Urine Extracellular Vesicle GATA2 mRNA Discriminates Biopsy Result in Men with Suspicion of Prostate Cancer.

PURPOSE: Prostate specific antigen has limited performance in detecting prostate cancer. The transcription factor GATA2 is expressed in aggressive prostate cancer. We analyzed the predictive value of urine extracellular vesicle GATA2 mRNA alone and in combination with a multigene panel to improve detection of prostate cancer and high risk disease. MATERIALS AND METHODS: GATA2 mRNA was analyzed in matched extracellular vesicles isolated from urines before and after prostatectomy (16) and paired urine and tissue prostatectomy samples (19). Extracellular vesicle GATA2 mRNA performance to distinguish prostate cancer and high grade disease was tested in training (52) and validation (165) cohorts. The predictive value of a multigene score including GATA2, PCA3 and TMPRSS2-ERG (GAPT-E) was tested in both cohorts. RESULTS: Confirming its prostate origin, urine extracellular vesicle GATA2 mRNA levels decreased significantly after prostatectomy and correlated with prostate cancer tissue GATA2 mRNA levels. In the training and validation cohort GATA2 discriminated prostate cancer (AUC 0.74 and 0.66) and high grade disease (AUC 0.78 and 0.65), respectively. Notably, the GAPT-E score improved discrimination of prostate cancer (AUC 0.84 and 0.72) and high grade cancer (AUC 0.85 and 0.71) in both cohorts when compared with each biomarker alone and PT-E (PCA3 and TMPRSS2-ERG). A GAPT-E score for high grade prostate cancer would avoid 92.1% of unnecessary prostate biopsies, compared to 61.9% when a PT-E score is used. CONCLUSIONS: Urine extracellular vesicle GATA2 mRNA analysis improves the detection of high risk prostate cancer and may reduce the number of unnecessary biopsies.

Primary radiotherapy vs conservative management for localized prostate cancer--a population-based study.

BACKGROUND: Radiotherapy is the most common curative cancer therapy used for elderly patients with localized prostate cancer. However, the effectiveness of this approach has not been established. The purpose of this study is to evaluate the long-term outcomes of primary radiotherapy compared with conservative management in order to facilitate treatment decisions. METHOD: This population-based study consisted of 57,749 patients with T1-T2 prostate cancers diagnosed during 1992-2007. We utilized an instrumental variable (IV) analytical approach with competing risk models to evaluate the outcomes of primary radiotherapy vs conservative management. The IV was comprised of combined health service areas with high- and low-use areas corresponding to the top and bottom tertile in radiotherapy usage rates. RESULTS: In patients with low-/intermediate-risk prostate cancer, 10-year prostate cancer-specific and overall survival was similar in high- and low-radiotherapy use areas (96.1 vs 95.4% and 56.6 vs 56.3%, respectively). In patients with high-risk disease, however, areas with high-radiotherapy use had a higher 10-year cancer-specific survival (90.2 vs 88.1%, difference 2.1%; 95% CI 0.3-4.0%) and 10-year overall survival (53.3 vs 50.2%, difference 3.1%; 95% CI 1.3-6.3%). Results were similar irrespective of the type of radiotherapy used. To assess the robustness of our choice of IV, we repeated the IV analytical approach using different IVs (using the median utilization rate as the cutoff) and found the results to be similar. CONCLUSIONS: Among men >65 years of age, the benefit of primary radiotherapy for localized disease is largely confined to patients with high-risk prostate cancer (Gleason scores 7-10).

The impact of PSA testing frequency on prostate cancer incidence and treatment in older men.

