Aberrant DNA repair reveals a vulnerability in histone H3.3-mutant brain tumors.

Pediatric high-grade gliomas (pHGG) are devastating and incurable brain tumors with recurrent mutations in histone H3.3. These mutations promote oncogenesis by dysregulating gene expression through alterations of histone modifications. We identify aberrant DNA repair as an independent mechanism, which fosters genome instability in H3.3 mutant pHGG, and opens new therapeutic options. The two most frequent H3.3 mutations in pHGG, K27M and G34R, drive aberrant repair of replication-associated damage by non-homologous end joining (NHEJ). Aberrant NHEJ is mediated by the DNA repair enzyme polynucleotide kinase 3'-phosphatase (PNKP), which shows increased association with mutant H3.3 at damaged replication forks. PNKP sustains the proliferation of cells bearing H3.3 mutations, thus conferring a molecular vulnerability, specific to mutant cells, with potential for therapeutic targeting.

Physician and patient concordance in reporting of appropriateness and prioritization for cataract surgery.

BACKGROUND/AIMS: Determine the association between physician-deemed and patient-reported appropriateness and prioritization for cataract surgery. METHODS: Prospective cohort study of 471 patients of 7 ophthalmologists referred for cataract surgery. Ophthalmologists rated patients for cataract surgery appropriateness and prioritization using a visual analogue scale of 0-10 preoperatively. All patients completed the eCAPS Quality of Life (QoL), while 313 completed the Catquest-9SF and EQ-5D questionnaires. Regression analyses were applied to determine demographic, clinical and patient-reported outcome measures (PROMs) associated with appropriateness and prioritization. RESULTS: Two clinical factors (study eye and fellow eye best-corrected visual acuity (BCVA)), 2 eCAPS (night driving difficulty, ability to take care of local errands), and 2 Catquest-9SF PROMs (recognizing faces, seeing to walk on uneven ground) were associated with appropriateness. In multivariable regression, the rating physician, 2 clinical criteria (study eye BCVA, anticipated postoperative BCVA) and 1 eCAPS QoL (night driving difficulty) were associated with appropriateness. Prioritization was associated with low income, 8 clinical criteria, 9 eCAPS, 5 Catquest-9SF, and 1 EQ-5D PROMs. In multivariable regression, 1 clinical criterion (study eye BCVA), 2 eCAPS QoL (night driving difficulty, ability to take care of local errands), and 2 Catquest-9SF PROMs (seeing prices, seeing to walk on uneven ground) were significantly associated. CONCLUSIONS: The eCAPS and Catquest-9SF questionnaires show some concordance with physician-deemed appropriateness, and more with prioritization. Binary conversions of PROM scales provide similar modelling, with minimal loss of explanatory power. As physician-deemed appropriateness and prioritization do not completely capture the patient perspective, PROMs may have a role in cataract surgery decision-making frameworks.

Predicting changes in cataract surgery health outcomes using a cataract surgery appropriateness and prioritization instrument.

OBJECTIVE: Determine whether items in a cataract surgery appropriateness and prioritization questionnaire can predict change in best corrected visual acuity (BCVA) and health related quality of life (HRQOL) following cataract surgery. METHODS: 313 patients with a cataract in Ontario, Canada were recruited to participate. BCVA was measured using the Snellen chart. HRQOL was measured using a generic instrument (EQ5D), a visual functioning instrument (Catquest-9SF), and an appropriateness and prioritization instrument (17 items). Outcomes were measured preoperatively and 3-6 months postoperatively. Descriptive statistics were used to describe demographics and outcomes. For each appropriateness and prioritization questionnaire item, a one-way ANOVA was used to compare group means of the change in BCVA, EQ5D, and Catquest-9SF. RESULTS: Participants had a mean age of 69 years and were 56% female. BCVA improved in 81%, EQ5D in 49.6%, and Catquest-9SF score in 84% of patients. Improvement in both BCVA and Catquest-9SF scores were found in 68.5% of patients. The ANOVA showed a statistically significant association between a change in BCVA and the ability to participate in social life, and a statistically significant association between a change in Catquest-9SF and glare, extent of impairment in visual function, safety and injury concerns, ability to work and care for dependents, ability to take care of local errands, ability to assist others and ability to participate in social life. CONCLUSIONS: Almost all patients had improved BCVA and/or visual functioning after surgery. Seven variables from the cataract appropriateness and prioritization instrument were found to be predictors of improvement in Catquest-9SF measuring visual functioning.

