Exploring the Impact of Controlled Ovarian Stimulation and Non-Invasive Oocyte Assessment in ART Treatments.

Invasive and noninvasive features are normally applied to select developmentally competent oocytes and embryos that can increase the take-home baby rates in assisted reproductive technology. The noninvasive approach mainly applied to determine oocyte and embryo competence has been, since the early days of IVF, the morphological evaluation of the mature cumulus-oocyte complex at the time of pickup, first polar body, zona pellucida thickness, perivitelline space and cytoplasm appearance. Morphological evaluation of oocyte quality is one of the options used to predict successful fertilization, early embryo development, uterine implantation and the capacity of an embryo to generate a healthy pregnancy to term. Thus, this paper aims to provide an analytical revision of the current literature relating to the correlation between ovarian stimulation procedures and oocyte/embryo quality. In detail, several aspects of oocyte quality such as morphological features, oocyte competence and its surrounding environment will be discussed. In addition, the main noninvasive features as well as novel approaches to biomechanical parameters of oocytes that might be correlated with the competence of embryos to produce a healthy pregnancy and live birth will be illustrated.

Alcohol sale status and homicide victimization in Kentucky, 2005-2012: Is there a spatial association?

To date, the association between the alcohol sale status of decedents' residence and alcohol-related homicide victimization have not been studied as far as we know. The current study aims to: i) determine whether homicide victims who were residents of wet counties had higher odds of testing positive for alcohol than their counterparts in moist or dry counties after adjusting for confounders; ii) determine whether homicides and alcohol-related homicides tend to cluster spatially; iii) determine whether the aforementioned associations exist only in highly-populated counties. A multilevel logistic regression analysis was used to analyze the data on homicide victims in the Kentucky Violent Death Reporting System from 2005 to 2012. Spatial statistics were used to determine the spatial autocorrelation in rates of homicides and alcohol-related homicides. Overall, 944 homicide victims were included. The male to female ratio was 3:1. About 32.8% of homicide victims tested positive for alcohol. About 33.0% of homicide decedents who were residents in wet counties tested positive for alcohol compared to 32.5% of their counterparts in moist/dry counties. Residence in wet counties was associated with a statistically insignificant increase in the unadjusted odds ratio (OR) of alcohol-related homicide victimization (OR=1.20, 95% CI=0.81-1.77) as well as the adjusted odds (aOR=1.33, 95% CI=0.83-2.12). There was no association between population size and alcohol-related homicide rate.

What Predicts an Advanced-Stage Diagnosis of Breast Cancer? Sorting Out the Influence of Method of Detection, Access to Care, and Biologic Factors.

BACKGROUND: Multiple studies have yielded important findings regarding the determinants of an advanced-stage diagnosis of breast cancer. We seek to advance this line of inquiry through a broadened conceptual framework and accompanying statistical modeling strategy that recognize the dual importance of access-to-care and biologic factors on stage. METHODS: The Centers for Disease Control and Prevention-sponsored Breast and Prostate Cancer Data Quality and Patterns of Care Study yielded a seven-state, cancer registry-derived population-based sample of 9,142 women diagnosed with a first primary in situ or invasive breast cancer in 2004. The likelihood of advanced-stage cancer (American Joint Committee on Cancer IIIB, IIIC, or IV) was investigated through multivariable regression modeling, with base-case analyses using the method of instrumental variables (IV) to detect and correct for possible selection bias. The robustness of base-case findings was examined through extensive sensitivity analyses. RESULTS: Advanced-stage disease was negatively associated with detection by mammography (P < 0.001) and with age < 50 (P < 0.001), and positively related to black race (P = 0.07), not being privately insured [Medicaid (P = 0.01), Medicare (P = 0.04), uninsured (P = 0.07)], being single (P = 0.06), body mass index > 40 (P = 0.001), a HER2 type tumor (P < 0.001), and tumor grade not well differentiated (P < 0.001). This IV model detected and adjusted for significant selection effects associated with method of detection (P = 0.02). Sensitivity analyses generally supported these base-case results. CONCLUSIONS: Through our comprehensive modeling strategy and sensitivity analyses, we provide new estimates of the magnitude and robustness of the determinants of advanced-stage breast cancer. IMPACT: Statistical approaches frequently used to address observational data biases in treatment-outcome studies can be applied similarly in analyses of the determinants of stage at diagnosis. Cancer Epidemiol Biomarkers Prev; 25(4); 613-23. ©2016 AACR.