To quantify the downstream impact of PSA testing on cancer characteristics and utilization of cancer therapies among men aged 70 or older, we utilized patients diagnosed with prostate cancer in 2004-2005 in the Surveillance, Epidemiology and End Results (SEER)-Medicare and their Medicare claims before their cancer diagnosis during 2000-2005. Among men in the highest testing group (4-6 PSA tests), 75% were diagnosed with low- or intermediate-risk of disease, but 77% received treatments within 180 days of cancer diagnosis. More than 45% of newly diagnosed patients in 2004-2005 had 4-6 PSA tests before their cancer diagnosis during 2000-2005. Men in the high testing group were 3.57 times more likely to receive cancer treatments (either surgery, radiation or hormonal therapy) when compared with men who had no previous PSA testing during the same time period. Among men aged 75+ diagnosed with low-risk cancer, men in the high testing group were 78% more likely to receive treatment than those who had no previous PSA testing. In conclusion, given the lack of evidence of effective treatment for elderly patients diagnosed with low- and intermediate-risk prostate cancer and our inability to distinguish indolent from aggressive cancer, more frequent PSA testing among elderly population may exacerbate the risk of overdiagnosis and overtreatment.

Treatment profile and complications associated with cryotherapy for localized prostate cancer: a population-based study.

The aim of this study was to assess the treatment patterns and 3-12-month complication rates associated with receiving prostate cryotherapy in a population-based study. Men >65 years diagnosed with incident localized prostate cancer in Surveillance Epidemiology End Results (SEER)-Medicare-linked database from 2004 to 2005 were identified. A total of 21,344 men were included in the study, of which 380 were treated initially with cryotherapy. Recipients of cryotherapy versus aggressive forms of prostate therapy (ie, radical prostatectomy or radiation therapy) were more likely to be older, have one co-morbidity, low income, live in the South and be diagnosed with indolent cancer. Complication rates increased from 3 to 12 months following cryotherapy. By the twelfth month, the rates for urinary incontinence, lower urinary tract obstruction, erectile dysfunction and bowel bleeding reached 9.8, 28.7, 20.1 and 3.3%, respectively. Diagnoses of hydronephrosis, urinary fistula or bowel fistula were not evident. The rates of corrective invasive procedures for lower urinary tract obstruction and erectile dysfunction were both <2.9% by the twelfth month. Overall, complications post-cryotherapy were modest; however, diagnoses for lower urinary tract obstruction and erectile dysfunction were common.

Treatments for prostate cancer in older men: 1984-1997.

OBJECTIVES: To examine the temporal trends in radical prostatectomy (RP), brachytherapy (BT), and external beam radiotherapy (EBRT) rates among men aged 65 years or older for the period 1984 to 1997. METHODS: We used the retrospective population-based analysis of treatments for prostate cancer among Medicare beneficiaries. The rates of RP were obtained from Part A (hospital) Medicare data for 20% of the national sample for 1984 to 1997. The BT and EBRT rates for the period 1993 to 1997 were obtained from a 5% national sample of Physician/Supplier Part B data. The rates of treatment, 30-day mortality, and readmissions were included. RESULTS: The rate of RP peaked in 1992. From 1993 to 1997, its use decreased by 6% among men aged 65 to 69 years, 34% among men aged 70 to 74 years, and 50% for men aged 75 years or older. However, by 1997, the RP + BT treatment rate again approached the 1992 levels of RP alone; BT was used twice as often as RP in men aged 75 years or older. By 1997, the RP + BT + EBRT rate exceeded the 1993 rate for men aged 65 to 69 years and was again approaching the 1993 rate for men aged 70 to 74 years. From 1984 to 1997, the presence of comorbid conditions gradually declined for RP and accounted for more than 60% of the decrease in the short term mortality during this period. Variations in RP use by geographic region have also decreased. CONCLUSIONS: RP is now more selectively targeted for treatment of prostate cancer in men older than 70 years than in the past. However, since BT has been substituted for radical surgery in many of these older men, the total population-based treatment rates have changed very little over time.

Interval after prostate specific antigen testing and subsequent risk of incurable prostate cancer.

