Identifying Adverse Events Using International Classification of Diseases, Tenth Revision Y Codes in Korea: A Cross-sectional Study.

OBJECTIVES: The use of administrative data is an affordable alternative to conducting a difficult large-scale medical-record review to estimate the scale of adverse events. We identified adverse events from 2002 to 2013 on the national level in Korea, using International Classification of Diseases, tenth revision (ICD-10) Y codes. METHODS: We used data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC). We relied on medical treatment databases to extract information on ICD-10 Y codes from each participant in the NHIS-NSC. We classified adverse events in the ICD-10 Y codes into 6 types: those related to drugs, transfusions, and fluids; those related to vaccines and immunoglobulin; those related to surgery and procedures; those related to infections; those related to devices; and others. RESULTS: Over 12 years, a total of 20 817 adverse events were identified using ICD-10 Y codes, and the estimated total adverse event rate was 0.20%. Between 2002 and 2013, the total number of such events increased by 131.3%, from 1366 in 2002 to 3159 in 2013. The total rate increased by 103.9%, from 0.17% in 2002 to 0.35% in 2013. Events related to drugs, transfusions, and fluids were the most common (19 446, 93.4%), followed by those related to surgery and procedures (1209, 5.8%) and those related to vaccines and immunoglobulin (72, 0.3%). CONCLUSIONS: Based on a comparison with the results of other studies, the total adverse event rate in this study was significantly underestimated. Improving coding practices for ICD-10 Y codes is necessary to precisely monitor the scale of adverse events in Korea.

Epidemiologic research on lung damage caused by humidifier disinfectants.

In April 2011 a tertiary hospital located in Seoul, Korea reported several cases of severe respiratory distress of unknown origin in young adults. To find the route of transmission, causative agent and patient risk factors of the outbreak, an investigation of the epidemic was initiated. A hospital based case-control study was conducted to indicate that humidifier detergent use was the cause of the outbreak. This information led the Ministry of Health and Welfare of Korea issued an order that humidifier detergents should be withdrawn from the market. Here, we describe the major events of planning, execution, and interpretation of the study, and discussions between researchers and public authorities following the decision to perform an epidemiologic study, chronologically.

Humidifier Disinfectants Are a Cause of Lung Injury among Adults in South Korea: A Community-Based Case-Control Study.

BACKGROUNDS: An outbreak of lung injury among South Korean adults was examined in a hospital-based case-control study, and the suspected cause was exposure to humidifier disinfectant (HD). However, a case-control study with community-dwelling controls was needed to validate the previous study's findings, and to confirm the exposure-response relationship between HD and lung injury. METHODS: Each case of lung injury was matched with four community-dwelling controls, according to age (±3 years), sex, residence, and history of childbirth since 2006 (for women). Environmental risk factors, which included type and use of humidifier and HD, were investigated using a structured questionnaire during August 2011. The exposure to HD was calculated for both cases and controls, and the corresponding risks of lung injury were compared. RESULTS: Among 28 eligible cases, 16 patients agreed to participate, and 60 matched controls were considered eligible for this study. The cases were more likely to have been exposed to HD (odds ratio: 116.1, 95% confidence interval: 6.5-2,063.7). All cases were exposed to HDs containing polyhexamethyleneguanidine phosphate, and the risk of lung injury increased with the cumulative exposure, duration of exposure, and exposure per day. CONCLUSIONS: This study revealed a statistically significant exposure-response relationship between HD and lung injury. Therefore, continuous monitoring and stricter evaluation of environmental chemicals' safety should be conducted.

ROC Estimation from Clustered Data with an Application to Liver Cancer Data.

In this article, we propose a regression model to compare the performances of different diagnostic methods having clustered ordinal test outcomes. The proposed model treats ordinal test outcomes (an ordinal categorical variable) as grouped-survival time data and uses random effects to explain correlation among outcomes from the same cluster. To compare different diagnostic methods, we introduce a set of covariates indicating diagnostic methods and compare their coefficients. We find that the proposed model defines a Lehmann family and can also introduce a location-scale family of a receiver operating characteristic (ROC) curve. The proposed model can easily be estimated using standard statistical software such as SAS and SPSS. We illustrate its practical usefulness by applying it to testing different magnetic resonance imaging (MRI) methods to detect abnormal lesions in a liver.

