Clinical Epidemiology最新文献

Purpose: Ibuprofen is used to treat acute pericarditis, but high-dose ibuprofen has also been associated with increased cardiovascular risks. We examined the cardiovascular safety of using ibuprofen for acute pericarditis.

Patients and methods: A Danish nationwide, population-based cohort study including patients ≥18 years with first-time acute pericarditis (n=12,381) during 1996-2020 was conducted. Ibuprofen use was modelled in two ways: First, we considered patients exposed based on the tablet strength of their first ibuprofen filling (a proxy for an intention-to-treat analysis). Second, we considered patients exposed in a time-varying manner (a proxy for an as-treated analysis). The primary outcome of major adverse cardiovascular events (MACE) was a composite of myocardial infarction, ischemic stroke, congestive heart failure, and cardiovascular death.

Results: In the intention-to-treat analysis, the 1-year risk of MACE was 1.37% (95% confidence interval [CI]: 1.03-1.79) for ibuprofen initiators and 4.32% (95% CI: 3.89-4.78) for non-initiators. Compared with non-initiators within 1-year follow-up, the adjusted hazard ratio for MACE was 0.75 (95% CI: 0.67-0.85) for initiators overall, 0.38 (95% CI: 0.28-0.52) for initiators of >400 mg tablets, and 0.87 (95% CI: 0.76-0.99) for initiators of ≤400 mg tablets. In the as-treated analysis, compared with no use, the hazard ratio associated with ibuprofen use was 0.69 (95% CI: 0.54-0.89) for MACE, 0.82 (95% CI: 0.54-1.26) for myocardial infarction, 0.74 (95% CI: 0.45-1.22) for ischemic stroke, 0.67 (95% CI: 0.47-0.96) for congestive heart failure, and 0.60 (95% CI: 0.31-1.17) for cardiovascular death.

Conclusion: Ibuprofen use for acute pericarditis was not associated with increased cardiovascular risks, supporting its safety in current practice.

Background: The Danish National Hospital Medication Register (DHMR), one of the first nationwide in-hospital medication registries in the world, contains detailed information on medication administration and dispensing.

Objective: To provide an overview of the information recorded in the DHMR and to highlight its strengths and limitations as a pharmacoepidemiological research tool.

Methods: We reviewed the registry´s geographic and clinical specialty coverage and medications recorded according to the main groups of the Anatomical Therapeutic Chemical classification system.

Results: From May 2018 through December 2023, the DHMR recorded data on more than 1.9 million unique patients from all approximately 50 public hospitals and associated hospital outpatient clinics, totaling 105.3 million recordings of hospital medication use. The registry records detailed data on the indication for medication, medication type, pharmaceutical form, dosage, and administration time, collected through electronic medical record systems. Although the data quality has not yet been evaluated in a scientific context, some potential limitations are known. These include regional differences in the data collection and a lack of data from certain clinical specialties. Due to its recent establishment in 2018, the registered number of patients treated may still be limited for some rarely used medications.

Conclusion: The DHMR is an important new resource for research in Denmark. Combined with the Danish National Prescription Registry, which covers all community pharmacies, it offers access to accurate data on medication exposure in the Danish population. Users should be aware of potential issues with lack of information before 2018.

Purpose: To investigate the prognostic implications of gender in nasopharyngeal carcinoma (NPC) utilizing data from two independent cohorts: the Xiamen (XM)-NPC cohort (an endemic area in China) and the United States Surveillance, Epidemiology, and End Results (SEER)-NPC cohort (a non-endemic area).

Methods: We included patients diagnosed with NPC from both the XM-NPC and SEER-NPC cohorts. Statistical analysis involved the chi-square test, Kaplan-Meier method, and multivariate Cox regression analyses.