PURPOSE: Studies of the potential effect of prostate specific antigen (PSA) screening on a less than yearly basis have been limited to computer simulations using relatively small sample sets. Primary clinical data on this relationship have not been generally available. We examined the relationship of less frequent testing and the risk of nonlocalized incurable cancer. The effect of testing frequency on the risk of prostate biopsy in men ultimately diagnosed with cancer was also assessed. MATERIALS AND METHODS: The study included a population based sample of 36,422 men 65 years old or older residing in 9 geographic areas with newly diagnosed prostate cancer during 1989 to 1993. The primary end point was the risk of nonlocalized cancer, as determined by logistic regression. Patient age, geographic region, year of diagnosis and race were included as covariates. RESULTS: In men who would be diagnosed with prostate cancer the risk of nonlocalized cancer did not differ in those tested 2 or 3 years compared with the risk in those tested 1 year before diagnosis (relative risk 1.00, 95% confidence interval 0.84 to 1.20 and 1.02, 95% confidence interval 0.74 to 1.41, respectively). However, the risk of prostate biopsy in these men was directly related to the number of PSA tests performed (test for trend p = 0.0061). CONCLUSIONS: Patients who choose to undergo PSA testing may be tested on a biennial instead of annual basis without an increased risks of nonlocalized cancer. Decreasing the frequency of PSA testing may lead to fewer prostate biopsies.

Transurethral resection of the prostate among medicare beneficiaries: 1984 to 1997. For the Patient Outcomes Research Team for Prostatic Diseases.

PURPOSE: We examine the epidemiology and associated risks of transurethral resection of the prostate among Medicare beneficiaries for the period 1984 to 1997. MATERIALS AND METHODS: We used hospital claims for transurethral resection of the prostate from a 20% national sample of Medicare beneficiaries for the period 1991 to 1997. Risk of mortality and reoperation were evaluated using life table methods and compared to those for the period 1984 to 1990. We also examined the association between surgical volume and adverse outcomes following resection using unique urologist identifier codes from the 1997 part B Medicare claims. RESULTS: Compared to 1984 to 1990, age adjusted rates of transurethral resection for benign prostatic hyperplasia (BPH) during 1991 to 1997 declined by approximately 50% for white (14.6 to 6.72/1,000) and 40% for black (11.8 to 6.58/1,000) men. Of the men who underwent resection for BPH during the recent period 53% were 75 years old or older but 30-day mortality in men 70 years old or older was significantly lower than that in 1984 to 1990. Since 1987 the 5-year risk for reoperation following transurethral resection for BPH has remained 5%. For resection performed in 1997 we observed no statistically significant association between urologist surgical volume and risks of reoperation or 30-day mortality. CONCLUSIONS: Compared to the peak period of its use in the 1980s, older men are now undergoing transurethral resection of the prostate. Nevertheless, outcomes for men 65 years old or older continue to be good.

Population-based study of relationships between hospital volume of prostatectomies, patient outcomes, and length of hospital stay.

BACKGROUND: Despite the large number of prostatectomies performed annually, few data exist regarding relationships between the volume of prostatectomies handled by a hospital, the length of a patient's stay in the hospital, and patient outcomes. We examined the effect of hospital prostatectomy volume and changes in the hospital volume on patient outcomes and the length of a patient's stay. METHODS: We collected data on 101 604 prostatectomies from Medicare claims filed from 1991 through 1994. By use of logistic regression and analysis of variance, we examined relationships between hospital load of prostatectomies, length of a patient's hospital stay, surgical complications, readmission rate, and mortality rate in a 30-day period following surgery. Statistical tests were two-sided. RESULTS AND CONCLUSIONS: Cross-sectional analyses revealed that, compared with high-volume hospitals, low-volume, medium-low-volume, and medium-high-volume hospitals had higher relative risks of readmission by 30% (95% confidence interval [CI] = 21%-39%), 16% (95% CI = 7%-25%), and 8% (95% CI = -1% to 17%), respectively; higher relative risks of serious complications by 43% (95% CI = 37%-48%), 25% (95% CI = 19%-31%), and 9% (95% CI = 3%-15%), respectively; and higher relative risks of mortality by 51% (95% CI = 25%-77%), 43% (95% CI = 17%-69%), and 42% (95% CI = 16%-68%), respectively. The mean length of a patient's stay in a low-volume hospital was 9% longer than that in a high-volume hospital (8.51 days [95% CI = 8.47-8.56] versus 7.81 days [95% CI = 7.77-7.85]; P for trend across all volume categories =.0001). Within-hospital longitudinal analyses revealed that hospitals with a relative increase in prostatectomy volume had a 57% greater reduction in the length of a patient's stay compared with those with a relative decrease in volume (P =.005). Changes in prostatectomy volume did not affect the frequency of complications, mortality, and readmission. These findings suggest that an increase in a given hospital's prostatectomy volume may facilitate a decrease in the length of a patient's stay without an adverse impact on patient outcomes.