Clinical and Demographic Factors Associated With Receipt of Non Guideline-concordant Initial Therapy for Nonmetastatic Prostate Cancer.

OBJECTIVES: To determine the extent to which initial therapy for nonmetastatic prostate cancer was concordant with nationally recognized guidelines using supplemented cancer registry data and what factors were associated with receipt of nonguideline-concordant care. METHODS: Initial therapy for 8229 nonmetastatic prostate cancer cases diagnosed in 2004 from cancer registries in 7 states was abstracted as part of the Centers for Disease Control's Patterns of Care Breast and Prostate Cancer study conducted during 2007 to 2009. The National Comprehensive Cancer Network clinical practice guidelines version 1.2002 was used as the standard of care based on recurrence risk group and life expectancy (LE). A multivariable model was used to determine risk factors associated with receipt of nonguideline-concordant care. RESULTS: Nearly 80% with nonmetastatic prostate cancer received guideline-concordant care for initial therapy. Receipt of nonguideline-concordant care (including receiving either less aggressive therapy or more aggressive therapy than indicated) was related to older age, African American race/ethnicity, being unmarried, rural residence, and especially to being in the high recurrence risk group where receiving less aggressive therapy than indicated occurred more often than receiving more aggressive therapy (adjusted OR=4.2; 95% CL, 3.5-5.2 vs. low-risk group). Compared with life table estimates adjusted for comorbidity, physicians tended to underestimate LE. CONCLUSIONS: Receipt of less aggressive therapy than indicated among high-risk group men with >5-year LE based on life table estimates adjusted for comorbidity was a concern. Physicians may tend to underestimate 5-year survival among this group and should be alerted to the importance of recommending aggressive therapy when warranted. However, based on more recent guidelines, among those with low-risk disease, the proportion considered to be receiving less aggressive therapy than indicated may now be lower because active surveillance is now considered appropriate.

Disparities in Colorectal Cancer Treatment Delay Within Appalachia--The Role of For-Profit Hospitals.

BACKGROUND: Appalachian residents have a higher overall cancer burden than the rest of the United States because of the unique features of the region. Treatment delays vary widely within Appalachia, with colorectal cancer patients undergoing median treatment delays of 5 days in Kentucky compared to 9 days for patients in Pennsylvania, Ohio, and North Carolina combined. OBJECTIVE: This study identified the source of this disparity in treatment delay using statistical decomposition techniques. METHODOLOGY: This study used linked 2006 to 2008 cancer registry and Medicare claims data for the Appalachian counties of Kentucky, Pennsylvania, Ohio, and North Carolina to estimate a 2-part model of treatment delay. An Oaxaca Decomposition of the 2-part model revealed the contribution of the individual determinants to the disparity in delay between Kentucky counties and the remaining 3 states. RESULTS: The Oaxaca Decomposition revealed that the higher percentage of patients treated at for-profit facilities in Kentucky proved the key contributor to the observed disparity. In Kentucky, 22.3% patients began their treatment at a for-profit facility compared to 1.4% in the remaining states. Patients initiating treatment at for-profit facilities explained 79% of the observed difference in immediate treatment (<2 days after diagnosis) and 72% of Kentucky's advantage in log days to treatment. CONCLUSIONS: The unique role of for-profit facilities led to reduced treatment delay for colorectal cancer patients in Kentucky. However, it remains unknown whether for-profit hospitals' more rapid treatment converts to better health outcomes for colorectal cancer patients.

Patient and provider perspectives on the relationship between multiple morbidity management and disease prevention.

Despite competing demands of multiple morbidity (MM) management and disease prevention, our recent survey of 1,153 Appalachian residents aged 50 to 76 documented that individuals with MM were more likely to obtain colorectal cancer screening (CRCS) than those without MM. Nearly two thirds of respondents obtained CRCS, and the more MM, the greater the likelihood of screening. To gain insight into this relationship, we conducted nine focus groups, six with providers and three with patients. Three main explanations emerged: (a) patients' MM increases providers' vigilance for other health vulnerabilities; (b) having MM increases patients' own vigilance; and (c) patients' vigilance may stem from experiencing more symptoms, having a family history of cancer, and having successfully obtained health care. More frequent contact with health care providers appears to encourage preventive referral, especially in low-income populations that otherwise may not receive such counselling. We highlight participant recommendations to improve MM management and prevention.