Rad5 dysregulation drives hyperactive recombination at replication forks resulting in cisplatin sensitivity and genome instability.

The postreplication repair gene, HLTF, is often amplified and overexpressed in cancer. Here we model HLTF dysregulation through the functionally conserved Saccharomyces cerevisiae ortholog, RAD5. Genetic interaction profiling and landscape enrichment analysis of RAD5 overexpression (RAD5OE) reveals requirements for genes involved in recombination, crossover resolution, and DNA replication. While RAD5OE and rad5Δ both cause cisplatin sensitivity and share many genetic interactions, RAD5OE specifically requires crossover resolving genes and drives recombination in a region of repetitive DNA. Remarkably, RAD5OE induced recombination does not require other post-replication repair pathway members, or the PCNA modification sites involved in regulation of this pathway. Instead, the RAD5OE phenotype depends on a conserved domain necessary for binding 3' DNA ends. Analysis of DNA replication intermediates supports a model in which dysregulated Rad5 causes aberrant template switching at replication forks. The direct effect of Rad5 on replication forks in vivo, increased recombination, and cisplatin sensitivity predicts similar consequences for dysregulated HLTF in cancer.

A role for the unfolded protein response stress sensor ERN1 in regulating the response to MEK inhibitors in KRAS mutant colon cancers.

BACKGROUND: Mutations in KRAS are frequent in human cancer, yet effective targeted therapeutics for these cancers are still lacking. Attempts to drug the MEK kinases downstream of KRAS have had limited success in clinical trials. Understanding the specific genomic vulnerabilities of KRAS-driven cancers may uncover novel patient-tailored treatment options. METHODS: We first searched for synthetic lethal (SL) genetic interactions with mutant RAS in yeast with the ultimate aim to identify novel cancer-specific targets for therapy. Our method used selective ploidy ablation, which enables replication of cancer-specific gene expression changes in the yeast gene disruption library. Second, we used a genome-wide CRISPR/Cas9-based genetic screen in KRAS mutant human colon cancer cells to understand the mechanistic connection between the synthetic lethal interaction discovered in yeast and downstream RAS signaling in human cells. RESULTS: We identify loss of the endoplasmic reticulum (ER) stress sensor IRE1 as synthetic lethal with activated RAS mutants in yeast. In KRAS mutant colorectal cancer cell lines, genetic ablation of the human ortholog of IRE1, ERN1, does not affect growth but sensitizes to MEK inhibition. However, an ERN1 kinase inhibitor failed to show synergy with MEK inhibition, suggesting that a non-kinase function of ERN1 confers MEK inhibitor resistance. To investigate how ERN1 modulates MEK inhibitor responses, we performed genetic screens in ERN1 knockout KRAS mutant colon cancer cells to identify genes whose inactivation confers resistance to MEK inhibition. This genetic screen identified multiple negative regulators of JUN N-terminal kinase (JNK) /JUN signaling. Consistently, compounds targeting JNK/MAPK8 or TAK1/MAP3K7, which relay signals from ERN1 to JUN, display synergy with MEK inhibition. CONCLUSIONS: We identify the ERN1-JNK-JUN pathway as a novel regulator of MEK inhibitor response in KRAS mutant colon cancer. The notion that multiple signaling pathways can activate JUN may explain why KRAS mutant tumor cells are traditionally seen as highly refractory to MEK inhibitor therapy. Our findings emphasize the need for the development of new therapeutics targeting JUN activating kinases, TAK1 and JNK, to sensitize KRAS mutant cancer cells to MEK inhibitors.

Primary care physician resource use changes associated with feedback reports.

