Weight changes following the initiation of new anti-hyperglycaemic therapies.

OBJECTIVE: The objective of this study was to quantify 1-year weight gain associated with the initiation of sulphonylurea (SU), metformin, insulin and thiazolidinedione (TZD) therapy in a representative real world population of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: The study population was 9546 members of Kaiser Permanente North-west (KPNW) who initiated an anti-hyperglycaemic drug between 1996 and 2002 and continued use of that drug for at least 12 months without adding other therapies. Change in weight was calculated as the annualized difference between baseline and follow-up weight and was adjusted for demographic and clinical characteristics. We then compared the weight changes observed in patients newly initiating SU, metformin, insulin and TZD therapies. RESULTS: After adjustment for demographic and clinical characteristics that might affect weight change, metformin initiators lost an average of 2.4 kg while all other groups gained weight. SU initiators gained the least (1.8 kg), followed by insulin initiators (3.3 kg) and TZD subjects (5.0 kg). All comparisons were highly statistically significant. CONCLUSIONS: In an observational study of 1-year weight changes following the initiation of SUs, metformin, insulin or TZDs, we found similar but somewhat smaller weight changes than those previously reported in clinical trials. Our observed weight changes could not be explained by the many other factors we tested and seemed to apply across the full spectrum of diabetes patients. Our report provides valuable information that will allow the patient and clinician to anticipate, and perhaps address, expected weight changes that accompany the initiation of anti-hyperglycaemic drugs.

A case-control study of erectile dysfunction among men diagnosed with panic disorder.

The association between panic disorder and erectile dysfunction (ED) among men was examined in the Integrated Healthcare Information Services National Managed Care Benchmark Database (IHCIS). The IHCIS is a fully de-identified, HIPAA compliant database and includes complete medical history for more than 17 million managed care lives; data from more than 30 US health plans, covering seven census regions; and patient demographics, including morbidity, age and gender. A total of 60,949 ED cases and 243,796 controls were included for analysis. Unconditional logistic regression analyses were first performed to assess the crude risk of ED, and adjusted risks of ED that accounted for comorbid conditions and comedications. A second set of analyses measured the crude and adjusted risks after restricting the patient population to men who were diagnosed with panic disorder at least 1 month prior to an ED diagnosis. In the first set of analyses, men with panic disorder were observed to have more than a two-fold increase in risk for ED (OR=2.29, 95% CI=2.03, 2.58). After adjusting for comorbid conditions, a 52% increase in risk of ED was observed (OR=1.52, 95% CI=1.34, 1.72). Following subsequent adjustment for comorbidities and comedications, a 33% increased risk of ED was detected (OR=1.33, 95% CI=1.17, 1.51). In the second set of analyses studying panic disorder that preceded ED, only a 13% higher risk was noted (OR=1.13, 95% CI=0.97, 1.31). However, after adjusting for comorbid conditions, a 25% reduction in risk was observed (OR=0.75, 95% CI=0.64, 0.88). A 35% risk reduction was seen after adjusting for comorbidities and comedications (OR=0.65, 95% CI=0.56, 0.77).

Should erectile dysfunction be considered as a marker for acute myocardial infarction? Results from a retrospective cohort study.