Individual, Area, and Provider Characteristics Associated With Care Received for Stages I to III Breast Cancer in a Multistate Region of Appalachia.

PURPOSE: We describe individual, area, and provider characteristics associated with care patterns for early-stage breast cancer in Appalachian counties of Kentucky, North Carolina, Ohio, and Pennsylvania. METHODS: Cases of stages I to III breast cancer from 2006 to 2008 were linked to Medicare claims occurring within 1 year of diagnosis. Rates of guideline-concordant endocrine therapy (n = 1,429), chemotherapy (n = 1,480), and radiation therapy (RT) after breast-conserving surgery were studied; RT was studied in women age ≥ 70 years with stage I estrogen receptor (ER) -positive/progesterone receptor (PR) -positive cancer, for whom RT was optional (n = 1,108), and in all others, for whom RT was guideline concordant (n = 1,422). Univariable and multivariable analyses were performed. Independent variables included age, race, county-level economic status, state, surgeon graduation year and volume, comorbidity, diagnosis year, Medicaid/Medicare dual status, histology, tumor size, tumor sequence, positive lymph nodes, ER/PR status, stage, trastuzumab use, and surgery type. RESULTS: Population mean age was 74 years; 97% were white. For endocrine therapy, chemotherapy, and RT, guideline concordance was 76%, 48%, and 83%, respectively. Where it was optional, 77% received RT. Guideline-concordant endocrine therapy was lower in North Carolina versus Pennsylvania (odds ratio [OR], 0.60; 95% CI, 0.41 to 0.88) and higher if surgeon graduated between 1984 and 1988 versus ≥ 1989 (OR, 1.58; 95% CI, 1.06 to 2.34). Guideline-concordant chemotherapy varied significantly by state, county-level economic status, and surgeon volume. In guideline-concordant RT, lower surgeon volume (v highest) predicted RT use (OR, 1.63; 95% CI, 1.61 to 2.36). In optional RT, North Carolina residence (v Pennsylvania; OR, 0.29; 95% CI, 0.17 to 0.48) and counties with higher economic status (OR, 0.61; 95% CI, 0.40 to 0.94) predicated RT omission. CONCLUSION: Notable variation in care by geographic and surgical provider characteristics provides targets for further research in underserved areas.

Clinical, sociodemographic, and service provider determinants of guideline concordant colorectal cancer care for Appalachian residents.

BACKGROUND: Colorectal cancer represents a significant cause of morbidity and mortality, particularly in Appalachia where high mortality from colorectal cancer is more prevalent. Adherence to treatment guidelines leads to improved survival. This paper examines determinants of guideline concordance for colorectal cancer. METHODS: Colorectal cancer patients diagnosed in 2006-2008 from 4 cancer registries (Kentucky, Ohio, Pennsylvania, and North Carolina) were linked to Medicare claims (2005-2009). Final sample size after exclusions was 2,932 stage I-III colon, and 184 stage III rectal cancer patients. The 3 measures of guideline concordance include adjuvant chemotherapy (stage III colon cancer, <80 years), ≥12 lymph nodes assessed (resected stage I-III colon cancer), and radiation therapy (stage III rectal cancer, <80 years). Bivariate and multivariate analyses with clinical, sociodemographic, and service provider covariates were estimated for each of the measures. RESULTS: Rates of chemotherapy, lymph node assessment, and radiation were 62.9%, 66.3%, and 56.0%, respectively. Older patients had lower rates of chemotherapy and radiation. Five comorbidities were significantly associated with lower concordance in the bivariate analyses: myocardial infarction, congestive heart failure, respiratory diseases, dementia with chemotherapy, and diabetes with adequate lymph node assessment. Patients treated by hospitals with no Commission on Cancer (COC) designation or lower surgical volumes had lower odds of adequate lymph node assessment. CONCLUSIONS: Clinical, sociodemographic, and service provider characteristics are significant determinants of the variation in guideline concordance rates of 3 colorectal cancer measures.

Treatment patterns for prostate cancer: comparison of Medicare claims data to medical record review.