OBJECTIVES: To measure changes in primary care physician (PCP) ordering rates for 4 global resource use measures before and after dissemination of physician feedback reports that provided peer-comparison resource use rates. We also explored whether physician practice characteristics (panel size, clinic size, and years of experience) were associated with resource use changes. STUDY DESIGN: Pre-post implementation study measuring physician resource use in an integrated healthcare system (2011-2014). METHODS: Kaiser Permanente Washington PCPs (N = 210) were provided annual feedback reports showing their personal ordering rates compared with those of their peers. Monthly physician ordering was measured from November 2011 to September 2014 (including prereport and postreport periods). We examined 4 physician ordering rates (specialty referrals, high-end imaging, laboratory tests, and 30-day prescriptions) per 1000 patients, adjusted for patient age, gender, and clinical complexity. RESULTS: After accounting for physician practice characteristics, monthly PCP ordering rates for high-end imaging significantly decreased by 0.8 images per 1000 patients (P <.01). In contrast, orders for laboratory tests and 30-day prescriptions significantly increased by 15.0 tests and 84.7 prescriptions per 1000 patients (both P <.01). We observed greater changes following feedback in physicians with fewer years of experience (≤10 years), who had 4.2 fewer specialty referrals (P = .01) and 101.3 more 30-day prescriptions (P <.01) compared with those with more experience (>20 years). CONCLUSIONS: Physician feedback reports may be associated with changes in physician resource use, and physicians with fewer years of experience may be more responsive to feedback reports. Better understanding of factors associated with changes in resource use is necessary for future targeted development of physician interventions.

Synthesis Of Research On Patient-Centered Medical Homes Brings Systematic Differences Into Relief.

The patient-centered medical home (PCMH) model emphasizes comprehensive, coordinated, patient-centered care, with the goals of reducing spending and improving quality. To evaluate the impact of PCMH initiatives on utilization, cost, and quality, we conducted a meta-analysis of methodologically standardized findings from evaluations of eleven major PCMH initiatives. There was significant heterogeneity across individual evaluations in many outcomes. Across evaluations, PCMH initiatives were not associated with changes in the majority of outcomes studied, including primary care, emergency department, and inpatient visits and four quality measures. The initiatives were associated with a 1.5 percent reduction in the use of specialty visits and a 1.2 percent increase in cervical cancer screening among all patients, and a 4.2 percent reduction in total spending (excluding pharmacy spending) and a 1.4 percent increase in breast cancer screening among higher-morbidity patients. These associations were significant. Identification of the components of PCMHs likely to improve outcomes is critical to decisions about investing resources in primary care.

Suicidal ideation among suburban adolescents: The influence of school bullying and other mediating risk factors.

OBJECTIVE: Prior research has identified multiple factors that influence suicidal ideation (SI) among bullied youth. The effects of school bullying on SI cannot be considered in isolation. In this study, we examined the influence of school bullying on SI, through a constellation of risks, which include depressive and anxiety symptoms, family conflict, and alcohol, tobacco, and other drug (ATOD) use. We also provide recommendations for therapists working with bullied youth. METHOD: Our sample consisted of 488 adolescents (ages 10-18 years) from a northern New Jersey, United States suburban community. Students were recruited through the district's physical education and health classes. Students responded to multiple measures, which included family cohesion/conflict, ATOD use, mental health indicators, SI, and school bullying experiences. Following preliminary analyses, several logistic regression models were used to assess the direct influence of bullying on SI, as well as the unique effects of family conflict, depressive and anxiety symptoms, and substance use. In addition, a parallel multiple mediating model with the PROCESS macro in SPSS was used to further assess mediating effects. RESULTS: Logistic regression results indicated that school bullying increased the odds of SI among males and females and that when mediating variables were added to the model, bullying no longer had a significant influence on SI. Overall, these results display that for both males and females, school bullying was a significant contributor to SI. Results from the parallel multiple mediating model further illustrated the mediating effects that family conflict, depression, and ATOD use had between bullying and SI. Some variation was noted based on gender. CONCLUSION: This study draws attention to the multiple experiences associated with school bullying on SI, and how these results may differ by gender. The results of this study are particularly important for those working directly and indirectly with bullied youth. Therapists that engage bullied youth need to consider the multiple spheres of influence that may increase SI among male and female clients. To holistically and adequately assess SI among bullied youth, therapists must also consider how these mechanisms vary between gender groups.

