1 Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI.
2 Department of Preventive Medicine, Eulji University School of Medicine, Daejeon, South Korea.
3 Department of Statistics, Seoul National University, Seoul, South Korea.
4 Department of Preventive Medicine, Hanyang University College of Medicine, Seoul, South Korea.
Received for publication April 1, 2004; accepted for publication June 3, 2004.
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ABSTRACT |
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hospitalization; nephritis, interstitial; pyelonephritis; recurrence; seasons
Abbreviations: Abbreviation: ICD-10, International Classification of Diseases, Tenth Revision.
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INTRODUCTION |
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In this paper, we describe the incidence, recurrence, seasonality, mortality, and medical costs of acute pyelonephritis for inpatients and outpatients. We used 19971999 South Korean nationwide health insurance claims data.
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MATERIALS AND METHODS |
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Mortality data
National mortality data in South Korea have been computerized since 1983. Mortality data originate from hospital medical records departments and the statistics division of the provincial government offices. Management of provincial statistics is ongoing, with central management in the Vital Statistics Division of the Korean National Statistical Office. Before national mortality data are provided for each year, the patient name and the last digit of the national registration number for each death record are removed to ensure patient confidentiality. Death records contain patient name, address, date of birth, national registration number, gender, date of death, cause of death, occupation and educational level, location at time of death, marital status, diagnosing provider, date that the death was reported, and place of death. Cause of death is coded by using ICD-10. In addition to the primary cause of death, a secondary cause of death is recorded for a limited number of records.
Definitions
We defined a case as any person whose primary discharge diagnosis was acute pyelonephritis: ICD-10 codes N10 (acute tubulo-interstitial nephritis) and N12 (tubulo-interstitial nephritis, not specified as acute or chronic). Episodes without a pyelonephritis claim during the previous year were considered sporadic; episodes with a pyelonephritis claim during the previous year were considered recurrent. When the time period between two episodes was more than 365 days, the second episode was considered sporadic. Two or more claims during a 14-day period were considered a single episode. Details of case selection criteria are shown in figure 1.
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The observation period used to calculate recurrence rates was defined as January 1, 1997, to September 30, 1999. We used this period because claims data for any given year are incomplete for treatment claims occurring in November and December of that same year because there is a 1- to 2-month lag in billing.
Data analysis
Incidence rates were calculated by using data from the 19971999 South Korea Census Bureau population projection for the denominator (46,286,503 in 1998) (9). Incidence rates by health insurance versus medical aid were calculated by using the covered population as the denominator (44,472,000 for health insurance and 1,322,696 for medical aid in 1998) (10). To verify seasonal variation, we used the Poisson dispersion test (11).
Using the national registration number, we linked the insurance data and national mortality data to calculate the mortality rate. We used the number of deaths within 1 month following treatment of pyelonephritis as the numerator (from national mortality data) and the number of pyelonephritis cases in 19971998 for the denominator (from insurance claims data).
To calculate the hazard ratios for recurrences, we used a Cox proportional hazards regression analysis that did not adjust for repeated recurrent events within a person. To adjust for repeated recurrent events within a person, we used a frailty model (12). We included all variables and tested all possible interactions; only significant interactions were included in the final model. For the analysis of multiple recurrences, the variable "previous interval of recurrence" was added to the model. Hazard ratios were calculated by exponentiating the coefficient.
Claims-based insurance data were linked to national mortality data by using national registration numbers. The Korean national registration number has 13 digits: six for birth date, one for gender, four for birthplace code, and one for birth order for babies who are born in the same place, are born on the same date, and are of the same gender. The last digit is a function of the previous 12. Therefore, we lacked information on only one informative digit, that indicating birth order. Since the number of possible birthplaces is 3,519 and the number of births per year is about 700,000, on average 0.27 births occur in each birthplace per day (700,000/(365 days x 2 genders x 3,519 birthplaces)). Therefore, when the last two digits of the national registration number are excluded, the probability of error in matching is very small: an estimated 0.93 x 106 (0.27 x 0.00357 x 0.27 x 0.00357, where the annual incidence rate of pyelonephritis is 0.00357 according to our results).
All analyses were conducted by using the SAS (version 8.1) software program (SAS Institute, Inc., Cary, North Carolina) and R program (13). Analysis of these data were approved by the Institutional Review Board of the University of Michigan on December 20, 2002.
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RESULTS |
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The annual incidence of acute pyelonephritis per 10,000 South Korea population was 35.7. The incidence of hospitalization for acute pyelonephritis was 9.96 per 10,000 for females and 1.18 per 10,000 for males. Outpatient incidence was higher: 49.1 per 10,000 for females and 11.4 per 10,000 for males. Approximately one of every seven patients was hospitalized (inpatients, 5.5 per 10,000; outpatients, 30.1 per 10,000). For every age after age 2 years, females had a higher incidence than males did, with average overall incidence rates of 59.0 per 10,000 for females and 12.6 per 10,000 for males. Sporadic episodes among females increased dramatically after 15 years of age until age 25 years. After age 25 years, incidence remained stable until 80 years of age (figure 2). By contrast, the incidence among males increased gradually with age.