BACKGROUND: As evidence-based guidelines increasingly define standards of care, the accurate reporting of patterns of treatment becomes critical to determine if appropriate care has been provided. We explore the level of agreement between claims and record abstraction for treatment regimens for prostate cancer. METHODS: Medicare claims data were linked to medical records abstraction using data from the Centers for Disease Control and Prevention's National Program of Cancer Registry-funded Breast and Prostate Patterns of Care study. The first course of therapy included surgery, radiation therapy (RT), and hormonal therapy with luteinizing hormone-releasing hormone agonists. RESULTS: The linked sample included 2765 men most (84.7%) of whom had stage II prostate cancer. Agreement was excellent for surgery (κ=0.92) and RT (κ=0.92) and lower for hormonal therapy (κ=0.71); however, most of the discrepancies were due to greater number of patients reported who received hormonal therapy in the claims database than in the medical records database. For some standard multicomponent management strategies sensitivities were high, for example, hormonal therapy with either combination RT (86.9%) or cryosurgery (96.6%). CONCLUSIONS: Medicare claims are sensitive for determining patterns of multicomponent care for prostate cancer and for detecting use of hormonal therapy when not reported in the medical records abstracts.

Impact of non-HIV related comorbidities on retention in HIV medical care: does retention improve over time?

The purpose of this study was to understand how the presence of comorbid conditions affects retention in HIV medical care over time. A retrospective cohort design employing a medical chart review was conducted. A generalized linear mixed model was used to determine the predictors that affect retention over time. The mean follow-up for the study population was 5.75 years, and only 48.6 % achieved optimal retention. During the study period, 882 non-HIV related comorbidities were diagnosed in 610 (44.9 %) patients of whom, approximately 31 % had ≥2 comorbidities diagnosed. In the mixed model, the number of comorbidities diagnosed during the study period was associated with improved retention over time (odds ratio = 2.28; 95 % confidence interval = 1.83-2.71). Having a non-HIV related comorbid condition was associated with improved retention, while those patients who were 'healthier' had worse retention. More research is needed to identify factors that improve retention and to quantify the impact of these factors.

Generic antiepileptic drug prescribing: a cross-sectional study.

The use of generic antiepileptic drugs (AEDs) in patients with epilepsy is controversial. The purpose of this study is to identify patient characteristics associated with increased odds of receiving a generic AED product. A large commercial database was used to identify patients with a primary diagnosis of epilepsy who were prescribed an AED during a three-month window. Data analysis found that those ≥65 years old had 15.7% greater odds of receiving a generic AED (OR = 1.157; 95% CI = 1.056-1.268). Patients with Medicaid were found to have 2.44 times the odds of having had a generic AED prescription (OR = 2.44; CI = 2.168-2.754). Patients residing in the Northeast had 12.6% decreased odds of receiving a generic AED (OR = 0.874; C I= 0.821-0.931). These patient characteristics could signify certain health care disparities and may represent potential confounders to future observational studies.

Regional, provider, and economic factors associated with the choice of active surveillance in the treatment of men with localized prostate cancer.

Data on initial treatment of 8232 cases of localized prostate cancer diagnosed in 2004 were obtained by medical record abstraction (including hospital and outpatient locations) from seven state cancer registries participating in the Centers for Disease Control and Prevention's Breast and Prostate Cancer Data Quality and Patterns of Care Study. Distinction was made between men receiving no therapy with no monitoring plan (no therapy/no plan [NT/NP]) and those receiving active surveillance (AS). Overall, 8.6% received NT/NP and 4.7% received AS. Older age at diagnosis, lower clinical risk group, and certain registry locations were significant predictors of use of both AS and NT/NP. AS was also related to having more severe comorbidities, whereas nonwhite race was predicted receiving NT/NP. Men receiving AS lived in areas with a higher number of urologists per 100 000 men than those receiving NT/NP. In summary, physician and clinical factors were stronger predictors of AS, whereas demographic and regional factors were related to receiving NT/NP. Physicians appear reluctant to recommend AS for younger patients with no comorbidities.

Defining care provided for breast cancer based on medical record review or Medicare claims: information from the Centers for Disease Control and Prevention Patterns of Care Study.

BACKGROUND: Description of care patterns is important as evidence-based guidelines increasingly dictate care. We explore the level of agreement between claims and record abstraction for guideline concordant multidisciplinary breast cancer care. METHODS: From the U.S. Centers for Disease Control and Prevention's National Program of Cancer Registries Patterns of Care study, in which medical record abstraction of breast cancer and treatment was accomplished, cases include breast cancer where Medicare claims were available. Components of care were breast-conserving surgery (BCS), mastectomy, node assessment, radiation (RT), and chemotherapy (CTX), including specific chemotherapeutic agents, and combinations. We compared Medicare claims with record abstraction, and measured concordance using the kappa statistic and sensitivity. RESULTS: The study sample consisted of 1762 women with stage 0 to 4 breast cancer. Level of agreement was excellent for surgery type (kappa = 0.84) and CTX (kappa = 0.89); agreement for RT therapy was slightly lower (kappa = 0.79). For standard multicomponent strategies, sensitivities and specificities were high; for example, 88.8%/93.5% for mastectomy plus nodes and 86.6%/95.4% for BCS plus nodes and RT. For selected, standard, multi-agent, adjuvant CTX regimens, sensitivities ranged from 66.3% to 68.8% (kappa 0.63-0.73). CONCLUSIONS: Medicare claims, compared with chart abstraction, is a reliable method for determining patterns of multicomponent care for breast cancer.

