Annals of clinical epidemiology最新文献

Secondary analyses of randomized controlled trials (RCTs) offer an efficient way to maximize the value of existing trial data and explore clinical questions beyond the original trial scope. This review outlines methodological considerations and best practices, emphasizing their role in evidence-based medicine. We describe major RCT data sources and summarize steps for accessing individual participant data. Key methods include formulating research questions, understanding trial design, data processing, statistical analysis, and clinical interpretation. Types of secondary analyses are discussed including subgroup analysis, biomarker studies, health economics, methodological research, adverse event analysis, and predictive modeling. Common challenges, such as data applicability, missingness, generalizability, and multiple testing, are summarized. With advances in data sharing, secondary analyses are expected to drive scientific discovery and provide more evidence for diagnosis and treatment patterns as long as rigorous standards and transparency are maintained.

Background: Extracorporeal membrane oxygenation (ECMO) is a vital intervention in patients with severe cardiogenic shock or respiratory failure who are unresponsive to conventional therapies. Despite advances in ECMO technology and management, complications such as infections, renal dysfunction, and post-intensive care syndrome remain significant challenges that contribute to high mortality. Existing registries have provided valuable insights but lack detailed data on infection management, rehabilitation practices, and other granular aspects of ECMO care. The Japan Intensive Care ECMO Consortium: Nationwide Effort for ECMO Care Optimization and Excellence (ECMO NEXT) study aims to address these gaps by establishing a comprehensive multicenter study in Japan.

Methods: This is a multicenter, retrospective cohort study conducted at 22 healthcare institutions in Japan, with data collected on ECMO cases between January 2018 and December 2023. Adults aged ≥18 years who underwent ECMO in the intensive care unit (ICU) during this period will be eligible. This study will focus on six predefined themes: post-decannulation fever, infection epidemiology, ventilator settings, ECMO-associated acute kidney injury and electrolyte abnormalities, rehabilitation practices, and venoarterial ECMO in toxicological emergencies and septic shock scenarios. Data-including clinical course, laboratory results, rehabilitation details, and outcomes-will be collected using a standardized electronic case report form on the Research Electronic Data Capture platform. Statistical models, including propensity score-based analyses, will be used to adjust for confounders and assess attributable risks.

Conclusions: The ECMO NEXT study provides high-resolution data to address the gaps in ECMO research, particularly in ICU management and post-ECMO recovery.

Background: Childhood vaccinations can be effective for preventing not only infectious diseases but also other diseases and traumas. This is because vaccines may have nonspecific immunological effects. Additionally, visits for vaccinations may benefit doctors in promoting the overall health of children. We assessed whether vaccination status at 24 months was associated with the incidence of all-cause hospitalization.

Methods: This retrospective cohort study used the vaccine records and healthcare claims from a Japanese city. We included children born between April 2014 and December 2020. Children who took all the following vaccine doses covered by the national immunization program at 24 months of age were defined as having an age-appropriate vaccination status: four doses of Hemophilus influenza type b, four of 13-valent pneumococcal conjugate, four of diphtheria, tetanus, acellular pertussis, and inactivated polio, three of hepatitis B virus, one of Bacille de Calmette et Guérin, one of measles and rubella, and one of varicella-zoster virus. A Cox regression model compared all-cause hospitalizations between children with and without age-appropriate vaccination, adjusting for sex, birth year, and comorbidities.

Results: We identified 2,492 children: 1,689 were age-appropriate vaccinated, and 803 were not. There was no significant difference in all-cause hospitalizations (adjusted hazard ratio, 0.93; 95% confidence interval, 0.69 to 1.3; P = 0.65).

Conclusions: The effect of age-appropriate vaccinations on the overall health of children may be small.

Background: Postpartum haemorrhage (PPH) is a major cause of maternal mortality worldwide. Previous studies have presented varying conclusions regarding the PPH risk in pregnant haemophilia carriers or women with von Willebrand disease (VWD). We aimed to evaluate PPH occurrence in this demographic using a nationwide inpatient database in Japan.

Methods: In this retrospective study, we identified women aged 15-49 years who gave birth while hospitalised between July 2010 and March 2021, using the Japanese Diagnosis Procedure Combination database. These pregnant women were categorised into three groups: the haemophilia, VWD, and control cohort groups. The assessed outcomes were PPH and interventions for bleeding. Multivariable logistic regression analyses were performed to assess the association between coagulation disorders and patient outcomes.

