Angiotensin blockade therapy and survival in pancreatic cancer: a population study.

BACKGROUND: Pancreatic cancer (PC) is one of the most aggressive and challenging cancer types to effectively treat, ranking as the fourth-leading cause of cancer death in the United States. We investigated if exposures to angiotensin II receptor blockers (ARBs) or angiotensin I converting enzyme (ACE) inhibitors after PC diagnosis are associated with survival. METHODS: PC patients were identified by ICD-9 diagnosis and procedure codes among the 3.7 million adults living in the Emilia-Romagna Region from their administrative health care database containing patient data on demographics, hospital discharges, all-cause mortality, and outpatient pharmacy prescriptions. Cox modeling estimated covariate-adjusted mortality hazard ratios for time-dependent ARB and ACE inhibitor exposures after PC diagnosis. RESULTS: 8,158 incident PC patients were identified between 2003 and 2011, among whom 20% had pancreas resection surgery, 36% were diagnosed with metastatic disease, and 7,027 (86%) died by December 2012. Compared to otherwise similar patients, those exposed to ARBs after PC diagnosis experienced 20% lower mortality risk (HR=0.80; 95% CI: 0.72, 0.89). Those exposed to ACE inhibitors during the first three years of survival after PC diagnosis experienced 13% lower mortality risk (HR=0.87; 95% CI: 0.80, 0.94) which attenuated after surviving three years (HR=1.14; 95% CI: 0.90, 1.45). CONCLUSIONS: The results of this large population study suggest that exposures to ARBs and ACE inhibitors after PC diagnosis are significantly associated with improved survival. ARBs and ACE inhibitors could be important considerations for treating PC patients, particularly those with the worst prognosis and most limited treatment options. Considering that these common FDA approved drugs are inexpensive to payers and present minimal increased risk of adverse events to patients, there is an urgent need for randomized clinical trials, large simple randomized trials, or pragmatic clinical trials to formally and broadly evaluate the effects of ARBs and ACE inhibitors on survival in PC patients.

Metformin exposure and survival in head and neck cancer: A large population-based cohort study.

WHAT IS KNOWN AND OBJECTIVE: Observational clinical studies of metformin for prevention and treatment of several cancer types have reported mixed findings. Although preclinical studies have suggested metformin may reduce head and neck cancer (HNC) proliferation, clinical evidence is limited. The objective of this large population-based study was to evaluate the relationship between metformin exposure following HNC diagnosis and all-cause mortality. METHODS: We conducted a retrospective cohort study using the Italian Emilia-Romagna Regional administrative healthcare database, which includes demographic, hospital and outpatient prescription information for ~4.5 million residents. Included patients were followed from the first hospital discharge (index) during the study period (01/2003-12/2012) with a diagnosis of HNC. Metformin exposure and select covariates were operationalized in a time-dependent manner during follow-up. Cox proportional hazards models estimated the covariate-adjusted time-dependent association between metformin exposure and all-cause mortality. RESULTS AND DISCUSSION: Among 7872 patients diagnosed with HNC, 708 (9.0%) were exposed to metformin after HNC diagnosis, and 3626 (46.1%) died during follow-up (median follow-up: 35.2 months). In the covariate-adjusted model, the all-cause mortality rate appeared lower (HR: 0.81, 95% CI: 0.61-1.09) among metformin exposed patients during the 2 years post-diagnosis, while the all-cause mortality rate appeared higher (HR: 1.20, 95% CI: 0.94-1.53) among exposed patients after 2 years post-diagnosis. Metformin was protective among patients ≤60 years of age (HR for the period of 0-2 years post-diagnosis: 0.22, 95% CI 0.09-0.56; HR for the period ≥2 years post-diagnosis: 0.56, 95% CI 0.26-1.22) but not in those >60 years. WHAT IS NEW AND CONCLUSION: In this population-based study of metformin in HNC, we found a modest protective association between metformin exposure and all-cause mortality in the 2-year post-diagnosis period. Age appeared to modify the association between metformin and HNC survival.