Results: The study identified 728 patients in the XM-NPC cohort and 2237 in the SEER cohort. In the XM-NPC cohort, 515 (70.7%) were male and 213 (29.3%) were female. In the SEER-NPC cohort, 1597 (71.4%) were male and 640 (28.6%) were female. The male-to-female ratio peaked at ≤25 years (2.33) and 46-55 years (2.79) in the XM-NPC cohort, and at ≤25 years (2.07) and 56-65 years (3.24) in the SEER-NPC cohort. The lowest ratios were observed among patients aged 26-35 years in both cohorts (XM-NPC: 1.64; SEER-NPC:1.38). In the XM-NPC cohort, females had significantly better overall survival (P=0.022) and distant metastasis-free survival (P=0.038) compared to males. Similarly, in the SEER-NPC cohort, gender was found to be an independent prognostic factor for overall survival, with females showing better outcomes (P=0.038). Consistent trends were observed in patients aged >45 years in both cohorts, while survival outcomes were comparable between genders in patients aged ≤45 years.

Conclusion: Gender independently influences survival outcomes of NPC in both endemic and non-endemic areas.

Purpose: We aimed to identify the association between heart failure (HF) with sepsis and its mortality through Mendelian randomization (MR) and observational studies.

Patients and methods: In MR study, we utilized public summary statistics from genome-wide association studies (GWAS). We conducted univariable, multivariable and network MR analyses to investigate causal relationships between HF and sepsis, and mediating roles of cytokines and growth factors. We performed an observational analysis using the MIMIC-IV database. Propensity score matching (PSM) and logistic regression models were employed to explore causal relationships between HF and sepsis, besides short-, medium-, and long-term mortality associated with sepsis.

Results: In univariable MR analysis, there was a causal relationship between genetically predicted HF (OR = 1.15, 95% CI = 1.02-1.29, P = 0.025) and sepsis. In multivariable and network MR analyses, βNGF was independently associated with sepsis. And it mediated 17.6% (95% CI 2.45-30.72%) of HF effect on sepsis. In the real-world observational study, acute on chronic diastolic (congestive) heart failure (DCHF) (OR = 1.59, 95% CI = 1.31-1.93, P < 0.001), acute DCHF (OR = 2.52, 95% CI = 1.61-3.95, P = 0.010), and acute diastolic heart failure (DHF) (OR = 1.52, 95% CI = 1.06-2.19, P = 0.024) after PSM were associated with occurrence of sepsis. Chronic systolic (congestive) heart failure (SCHF) was associated with increased 28-day (OR = 1.75, 95% CI = 1.06-2.91, P = 0.030), 1-year (OR = 1.80, 95% CI = 1.08-3.00, P = 0.023), and 2-year (OR = 1.86, 95% CI = 1.12-3.10, P = 0.018) mortality in sepsis.

Conclusion: Observational and MR analyses showed a causal relationship between HF and sepsis. Chronic SCHF was related to increased short/long-term mortality in sepsis. Our study indicated βNGF a key factor in HF-induced sepsis.

Purpose: To assess the positive predictive value (PPV) of the diagnostic codes for hypertrophic cardiomyopathy (HCM) in the Danish National Patient Register (DNPR) and identify factors affecting the PPV.

Patients and methods: We randomly sampled 200 patients registered in DNPR with the diagnostic codes DI421 (obstructive) or DI422 (non-obstructive) HCM, from Eastern Denmark, between December 1^st, 2017, and September 16^th, 2021. We assessed patients' medical records and classified whether the diagnosis of HCM was correct, incorrect, or uncertain according to the European Society of Cardiology (ESC) guidelines. Overall PPVs were estimated for all hospitals irrespective of specialty and for dedicated centers for inherited cardiac diseases.