A Synthetic Dosage Lethal Genetic Interaction Between CKS1B and PLK1 Is Conserved in Yeast and Human Cancer Cells.

The CKS1B gene located on chromosome 1q21 is frequently amplified in breast, lung, and liver cancers. CKS1B codes for a conserved regulatory subunit of cyclin-CDK complexes that function at multiple stages of cell cycle progression. We used a high throughput screening protocol to mimic cancer-related overexpression in a library of Saccharomyces cerevisiae mutants to identify genes whose functions become essential only when CKS1 is overexpressed, a synthetic dosage lethal (SDL) interaction. Mutations in multiple genes affecting mitotic entry and mitotic exit are highly enriched in the set of SDL interactions. The interactions between Cks1 and the mitotic entry checkpoint genes require the inhibitory activity of Swe1 on the yeast cyclin-dependent kinase (CDK), Cdc28. In addition, the SDL interactions of overexpressed CKS1 with mutations in the mitotic exit network are suppressed by modulating expression of the CDK inhibitor Sic1. Mutation of the polo-like kinase Cdc5, which functions in both the mitotic entry and mitotic exit pathways, is lethal in combination with overexpressed CKS1 Therefore we investigated the effect of targeting the human Cdc5 ortholog, PLK1, in breast cancers with various expression levels of human CKS1B Growth inhibition by PLK1 knockdown correlates with increased CKS1B expression in published tumor cell data sets, and this correlation was confirmed using shRNAs against PLK1 in tumor cell lines. In addition, we overexpressed CKS1B in multiple cell lines and found increased sensitivity to PLK1 knockdown and PLK1 drug inhibition. Finally, combined inhibition of WEE1 and PLK1 results in less apoptosis than predicted based on an additive model of the individual inhibitors, showing an epistatic interaction and confirming a prediction of the yeast data. Thus, identification of a yeast SDL interaction uncovers conserved genetic interactions that can affect human cancer cell viability.

Physician Service Attribution Methods for Examining Provision of Low-Value Care.

OBJECTIVES: There has been significant research on provider attribution for quality and cost. Low-value care is an area of heightened focus, with little of the focus being on measurement; a key methodological decision is how to attribute delivered services and procedures. We illustrate the difference in relative and absolute physician- and panel-attributed services and procedures using overuse in cervical cancer screening. STUDY DESIGN: A retrospective, cross-sectional study in an integrated health care system. METHODS: We used 2013 physician-level data from Group Health Cooperative to calculate two utilization attributions: (1) panel attribution with the procedure assigned to the physician's predetermined panel, regardless of who performed the procedure; and (2) physician attribution with the procedure assigned to the performing physician. We calculated the percentage of low-value cervical cancer screening tests and ranked physicians within the clinic using the two utilization attribution methods. RESULTS: The percentage of low-value cervical cancer screening varied substantially between physician and panel attributions. Across the whole delivery system, median panel- and physician-attributed percentages were 15 percent and 10 percent, respectively. Among sampled clinics, panel-attributed percentages ranged between 10 percent and 17 percent, and physician-attributed percentages ranged between 9 percent and 13 percent. Within a clinic, median panel-attributed screening percentage was 17 percent (range 0 percent-27 percent) and physician-attributed percentage was 11 percent (range 0 percent-24 percent); physician rank varied by attribution method. CONCLUSIONS: The attribution method is an important methodological decision when developing low-value care measures since measures may ultimately have an impact on national benchmarking and quality scores. Cross-organizational dialogue and transparency in low-value care measurement will become increasingly important for all stakeholders.

Relationship between cardiovascular risk and lipid testing in one health care system: a retrospective cohort study.