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The probability of recurrence increased with the number of previous recurrences. Following a sporadic episode, the risk of a recurrence within 12 months was 9.2 percent for females and 5.7 percent for males. Among persons with four previous episodes, the risk of a fifth episode within 12 months was 53.0 percent for females and 50.0 percent for males (table 2). The recurrence rate varied by interval of previous recurrence; the chance of a third recurrence for those with a second recurrence within 61 days was 41.1 percent; however, if the time period between the first and second recurrences was 121 days, the risk of a third recurrence was 24.1 percent. Median intervals between recurrences shortened with frequency of recurrence for both males and females. One male (aged 42 years) experienced 27 episodes in 3 years. Among sporadic cases, one woman aged 45 years experienced 14 recurrences within 17 months, which was the maximum number of recurrences recorded.
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The hazard ratio for any recurrence increased with age and was significantly higher for females, outpatients, and those receiving medical aid (table 3). There was a significant interaction between gender and care type: when male inpatients were considered the reference group, male outpatients, female inpatients, and female outpatients had 1.35, 1.89, and 1.99 times higher hazards for recurrence, respectively. Hospital size also made a difference: when those treated as inpatients in hospitals (30 beds) were used as the reference group, the hazard ratios for hospital outpatients, clinic (<30 beds) inpatients, and clinic outpatients were 1.35, 1.12, and 1.99, respectively. Seasonal differences in the hazard ratio were smaller, with slightly higher hazards for the winter and spring seasons than for the fall season.
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Mortality
The overall mortality rate per 1,000 pyelonephritis cases was 1.2 (females, 1.0; males, 2.0). When we considered just renal or infectious disease as the cause of death noted on the death certificate, the mortality rate was 0.2 per 1,000 for females and 0.3 per 1,000 for males. Among hospitalized patients, the average mortality rate was 2.1 per 1,000 (females, 1.7; males, 5.3). For renal or infectious disease as the cause of death, the mortality rate for hospitalized cases was 0.5 per 1,000 for females and 0.6 per 1,000 for males. Renal or infectious disease accounted for 18 percent, cancer for 21 percent, cardiovascular disease for 19 percent, senility for 10 percent, diabetes complications for 8 percent, and gastrointestinal disease for 7 percent of all deaths occurring in 1 month following acute pyelonephritis.
Treatment duration and costs
Treatment duration per episode (8.4 days) was similar for males and females, averaging 7.2 days for outpatients and 14.1 days for inpatients. The average number of visits per outpatient episode was 2.9. The average duration of hospitalization per inpatient episode was 7.9 days. The 95 percent confidence intervals for treatment duration were very close to the mean.
The medical cost (clinic charge per physician visit + cost per prescription + hospitalization charge) increased each year. Therefore, the average cost was calculated by using the most recent year, 1999. The average medical cost per episode for hospitalized patients was $513.60 (females, $511.00; males, $535.40). Among outpatients, the average medical cost per episode was $57.30 (females, $59.00; males, $50.70). The total medical costs for acute pyelonephritis were $15.1 million, $16.9 million, and $17.6 million in 1997, 1998, and 1999, respectively. The cost for pyelonephritis was 0.2 percent of the national total medical cost for 1999 ($9.75 billion).
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DISCUSSION |
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Age and gender differences in our data were similar to those in previous studies (2, 6). The hospitalization rate per 10,000 population among females (9.96) and males (1.18) was slightly lower than that reported for the United States (females, 11.7; males, 2.4) but higher than that for US Asian/Pacific Islanders (females, 5.4; males, 0.9) (2). There were no comparable data regarding outpatient incidence rates. The outpatient incidence was five times higher than the inpatient incidence for females and 10 times higher for males.
Recurrence of pyelonephritis is a significant problem, accounting for 15.2 percent of all acute pyelonephritis episodes occurring in South Korea in 1998. The frequency of recurrence was consistent with that in the one previous report we found (5). This study, conducted in 1973 among females aged 1535 years hospitalized for pyelonephritis, found a 6-month recurrence of 23 percent (16 per 74) and a 3-year recurrence of 40 percent (29 per 74) (5).
Female sex was the most important risk factor for recurrence. This finding might be partially explained by anatomic differences, which are known to cause a higher incidence of all urinary tract infections in females. The observed variation in recurrence rates by medical care type, payer type, and level of hospital (number of beds) may relate to treatment type, duration, or both, which may modify the risk of recurrence. Alternatively, underlying morbidities and disease severity may also play a role. Some underlying conditions, such as diabetes, may predispose to pyelonephritis (6).