The association between erectile dysfunction (ED) and acute myocardial infarction (AMI) among men was examined in the Integrated Healthcare Information Services National Managed Care Benchmark Database (IHCIS). The IHCIS is a fully de-identified, HIPAA-compliant database and includes complete medical history for more than 17 million managed care lives; data from more than 30 US health plans, covering seven census regions; and patient demographics, including morbidity, age and gender. A total of 12,825 ED patients and an equal number of male patients without ED were included in the retrospective cohort study. Logistic regression analyses were performed to assess the adjusted risk of AMI that accounted for age at ED diagnosis, smoking, obesity and medications including ACE inhibitors, beta blockers and statins. The cohort of men with ED were observed to have a two-fold increase in the risk for AMI (OR=1.99, 95% CI=1.17, 3.38) after adjusting for age at ED diagnosis, smoking, obesity, and use of ACE inhibitors, beta blockers and statins. Some evidence of a possible trend toward increased risk was detected by age group. After controlling for the aforementioned covariates and compared to men 30-39 y of age, it was noted that patients 40-44 y of age were 3.8 times more likely to develop an AMI (OR=3.76, 95% CI=1.21, 11.7), 45- to 49-y-old men were also more than three times as likely to have an AMI (OR=3.14, 95% CI=1.03, 9.64), and 50- to 55-y-old patients had a four-fold increased risk of developing AMI (OR=4.04, 95% CI=1.39, 11.7). The risk becomes more pronounced with increasing age, indicating the need for cardiologists and internists to monitor ED patients who may not necessarily present with cardiovascular symptoms.

Antihypertensive treatment and erectile dysfunction in a cohort of type II diabetes patients.

The association between different antihypertensive drugs and erectile dysfunction (ED) was examined in a cohort of type II diabetes patients identified in the UK General Practice Research Database (GPRD). The GPRD contains details of diagnoses, prescribing, investigations, risk factors, outcomes, and hospital referrals, together with basic demographic information for approximately six million patients from more than 450 representative general practices throughout the UK. A total of 634 cases and 2526 controls were included for analysis. Unconditional logistic regression analysis was performed to assess the risk of ED after adjusting for age at diabetes diagnosis date, cigarette smoking, depression, glycemic control, use of HMG-CoA reductase inhibitors, use of histamine receptor antagonists, use of digitalis medicines, and use of nitrates. Increased risk of ED was observed among patients taking the following antihypertensives: ACE inhibitors (OR=1.47, 95% CI=1.21, 1.80) and alpha blockers (OR=1.54, 95% CI=1.11, 2.12). However, we identified a nearly 30% reduction in risk among patients on diuretics (OR=0.73, 95% CI=0.54, 0.99). No statistically significant increase in risk was observed among users of beta blockers and calcium channel blockers (OR=1.05, 95% CI=0.85, 1.31) and (OR=1.14, 95% CI=0.91, 1.43), respectively. The results of this study confirm the strong and recognized effect of comorbidities in a diabetic population, but also require additional experimental and observational studies to further understand the potential benefit of diuretics and other ED treatments such as PDE5 inhibitors.

Is erectile dysfunction predictive of peripheral vascular disease?

The association between erectile dysfunction (ED) and peripheral vascular disease (PVD) among men was examined in the Integrated Healthcare Information Services National Managed Care Benchmark Database (IHCIS). The IHCIS is a fully de-identified, Health Insurance Portability and Accountability Act compliant database and includes complete medical histories for more than 17 million managed-care lives; data from more than 30 US health plans, covering seven census regions; and patient demographics, including morbidity, age and gender. A total of 12 825 ED patients and an equal number of male patients without ED were included in the retrospective cohort study. Logistic regression analyses were performed to assess the adjusted risk of PVD that accounted for age at ED diagnosis, smoking, obesity and medications including angiotensin converting enzyme (ACE) inhibitors, beta blockers and statins. The cohort of men with ED were observed to have a 75% increase in risk for PVD (odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.06, 2.90) after adjusting for age at ED diagnosis, smoking, obesity and use of ACE inhibitors, beta blockers and statins. Some evidence of a possible trend towards increased risk was detected by age group. After controlling for the aforementioned covariates and compared to men aged 30-39 years, it was noted that patients aged 40-44 years were 2.1 times more likely to develop PVD (OR = 2.07, 95% CI = 0.89, 4.81), 45-49-year-old men were also more than twice as likely to have PVD (OR = 2.32, 95% CI = 1.03, 5.22), and 50-55-year-old patients had a three-fold increased risk of developing PVD (OR = 3.00, 95% CI = 1.40, 6.43). The results of this study indicate that ED may serve as a marker for PVD. The risk becomes more pronounced with increasing age, indicating the need for cardiologists and internists to monitor ED patients who may not necessarily present with cardiovascular symptoms.