Effect of age and surgical approach on complications and short-term mortality after radical prostatectomy--a population-based study.

OBJECTIVES: To use population-based data to accurately delineate the types and incidence of complications, risk of readmission, and influence of age and surgical approach on short-term mortality after radical prostatectomy. METHODS: Medicare claims from 1991 to 1994 were used to identify and quantify the types and risks of complications, rehospitalization within 90 days, and mortality at 30 and 90 days after perineal or retropubic prostatectomy. Logistic regression was used to determine the relationships between age, surgical approach, and short-term outcomes while adjusting for potential confounders. RESULTS: On the basis of data from 101,604 men, complications affected 25.0% to 28.8% of patients treated with the perineal or retropubic approach. The retropubic approach had a higher risk of respiratory complications (relative risk [RR] = 1.53, 95% confidence interval [CI] 1.37 to 1.71) and miscellaneous medical complications (RR = 1.77, 95% CI 1.60 to 1.97) and a lower risk of miscellaneous surgical complications (RR = 0.86, 95% CI 0.78 to 0.94). Differences in medically related gastrointestinal complications partially accounted for the differences in miscellaneous medical complications. Rectal injury with the perineal approach was only approximately 1% to 2%. Readmission within 90 days was necessary for 8.5% to 8.7% of patients who underwent the retropubic or perineal approach. The 30-day mortality was less than 0.5% for men aged 65 to 69; it approached 1% for men aged 75 and older. CONCLUSIONS: Complications and readmission after prostatectomy are substantially more common than previously recognized. Notable differences exist in the incidence of respiratory and nonsurgical gastrointestinal complications, although many short-term outcomes are comparable for the two approaches. Older age is associated with elevated surgical mortality and complications.

Use of radical prostatectomy among Medicare beneficiaries before and after the introduction of prostate specific antigen testing.

PURPOSE: We monitored the use of radical prostatectomy in medicare beneficiaries before and after the introduction of prostate specific antigen (PSA) testing. MATERIALS AND METHODS: Radical prostatectomies performed on medicare beneficiaries between 1984 and 1995 were identified through the medicare claims data base. Medicare enrollment files were used to define the population at risk and age-adjusted rates were standardized to the 1990 United States medicare population. RESULTS: Rates of radical prostatectomy have steadily increased since 1984. A sharp increase in radical prostatectomy rates followed the institution of PSA testing after which a prominent decrease, particularly among older age groups, was evident. During the peak year of 1992 the age-adjusted rates of radical prostatectomy for white and black men 65 to 79 years old in the United States were 461.2 and 294.5/100,000 men. Between 1992 and 1995 the rates of radical prostatectomy among white men decreased by 22, 47 and 69% for patients 65 to 69, 70 to 74 and 75 to 79 years old, respectively. The corresponding changes among black men were +6, -18 and -47%, respectively. Differences in the age-adjusted rates between white and black men have narrowed in recent years, ranging from 166.7 (1992) to 29.7 (1995)/100,000 men. CONCLUSIONS: Recent years have been marked by a rapid increase in the use of radical prostatectomy, which peaked in 1992. Subsequent to 1992 a sharp decrease occurred, which was particularly evident in older and white men. Racial differences in the use of radical prostatectomy have narrowed in recent years.

Population-based study of long-term survival in patients with clinically localised prostate cancer.