Assessing adverse events of postprostatectomy radiation therapy for prostate cancer: evaluation of outcomes in the Regione Emilia-Romagna, Italy.

PURPOSE: Although the likelihood of radiation-related adverse events influences treatment decisions regarding radiation therapy after prostatectomy for eligible patients, the data available to inform decisions are limited. This study was designed to evaluate the genitourinary, gastrointestinal, and sexual adverse events associated with postprostatectomy radiation therapy and to assess the influence of radiation timing on the risk of adverse events. METHODS: The Regione Emilia-Romagna Italian Longitudinal Health Care Utilization Database was queried to identify a cohort of men who received radical prostatectomy for prostate cancer during 2003 to 2009, including patients who received postprostatectomy radiation therapy. Patients with prior radiation therapy were excluded. Outcome measures were genitourinary, gastrointestinal, and sexual adverse events after prostatectomy. Rates of adverse events were compared between the cohorts who did and did not receive postoperative radiation therapy. Multivariable Cox proportional hazards models were developed for each class of adverse events, including models with radiation therapy as a time-varying covariate. RESULTS: A total of 9876 men were included in the analyses: 2176 (22%) who received radiation therapy and 7700 (78%) treated with prostatectomy alone. In multivariable Cox proportional hazards models, the additional exposure to radiation therapy after prostatectomy was associated with increased rates of gastrointestinal (rate ratio [RR] 1.81; 95% confidence interval [CI] 1.44-2.27; P<.001) and urinary nonincontinence events (RR 1.83; 95% CI 1.83-2.80; P<.001) but not urinary incontinence events or erectile dysfunction. The addition of the time from prostatectomy to radiation therapy interaction term was not significant for any of the adverse event outcomes (P>.1 for all outcomes). CONCLUSION: Radiation therapy after prostatectomy is associated with an increase in gastrointestinal and genitourinary adverse events. However, the timing of radiation therapy did not influence the risk of radiation therapy-associated adverse events in this cohort, which contradicts the commonly held clinical tenet that delaying radiation therapy reduces the risk of adverse events.

Variation among local health units in follow-up care of breast cancer patients in Emilia-Romagna, Italy.

AIMS AND BACKGROUND: This study examines the patterns of follow-up care for breast cancer survivors in one region in Italy. METHODS AND STUDY DESIGN: This retrospective analysis included 10,024 surgically treated women, with incident cases of breast cancer in the years 2002-2005 who were alive 18 months after their incidence date. Rates of use of follow-up mammograms, abdominal echogram, bone scans and chest x-rays were estimated from administrative data and compared by Local Health Unit (LHU) of residence. Logistic regression analyses were performed to assess possible "overuse", accounting for patient age, cancer stage, type of surgery and LHU of residence. RESULTS: A total of 7168 (72.1%) women received a mammogram within 18 months of their incidence date, while 6432 (64.2%) had an abdominal echogram, 3852 (38.4%) had a bone scan and 5231 (52.2%) had a chest x-ray. The rates of use of abdominal echograms, bone scans and chest x-rays were substantially higher in the population of breast cancer survivors than in the general female population. Taking account of patient age, cancer stage at diagnosis and type of surgery, multivariate analyses demonstrated significant variation in the use of these tests by LHU of residence. CONCLUSIONS: The observed variation in the use of abdominal echograms, bone scans and chest x-rays supports the conclusion that there is substantial misuse of these tests in the population of postsurgical breast cancer patients in the Emilia-Romagna region in Italy. In the absence of a documented survival benefit, overtesting has both a human and financial cost. We recommend additional review of the methods of follow-up care in breast cancer patients in the LHUs of Emilia-Romagna, with the aim of developing, disseminating and evaluating the implementation of specific guidelines targeting primary care physicians and oncologists providing care to breast cancer survivors. Patient education materials may also help to reduce unnecessary testing.