[Environmental pollution and childhood morbidity]. / Znecistené ovzdusí a nemocnost detí.

BACKGROUND: A study of morbidity of children aged 0 to 3 years was organized in two districts in the Czech Republic. Comparisons were drawn between children living in district Teplice, known for its high air pollution, and those living in Practice, the district with consistently lower particulate and SO2 exposures. METHODS AND RESULTS: 452 children of the follow up study were born between May 1994 and December 1996. Childhood morbidity during the first three years of life was obtained from their pediatric records. Diagnoses were coded using the International Classification of Diseases--the 10th edition, and categorized into broad groups. Children born in Teplice experienced a significantly higher rate of otitis media (and otalgia), gastrointestinal infections, upper respiratory infections, and pneumonia, but they did not differ in the risk of bronchitis or that of viral infections such as varicella. These findings remained valid after the multiple linear regression models were calculated and adjusted for education, maternal age, maternal smoking, and other smokers in the household, breastfeeding, and attendance at the day care. CONCLUSIONS: Air pollution may alter early childhood susceptibility to infection, but other differences between the districts have to be considered: systematic diagnostic differences for several health outcomes between pediatricians in Teplice and Practice, differences in health-care seeking approach of parents, and some hitherto unidentified factors.

Childhood morbidity and air pollution in the Teplice program.

BACKGROUND: A study of morbidity of children aged 0 to 3 years was conducted in two districts in the Czech Republic. Comparisons were made between children living in Teplice district, known for its high air pollution, and children living in Practice, a district with consistently lower particulate and SO2 exposures. METHODS AND RESULTS: The children were selected for the follow up based on deliveries from May 1994 to December 1966. Childhood morbidity during the first three years of life of 452 children was extracted from their pediatric records. Diagnoses were coded using the International Classification of Diseases--10th edition, and categorized into broad groupings. Children born in Teplice experienced a significantly higher rate of otitis media and otalgia, gastrointestinal infections, upper respiratory infections, and pneumonia, but did not differ in their risk for bronchitis or for viral infections such as varicella. These findings remained after multiple linear regression models adjusted for education, maternal age, maternal smoking, and other smokers in the household, breastfeeding, and attendance at day care. CONCLUSIONS: Air pollution may alter early childhood susceptibility to infection, but other differences between the districts must be considered: systematic diagnostic differences for several health outcomes comparing pediatricians in Teplice vs. Practice, differences in health-care seeking behavior by the parents, and inadequate control for confounding.

Breath-hold 3D gradient-echo MR imaging of the lung parenchyma: evaluation of reproducibility of image quality in normals and preliminary observations in patients with disease.

This study evaluates the reproducibility and image quality of a three-dimensional (3D) gradient-echo sequence for imaging the lung parenchyma, with and without gadolinium administration, using a 2D spoiled gradient-echo sequence for comparison. Twenty patients without lung disease (normals) and five patients with lung disease (lung disease) underwent paired 2D and 3D gradient-echo sequences, without contrast (24 patients) and with contrast (18 patients). Images were retrospectively reviewed independently in a blinded fashion by two investigators. Artifacts and demonstration of central lung, peripheral lung, heart, pulmonary arteries, and esophagus were evaluated. Image quality of the central lung was rated as fair or good in 5 and 4 (reader one and two) patients with non-contrast 2D gradient-echo, 24 and 25 patients with non-contrast 3D gradient-echo, 3 and 1 patient(s) with contrast-enhanced 2D gradient-echo, and 19 and 19 patients with contrast-enhanced 3D gradient-echo imaging. Differences in image quality between 2D and 3D sequences were significant (P < 0.001). Heart-related phase artifacts were negligible in 2 and 0 patients with non-contrast 2D gradient-echo, 23 and 25 patients with non-contrast 3D gradient-echo, 0 and 0 patients with contrast-enhanced 2D gradient-echo, and 17 and 19 patients with contrast-enhanced 3D gradient-echo imaging. Differences in heart-related phase artifact in the central lung between 2D and 3D sequences were significant (P = 0.001). Infiltrates, lung cancer, and pulmonary metastasis were better shown on the gadolinium-enhanced 3D gradient-echo sequences than on the other sequences. Breath-hold 3D gradient-echo imaging results in good image quality and negligible image artifacts and is superior to 2D spoiled gradient-echo imaging. Preliminary results in patients with disease appear promising.