BACKGROUND: Choice of treatment in localised prostate cancer has been hampered by a lack of unbiased, representative data on outcome. Most existing data have come from small cohorts at specialised academic centres; precise overall and cancer-grade-specific data are not available, and the data are subject to differential staging bias. Randomised clinical trials have been undertaken, but the results will not be available for another decade. We have carried out a large population-based study to ascertain overall and prostate-cancer-specific survival in men treated by prostatectomy, radiotherapy, or conservative management. METHODS: Data for 59,876 cancer-registry patients aged 50-79 were analysed. We examined the effect of differential staging of prostate cancer by analysing the data both by intention to treat and by treatment received. Estimated survival was calculated by the Kaplan-Meier method. FINDINGS: By the intention-to-treat approach, 10-year prostate-cancer-specific survival for grade 1 cancer was 94% (95% CI 91-95) after prostatectomy, 90% (87-92) after radiotherapy, and 93% (91-94) after conservative management. The corresponding survival figures in grade 2 cancers were 87% (85-89), 76% (72-79), and 77% (74-80); those in grade 3 cancer were 67% (62-71), 53% (47-58), and 45% (40-51). Although the intention-to-treat and treatment-received analyses yielded similar results for radiotherapy and conservative management, the 10-year disease-specific survival after prostatectomy differed substantially (83% [81-84] by intention to treat vs 89% [87-91] by treatment received). INTERPRETATION: The overall and cancer-grade-specific survival found in this study differ substantially from those in previous studies. Previous studies that used a treatment-received approach have generally overestimated the benefits of radical prostatectomy. We found that grade 3 tumours are highly aggressive irrespective of stage.

Outcomes of external-beam radiation therapy for prostate cancer: a study of Medicare beneficiaries in three surveillance, epidemiology, and end results areas.

PURPOSE: This study was designed to obtain representative estimates of the quality of life and probabilities of possible adverse effects among Medicare-age patients treated with external-beam radiation therapy for prostate cancer. METHODS: Patients treated for local or regional prostate cancer with high-energy external-beam radiation between 1989 and 1991 were sampled from a claims data base of the Surveillance, Epidemiology, and End Results (SEER) program from three regions. Patients were surveyed primarily by mail, with telephone follow-up evaluation of non-respondents. There were 621 respondents (83% response rate). The results were compared with data from a previously published national survey of Medicare-age men who had undergone radical prostatectomy. RESULTS: Although they were older at the time of treatment, radiation patients were less likely than surgical patients to wear pads for wetness (7% v 32%) and had a lower rate of impotence (23% v 56% for men < 70 years), while they were more likely to report problems with bowel dysfunction (10% v 4%). Both groups reported generally positive feelings about their treatments. Radiation and surgical patients reported similar rates of additional subsequent treatment (24% v 26% at 3 years after primary treatment). However, radiation patients were less likely to say they were cancer-free, and they reported more worry about cancer than did surgical patients. CONCLUSION: The health-related quality of life of radiation and surgical patients, on average, is similar, but the pattern of experience with adverse consequences of treatment differs by treatment.

Heterogeneity of hip fracture: age, race, sex, and geographic patterns of femoral neck and trochanteric fractures among the US elderly.

To explore potential etiologic differences in the two major types of hip fracture, the authors computed the incidence rates of fractures of the femoral neck and trochanteric region of the proximal femur using a 5 percent sample of the US Medicare population aged 65-99 years. For the period they examined, July 1, 1986, through June 30, 1990, the rates of both hip fracture types increased with age in all race and sex categories. The proportion of hip fractures that occurred in the trochanteric region rose steeply with age among white women, but not among black women, white men, or black men. Within the United States, a north-to-south gradient in rates of both fracture types was observed among women, while no clear pattern was found for men. These findings raise the possibility of etiologic differences in the two fracture types, and the results provide further evidence of sex and racial differences in the risk of osteoporotic fractures.

Follow-up prostate cancer treatments after radical prostatectomy: a population-based study.