Results: We identified 113 pregnant women in the haemophilia group, 184 in the VWD group, and 1,459,451 in the control group. The outcomes of multivariable logistic regression analyses demonstrated that PPH occurrence was not higher in the haemophilia group (odds ratio, 0.74; 95% confidence interval, 0.46-1.17) than in the control group. Conversely, the VWD group was significantly associated with PPH (odds ratio, 1.46; 95% confidence interval, 1.05-2.02) and a higher incidence of interventions for bleeding (odds ratio, 2.49; 95% confidence interval, 1.55-4.00).

Conclusions: Despite the absence of a substantial correlation between haemophilia and PPH in pregnant haemophilia carriers, a discernible association emerged between VWD and PPH in pregnant women. Healthcare providers need to be mindful of the high prevalence of undiagnosed VWD and prepare adequately for delivery.

Background: Routinely collected medical data, such as electronic medical records (EMRs) and medical claims, are necessary for developing disease registries. This study aimed to develop an otologic surgery registry by integrating data from EMRs, medical claims, and otorhinolaryngology department information systems (ORL-DIS) and to assess the agreement of hearing tests between registry-determined evaluations (RDE) and surgeon-determined evaluations (SDE).

Methods: A stapes surgery registry was developed by linking data from ORL-DIS, EMRs, and medical claims from two hospitals in Japan. SDE were recorded by the surgeons, whereas RDE were automatically assigned by the registry system. This study focused on pre- and postoperative hearing evaluations. Pure-tone averages (PTA) for air conduction (AC) and bone conduction (BC) were calculated. Agreement between SDE and RDE was assessed using Bland-Altman plots, and mean differences and 95% limits of agreement (95% LoA) were calculated. In SDE, cases with incomplete data were excluded.

Results: A total of 164 patients (187 cases) were included. The Bland-Altman analysis revealed a high agreement between preoperative AC-PTA (mean difference: -1.61 dB; 95% LoA: -12.5 to 9.29 dB) and BC-PTA (mean difference: -1.05 dB; 95% LoA: -13.9 to 11.8 dB) measurements by SDE and RDE. Additionally, postoperative improvements showed a moderate agreement. The integration of audiometric data into the registry significantly reduced manual errors.

Conclusion: This study successfully established the first otologic surgery registry in Japan that integrates audiometric data from EMRs. This registry provides a valuable resource for analyzing surgical outcomes and a framework for future otologic research.

Single-arm trials (SATs) are clinical studies without a parallel control group, serving as a vital alternative to randomized controlled trials (RCTs) in scenarios where traditional trial designs are impractical. These trials are particularly relevant in rare diseases, advanced malignancies, novel treatment modalities, and life-threatening conditions, where ethical concerns, logistical challenges, or small patient populations limit the feasibility of RCTs. SATs enable expedited evaluation of therapeutic interventions, often forming the foundation for regulatory approvals. This article explores the principles, applications, and methodological considerations of SATs. Their advantages include smaller sample size requirements, faster timelines, and regulatory acceptance by agencies such as the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA). Despite these benefits, SATs face challenges, such as potential biases due to the lack of a control group, limitations in endpoints, and reliance on historical controls that may compromise result validity. Best practices in SAT design are outlined, including refining scientific questions, defining eligibility criteria, selecting clinically meaningful endpoints, and employing robust statistical methods like Simon's two-stage design and Bayesian approaches.

Propensity score (PS) is the probability of the exposure being assigned, conditional on the observed baseline covariates. Many observational studies have used PS analyses to investigate the effects of exposure on outcomes. This report reviews the five steps of PS analyses: 1) calculating PS; 2) checking the overlap of PS; 3) implementing a matching or weighting method including PS matching, inverse-probability-of-treatment weighting, standardized mortality ratio weighting, matching weighting, and overlap weighting; 4) diagnosing the covariate balance; and 5) comparing the outcomes. Two groups are often compared in PS analyses; however, three-group comparisons can provide clinicians with more benefits in many situations in routine clinical practice. Thus, we describe not only two-group comparisons but also three-group comparisons by introducing a few studies that used generalized PS to compare three groups.

Background: Diabetic nephropathy is a common complication of diabetes. We investigated the risk factors for diabetic nephropathy in individuals newly diagnosed with type 2 diabetes.