Once a person experienced multiple recurrences, only the previous interval between pyelonephritis episodes, an age of 65 years or older, and the level of hospital significantly predicted a subsequent recurrence; gender had no effect. This finding suggests that the time between recurrences may be a potentially useful clinical and research marker. Some persons have a propensity to recurrence, and some bacterial strains may be harder to clear either in general or in particular for a host with a propensity to recurrence (15). While it is impossible to determine with these types of data, it might be that different types or durations of treatments may be indicated for those with a short time between recurrences. A recent study suggested a positive association of history of urinary tract infections with development of renal cell carcinoma, so identifying treatments to minimize recurrences may decrease not only associated morbidity but also potential sequelae (16).
We observed a strong seasonal trend in acute pyelonephritis incidence. Seasonal trends provide useful clues to understanding transmission patterns. Explanations for seasonality can be grouped into three types: pathogen appearance and disappearance, environmental changes, and host-behavior changes (17). Seasonal variation in acute pyelonephritis may be due to increased host resistance in the winter season or decreased virulence of the pathogen during that time. Escherichia coli, the most common cause of pyelonephritis and all urinary tract infections, are transmitted by person-to-person direct contact and by contaminated food or water. Presumably, uropathogenic E. coli are also transmitted by these modes, but the relative contributions of each mode are uncertain (15). Transmission by contaminated water might contribute to a summer peak of pyelonephritis. However, the only known documented seasonal variation in urinary tract infection caused by Staphylococcus saprophyticus has a late autumn peak (18).
In 1997, in-hospital mortality in the United States was 7.3 per 1,000 hospitalizations for females and 16.5 for males (2). These mortality rates were two to three times higher than our results (females, 1.7; males, 5.3). However, in both sets of data, the mortality rate for males was higher. Average treatment duration for outpatients (7.2 days) and for inpatients (14.1 days) was similar to the treatment duration recommended by the Infectious Disease Society of America (19). However, since we did not have data about antibiotics and complications, it is difficult to comment on the appropriateness of the treatment duration.
A strength of our study was the use of national health insurance data, a very large and comprehensive database that enabled us to analyze trends for both inpatients and outpatients. Estimates of mortality required linking mortality with insurance claims data, which may lead to errors in linkage, but we estimate that these errors were very small (refer to the Materials and Methods section). However, a problem with using administrative data to measure population-based rates of disease is the reliability of the diagnoses. Nicolle et al. (6) reported that 80 percent of patients with a discharge diagnosis of acute pyelonephritis met audit criteria for admission for acute pyelonephritis. In another study using South Korea health insurance data, the validity of diagnosis for aseptic meningitis in children was 88 percent (20). Since clinical symptoms, along with urinalysis or bacterial cultures, were not used to define the diagnosis, it is possible that the results were biased toward an overestimation of the incidence of acute pyelonephritis because other types of acute tubulo-interstitial nephritis cannot be excluded (e.g., drug induced). If information on treatment type (e.g., antibiotics) were available, this bias might be improved.
By contrast, additional cases may have been coded under other diagnoses, such as urinary tract infection or septicemia, which would lead to an underestimation of the true rates. Furthermore, until July 2000, patients in South Korea could obtain antibiotics at a drugstore without prescription, which might lead to an underestimation of the diagnosis of acute pyelonephritis, especially of recurrence. Following the institution of prescriptions for antibiotics, the number of claims for acute tubulo-interstitial nephritis (ICD-10 code N10) increased about 10.4 percent in 2001 and 13.6 percent in 2002 (21, 22) compared with the average number of claims during 19971999.
Nonetheless, we think that, overall, the rates of acute pyelonephritis based on the health insurance data are likely to be a reasonable approximation of the true rates. We used ICD-10 codes N10 (acute tubulo-interstitial nephritis) and N12 (tubulo-interstitial nephritis, not specified as acute or chronic) to define acute pyelonephritis because multiple recurrent cases can be coded as N12 and this selection of codes is consistent with other research (2). In conclusion, acute pyelonephritis occurs frequently in females and among males and females aged 60 years or older. The incidence among females treated as outpatients was five times higher than that for females treated as inpatients, and 10 times higher for males. Recurrences were common and occurred more frequently in females, those aged 45 years or older, those treated as outpatients, and persons receiving medical aid rather than having health insurance. The recurrence rate increased both with frequency of recurrence and shorter intervals between recurrences. There was a clear summer seasonal trend. Further research regarding the frequent recurrent group and the seasonality pattern is needed.
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ACKNOWLEDGMENTS |
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NOTES |
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REFERENCES |
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