Voice Changes in Elderly Adults: Prevalence and the Effect of Social, Behavioral, and Health Status on Voice Quality.

OBJECTIVES: To estimate the prevalence of dysphonia and the effect of several risk factors on vocal quality in a representative population of older adults. DESIGN: Cross-sectional. SETTING: Korea. PARTICIPANTS: Individuals aged 65 and older who underwent laryngoscopy from 2008 to 2010 (N = 3,759). MEASUREMENTS: The prevalence of dysphonia and the effect of potential risk factors on voice quality in elderly adults were measured. RESULTS: The mean age of participants was 72.4. The prevalence of dysphonia was 8.5% (95% confidence interval (CI) = 7.4-9.8). There was no significant difference in prevalence according to age. Multivariable analysis after adjusting for age, sex, vocal fold disease, and all variables that were identified in the univariate analysis revealed that urban residence (odds ratio (OR) = 1.83, 95% CI = 1.11-3.04), underweight (OR = 2.79, 95% CI = 1.45-5.38) or normal weight (OR = 1.63, 95% CI = 1.03-2.59), poor (OR = 2.00, 95% CI = 1.19-3.34) or intermediate (OR = 2.08, 95% CI = 1.15-3.78) subjective health status, asthma (OR = 2.08, 95% CI = 1.12-3.86), chronic obstructive pulmonary disease (OR = 2.49, 95% CI = 1.10-5.62), thyroid disease (OR = 3.08, 95% CI = 1.50-6.34), and vocal fold disease (OR = 3.72, 95% CI = 2.16-6.42) were independently associated with dysphonia in elderly adults. CONCLUSION: This study provides valuable information regarding the prevalence of dysphonia and the risk factors that contribute to vocal quality in older adults. These factors are mostly associated with social, behavioral, and underlying health status variables. Multidisciplinary treatment should be considered to improve voice conditions in elderly adults.

Vegetable intake, but not fruit intake, is associated with a reduction in the risk of cancer incidence and mortality in middle-aged Korean men.

BACKGROUND: Few prospective studies have examined the preventive role of fruit and vegetable intakes against cancer in Asian populations. OBJECTIVE: This prospective study evaluated the associations between total fruit intake, total vegetable intake, and total fruit and vegetable intake and total cancer incidence and mortality. METHODS: This prospective cohort study included 14,198 men 40-59 y of age enrolled in the Seoul Male Cohort Study from 1991 to 1993. Fruit and vegetable intakes were assessed by a validated food-frequency questionnaire. We used Cox proportional hazard regression models to compute RR ratios and 95% CIs. RESULTS: During the follow-up period from 1993 to 2008, 1343 men were diagnosed with cancer, and 507 died of cancer. Total vegetable intake was linearly associated with cancer incidence but was nonlinearly associated with cancer mortality; by comparing ≥ 500 g/d with <100 g/d of total vegetable intake, the multivariable-adjusted RR for total cancer incidence was 0.72 (95% CI: 0.58, 0.90; P-trend: 0.02; P-nonlinearity: 0.06). For total cancer mortality, the multivariable-adjusted RRs comparing 100 to <200 g/d, 200 to <300 g/d, 300 to <500 g/d, and ≥ 500 g/d with <100 g/d of total vegetable intake were 0.68 (95% CI: 0.53, 0.88), 0.75 (95% CI: 0.57, 0.98), 0.72 (95% CI: 0.54, 0.95), and 0.67 (95% CI: 0.47, 0.95), respectively (P-trend: 0.09; P-nonlinearity: 0.01). No associations were found between total fruit intake and total cancer incidence and mortality; ≥ 300 g/d vs. <50 g/d, RR: 1.04 (95% CI: 0.87, 1.25; P-trend = 0.56) for incidence and RR: 0.89 (95% CI: 0.66, 1.21; P-trend = 0.71) for mortality. CONCLUSIONS: Our findings suggest that total vegetable intake is linearly associated with cancer incidence but nonlinearly associated with total cancer mortality in middle-aged Korean men. However, total fruit intake is not associated with total cancer incidence or mortality.