Methods: Data from the Japanese Diagnosis Procedure Combination in-patient database (April 2008 to December 2018) were analyzed. The endpoint was subsequent diabetic nephropathy diagnosis or as the time when estimated glomerular filtration rate become <60 ml/min/1.73 m². Candidate risk factors included age, Hemoglobin A1c, log-transformed triglyceride, total cholesterol, and high-density lipoprotein cholesterol levels, body mass index, and estimated glomerular filtration rate. Eligible individuals with type 2 diabetes without complications who had pre- and post-diagnosis Hemoglobin A1c and serum creatinine measurements, and a history of hypertension or cardiovascular disease pre-diagnosis. Those with pre-existing kidney diseases, nephropathy onset pre-diagnosis, estimated glomerular filtration rate <60 ml/min/1.73 m² on or before diabetes diagnosis, or age <20 years at diabetes diagnosis were excluded. A multivariate Cox proportional hazards model (p = 0.2 backward selection) was employed.

Results: Of 2,664 eligible individuals (1,775 men, 889 women), 325 men and 175 women developed diabetic nephropathy during follow-up. Cumulative incidence within 5 years was 29.0% in men and 32.5% in women. Age and estimated glomerular filtration rate in both sexes, and total cholesterol in men were significant.

Conclusions: Age, estimated glomerular filtration rate, and lipid pose potential risks for diabetic nephropathy onset within 5 years of diabetes diagnosis in individuals with hypertension. Collectively, our findings highlight the importance of early monitoring and intervention in this high-risk.

Background: This study aimed to compare telephone follow-ups for patients with urologic malignancies in Japan before and during the COVID-19 pandemic.

Methods: Using the database of the Japan Medical Data Center Co., Ltd., we identified patients with urologic malignancies who underwent at least one telephone follow-up between April 2014 and March 2020.The self-controlled case series method was used to calculate the incidence rate ratio of telephone follow-up utilization for the pandemic using the pre-pandemic period as a reference.

Results: Of the 289 patients, 31 were women. Their median age was 80 years, and the median observation period was 28 months.The incidence rate ratio for telephone follow-up utilization during the pandemic was 17.8 compared to that of the pre-pandemic period. In an analysis stratified by type of carcinoma, the incidence rate ratios were higher in all strata than they were before the pandemic. However, among male patients with genital malignancies, particularly prostate cancers, the incidence rate ratio was lower than in other strata.According to analysis stratified by age, the usage of telephone follow-up for men in their 50s or younger was particularly low. Additionally, the interval between face-to-face visits increased in patients over 60 years-of-age.

Conclusions: The telephone follow-up among patients with urologic malignancies in Japan increased significantly during the early phase of the COVID-19 pandemic. Our results indicate that telephone follow-up can potentially be a valuable patient-doctor communication tool.

Background: Mirogabalin has a mechanism similar to that of pregabalin in the treatment of neuropathic pain. However, it remains unclear whether these drugs differ in terms of serious side effects, such as fall-related fractures, in older patients. This study aimed to investigate whether mirogabalin is associated with a decrease in adverse events, including fall-related fractures, compared with pregabalin.

Methods: We performed a retrospective cohort study using the DeSC database, a large administrative claims database in Japan. This study included 130,244 patients ≥65 years taking mirogabalin or pregabalin between April 2019 and May 2021. The primary outcome was defined as the occurrence of fractures or switching to other medications and was compared between those receiving mirogabalin and pregabalin using Kaplan-Meier curves and multivariable Cox proportional hazards models. A sensitivity analysis was performed regarding patients who received mirogabalin or pregabalin without other analgesic medications at the initial dose.

Results: During a median follow-up of 2.8 months, 29,686 (22.8%) and 100,558 (77.2%) received mirogabalin and pregabalin, respectively. The rates of the outcome in the mirogabalin and pregabalin groups were 50.1 and 42.8 per 100 person-years. Cox regression analysis showed that mirogabalin was associated with a lower risk of the outcome (hazard ratio, 0.93; 95% confidence interval, 0.87-1.00). However, sensitivity analysis did not demonstrate a difference in the outcome between the mirogabalin and pregabalin groups without other analgesic medications (hazard ratio, 0.93; 95% confidence interval, 0.86-1.01).

Conclusions: Our analyses suggest that the outcome may be less likely in the mirogabalin group; however, the difference appears to be clinically insignificant. Further studies are warranted to confirm these findings.