Complex renal cysts: findings on MR imaging.

OBJECTIVE: We retrospectively evaluated our experience with complex cystic renal masses on MR imaging, using T1-weighted, T2-weighted, and gadolinium-enhanced images, to determine whether imaging features could permit distinction between benign and malignant lesions. MATERIALS AND METHODS: Thirty-seven patients with complex cystic renal lesions were included in this retrospective study. The patients selected had undergone T1-weighted, T2-weighted, and gadolinium-enhanced MR imaging examinations using 1.5-T scanners, with at least one of the following findings: cyst fluid of heterogeneous signal intensity, mural irregularity, septa, mural masses or nodules, increased mural thickness, or intense mural enhancement. The diagnosis was established by histology in 19 patients and by follow-up studies in the remaining 18 patients. RESULTS: Fifty-five complex renal cystic lesions were present in the 37 patients. Among the 55 lesions, of 37 that contained fluid of a heterogeneous signal intensity, eight were malignant (22%); of 16 with irregular walls, 10 were malignant (63%); of four with septa, two were malignant (50%); of four with mural masses or nodules, three were malignant (75%); of 14 with a thick wall (>2 mm), 10 were malignant (71%); and of 32 with intense mural enhancement, 14 were malignant (44%). As independent variables, mural irregularity, mural masses or nodules, increased mural thickness, and intense mural enhancement each were highly associated with malignancy (p = .0003-.0022). The combination of mural irregularity and intense mural enhancement had the highest correlation with malignancy (p = .0002). CONCLUSION: The combination of mural irregularity and intense mural enhancement is a strong predictor of malignancy in renal cystic lesions. However, the appearance of benign and malignant lesions may overlap, suggesting that distinct separation of these entities is not currently possible in all cases with MR imaging.

Ethnic differences in knowledge and attitudes about BRCA1 testing in women at increased risk.

Informed consent for BRCA1 mutation testing will require adequate knowledge of patterns of inheritance of cancer and the benefits, limitations, and risks of DNA testing. This study examined knowledge about the inheritance of breast cancer and attitudes about genetic testing for breast-ovarian cancer susceptibility in women at increased risk. Knowledge and attitudes were measured in 407 African American and Caucasian women aged 18-75 who had at least one first-degree relative (FDR) with breast and/or ovarian cancer. The average knowledge score was 6.0 out of a total of 11 (S.D. = 2.15). Compared to Caucasian women, African American women had lower levels of knowledge and had more positive attitudes about the benefits of genetic testing. There were no significant ethnic differences in attitudes about the limitations and risks of testing, however, income was negatively associated with this outcome. Ethnic differences in knowledge and attitudes about genetic testing for breast-ovarian cancer risk may be attributable to differences in exposure to genetic information and referral by health care providers.

Gender and ethnic differences in readiness to change smoking behavior.