Model for assessing cardiovascular risk in a Korean population.

BACKGROUND: A model for predicting cardiovascular disease in Asian populations is limited. METHODS AND RESULTS: In total, 57 393 consecutive asymptomatic Korean individuals aged 30 to 80 years without a prior history of cardiovascular disease who underwent a general health examination were enrolled. Subjects were randomly classified into the train (n=45 914) and validation (n=11 479) cohorts. Thirty-one possible risk factors were assessed. The cardiovascular event was a composite of cardiovascular death, myocardial infarction, and stroke. In the train cohort, the C-index (95% confidence interval) and Akaike Information Criterion were used to develop the best-fitting prediction model. In the validation cohort, the predicted versus the observed cardiovascular event rates were compared by the C-index and Nam and D'Agostino χ(2) statistics. During a median follow-up period of 3.1 (interquartile range, 1.9-4.3) years, 458 subjects had 474 cardiovascular events. In the train cohort, the best-fitting model consisted of age, diabetes mellitus, hypertension, current smoking, family history of coronary heart disease, white blood cell, creatinine, glycohemoglobin, atrial fibrillation, blood pressure, and cholesterol (C-index =0.757 [0.726-0.788] and Akaike Information Criterion =7207). When this model was tested in the validation cohort, it performed well in terms of discrimination and calibration abilities (C-index=0.760 [0.693-0.828] and Nam and D'Agostino χ(2) statistic =0.001 for 3 years; C-index=0.782 [0.719-0.846] and Nam and D'Agostino χ(2) statistic=1.037 for 5 years). CONCLUSIONS: A risk model based on traditional clinical and biomarkers has a feasible model performance in predicting cardiovascular events in an asymptomatic Korean population.

A cluster of lung injury cases associated with home humidifier use: an epidemiological investigation.

BACKGROUND: In April 2011 a tertiary hospital in Seoul, Korea reported several cases of severe respiratory distress of unknown origin in young adults. METHODS: To find the route of transmission, causative agent and patient risk factors of the outbreak, an investigation of the epidemic was initiated. Clinicopathological conferences led to the suspicion that the cases related to an inhalation injury. An age- and sex-matched case-control study was therefore performed to examine the inhalation exposure of the patients to various agents. RESULTS: Of the 28 confirmed cases, 18 agreed to participate. A total of 121 age- and sex-matched controls with pulmonary, allergic or obstetric disease were selected. All patients and controls completed questionnaires with questions about exposure to various inhalants. The crude ORs for patient exposure to indoor mould, humidifier use, humidifier detergent use and insecticide use were 4.4 (95% CI 1.5 to 13.1), 13.7 (95% CI 1.8 to 106.3), 47.3 (95% CI 6.1 to 369.7) and 3.9 (95% CI 1.3 to 11.7), respectively. However, when considered concurrently, indoor mould and insecticide use lost statistical significance. Moreover, humidifier use was ruled out as the cause because of a lack of biological plausibility and the weak strength of the association. This suggested that humidifier disinfectant was the cause of the outbreak. This information led the Korean government to order the removal of humidifier detergents from the market. In the years following the ban, no additional cases were detected. CONCLUSIONS: Epidemiological evidence strongly suggests that the lung injury outbreak was caused by humidifier detergent use at home.

A cluster of lung injury associated with home humidifier use: clinical, radiological and pathological description of a new syndrome.

BACKGROUND: Over a few months in the spring of 2011, a cluster of patients with severe respiratory distress were admitted to our intensive care unit (ICU). Household clustering was also observed. Extensive laboratory investigations failed to detect an infectious cause. METHODS: Clinical, radiological and pathological investigations were conducted and the Korean Center for Disease Control performed epidemiological studies. RESULTS: The case series consisted of 17 patients. Their median age was 35 (range 28-49) years. Six were pregnant at presentation and four had given birth 2 weeks previously. All presented with cough and dyspnoea. In the majority of patients (14/17), multifocal areas of patchy consolidation were identified in the lower lung zones on the initial CT. As the condition progressed, the patchy consolidation disappeared (10/13) and diffuse centrilobular ground-glass opacity nodules started to predominate and persist. Pathological specimens (11/17) showed a bronchiolocentric, temporally homogenous, acute lung injury pattern with sparing of the subpleural and peripheral alveolar areas. Ten patients required mechanical ventilation, eight of whom subsequently received extracorporeal life support. Four of the latter underwent lung transplantation. Five of the six patients in the ICU who did not receive lung transplantation died. An epidemiological investigation revealed that all patients had used humidifier disinfectants in their homes. CONCLUSIONS: This case series report showed that lung injury and respiratory failure can occur as a result of inhaling humidifier disinfectants. This emphasises the need for more stringent safety regulations for potentially toxic inhalants that might be encountered in the home.

