised to a 12-week TRE regimen (18 h fast/6 h eating window) or 'ad libitum' regimen (no time-restriction), and then crossed over to the alternative regimen for a further 12 weeks.RESULTS: TRE was a feasible intervention with near-total compliance in those completing the intervention; however, there were considerable difficulties with recruitment. A total of 70 were eligible to participate, of which ultimately 15 were recruited, and 11 completed the study (4 [27%] drop-outs due to commitment/study duration). There were no serious adverse events in the TRE group. Compliance [%(SD)] with TRE was 94.7(4.5)%, and 10 participants were keen to continue the intervention post-study. Whilst the study was not powered to detect changes in metabolic or anthropometric indices, exploratory analysis showed a decrease in HbA1c (p = 0.04), weight (p = 0.001), BMI (p = 0.001), hip circumference (p = 0.05) and waist circumference (p = 0.001) in the TRE group compared to the ad libitum eating group.CONCLUSION: In a 12-week cross-over feasibility study, TRE was a safe and feasible intervention. Recruitment was challenging and with limited numbers, the TRE group showed a decrease in HbA1c and anthropometric indices compared to the 'ad libitum' group.TRIAL REGISTRATION: NCT05126199.</p
Effect of gutta-percha removal methods on fiber-post bond strength
No full textObjectives: This study evaluated the effect of three root canal filling material (RCFM) removal techniques—mechanical, thermo-mechanical, and chemico-mechanical—on the micro push-out bond strength of fiber posts to root dentin in endodontically treated teeth.Materials and Methods: Forty-five single-rooted human premolars were endodontically treated and randomly allocated into three groups (n = 15) according to the RCFM removal technique used during post-space preparation: mechanical, thermo-mechanical, or chemico-mechanical. Fiber posts were luted using a dual-cure resin cement. Roots were embedded in resin and sectioned into coronal, middle, and apical thirds. Micro push-out bond strength was measured using a universal testing machine. Failure modes were examined under a stereomicroscope and validated using scanning electron microscopy. Statistical analysis used two-way ANOVA and Chi-square tests (α = 0.05). Results: Both the thermo-mechanical and mechanical groups showed significantly higher bond strength values than the chemico-mechanical group (p < 0.001). Across all groups, the coronal third recorded the highest bond strength, while the apical third presented the lowest values (p < 0.001). Adhesive failure at the dentin–cement interface was the most frequent failure mode. Conclusions: The gutta-percha removal technique and the root canal region significantly influence fiber-post bond strength. Solvent-based chemico-mechanical methods may adversely affect adhesion quality. Clinical Relevance: Thermo-mechanical and mechanical removal techniques may provide more reliable post retention during retreatment procedures, improving adhesion and reducing the risk of post debonding in daily practice
A famous rhizoma dioscoreae herbal formula (Wubi Shanyao pill) delays renal aging in natural aging mice
No full textBackground Renal aging is particularly important in systemic organ injuries caused by aging, characterized by the accumulation of p53 and the consequent cell cycle arrest and apoptosis. Wubi Shanyao pills (WBSY), a classic formula based on traditional Chinese medicine theory, have been widely used to treat patients with spleen-kidney deficiency for centuries. In this study, we investigated the retarding effect of WBSY on kidney natural aging process and its possible molecular mechanisms. Objective This study aimed to evaluate the efficacy of WBSY in delaying the natural aging process of kidneys and to elucidate the underlying molecular mechanisms involving the p53 signaling pathway. Methods We treated the natural aging BALB/c mice by intragastrical administration of WBSY (0.375, 0.75 and 1.5 g/kg/d) for 10 weeks and investigated the effect of WBSY on aging symptoms and renal function. In addition, the detection of senescence and injure in mouse kidneys via hematoxylin and eosin (H&E), immunofluorescence (IF), senescence-associated β-galactosidase (SA-β-Gal) and TdT-mediated dUTP nick end labeling (TUNEL) staining. Finally, by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) staining and western blotting (WB), we examined the expression levels of senescence-associated biomarkers and p53 signaling pathways (including the cell cycle and apoptosis pathways) in the kidneys of mice. Results The findings showed that treatment of WBSY significantly improved the aging-induced physiological changes and renal injury in aging mice. Meanwhile, WBSY treatment delayed telomere shortening as well as down regulated the positive expression of β-galactosidase, phosphorylated histone H2AX (γ-H2AX), p16 and p19 in the kidney tissues. Furthermore, mechanistic investigations revealed that WBSY treatment reduced p53 expression at both the transcriptional and translational levels, thereby down-regulating its downstream p21, Bcl-2 associated X (Bax) and Caspase-3 expression, while up-regulating cyclin dependent kinase 2 (CDK2), retinoblastoma (Rb) and B-cell lymphoma-2 (Bcl-2) expression. Conclusion Taken together, WBSY inhibited factors related to aging, cell cycle and apoptosis, and ameliorated kidney aging in naturally aged mice
Layering & embedding: Constructing assemblies along lines of landscape on Hook Head peninsula
No full textEutectic systems embedded within implantable matrices for improved postsurgical wound management and recovery
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