BACKGROUND: Radical prostatectomy is one of the most commonly used curative procedures for the treatment of localized prostate cancer. The probability that a patient will undergo additional cancer therapy after this procedure is largely unknown. PURPOSE: The objective was to determine the likelihood of additional cancer therapy after radical prostatectomy. METHODS: Data for this study were derived from a linked dataset that combined information from the Surveillance, Epidemiology, and End Results Program and Medicare hospital and physician claims. Records were included in this study if patient histories met the following criteria: (a) residing in Connecticut, Washington (Seattle-Puget Sound), or Georgia (Metropolitan Atlanta); (b) having been diagnosed with prostate cancer during the period from January 1, 1985, through December 31, 1991; (c) undergoing radical prostatectomy by December 31, 1992; and (d) having no evidence of other types of cancer. Patients were considered to have had additional cancer therapy if they had had radiation therapy, orchiectomy, and/or androgen-deprivation therapy by injection after radical prostatectomy. The interval between the initial treatment and any follow-up treatment was calculated from the date of radical prostatectomy to the 1st day of the follow-up cancer therapy. All presented probabilities are based on Kaplan-Meier estimates. RESULTS: The study population consisted of 3494 Medicare patients, 3173 of whom underwent radical prostatectomy within 3 months of prostate cancer diagnosis. Although radical prostatectomy is often reserved for localized cancer, less than 60% (1934) of patients whose records were included in this study had organ-confined disease, according to final surgical pathology. Overall, the 5-year cumulative incidence of having any additional cancer treatment after radical prostatectomy reached 34.9% (95% confidence interval [CI] = 31.5%-38.5%). For patients with pathologically organ-confined cancer, the 5-year cumulative incidence was 24.3% (95% CI = 20.0%-29.3%) overall and ranged from 15.6% (95% CI = 9.7%-24.5%) for well-differentiated cancer (Gleason scores 2-4) to 41.5% (95% CI = 27.9%-58.4%) for poorly differentiated cancer (Gleason scores 8-10). The corresponding figures for pathologically regional cancer were 22.7% (95% CI = 12.0%-40.5%) and 68.1% (95% CI = 58.7%-77.1%). CONCLUSION: Further treatment of prostate cancer was done in about one third of patients who had had a radical prostatectomy with curative intent and in about one quarter of patients who were found to have organ-confined disease. IMPLICATIONS: Given the common requirement for follow-up cancer treatments after radical prostatectomy and the uncertainties about the effectiveness of the various follow-up treatment strategies, further investigation of these treatments is warranted.

Effect of radical prostatectomy for prostate cancer on patient quality of life: results from a Medicare survey.

OBJECTIVES: To assess patient responses to radical prostatectomy and its effects. METHODS: A national sample was taken of 1072 Medicare patients who underwent radical prostatectomy for prostate cancer (1988 through 1990) by mail, telephone, and personal interviews. The effects of the surgery and its complications on these patients' lives were studied through: (1) patient ratings of the extent to which sexual and urinary dysfunctions were "problems" in their lives; (2) two general measures of quality of life, the Mental Health Index and the General Health Index; (3) patient reports of how they felt about the results of treatment and whether they would choose surgery again. RESULTS: On average, dripping urine, particularly to the point where subjects were wearing pads, had a more significant effect on patients than loss of sexual function; incontinence had significant adverse effects on the measures of quality of life and self-reported results of surgery. Overall, postsurgical patients scored comparatively high on the quality of life measures (similar to a cohort of patients with benigh prostatic hyperplasia who had undergone transurethral resection of the prostate), reported feeling positive about the results (81%), and would choose surgical treatment again (89%). Nonetheless, there was variability in patient response to the effects of surgery. CONCLUSIONS: The results demonstrate the ability of many Medicare patients to adapt to adverse outcomes, such as loss of sexual function and incontinence. They also provide evidence of the variability of individual patients' responses to surgical results and reinforce the importance of individualized decision making for patients facing a decision about radical prostatectomy for prostate cancer.

Transurethral resection of the prostate among Medicare beneficiaries in the United States: time trends and outcomes. Prostate Patient Outcomes Research Team (PORT).