Results: Of the 200 patients, seven were excluded; six were younger than 18 years when initially diagnosed and one adult patient had requested that their medical records be unavailable for research purposes. Of the 193 patients (median age 61 years, Interquartile range (IQR) 50-70, 40% female) with medical records available for assessment, 148 (77%) patients were registered correctly, 41 (21%) were incorrectly registered and for four (2%) patients there was insufficient data to determine if the diagnosis was correct. The overall PPV was 0.77 (95% confidence interval (CI) 0.70-0.82). The PPV for patients diagnosed in dedicated centers for inherited cardiac diseases was 0.91 (95% CI 0.84-0.95). For patients diagnosed in a dedicated center for inherited cardiac diseases with more than one clinical visit, the PPV increased to 0.99 (95% CI 0.93-1), however with the risk of a reduced sensitivity as these patients constituted only 52% of the correctly registered patients.

Conclusion: The overall PPV of the HCM diagnostic codes in the DNPR was 0.77 (95% CI 0.70-0.82). The validity of the diagnosis was higher at dedicated centers for inherited cardiac diseases. These findings may prove useful for future register-based research.

Purpose: To validate the International Classification of Diseases, 10th Revision (ICD-10) codes for Guillain-Barré syndrome (GBS) in Taiwan's insurance claims database.

Methods: We identified adult patients hospitalized at any Chang Gung Memorial Foundation branch hospital between January 1st, 2017, and December 31st, 2022, with ICD-10 code G61.0 in any of the five discharge diagnosis positions, indicating possible Guillain-Barré syndrome. We then validated the possible GBS diagnosis using data from electronic medical records of the identified patients, based on the diagnostic criteria established by the National Institute of Neurological Disorders and Stroke. We determined the positive predictive values (PPV) of various operational definitions, including the position (primary or other) where the code was recorded in the discharge diagnosis, nerve conduction study (NCS) claims, and / or specific GBS treatments.

Results: The final validation cohort of 484 patients with ICD-10 code for GBS in the discharge diagnosis was found to include 368 true GBS patients. Identifying inpatients using only the ICD-10 code for GBS in any of the five positions for discharge diagnosis yielded a PPV of 76.0%. With more restrictive definitions (primary diagnosis only, or requiring additional claims for NCS and/or treatments), the PPV tended to increase, but with fewer true GBS patients identified. Using ICD-10 GBS code in the primary diagnosis plus NCS and treatment claims yielded the highest PPV (98.3%); however, 140 (38.0%) of the true GBS patients were missed using this definition. In contrast, using the ICD-10 GBS code in any position, plus claims for NCS, achieved a relatively good PPV (85.8%) with minimal loss of true GBS patients (13, ie, 3.5%).

Conclusion: In Taiwan's NHI claims data, identifying true GBS patients using only the ICD-10 code yielded a PPV of 76.0%; however, adding claims for diagnostic procedure and GBS treatment increased the PPV to 98.3%.

Purpose: Understanding the long-term safety of disease-modifying therapies for multiple sclerosis (MS) in routine clinical practice can be undertaken through registry-based studies. However, variability of data quality across such sources poses the challenge of data fit for regulatory decision-making. CLARION, a non-interventional cohort safety study of cladribine tablets, combines aggregated data from MS registries/data sources, except in Germany (which utilizes primary data collection). We describe the application of key data quality indicators (DQIs) within CLARION to evaluate data quality over time, as recommended by the European Medicines Agency (EMA) guideline on registry-based studies.

Methods: DQIs were defined with participating registries/sources; they were used to assess data quality according to the EMA Data Quality Framework, addressing consistency, accuracy, completeness, and study representativeness. DQIs were associated with potential remedial measures if data quality was not met. DQIs were summarized overall and for individual MS registries/data sources to November 1, 2022.

Results: A total of 28 DQIs were analyzed using data from 5069 patients arising from eight MS registries/data sources and 14 countries. The Representativeness DQIs showed that 72.0% of patients were female, median age at MS diagnosis was 29.0 to 43.3 years, and 93.5% had relapsing-remitting MS. Consistency DQIs showed a total of 2899 patients had achieved at least two years of follow-up; 6.9% did not have any recorded visits during this timeframe. Discrepant values were assessed as part of Accuracy DQIs, and improvements over time were noted for recorded dates of MS onset and diagnosis. Regarding Completeness DQIs, 191/5069 (3.8%) patients were lost to follow-up.