Influence of race, insurance, socioeconomic status, and hospital type on receipt of guideline-concordant adjuvant systemic therapy for locoregional breast cancers.

PURPOSE: For breast cancer, guidelines direct the delivery of adjuvant systemic therapy on the basis of lymph node status, histology, tumor size, grade, and hormonal receptor status. We explored how race/ethnicity, insurance, census tract-level poverty and education, and hospital Commission on Cancer (CoC) status were associated with the receipt of guideline-concordant adjuvant systemic therapy. METHODS: Locoregional breast cancers diagnosed in 2004 (n = 6,734) were from the National Program of Cancer Registries-funded seven-state Patterns of Care study of the Centers for Disease Control and Prevention. Predictors of guideline-concordant (receiving/not receiving) adjuvant systemic therapy, according to National Comprehensive Cancer Network Guidelines, were explored by logistic regression. RESULTS: Overall, 35% of women received nonguideline chemotherapy, 12% received nonguideline regimens, and 20% received nonguideline hormonal therapy. Significant predictors of nonguideline chemotherapy included Medicaid insurance (odds ratio [OR], 0.66; 95% CI, 0.50 to 0.86), high-poverty areas (OR, 0.77; 95% CI, 0.62 to 0.96), and treatment at non-CoC hospitals (OR, 0.69; 95% CI, 0.56 to 0.85), with adjustment for age, registry, and clinical variables. Predictors of nonguideline regimens among chemotherapy recipients included lack of insurance (OR, 0.47; 95% CI, 0.25 to 0.92), high-poverty areas (OR, 0.71; 95% CI, 0.51 to 0.97), and low-education areas (OR, 0.65; 95% CI, 0.48 to 0.89) after adjustment. Living in high-poverty areas (OR, 0.78; 95% CI, 0.64 to 0.96) and treatment at non-CoC hospitals (OR, 0.68; 95% CI, 0.55 to 0.83) predicted nonguideline hormonal therapy after adjustment. ORs for poverty, education, and insurance were attenuated in the full models. CONCLUSION: Sociodemographic and hospital factors are associated with guideline-concordant use of systemic therapy for breast cancer. The identification of modifiable factors that lead to nonguideline treatment may reduce disparities in breast cancer survival.

Does comorbidity explain the ethnic inequalities in cervical cancer survival in New Zealand? A retrospective cohort study.

BACKGROUND: There are large ethnic differences in cervical cancer survival in New Zealand that are only partly explained by stage at diagnosis. We investigated the association of comorbidity with cervical cancer survival, and whether comorbidity accounted for the previously observed ethnic differences in survival. METHODS: The study involved 1,594 cervical cancer cases registered during 1994-2005. Comorbidity was measured using hospital events data and was classified using the Elixhauser instrument; effects on survival of individual comorbid conditions from the Elixhauser instrument were also assessed. Cox regression was used to estimate adjusted cervical cancer mortality hazard ratios (HRs). RESULTS: Comorbidity during the year before diagnosis was associated with cervical cancer-specific survival: those with an Elixhauser count of ≥3 (compared with a count of zero) had a HR of 2.17 (1.32-3.56). The HR per unit of Elixhauser count was 1.25 (1.11-1.40). However, adjustment for the Elixhauser instrument made no difference to the mortality HRs for Maori and Asian women (compared to 'Other' women), and made only a trivial difference to that for Pacific women. In contrast, concurrent adjustment for 12 individual comorbid conditions from the Elixhauser instrument reduced the Maori HR from 1.56 (1.19-2.05) to 1.44 (1.09-1.89), i.e. a reduction in the excess risk of 21%; and reduced the Pacific HR from 1.95 (1.21-3.13) to 1.62 (0.98-2.68), i.e. a reduction in the excess risk of 35%. CONCLUSIONS: Comorbidity is associated with cervical cancer-specific survival in New Zealand, but accounts for only a moderate proportion of the ethnic differences in survival.