OBJECTIVES: The purpose of this study was to examine the epidemiology of transurethral resection of the prostate (TURP) and associated risks among Medicare beneficiaries during the period of 1984 to 1990. METHODS: Medicare hospital claims for a 20% national sample of Medicare beneficiaries were used to identify TURPs performed during the study period. All reported rates were adjusted to the composition of the 1990 Medicare population. Risks of mortality and reoperation were evaluated using life-table methods. RESULTS: The age-adjusted rate of TURP reached a peak in 1987 and declined thereafter. Similar trends were observed for all age groups. In 1990, the rates of TURP (including all indications) were approximately 25, 19, and 13 per 1000 for men over the age of 75, 70 to 74, and 65 to 69, respectively. The 30-day mortality following TURP for the treatment of benign prostatic hyperplasia (BPH) decreased from 1.20% in 1984 to 0.77% in 1990 (linear trend, p = 0.0001). The cumulative incidence of a second TURP among men with BPH has likewise decreased steadily over time; in this study, the average was 7.2% over 7 years (5.5% when the indication for the second TURP was restricted to BPH only). CONCLUSIONS: The rate of TURP has been declining since 1987, conceivably due to increasing availability of alternative treatments or changes in treatment preferences of patients and physicians. Over the same period, the outcomes following TURPs have improved, perhaps due to improved surgical care and changes in patient selection.

Decline of serum cobalamin levels with increasing age among geriatric outpatients.

The level of serum cobalamin declines with increasing age. Among 100 consecutive geriatric outpatients who were seen in office-based settings for various acute and chronic medical illnesses but not for cobalamin deficiency-related diseases, 11% had serum cobalamin levels from 148 to 295 pmol/L. The average annual serum cobalamin level decline was 18 pmol/L for patients who had higher initial serum cobalamin levels (actual range, from 224 to 292 pmol/L). The average annual serum cobalamin decline was 28 pmol/L, which was much higher, for patients who had lower initial serum cobalamin levels (actual range, from 157 to 221 pmol/L). Patients with initial serum cobalamin levels of 148 pmol/L or below received treatment immediately, and their declines could not be studied.

Standardized rates of recurrent outcomes.

Longitudinal studies are often concerned with estimating the rate of an event that may recur. Examples are nonmelanoma skin cancer rates, screening rates for breast cancer using mammography and hospital admission rates. We propose simple estimators for directly and indirectly standardized summary rates and relative rates of recurrent events and their variances. We also develop an estimator of the excess rate in an area if the rate in another area applied. For non-recurrent events, the estimators are identical to the usual standardized summary rates. The estimators are independent of the underlying distribution of the event of interest and allow for unequal follow-up times and event rate heterogeneity among individuals. The method is not computationally intensive and does not require specialized software. We illustrate the application of the method in a retrospective cohort study of hospital utilization patterns of Medicare enrollees in Boston and New Haven over a three and a half year period.

Internal validation of Medicare claims data.

The Medicare database is commonly used for epidemiology and health services research, but validation of its data by chart review or questionnaire may be difficult and expensive. Since hospital and physician bills are independent in Medicare, however, these two data sources can be used to supplement and corroborate each other. This "internal validation" is illustrated here for hip fracture and prostatectomy. Agreement of the hospital and physician data streams regarding site of hip fracture (neck vs other), treatment of hip fracture (internal fixation vs arthroplasty), and type of prostatectomy (transurethral resection of prostate, open, or radical) was excellent, with percentage of agreement generally between 89% and 99%, and kappa statistics typically between 0.74 and 0.95. When validation with outside data sources is not readily available, such internal validation of Medicare data may be valuable.

Treatment and survival among elderly Americans with hip fractures: a population-based study.

OBJECTIVES: This study was undertaken to examine the patterns of treatment and survival among elderly Americans with hip fracture. METHODS: A 5% national sample of Medicare claims was used to identify patients who sustained hip fractures between 1986 and 1989. In comparing treatment patterns across regions, direct standardization was used to derive age- and race-adjusted percentages. Logistic regression and Cox regression were used to examine short- and long-term survival. RESULTS: In the United States, 64% of femoral neck fractures were treated with arthroplasty; 90% of pertrochanteric fractures were treated with internal fixation. Higher short- and long-term mortality was associated with being male, being older, residing in a nursing home prior to fracture, having a higher comorbidity score, and having a pertrochanteric fracture. Blacks and Whites had similar 90-day postfracture mortality, but Blacks had a higher mortality later on. For femoral neck fracture, internal fixation has a modestly lower short-term mortality associated with it than arthroplasty has. CONCLUSION: Variation in the treatment of hip fracture was modest, The increased delayed mortality after hip fracture among Blacks requires further study.