The Transtheoretical Model has been used extensively to investigate smoking behavior. However, gender and ethnic differences in key constructs of the Transtheoretical Model have not been fully evaluated. This gap in the literature is addressed in this brief report. We examined gender and ethnic differences in stages of change (readiness to quit smoking), perceived pros (benefits) and cons (costs) of smoking, and self-efficacy (confidence) in ability to quit among smokers seeking cessation treatment. Participants were 330 smokers ages 18 to 75, who responded to advertisements for a free minimal-contact smoking cessation program. Thirty percent of women were confident they could quit smoking compared to 53% of men. Women reported more pros of smoking and more cons of smoking than men. White smokers reported more pros of smoking than African smokers. These findings highlight the need to bolster quitting confidence among women and to identify alternatives to the pros of smoking relevant to women smokers.

Controlled trial of pretest education approaches to enhance informed decision-making for BRCA1 gene testing.

BACKGROUND: In response to the isolation of the BRCA1 gene, a breast-ovarian cancer-susceptibility gene, biotechnology companies are already marketing genetic tests to health care providers and to the public. Initial studies indicate interest in BRCA1 testing in the general public and in populations at high risk. However, the optimal strategies for educating and counseling individuals have yet to be determined. PURPOSE: Our goal was to evaluate the impact of alternate strategies for pretest education and counseling on decision-making regarding BRCA1 testing among women at low to moderate risk who have a family history of breast and/or ovarian cancer. METHODS: A randomized trial design was used to evaluate the effects of education only (educational approach) and education plus counseling (counseling approach), as compared with a waiting-list (control) condition (n = 400 for all groups combined). The educational approach reviewed information about personal risk factors, inheritance of cancer susceptibility, the benefits, limitations, and risks of BRCA1 testing, and cancer screening and prevention options. The counseling approach included this information, as well as a personalized discussion of experiences with cancer in the family and the potential psychological and social impact of testing. Data on knowledge of inherited cancer and BRCA1 test characteristics, perceived risk, perceived benefits, limitations and risks of BRCA1 testing, and testing intentions were collected by use of structured telephone interviews at baseline and at 1-month follow-up. Provision of a blood sample for future testing served as a proxy measure of intention to be tested (in the education and counseling arms of the study). The effects of intervention group on study outcomes were evaluated by use of hierarchical linear regression modeling and logistic regression modeling (for the blood sample outcome). All P values are for two-sided tests. RESULTS: The educational and counseling approaches both led to significant increases in knowledge, relative to the control condition (P < .001 for both). The counseling approach, but not the educational approach, was superior to the control condition in producing significant increases in perceived limitations and risks of BRCA1 testing (P < .01) and decreases in perceived benefits (P < .05). However, neither approach produced changes in intentions to have BRCA1 testing. Prior to and following both education only and education plus counseling, approximately one half of the participants stated that they intended to be tested; after the session, 52% provided a blood sample. CONCLUSIONS: Standard educational approaches may be equally effective as expanded counseling approaches in enhancing knowledge. Since knowledge is a key aspect of medical decision-making, standard education may be adequate in situations where genetic testing must be streamlined. On the other hand, it has been argued that optimal decision-making requires not only knowledge, but also a reasoned evaluation of the positive and negative consequences of alternate decisions. Although the counseling approach is more likely to achieve this goal, it may not diminish interest in testing, even among women at low to moderate risk. Future research should focus on the merits of these alternate approaches for subgroups of individuals with different backgrounds who are being counseled in the variety of settings where BRCA1 testing is likely to be offered.

BRCA1 testing in families with hereditary breast-ovarian cancer. A prospective study of patient decision making and outcomes.