The validity of testicular catch-up growth and serum FSH levels in the long-term postoperative assessment of laparoscopic varicocele correction in adolescents.

BACKGROUND: Postoperative assessment after varicocele surgery in adolescence is commonly centred around catch-up growth of the testis. There is paucity of evidence on the correlation of catch-up growth with underlying testicular function in these patients. AIMS: To assess the reliability of catch-up growth of the testis as an indicator of normalization of testicular function and the utility of serum FSH levels in the long-term postoperative assessment of varicocele surgery in adolescence. MATERIALS AND METHODS: Prospective cohort study of young adults (18-27 years) who had laparoscopic varicocele correction in adolescence (11-16 years). Evaluation included serum FSH levels, scrotal ultrasonography and semen analysis. ANALYSIS: Anatomical and functional parameters of participants with equal and normal testicular size were compared to those of participants with persistent testicular hypotrophy or hypertrophy. Sensitivity and positive predictive value of postoperative serum FSH levels were estimated and elevated levels of serum FSH were checked for association with suboptimal outcomes of varicocele correction. RESULTS: The serum FSH levels of participants with unequal testicular sizes (n=6, median 6.65 IU/l), which included testicular hypertrophy (n=3, median 7.2 IU/l) and persistent testicular hypotrophy (n=3, median 6.1 IU/l), were significantly higher than the group with equal testicular sizes (n=8, median 3.5 IU/l; P=0.014, Mann-Whitney U test). Postoperative elevated serum FSH levels were significantly associated with suboptimal outcomes of varicocele surgery (P=0.015, Fisher's exact test). The test also had a high positive predictive value. CONCLUSIONS: Testicular catch-up growth may not be a reliable postoperative assessment criterion by itself. Serum FSH levels may be of value in detecting suboptimal outcomes of varicocele surgery in adolescents.

Rural Residents' Perspectives on Multiple Morbidity Management and Disease Prevention.

Middle-aged and older adults often experience several simultaneously occurring chronic conditions or "multiple morbidity" (MM). The task of both managing MM and preventing chronic conditions can be overwhelming, particularly in populations with high disease burdens, low socioeconomic status, and health care provider shortages. This article sought to understand Appalachian residents' perspectives on MM management and prevention. Forty-one rural Appalachian residents aged 50 and above with MM were interviewed about disease management and colorectal cancer (CRC) prevention. Transcripts were examined for overall analytic categories and coded using techniques to enhance transferability and rigor. Participants indicate facing various challenges to prevention due, in part, to conditions within their rural environment. Patients and providers spend significant time and energy on MM management, often precluding prevention activities. This article discusses implications of MM management for CRC prevention and strategies to increase disease prevention among this rural, vulnerable population burdened by MM.

Burden of common multiple-morbidity constellations on out-of-pocket medical expenditures among older adults.

PURPOSE: On average, adults aged 60 years or older have 2.2 chronic diseases, contributing to the over 60 million Americans with multiple morbidities. We aimed to understand the financial implications of the most frequent multiple morbidities among older adults. DESIGN AND METHODS: We analyzed Health and Retirement Study data, determining out-of-pocket medical expenses from 1998 and 2002 separately and examining differences in the impact of multiple-morbidity constellations on these expenses. We paid particular attention to the most common disease constellations - hypertension, arthritis, and heart disease. RESULTS: An increasing prevalence of multiple morbidity (58% compared with 70% of adults had two or more chronic conditions in 1998 and 2002, respectively) was accompanied by escalating out-of-pocket expenditures (2,164 dollars in 1998, increasing by 104% to 3,748 dollars in 2002). Individuals with two, three, and four chronic conditions had health care expenditure increases of 41%, 85%, and 100%, respectively, over 4 years. Such patterns were particularly noticeable among the oldest old, those with higher educational attainment, and women, although having supplementary health insurance or Medicaid mitigated these expenses. Finally, there were significant differences in out-of-pocket expenditure levels among the multiple-morbidity combinations. IMPLICATIONS: Increasing rates of multiple morbidities in conjunction with escalating health care costs and stable or declining incomes among elders warrant creative attention from providers, researchers, and policy makers. Further understanding how specific multiple-morbidity constellations impact out-of-pocket spending moves us closer to effective interventions to support vulnerable elders.