The goal of a clinical study is to determine the factors associated with a disease and to assess the efficacy and safety of an investigational drug, procedure, or device. Since clinical study designs vary due to unique requirements of individual studies, the aims of this report are to educate researchers on the different types of studies and to assist researchers in choosing the optimal study type to fulfill their individual requirements. Clinical studies are classified into the two main types, observational studies and clinical trials, depending on the presence or absence of an intervention. Observational studies include case-control studies, cohort studies, and cross-sectional studies. Case-control and cohort studies may be prospective or retrospective, and case-control studies may be nested or not. Clinical trials may be pragmatic and may be controlled or noncontrolled; randomized or nonrandomized; open label or blinded; and parallel, crossover, or factorial. These observational and clinical trial designs are reviewed. Each type of clinical study has advantages and disadvantages. Therefore, researchers must consider these in choosing the design best suited for achieving their study objectives.

Background: We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients. Methods: A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001–2008) and the post-intervention (2009–2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patientdays, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ2 . Results: The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period (P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = −16.5; 95% confidence interval [CI], −30.6 to −2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period (P = 0.881). Conclusion The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia.

Purpose: We performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma. Materials and Methods: The study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed. Results: An ANC of 32.5/μL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/μL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC. Conclusion In neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual’s susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered.

We aimed to investigate associations of dietary diversity (DD) with gut microbial diversity and the development of hen's egg allergy (HEA) in infants. We enrolled 68 infants in a highrisk group and 32 infants in a control group based on a family history of allergic diseases. All infants were followed from birth until 12 months of age. We collected infant feeding data, and DD was defined using 3 measures: the World Health Organization definition of minimum DD, food group diversity, and food allergen diversity. Gut microbiome profiles and expression of cytokines were evaluated by bacterial 16S rRNA sequencing and real-time reverse transcriptase-polymerase chain reaction. High DD scores at 3 and 4 months were associated with a lower risk of developing HEA in the high-risk group, but not in the control group. In the high-risk group, high DD scores at 3, 4, and 5 months of age were associated with an increase in Chao1 index at 6 months. We found that the gene expression of IL-4, IL-5, IL-6, and IL-8 were higher among infants who had lower DD scores compared to those who had higher DD scores in high-risk infants. Additionally, high-risk infants with a higher FAD score at 5 months of age showed a reduced gene expression of IL-13. Increasing DD within 6 months of life may increase gut microbial diversity, and thus reduce the development of HEA in infants with a family history of allergic diseases.

Objectives: ：The high lifetime prevalence of depression in Korea is related to problems such as suicide and decreased productivity, as well as the cost of disease due to increased use of medical services, which can cause great socioeconomic loss. Therefore, in this study, the burden of disease of depression and the importance of managing mental health diseases, which are increasing day by day, are suggested to be helpful in determining priorities in health policy establishment. Methods: ：In this study, the socio-economic cost of depression was calculated by dividing it into direct cost and indirect cost. For statistical data, data from the National Health Insurance Service of the public and statistics on diseases of national interest were mainly used. Results: ：As a result, the socio-economic cost of depression in 2019 estimated in this study was calculated to be a total of KRW 4.83 trillion, with direct costs 692.9 billion won and indirect costs 4.13 trillion won. Among them, the cost due to decrease in work performance accounted for the largest portion, accounting for 65.5%. Conclusions ：As the socio-economic burden due to depression is expected to increase in the future, it is necessary to establish a systematic funding plan for the treatment and management of depressed patients in daily life.

Objective: Adult attention deficit hyperactivity disorder (ADHD) has a heterogeneous clinical presentation with patients showing very frequent emotional problems. In the present study, patients with adult ADHD were subtyped based on their psychopathology using a person-centered approach. Methods: In the present chart review study, detailed findings of psychological evaluation conducted as part of routine care were utilized. A total of 77 subjects with adult ADHD were included in the analysis. Detailed ADHD symptoms, psychiatric comorbid Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses, and severity of mood and anxiety symptoms were evaluated in the person-centered analysis. Results: Three clusters were generated using clustering analysis. DSM comorbid conditions did not significantly impact the clustering. Cluster 1 consisted of ADHD combined presentation (ADHD-C) with less mood symptoms, cluster 2 of ADHD predominantly inattentive presentation and cluster 3 of ADHD-C with significant mood symptoms. Patients in cluster 3 had adulthood functional impairment more frequently compared with patients in cluster 1. Patients in cluster 3 showed recurrent thoughts of death and suicidal ideation more frequently compared with patients in cluster 1. Conclusion Further studies are needed to confirm the relationships observed in the present study.

Objective: Adult attention deficit hyperactivity disorder (ADHD) has a heterogeneous clinical presentation with patients showing very frequent emotional problems. In the present study, patients with adult ADHD were subtyped based on their psychopathology using a person-centered approach. Methods: In the present chart review study, detailed findings of psychological evaluation conducted as part of routine care were utilized. A total of 77 subjects with adult ADHD were included in the analysis. Detailed ADHD symptoms, psychiatric comorbid Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses, and severity of mood and anxiety symptoms were evaluated in the person-centered analysis. Results: Three clusters were generated using clustering analysis. DSM comorbid conditions did not significantly impact the clustering. Cluster 1 consisted of ADHD combined presentation (ADHD-C) with less mood symptoms, cluster 2 of ADHD predominantly inattentive presentation and cluster 3 of ADHD-C with significant mood symptoms. Patients in cluster 3 had adulthood functional impairment more frequently compared with patients in cluster 1. Patients in cluster 3 showed recurrent thoughts of death and suicidal ideation more frequently compared with patients in cluster 1. Conclusion Further studies are needed to confirm the relationships observed in the present study.

Background: and PurposeSleep disturbance is common in patients with primary headache disorders. We were interest in whether poor sleep quality affects patients directly or via increases in the frequency and severity of headaches. To that end, we investigated the direct and indirect effects of sleep quality on the headache-related impact among patients with primary headache disorders. Methods: We analyzed migraine and tension-type headache (TTH) in patients included in the headache registry of our headache clinic from October 2015 to May 2018. We collected information on the headache frequency, severity, and psychological status. Sleep quality and headache-related impact were measured using the Pittsburgh Sleep Quality Index and Headache Impact Test-6, respectively. We performed path analyses with headache frequency and severity as covariates to determine the direct effect of sleep quality on the headache-related impact, and the indirect effects mediated by increases in the headache frequency and severity. Results: This study included 915 patients: 784 with migraine and 131 with TTH. Worse sleep quality was independently associated with greater headache-related impact in both patients with migraine and those with TTH. Path analysis revealed a direct effect (β=0.207,p<0.001) of sleep quality and an indirect effect mediated by headache frequency and severity (β=0.067, p=0.004) on the headache-related impact in migraine. In TTH, only direct effects of sleep quality on the headache-related impact were significant (β=0.224, p=0.004). Conclusions We suggest that poor sleep quality can directly increase the headache-related impact in both patients with migraine and TTH as well as indirectly by increasing the headache frequency and severity in patients with migraine.