OBJECTIVES: To identify predictors of utilization of breast-ovarian cancer susceptibility (BRCA1 gene) testing and to evaluate outcomes of participation in a testing program. DESIGN: Prospective cohort study with baseline interview assessment of predictor variables (eg, sociodemographic factors, knowledge about hereditary cancer and genetic testing, perceptions of testing benefits, limitations, and risks). BRCA1 test results were offered after an education and counseling session in a research setting. Outcome variables (including depression, functional health status, and prophylactic surgery plans [follow-up only]) were assessed at baseline and 1-month follow-up interviews. PARTICIPANTS: Adult male and female members (n=279) of families with BRCA1-linked hereditary breast-ovarian cancer (HBOC). RESULTS: Of subjects who completed a baseline interview (n=192), 60% requested BRCA1 test results (43% of all study subjects requested results). Requests for results were more frequent for persons with health insurance (odds ration [OR], 3.74; 95% confidence interval [CI], 2.06-6.80); more first-degree relatives affected with breast cancer (OR, 1.59; 95% CI, 1.16-2.16); more knowledge about BRCA1 testing (OR, 1.85; 95% CI, 1.36-2.50); and indicating that test benefits are important (OR, 1.45; 95% CI, 1.13-1.86). At follow-up, noncarriers of BRCA1 mutations showed statistically significant reductions in depressive symptoms and functional impairment compared with carriers and nontested individuals. Individuals identified as mutation carriers did not exhibit increases in depression and functional impairment. Among unaffected women with no prior prophylactic surgery, 17% of carriers (2/12) intended to have mastectomies and 33% (4/12) to have oophorectomies. CONCLUSIONS: Only a subset of HBOC family members are likely to request BRCA1 testing when available. Rates of test use may be higher in persons of a higher socioeconomic status and those with more relatives affected with breast cancer. For some high-risk individuals who receive test results in a research setting that includes counseling, there may be psychological benefits. More research is needed to assess the generalizability of these results and evaluate the long-term consequences of BRCA1 testing.

Genetic testing for colon cancer susceptibility: Anticipated reactions of patients and challenges to providers.

The commercial availability of genetic tests for colon cancer susceptibility is creating new opportunities and challenges for both patients and providers. To provide information useful in the education and counseling of individuals considering genetic testing, we conducted structured interviews with 45 male and female first-degree relatives of colorectal cancer patients. Fifty-one percent of respondents indicated that they definitely would want to obtain a genetic test for colon cancer susceptibility when it is available and 31% said that they probably would want to be tested. Interest in genetic testing was significantly higher among persons with less formal education and those with a Catholic religious preference. Motivations for genetic testing included the following: to know if more screening tests are needed, to learn if one's children are at risk and to be reassured. Barriers to testing included concerns about insurance, test accuracy and how one's family would react emotionally. Most participants anticipated that they would become depressed and anxious if they tested positive for a mutation, while many would feel guilty and still worry if they tested negative. Of note, about one-half of respondents expected that they would decrease their use of screening tests and make fewer attempts to reduce dietary fat if they tested negative. These preliminary results underscore the importance of educating patients about the potential risks, benefits and limitations of genetic testing, with particular emphasis on the possibility of adverse psychological effects and implications for health insurance. The potential for false reassurance following a negative test result should be addressed by emphasizing the residual risks of cancer among non-carriers of predisposing mutations.

Awareness of heightened breast cancer risk among first-degree relatives of recently diagnosed breast cancer patients. The High Risk Breast Cancer Consortium.

This investigation had two goals: (a) to determine the proportion of first-degree relatives of recently diagnosed breast cancer patients who are unaware of their elevated risk for breast cancer; and (b) to identify demographic medical, and lifestyle factors that characterize these women. The ultimate objective was to identify women at increased risk who could benefit from breast cancer risk education. Three hundred ninety-five female first-degree relatives, ages 30-75 years, completed a structured telephone interview. Twenty-five % of these women believed that their risk for breast cancer was the "same as or lower than" women who do not have a family history of breast cancer, despite the fact that they had an objectively increased risk. Bivariate analyses revealed that women who were unmarried (chi2 = 14.8; P = 0.001) and had less than or equal to a high school education (chi2 = 9.2; P = 0.002) were significantly less likely to perceive themselves as being at increased risk for breast cancer. In addition, almost one-half of African-American women were unaware of their increased risk compared to only 19% of white women (chi2 = 29.9; P < 0.001). More smokers were unaware of their elevated risk compared to nonsmokers (43 versus 21%; chi2 = 15.1; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)