BACKGROUND: The US Preventive Services Taskforce (USPSTF) recommends routine lipid screening beginning age 35 for men [1]. For women age 20 and older, as well as men age 20-34, screening is recommended if cardiovascular risk factors are present. Prior research has focused on underutilization but not overuse of lipid testing. The objective is to document over- and under-use of lipid testing in an insured population of persons at low, moderate and high cardiovascular disease (CVD) risk for persons not already on statins. METHODS: The study is a retrospective cohort study that included all adults without prior CVD who were continuously enrolled in a large integrated healthcare system from 2005 to 2010. Measures included lipid test frequency extracted from administrative data and Framingham cardiovascular risk equations applied using electronic medical record data. Five year lipid testing patterns were examined by age, sex and CVD risk. Generalized linear models were used to estimate the relative risk for over testing associated with patient characteristics. RESULTS: Among males and females for whom testing is not recommended, 35.8 % and 61.5 % received at least one lipid test in the prior 5 years and 8.4 % and 24.4 % had two or more. Over-testing was associated with age, race, comorbidity, primary care use and neighborhood income. Among individuals at moderate and high-risk (not already treated with statins) and for whom screening is recommended, between 21.4 % and 25.1 % of individuals received no screening in the prior 5 years. CONCLUSIONS: Based on USPSTF lipid screening recommendations, this study documents substantial over-testing among individuals with low CVD risk and under-testing among individuals with moderate to high-risk not already on statins. Opportunity exists to better focus lipid screening efforts appropriate to CVD risk.

Do depressed newly diagnosed cancer patients differentially benefit from nurse navigation?

OBJECTIVE: To examine whether the effects of a nurse navigator intervention for cancer vary with baseline depressive symptoms. METHOD: Participants were enrolled in a randomized controlled trial of a nurse navigation intervention for patients newly diagnosed with lung, breast or colorectal cancer (N=251). This exploratory analysis used linear regression models to estimate the effect of a nurse navigator intervention on patient experience of care. Models estimated differential effects by including interactions between randomization group and baseline depressive symptoms. Baseline scores on the 9-item Patient Health Questionnaire (PHQ) were categorized into 3 groups: no depression (PHQ=0-4, N=138), mild symptoms of depression (PHQ=5-9, N=76) and moderate to severe symptoms (PHQ=10 or greater, N=34). Patient experience outcomes were measured by subscales of the Patient Assessment of Chronic Illness Care (PACIC) and subscales from an adaptation of the Picker Institute's patient experience survey at 4-month follow-up. RESULTS: With the exception of the PACIC subscale of delivery system/practice design, interaction terms between randomization group and PHQ-9 scores were not statistically significant. CONCLUSIONS: The intervention was broadly useful; we found that it was equally beneficial for both depressed patients and patients who were not significantly depressed in the first 4 months postdiagnosis. However, because of the small sample size, we cannot conclude with certainty that patients with depressive symptoms did not differentially benefit from the intervention.

Perspectives of cancer survivors on the role of different healthcare providers in an integrated delivery system.

PURPOSE: The purpose of this paper is to describe patient perspectives on survivorship care 1 year after cancer diagnosis. METHODS: The study was conducted at an integrated healthcare delivery system in western Washington State. Participants were patients with breast, colorectal, and lung cancer who had enrolled in a randomized control trial (RCT) of oncology nurse navigation to improve early cancer care. Those alive and enrolled in the healthcare system 1 year after diagnosis were eligible for this analysis. Participants completed surveys by phone. Questions focused on receipt of treatment summaries and care plans; discussions with different providers; patient opinions on who does and should provide their care; and patient perspectives primary care providers' (PCP) knowledge and skills related to caring for cancer survivors RESULTS: Of the 251 participants in the RCT, 230 (91.6%) responded to the 12-month phone survey and were included in this analysis; most (n = 183, 79.6%) had breast cancer. The majority (84.8%) considered their cancer specialist (e.g., medical, radiation, surgical or gynecological oncologist) to be their main provider for cancer follow-up and most (69.4%) had discussed follow-up care with that provider. Approximately half of patients were uncertain how well their PCP communicated with the oncologist and how knowledgeable s/he was in caring for cancer survivors. CONCLUSIONS: One year after diagnosis, cancer survivors continue to view cancer specialists as their main providers and are uncertain about their PCP's skills and knowledge in managing their care. Our findings present an opportunity to help patients understand what their PCPs can and cannot provide in the way of cancer follow-up care. IMPLICATIONS FOR CANCER SURVIVORS: Additional research on care coordination and delivery is necessary to help cancer survivors manage their care between primary care and specialty providers.