Statins and colorectal cancer risk: a longitudinal study.

PURPOSE: Studies evaluating the association between statins and colorectal cancer (CRC) have used various methods to address bias and have reported mixed findings. We sought to assess the association in a large cohort of residents in Emilia-Romagna, Italy, using multiple methods to address different sources of confounding. We also sought to explore potential effect measure modification by sex. METHODS: We conducted a retrospective cohort study using the 2003-2010 healthcare database of Emilia-Romagna, Italy. We identified all initiators of statins; initiators of glaucoma medications served as the comparison group to account for confounding by healthy user bias. We followed patients longitudinally to identify CRC cases in hospital discharge data. We used multivariable Cox regression analyses to adjust for confounding by CRC risk factors and we conducted a sensitivity analysis using propensity score matching. RESULTS: After multivariable adjustment, initiators of statins had a lower incidence rate of CRC as compared to initiators of glaucoma drugs [hazard ratio (HR) 0.79; 95 % CI 0.69-0.90]. In sex-stratified analyses we observed a protective effect in men (HR 0.77; 95 % CI 0.67-0.88) but not in women (HR 0.96; 95 % CI 0.82-1.1). Results were similar in propensity score analyses. CONCLUSIONS: After adjusting for observed risk factors, statin initiation versus glaucoma drug initiation was associated with a reduced risk of CRC in men but not in women. While this study is subject to many limitations, it corroborates a previous study that found sex differences in the association between statins and CRC.

Using administrative data to identify and stage breast cancer cases: implications for assessing quality of care.

AIMS AND BACKGROUND: The study evaluated the use of Italian hospital discharge data (SDO, scheda di dimissione ospedaliera) for identifying women with incident breast cancer, determining stage at diagnosis and assessing quality of care. STUDY DESIGN: Women aged 20+ years residing in the Regione Emilia-Romagna, Italy, between 2002 and 2005 were studied. Case identification using algorithms based on ICD-9-CM codes on hospital discharge data were compared with AIRTUM-accredited cancer registry data. Sensitivity, specificity and positive predictive value were computed overall, by age and cancer stage. Compliance with guidelines for radiation therapy using registry and hospital data were compared. RESULTS: A total of 11,615 women was identified by AIRTUM-accredited cancer registries as incident cases, whereas 10,876 women were identified by the SDO algorithm. Sensitivity was 84.8%, specificity was 99.9%, and the positive predictive value was 90.6%. Of the 1,022 who were false positives, 363 (35.5%) were women identified in registry data as having an incident case prior to 2002 and therefore were not included in the analysis. There were 1,761 false negatives; nearly 50% were over 70 years of age or did not undergo a surgical procedure and therefore were not included in our SDO-based case finding. Sensitivity declined as the patient population became older. However, we observed relatively good positive predictive value for all age groups. Algorithms using the SDO data did not clearly identify specific cancer stages. However, the algorithm may have utility where stages are grouped together for use in quality measures. CONCLUSIONS: Cases were identified with good sensitivity, specificity and positive predictive value with SDO data, with better rates than similar previously published algorithms based on Italian data. These hospital claims-based algorithms facilitate quality of care analyses for large populations when registry data are not available by identifying individual women and their subsequent use of health care services.

Physicians' empathy and clinical outcomes for diabetic patients.