Cardiovascular health metrics and all-cause and cardiovascular disease mortality among middle-aged men in Korea: the Seoul male cohort study.

OBJECTIVES: This study estimated the association of cardiovascular health behaviors with the risk of all-cause and cardiovascular disease (CVD) mortality in middle-aged men in Korea. METHODS: In total, 12 538 men aged 40 to 59 years were enrolled in 1993 and followed up through 2011. Cardiovascular health metrics defined the following lifestyle behaviors proposed by the American Heart Association: smoking, physical activity, body mass index, diet habit score, total cholesterol, blood pressure, and fasting blood glucose. The cardiovascular health metrics score was calculated as a single categorical variable, by assigning 1 point to each ideal healthy behavior. A Cox proportional hazards regression model was used to estimate the hazard ratio of cardiovascular health behavior. Population attributable risks (PARs) were calculated from the significant cardiovascular health metrics. RESULTS: There were 1054 total and 171 CVD deaths over 230 690 person-years of follow-up. The prevalence of meeting all 7 cardiovascular health metrics was 0.67%. Current smoking, elevated blood pressure, and high fasting blood glucose were significantly associated with all-cause and CVD mortality. The adjusted PARs for the 3 significant metrics combined were 35.2% (95% confidence interval [CI], 21.7 to 47.4) and 52.8% (95% CI, 22.0 to 74.0) for all-cause and CVD mortality, respectively. The adjusted hazard ratios of the groups with a 6-7 vs. 0-2 cardiovascular health metrics score were 0.42 (95% CI, 0.31 to 0.59) for all-cause mortality and 0.10 (95% CI, 0.03 to 0.29) for CVD mortality. CONCLUSIONS: Among cardiovascular health behaviors, not smoking, normal blood pressure, and recommended fasting blood glucose levels were associated with reduced risks of all-cause and CVD mortality. Meeting a greater number of cardiovascular health metrics was associated with a lower risk of all-cause and CVD mortality.

Cigarette smoking and prostate cancer risk: negative results of the Seoul Male Cancer Cohort Study.

We evaluated cigarette smoking as a risk factor for prostate cancer in a prospective, population-based cohort study. The subjects were 14,450 males among the participants in the Seoul Male Cancer Cohort Study who had at least 1-year follow-up. They were followed up between 1993 and 2008. During the 16-year follow-up period, 87 cases of prostate cancer occurred over the 207,326 person-years of the study. The age-adjusted relative risks of past and current smokers at entry were 0.60 (95%CI: 0.34-1.06) and 0.70 (95%CI: 0.43-1.13), respectively, suggesting that cigarette smoking may not be a risk factor for prostate cancer. The relationship between prostate cancer and other modifiable factors, such as Westernized diet, should be studied with the goal of establishing prevention programs for prostate cancer.

Pulmonary tuberculosis and lung cancer risk in current smokers: the Seoul Male Cancer Cohort Study.

Authors evaluated pulmonary tuberculosis (PTB) history as a risk factor for lung cancer in current male smokers in a prospective, population-based cohort study. The subjects were the 7,009 males among the participants in the Seoul Male Cancer Cohort Study for whom there was full information on PTB history and smoking habits. With a 16-yr follow-up, 93 cases of lung cancer occurred over the 99,965 person-years of the study. The estimated relative risk (RR) of PTB history of current smokers in lung cancer after adjusting for three confounders - intake of coffee and tomatoes, and age at entry - was 1.85 (95% CI: 1.08-3.19). The observed joint RRs and attributable risks (ARs) across strata of three confounders were greater than the expected, indicating a positive interaction. Thus a history of PTB in current smokers may be another risk factor for lung cancer. Based on a synergic interaction, a heavy male smoker with a PTB history would be expected to belong to the group at high risk of lung cancer.