Nurse navigators in early cancer care: a randomized, controlled trial.

PURPOSE: To determine whether a nurse navigator intervention improves quality of life and patient experience with care for people recently given a diagnosis of breast, colorectal, or lung cancer. PATIENTS AND METHODS: Adults with recently diagnosed primary breast, colorectal, or lung cancer (n = 251) received either enhanced usual care (n = 118) or nurse navigator support for 4 months (n = 133) in a two-group cluster randomized, controlled trial with primary care physicians as the units of randomization. Patient-reported measures included the Functional Assessment of Cancer Therapy-General (FACT-G) Quality of Life scale, three subscales of the Patient Assessment of Chronic Illness Care (PACIC), and selected subscales from a cancer adaptation of the Picker Institute's patient experience survey. Self-report measures were collected at baseline, 4 months, and 12 months. Automated administrative data were used to assess time to treatment and total health care costs. RESULTS: There were no significant differences between groups in FACT-G scores. Nurse navigator patients reported significantly higher scores on the PACIC and reported significantly fewer problems with care, especially psychosocial care, care coordination, and information, as measured by the Picker instrument. Cumulative costs after diagnosis did not differ significantly between groups, but lung cancer costs were $6,852 less among nurse navigator patients. CONCLUSION: Compared with enhanced usual care, nurse navigator support for patients with cancer early in their course improves patient experience and reduces problems in care, but did not differentially affect quality of life.

Examining tobacco outlet concentration in New Jersey: does income and ethnicity matter?

This study examined the geographic association between tobacco outlet density and the demographic indicators of median household income and percentage of Hispanic residents in New Jersey. Tobacco outlet density was assessed by examining all tobacco retailers licensed in 2004 in New Jersey, and demographic variables were based on the 2000 United States Census. Results indicated that the percentage of Hispanic residents and median household income were both salient predictors of tobacco outlet density. We also observed that income level moderated the relationship between the percentage of Hispanics residents and tobacco outlet density. Implications for environmentally based tobacco prevention and control initiatives are discussed.

Patterns of preoperative consultation and surgical specialty in an integrated healthcare system.

BACKGROUND: Many patients scheduled for elective surgery are referred for a preoperative medical consultation. Only limited data are available on factors associated with preoperative consultations. The authors hypothesized that surgical specialty contributes to variation in referrals for preoperative consultations. METHODS: This is a cohort study using data from Group Health Cooperative, an integrated healthcare system. The authors included 13,673 patients undergoing a variety of common procedures-primarily low-risk surgeries-representing six surgical specialties, in 2005-2006. The authors identified consultations by family physicians, general internists, pulmonologists, or cardiologists in the 42 days preceding surgery. Multivariable logistic regression was used to estimate the association between surgical specialty and consultation, adjusting for potential confounders including the revised cardiac risk index, age, gender, Deyo comorbidity index, number of prescription medications, and 11 medication classes. RESULTS: The authors found that 3,063 (22%) of all patients had preoperative consultations, with significant variation by surgical specialty. Patients having ophthalmologic, orthopedic, or urologic surgery were more likely to have consultations compared with those having general surgery-adjusted odds ratios (95% CI) of 3.8 (3.3-4.2), 1.5 (1.3-1.7), and 2.3 (1.8-2.8), respectively. Preoperative consultations were more common in patients with lower revised cardiac risk scores. CONCLUSION: There is substantial practice variation among surgical specialties with regard to the use of preoperative consultations in this integrated healthcare system. Given the large number of consultations provided for patients with low cardiac risk and for patients presenting for low-risk surgeries, their indications, the financial burden, and cost-effectiveness of consultations deserve further study.

Physician-patient colorectal cancer screening discussions by physicians' screening rates.