PURPOSE: To test the hypothesis that physicians' empathy is associated with positive clinical outcomes for diabetic patients. METHOD: A correlational study design was used in a university-affiliated outpatient setting. Participants were 891 diabetic patients, treated between July 2006 and June 2009, by 29 family physicians. Results of the most recent hemoglobin A1c and LDL-C tests were extracted from the patients' electronic records. The results of hemoglobin A1c tests were categorized into good control (<7.0%) and poor control (>9.0%). Similarly, the results of the LDL-C tests were grouped into good control (<100) and poor control (>130). The physicians, who completed the Jefferson Scale of Empathy in 2009, were grouped into high, moderate, and low empathy scorers. Associations between physicians' level of empathy scores and patient outcomes were examined. RESULTS: Patients of physicians with high empathy scores were significantly more likely to have good control of hemoglobin A1c (56%) than were patients of physicians with low empathy scores (40%, P < .001). Similarly, the proportion of patients with good LDL-C control was significantly higher for physicians with high empathy scores (59%) than physicians with low scores (44%, P < .001). Logistic regression analyses indicated that physicians' empathy had a unique contribution to the prediction of optimal clinical outcomes after controlling for physicians' and patients' gender and age, and patients' health insurance. CONCLUSIONS: The hypothesis of a positive relationship between physicians' empathy and patients' clinical outcomes was confirmed, suggesting that physicians' empathy is an important factor associated with clinical competence and patient outcomes.

Increasing appropriateness of hospital admissions in the Emilia-Romagna region of Italy.

OBJECTIVES: The Emilia-Romagna region of Italy has reduced the number of available hospital beds and introduced financial incentives to curb hospital use. The goal of this study was to assess the impact of these policies on changes over time in the number of acute hospital admissions classified in diagnosis related groups (DRGs) that could be treated safely and effectively in alternative, less costly settings. METHODS: The assessment of the appropriate site of care was based on analysis of hospital discharge data for all hospitals for the selected diagnosis related groups in the Emilia-Romagna region for 2001 to 2005. The necessity for acute hospital admission was based on the severity of a patient's principal diagnosis, co-morbid diseases and, for surgical admissions, procedure performed. RESULTS: From 2001 to 2005, potentially inappropriate medical admissions of more than one day decreased from 20,076 to 11,580, a 42% decrease. Inappropriate admissions decreased in both public and private hospitals but there remained a higher rate of inappropriate admissions to private hospitals. Potentially inappropriate medical admissions accounted for 128,319 bed-days in 2001 and 68,968 bed-days in 2005, a reduction of 59,351 bed-days. Potentially inappropriate surgical admissions decreased from 7383 in 2001 to 4349 in 2005, a 41% decrease. Bed-days consumed by inappropriate surgical admissions decreased from 23,181 in 2001 to 13,660 in 2005. CONCLUSIONS: The Emilia-Romagna region has succeeded in reducing the use of acute hospital beds for patients in selected diagnosis related groups. However, there are still substantial numbers of admissions that could potentially be treated in less costly settings.

Using pharmacy data to identify those with chronic conditions in Emilia Romagna, Italy.

BACKGROUND AND OBJECTIVES: Automated pharmacy data have been used to develop a measure of chronic disease status in the general population. The objectives of this project were to refine and apply a model of chronic disease identification using Italian automated pharmacy data; to describe how this model may identify patterns of morbidity in Emilia Romagna, a large Italian region; and to compare estimated prevalence rates using pharmacy data with those available from a 2000 Emilia Romagna disease surveillance study. METHODS: Using the Chronic Disease Score, a list of chronic conditions related to the consumption of drugs under the Italian pharmaceutical dispensing system was created. Clinical review identified medication classes within the Italian National Therapeutic Formulary that were linked to the management of each chronic condition. Algorithms were then tested on pharmaceutical claims data from Emilia Romagna for 2001 to verify the applicability of the classification scheme. RESULTS: Thirty-one chronic condition drug groups (CCDGs) were identified. Applying the model to the pharmacy data, approximately 1.5 million individuals (37.1%) of the population were identified as having one or more of the 31 CCDGs. The 31 CCDGs accounted for 77% (E556 million) of 2001 pharmaceutical expenditures. Cardiovascular diseases, rheumatological conditions, chronic respiratory illness, gastrointestinal diseases and psychiatric diseases were the most frequent chronic conditions. External validation comparing rates of the diseases found through using pharmacy data with those of a 2000 Emilia Romagna disease surveillance study showed similar prevalence of illness. CONCLUSIONS: Using Italian automated pharmacy data, a measure of population-based chronic disease status was developed. Applying the model to pharmaceutical claims from Emilia Romagna 2001, a large proportion of the population was identified as having chronic conditions. Pharmacy data may be a valuable alternative to survey data to assess the extent to which large populations are affected by chronic conditions.