Lung cancer incidence by smoking status in Korean men: 16-years of observations in the Seoul Male Cancer Cohort study.

The relative risk (RR) of smoking and mortality of lung cancer in British doctors was previously reported to have increased throughout a 40-yr period. Here, we evaluated this RR based on the incidence of lung cancer in Korean men using a longer follow-up period. We compared our data to the RR reported in a study using a 10-yr follow-up period; the subjects and methods were identical to those of the previous paper with the exception of the follow-up period, which ended on December 31, 2008. We found that the RR of smoking habits in patients with lung cancer did not increase, and that the data showed narrowing 95% confidence intervals over a longer observation in Korean men. Estimated lung cancers attributable to smoking were 55.6%. These results highlight the need for an intervention program to help patients quit smoking in Korea.

Development and validation of comorbidity index in South Korea.

OBJECTIVE: This study aims to develop and validate a new comorbidity index using data from hospitalized patients in South Korea. STUDY DESIGN: Retrospective cohort study. SETTING: Hospital inpatients. STUDY PARTICIPANTS: Data from 4677 hospitalized patients aged 40-79 who had admitted in a medical center in Korea between September and December in 1997 were individually linked to national mortality data through December 2007. Among them, 3274 patients (70%) were randomly included in the development data set and the other 1403 patients (30%) in the validation data set. Another 3413 liver cancer patients from the same hospital were used to validate the index. MAIN MEASURE: Comorbidity index and mortality risk. RESULTS: Based on mortality using stratified Cox regression analyses, comorbidity scores ranging from 1 to 4 were assigned for 20 comorbid conditions. Summation of the scores produced the new comorbidity index (Asan comorbidity index, ACI). C-indices in the Cox regression analyses showed the greatest increase [0.589 (95% confidence interval, 0.568-0.609) in age- and sex-adjusted model; 0.697 (0.678-0.716) in the ACI and 0.664 (0.645-0.684) in the Charlson comorbidity index, respectively] when the ACI was added in the validation models. CONCLUSIONS: A newly developed comorbidity index using Korean hospitalized patient data based on the International Classification of Disease, 10th Revision (ICD-10) was valid among both general medical inpatients and liver cancer patients. This index may well be widely used in various health-care settings in Korea where patients' information on health conditions is coded with ICD-10.

Cancer rehabilitation: experience, symptoms, and needs.

The aim of this study was to examine the experience of cancer patients undergoing rehabilitation, to identify symptoms associated with rehabilitation from cancer, and to assess the need for rehabilitation services for cancer patients. Cancer patients (n = 402) at the Asan Medical Center (Seoul, Korea) were enrolled from June to September 2008. A chart review was used to collect demographic and clinical data, including type of cancer, current treatment, time from initial diagnosis to screening, and cancer stage. Each participant provided informed consent and was then given a questionnaire that asked about experience with rehabilitation, symptoms associated with rehabilitation, and the need for different types of rehabilitation services. Clinicians recommended rehabilitation for 8.5% of patients, and 6.7% underwent rehabilitation. Among study patients, 83.8% had one or more symptoms associated with rehabilitation, and 71.6% of patients with symptoms wanted rehabilitation management. The need for rehabilitation was associated with the presence of metastasis, advanced cancer stage, time to diagnosis, and type of current treatment. Our results provide specific information about particular functional symptoms and the rehabilitative needs of subgroups of cancer patients. It is suggested to develop and implement rehabilitation programs for cancer patients.

Tetralogy of Fallot without the infundibular septum-restricted growth of the pulmonary valve annulus after annulus preservation may render the right ventricular outflow tract obstructive.