Conclusion: The application of 28 DQIs within the CLARION study has helped with understanding, not only intrinsic and question-specific determinants of data quality, but also tracking the quality of post-authorization safety data obtained from MS registries/data sources, thereby providing a foundation for the regulatory decision-making process.

Background: Prealbumin is a symbol of protein nutrition and is involved in anti-inflammatory and neuron regeneration, but its association with the prognosis of ischemic stroke remains unclear. We aimed to prospectively explore the associations between serum prealbumin levels and adverse clinical outcomes after ischemic stroke in a large-scale cohort study.

Methods: We measured serum prealbumin levels among 6609 ischemic stroke patients admitted at Minhang hospital. The primary outcome was composite of death and major disability (modified Rankin Scale [mRS] score ≥ 3) at 3 months after stroke onset, and secondary outcomes included death and the ordered 7-level categorical score of mRS.

Results: During 3 months of follow-up, a total of 2118 patients developed the primary outcome. After multivariable adjustment, high prealbumin levels were associated with a decreased risk of primary outcome (odds ratio, 0.71; 95% CI, 0.59-0.85; P _trend< 0.0001) when 2 extreme quartiles were compared. Each unit increase of log-transformed prealbumin was associated with a 42% (95% CI, 28-53%) decreased risk of primary outcome. There was a better shift in the distribution of mRS score at 3 months with higher quartiles of serum prealbumin in ischemic stroke patients (P _trend< 0.0001). Multivariable-adjusted spline regression model showed a linear relationship between prealbumin and the risk of primary outcome (P for linearity = 0.0036).

Conclusion: High serum prealbumin level was independently associated with decreased risks of adverse clinical outcomes among ischemic stroke patients. Our findings suggested that prealbumin may be a valuable prognostic biomarker and indicated the importance of keeping nourished in the daily life.

Purpose: Graves' disease (GD) is one of the most common causes of thyrotoxicosis. It has been proposed to identify incident GD by using the GD-specific code, E05.0, of the 10th revision of the International Classification of Disease (ICD-10) in the Danish National Patient Register (DNPR). We aimed to report the incidence of GD and to investigate the validity and completeness of E05.0 registration using Aalborg University Hospital (AaUH) as a single centre-sample.

Patients and methods: The study included registry data from 2020 to 2022. The study population (n=2,893) comprised all people (15-99 years) in the catchment area of AaUH (n=244,872) with either positive anti-thyroid stimulating hormone receptor antibodies (TRAb), or registered with a thyroid disease related ICD-10 code E03.0-E07.9, O99.2 or O90.5 at the Department of Endocrinology, AaUH. To identify incident cases, all subjects occurring for the first time in 2020 were excluded (n=2,339). The incident subjects were categorized into a general practice (n=63) or hospital care group (n=491) and underwent GD verification by biochemical tests and thyroid imaging. Validity was evaluated by positive (PPV) and negative (NPV) predictive values and completeness of E05.0 registration was estimated to the total number of verified GD subjects in hospital care only and in overall (groups combined).

Results: One hundred thirty-one incident GD subjects were identified corresponding to an incidence of 26.8 per 100,000/year. E05.0 had a PPV of 90% [95% CI: 81;96] and a NPV of 90% [95% CI: 85;93] to identify incident cases of GD. Completeness was estimated to be 73% [95% CI: 63;82] in hospital care and 50-60% [95% CI: 41;68] in overall.

Conclusion: We report on a similar incidence of GD as previous studies in Denmark. Despite a high PPV, incident cases of GD could not adequately be identified by E05.0 in DNPR due to low completeness. Researchers should rely on biochemical test results to identify incident GD.