Long-term retention of graduates from a program to increase the supply of rural family physicians.

PURPOSE: To determine the long-term retention of rural family physicians graduating from the Physician Shortage Area Program (PSAP) of Jefferson Medical College. METHOD: Of the 1,937 Jefferson graduates from the classes of 1978-1986, the authors identified those practicing rural family medicine when their practice location was first determined. The number and percent of PSAP and non-PSAP graduates practicing family medicine in the same rural area in 2002 were then identified, and compared to the number of those graduates practicing rural family medicine when they were first located in practice 11-16 years earlier. RESULTS: After 11-16 years, 68% (26/38) of the PSAP graduates were still practicing family medicine in the same rural area, compared with 46% (25/54) of their non-PSAP peers (p = .03). Survival analysis showed that PSAP graduates practice family medicine in the same rural locality longer than non-PSAP graduates (p = .04). CONCLUSIONS: These results are the first to show long-term rural primary care retention that is longer than the median duration. This outcome combined with previously published outcomes show that the PSAP represents the only program that has resulted in multifold increases in both recruitment (eight-fold) and long-term retention (at least 11-16 years). In light of recent national recommendations to increase the total enrollment in medical schools, allocating some of this growth to developing and expanding programs similar to the PSAP would make a substantial and long lasting impact on the rural physician workforce.

Genetic and environmental influences on the organisation of semantic memory in the brain:is "living things" an innate category?

The organisation of semantic memory into separately lesionable or imageable components must be determined by some combination of genetic and environmental factors. Little is known about the relative contributions of these two factors in establishing the functional architecture of semantic memory. By assessing the semantic memory impairment of an individual who sustained brain damage as a newborn, it is possible to place an upper bound on the contribution of post-natal experience. The present case study demonstrates a profound and enduring impairment in knowledge of "living things" following posterior cerebral artery infarctions at approximately 1 day of age. The design of the two experiments reported here allows us to characterise the subject's semantic memory impairment in terms of its scope and selectivity. The impairment affects both the naming of pictures of living things and the retrieval of verbal information about living things. It cannot be accounted for by differences in the difficulty of retrieving knowledge of living and nonliving things, as the living and nonliving items were equated for difficulty in each experiment. When visual and nonvisual information were queried separately for living and nonliving things, the impairment was manifest for both kinds of information about living things, but for neither kind of information about nonliving things. Because this impairment resulted from brain damage sustained too early for experience to have contributed to the organisation of semantic memory, this case study supports a genetic basis for the living-nonliving distinction in semantic memory.

Evaluations of medical students' clinical experiences in a family medicine clerkship: differences in patient encounters by disease severity in different clerkship sites.

BACKGROUND AND OBJECTIVES: Evaluation of medical students'clinical encounters is an essential component of optimizing their educational experience. In this study, we collected data on the diagnoses and disease severity in student-patient encounters at different family medicine clerkship sites. METHODS: Participants were 582 third-year medical students who completed a total of 7,515 specially designed patient encounter cards in a 6-week family medicine clerkship atfive training sites over 3 years. RESULTS: Variation was found in the average number of encounters in different clerkship sites. The findings for three frequently encountered diseases (essential hypertension, diabetes mellitus, and upper respiratory infection) showed significant differences in the proportions of patients at different stages of the disease in different clerkship sites. CONCLUSIONS: Students at different clerkship sites experience different numbers of encounters with patients and significant variation in the illness severity of patients seen in those encounters.