OBJECTIVE: Tetralogy of Fallot (ToF) with infundibular septal deficiency (ISD) is commonly associated with postoperative right ventricular outflow tract obstruction (RVOTO), presumably caused by subpulmonary extension of ventricular septal defect (VSD) and restricted growth of the pulmonary valve annulus (PVA). We sought to determine the postoperative growth of the PVA after annulus preservation according to the presence or absence of the infundibular septum. METHODS: A retrospective review of 90 patients who underwent surgical repair of ToF between June 1997 and August 2008 was performed. Median age at operation was 9.5 months. Infundibular septum was absent in 15 (15/90, 17%). PVA was preserved in 71 patients (71/90, 79%), including 13 patients with ISD (13/15, 87%). RESULTS: Median follow-up duration was 39 months (2 months to 13 years). There was no early mortality and one late noncardiac death. Among the patients with PVA preservation, reoperation for RVOTO was performed in 4 patients (4/71, 6%), including 3 patients without the infundibular septum. ISD was identified as the only risk factor in reoperation for RVOTO after PVA preservation (RR: 21.85, P = .007). Among the patients who underwent repair with PVA preservation during infancy (n = 43), PVA (Z-score) increased postoperatively in patients with the infundibular septum (+ 0.021/month, P = .009), whereas the changes in PVA (Z-score) were nonsignificant in patients with ISD (-0.021/month, P = .306), with a marginal intergroup difference (P = .056). CONCLUSIONS: PVA preservation in ToF with ISD may be associated with a higher risk for postoperative RVOTO, which can be attributed to the restricted growth of the PVA.

[Construction and validation of hospital-based cancer registry using various health records to detect patients with newly diagnosed cancer: experience at Asan Medical Center].

OBJECTIVES: An accurate estimation of cancer patients is the basis of epidemiological studies and health services. However in Korea, cancer patients visiting out-patient clinics are usually ruled out of such studies and so these studies are suspected of underestimating the cancer patient population. The purpose of this study is to construct a more complete, hospital-based cancer patient registry using multiple sources of medical information. METHODS: We constructed a cancer patient detection algorithm using records from various sources that were obtained from both the in-patients and out-patients seen at Asan Medical Center (AMC) for any reason. The medical data from the potentially incident cancer patients was reviewed four months after first being detected by the algorithm to determine whether these patients actually did or did not have cancer. RESULTS: Besides the traditional practice of reviewing the charts of in-patients upon their discharge, five more sources of information were added for this algorithm, i.e., pathology reports, the national severe disease registry, the reason for treatment, prescriptions of chemotherapeutic agents and radiation therapy reports. The constructed algorithm was observed to have a PPV of 87.04%. Compared to the results of traditional practice, 36.8% of registry failures were avoided using the AMC algorithm. CONCLUSIONS: To minimize loss in the cancer registry, various data sources should be utilized, and the AMC algorithm can be a successful model for this. Further research will be required in order to apply novel and innovative technology to the electronic medical records system in order to generate new signals from data that has not been previously used.

Mass screening for prostate cancer in Korea: a population based study.

PURPOSE: We investigated the detection rate of prostate cancer in Korean men through a population based mass screening test. MATERIALS AND METHODS: In June 2007 serum prostate specific antigen was examined in 3,943 residents in the Gangneung (1,429), Daegu (1,396) and Jeonju (1,118) areas who were 55 years or older with prostate specific antigen 3.0 ng/ml or greater considered the criterion for 12-site transrectal biopsy recommendation. The serum prostate specific antigen distribution and the cancer detection rate were analyzed according to participant regions and age groups. RESULTS: Mean +/- SD serum prostate specific antigen in the entire cohort was 2.4 +/- 8.6 ng/ml. It significantly increased with increasing age, that is 1.2, 2.2, 3.4 and 4.7 ng/ml in the groups 55 to 64, 65 to 74, 75 to 84 and 85 years or older, respectively (p <0.0001). However, no regional differences were noted among Gangneung, Daegu and Jeonju (2.2, 2.7 and 2.3 ng/ml, respectively, p = 0.290). Biopsy candidates represented 7.3% (48 men), 17.7% (395), 25.5% (240) and 32.7% (36) of the 55 to 64, 65 to 74, 75 to 84 and 85 years or older groups, respectively, or 18.2% of the entire cohort of 719. Of biopsy candidates 268 (37.3%) had undergone biopsy, of whom cancer was detected in 76 (28.4%) for a cancer detection rate and estimated cancer detection rate of 1.93% and 5.17%, respectively. The age adjusted estimated cancer detection rate (55 years or older) was 3.36%. Cancer detection increased significantly with increasing prostate specific antigen, that is 12.3% at 3.0 to 4.0 ng/ml, 27.3% at 4.1 to 10.0 and 64.1% at greater than 10.0. The Gleason score was 2-6 in 41 men (53.9%), 7 in 14 (18.4%) and 8-10 in 21 (27.6%). CONCLUSIONS: The estimated cancer detection rate in Korean men 55 years or older was 3.36%. The significance of the high rate in this population should be determined through repeat screening and further surveillance in the future.