BACKGROUND: Most physicians report routinely recommending colorectal cancer (CRC) screening, but many eligible patients are not screened. To better understand this finding, we explored the relationship between the content of hypothetical patient-physician CRC screening discussions and CRC screening rates in physicians' practices. METHODS: Semistructured interviews, including role-playing, with 24 primary care physicians explored their CRC screening approach with average-risk patients. Qualitative analysis examined physician-reported components of the CRC screening discussion, then compared findings between physicians with high (≥60%, n = 16) and low (≤45%, n = 8) CRC screening rates (based on HEDIS criteria). We conducted no statistical tests because of the small sample size and its exploratory aims. RESULTS: High screeners used dramatic language (eg, patient stories) and mentioned risk of death, disability, or surgery from CRC in screening discussion role-plays more often than low screeners. High screeners frequently offered fecal occult blood testing, flexible sigmoidoscopy, and colonoscopy as equally acceptable screening options. High screeners more commonly described solutions for overcoming CRC screening barriers. CONCLUSIONS: Encouraging providers to use risk-specific messaging about the consequences of CRC, offering screening option choices, and promoting a problem-solving approach to surmount barriers are potential strategies for increasing CRC screening rates.

Evaluating components of dental care utilization among adults with diabetes and matched controls via hurdle models.

BACKGROUND: About one-third of adults with diabetes have severe oral complications. However, limited previous research has investigated dental care utilization associated with diabetes. This project had two purposes: to develop a methodology to estimate dental care utilization using claims data and to use this methodology to compare utilization of dental care between adults with and without diabetes. METHODS: Data included secondary enrollment and demographic data from Washington Dental Service (WDS) and Group Health Cooperative (GH), clinical data from GH, and dental-utilization data from WDS claims during 2002-2006. Dental and medical records from WDS and GH were linked for enrollees continuously and dually insured during the study. We employed hurdle models in a quasi-experimental setting to assess differences between adults with and without diabetes in 5-year cumulative utilization of dental services. Propensity score matching adjusted for differences in baseline covariates between the two groups. RESULTS: We found that adults with diabetes had lower odds of visiting a dentist (OR = 0.74, p < 0.001). Among those with a dental visit, diabetes patients had lower odds of receiving prophylaxis (OR = 0.77), fillings (OR = 0.80) and crowns (OR = 0.84) (p < 0.005 for all) and higher odds of receiving periodontal maintenance (OR = 1.24), non-surgical periodontal procedures (OR = 1.30), extractions (OR = 1.38) and removable prosthetics (OR = 1.36) (p < 0.001 for all). CONCLUSIONS: Patients with diabetes are less likely to use dental services. Those who do are less likely to use preventive care and more likely to receive periodontal care and tooth-extractions. Future research should address the possible effectiveness of additional prevention in reducing subsequent severe oral disease in patients with diabetes.

Biopsy follow-up of prostate-specific antigen tests.

BACKGROUND: A prostate-specific antigen (PSA) level above 4 ng/mL has historically been recognized as an appropriate threshold to recommend biopsy; however the risk of high-grade disease observed among men with lower PSA levels in the Prostate Cancer Prevention Trial has led to calls to change the criteria for biopsy referral. PURPOSE: To aid providers when discussing aggressiveness of biopsy by cataloging available community biopsy patterns and determine whether lower PSA thresholds are being used to recommend biopsy. METHODS: Laboratory and biopsy records were reviewed among 59,764 men in a large Washington State health plan between 1998 and 2007. Follow-up in the 12-month period after a test was categorized as biopsy, urology visit without biopsy, additional PSA testing with no urology visit, or no PSA-related follow-up. Data analysis occurred between 2010 and 2011. RESULTS: Twenty-eight percent of tests with PSA levels ≥4.0 ng/mL, 2.9% of tests with levels between 2.5 and 4.0 ng/mL, and 0.4% of tests with levels <2.5 ng/mL were followed with a biopsy within 12 months. More than 40% of elevated tests (≥4.0 ng/mL) were followed by a urologist visit without a biopsy, and more than 30% of tests ≥4.0 did not have any PSA-related follow-up within 12 months. PSA velocity, defined as annualized rate of change in PSA level, was strongly associated with biopsy, especially when absolute PSA was <4.0 ng/mL. There appear to be no discernable temporal trends in biopsy thresholds or practice patterns based on PSA lower levels or velocity. CONCLUSIONS: Despite recent calls to more aggressively recommend biopsy at lower PSA thresholds, the practice in this large health plan has remained consistent over time.