Ruptured sinus of Valsalva aneurysm: transaortic repair may cause sinus of Valsalva distortion and aortic regurgitation.

OBJECTIVES: Recurrent or newly developing aortic regurgitation is a critical problem after the repair of ruptured sinus of Valsalva aneurysm. METHODS: A retrospective review of 56 patients who underwent surgical repair of ruptured sinus of Valsalva aneurysm between June 1990 and August 2006 was performed. Rupture of the right coronary sinus into the right ventricle was the most common anatomic type (39/56, 69.6%). Preoperative aortic regurgitation equal to or greater than grade II (n = 8, 17.9%) was managed by repair (aortic valvuloplasty, n = 5) or replacement (n = 3). Ruptured sinus of Valsalva aneurysm was repaired primarily (n = 7) or by patching (n = 10) through an aortotomy in 17 patients (transaortic group). In the remaining patients (n = 39), ruptured sinus of Valsalva aneurysm was repaired primarily from the chamber into which the corresponding aortic sinus ruptured, and the aneurysmal sac was reinforced with a supporting patch (non-transaortic group). RESULTS: Median follow-up duration was 46 months (0.4-177 months). There were 2 late deaths. Excluding 3 patients with aortic valve replacement on aneurysm repair, 11 patients (11/53, 21%) had recurrent or new-onset significant aortic regurgitation (> or = II/IV) during the follow-up period. By multivariable analysis, aortic valvuloplasty at initial operation was the only significant risk factor for postoperative aortic regurgitation (P < .001). After adjustment, the non-transaortic approach appeared to be associated with a lower risk of postoperative aortic regurgitation, with marginal significance (hazard ratio 0.28; P = .058). Five-year freedom from significant aortic regurgitation in the transaortic and non-transaortic groups was 68% +/- 12% and 94% +/- 4%, respectively. CONCLUSION: Transaortic repair of ruptured sinus of Valsalva aneurysm may cause postoperative aortic regurgitation by progressive distortion of the aortic sinus geometry.

Randomized comparison of four-times-daily versus once-daily intravenous busulfan in conditioning therapy for hematopoietic cell transplantation.

Sixty patients were randomized to receive intravenous busulfan (iBU) either as 0.8 mg/kg, over 2 hours 4 times a day (BU4 arm) or 3.2 mg/kg, over 3 hours once a day (BU1 arm) in conditioning therapy for hematopoietic cell transplantation. The complete pharmacokinetic parameters for the first busulfan dose were obtained from all patients and were comparable between the 2 arms: for the BU4 and BU1 groups, elimination half-life (mean+/-SD) was 2.75+/-0.22 versus 2.83+/-0.21 hours, estimated daily AUC was 6058.0+/-1091.9 versus 6475.5+/-1099.4 microM.min per day, and clearance was 2.05+/-0.36 versus 1.91+/-0.31 mL/min/kg, respectively. Times to engraftment after transplantation were similar between the 2 arms. No significant differences were evident in the occurrence of acute graft-versus-host disease (aGVHD) and hepatic veno-occlusion disease (VOD). Moreover, other toxicities observed within 100 days after transplantation were not significantly different between the 2 arms. The cumulative incidence of nonrelapse mortality was 20.8% in BU4 arm and 13.3% in BU1 arm. In conclusion, our randomized study demonstrates that the pharmacokinetic profiles and posttransplant complications are similar for once-daily iBU and traditional 4-times-daily iBU.