Identification and outcomes of KDIGO-defined chronic kidney disease in 1.4 million U.S. Veterans with heart failure.

AIMS: According to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline, the definition of chronic kidney disease (CKD) requires the presence of abnormal kidney structure or function for >3 months with implications for health. CKD in patients with heart failure (HF) has not been defined using this definition, and less is known about the true health implications of CKD in these patients. The objective of the current study was to identify patients with HF who met KDIGO criteria for CKD and examine their outcomes. METHODS AND RESULTS: Of the 1 419 729 Veterans with HF not receiving kidney replacement therapy, 828 744 had data on ≥2 ambulatory serum creatinine >90 days apart. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (n = 185 821) or urinary albumin-to-creatinine ratio (uACR) >30 mg/g (n = 32 730) present twice >3 months apart. Normal kidney function (NKF) was defined as eGFR ≥60 ml/min/1.73 m2, present for >3 months, without any uACR >30 mg/g (n = 365 963). Patients with eGFR <60 ml/min/1.73 m2 were categorized into four stages: 45-59 (n = 72 606), 30-44 (n = 74 812), 15-29 (n = 32 077), and <15 (n = 6326) ml/min/1.73 m2. Five-year all-cause mortality occurred in 40.4%, 57.8%, 65.6%, 73.3%, 69.7%, and 47.5% of patients with NKF, four eGFR stages, and uACR >30mg/g (albuminuria), respectively. Compared with NKF, hazard ratios (HR) (95% confidence intervals [CI]) for all-cause mortality associated with the four eGFR stages and albuminuria were 1.63 (1.62-1.65), 2.00 (1.98-2.02), 2.49 (2.45-2.52), 2.28 (2.21-2.35), and 1.22 (1.20-1.24), respectively. Respective age-adjusted HRs (95% CIs) were 1.13 (1.12-1.14), 1.36 (1.34-1.37), 1.87 (1.84-1.89), 2.24 (2.18-2.31) and 1.19 (1.17-1.21), and multivariable-adjusted HRs (95% CIs) were 1.11 (1.10-1.12), 1.24 (1.22-1.25), 1.46 (1.43-1.48), 1.42 (1.38-1.47), and 1.13 (1.11-1.16). Similar patterns were observed for associations with hospitalizations. CONCLUSION: Data needed to define CKD using KDIGO criteria were available in six out of ten patients, and CKD could be defined in seven out of ten patients with data. HF patients with KDIGO-defined CKD had higher risks for poor outcomes, most of which was not explained by abnormal kidney structure or function. Future studies need to examine whether CKD defined using a single eGFR is characteristically and prognostically different from CKD defined using KDIGO criteria.

Impact of the COVID-19 Pandemic on the Provision of Dialysis Service and Mortality in Veterans Receiving Maintenance Hemodialysis in the VA: An Interrupted Time-Series Analysis.

INTRODUCTION: According to the US Renal Data System (USRDS), patients with end-stage kidney disease (ESKD) on maintenance dialysis had higher mortality during early COVID-19 pandemic. Less is known about the effect of the pandemic on the delivery of outpatient maintenance hemodialysis and its impact on death. We examined the effect of pandemic-related disruption on the delivery of dialysis treatment and mortality in patients with ESKD receiving maintenance hemodialysis in the Veterans Health Administration (VHA) facilities, the largest integrated national healthcare system in the USA. METHODS: Using national VHA electronic health records data, we identified 7,302 Veterans with ESKD who received outpatient maintenance hemodialysis in VHA healthcare facilities during the COVID-19 pandemic (February 1, 2020, to December 31, 2021). We estimated the average change in the number of hemodialysis treatments received and deaths per 1,000 patients per month during the pandemic by conducting interrupted time-series analyses. We used seasonal autoregressive moving average (SARMA) models, in which February 2020 was used as the conditional intercept and months thereafter as conditional slope. The models were adjusted for seasonal variations and trends in rates during the pre-pandemic period (January 1, 2007, to January 31, 2020). RESULTS: The number (95% CI) of hemodialysis treatments received per 1,000 patients per month during the pre-pandemic and pandemic periods were 12,670 (12,525-12,796) and 12,865 (12,729-13,002), respectively. Respective all-cause mortality rates (95% CI) were 17.1 (16.7-17.5) and 19.6 (18.5-20.7) per 1,000 patients per month. Findings from SARMA models demonstrate that there was no reduction in the dialysis treatments delivered during the pandemic (rate ratio: 0.999; 95% CI: 0.998-1.001), but there was a 2.3% (95% CI: 1.5-3.1%) increase in mortality. During the pandemic, the non-COVID hospitalization rate was 146 (95% CI: 143-149) per 1,000 patients per month, which was lower than the pre-pandemic rate of 175 (95% CI: 173-176). In contrast, there was evidence of higher use of telephone encounters during the pandemic (3,023; 95% CI: 2,957-3,089), compared with the pre-pandemic rate (1,282; 95% CI: 1,241-1,324). CONCLUSIONS: We found no evidence that there was a disruption in the delivery of outpatient maintenance hemodialysis treatment in VHA facilities during the COVID-19 pandemic and that the modest rise in deaths during the pandemic is unlikely to be due to missed dialysis.

Risk of Stroke in Older Adults With Heart Failure.

Heart failure (HF) is a risk factor for incident stroke. However, less is known about the independent nature of this association and to what extent various baseline characteristics may mediate this risk. Of the 5,795 community-dwelling adults aged ≥65 years in the Cardiovascular Health Study, 5,448 were free of baseline stroke, of whom 229 had baseline HF. We used a multivariable-adjusted Cox regression model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for centrally adjudicated incident stroke associated with HF. Participants had a mean age of 73 years, 58% were women, and 15% were African-American. During 23 years of follow-up, incident stroke occurred in 18.8% and 19.3% of those with and without HF, respectively, but the time to first stroke was shorter in those with HF (age-gender-race-adjusted HR 1.64, 95% CI 1.21 to 2.25). The association remained essentially unchanged after adjustments for tobacco, alcohol, and physical activity (HR 1.63, 95% CI 1.21 to 2.24), attenuated after adjustment for hypertension, atrial fibrillation, myocardial infarction, and diabetes mellitus (HR 1.26, 95% CI 0.92 to 1.72), and further attenuated after additional adjustment for 10 baseline functional and subclinical variables (HR 1.05, 95% CI 0.76 to 1.46). In conclusion, despite a similar 23-year stroke incidence, time to first stroke was shorter in older adults with HF than without. However, this extra risk appears to be mediated primarily by 4 cardiovascular diseases that are also risk factors for HF. These findings highlight the importance of the primary prevention of these HF risk factors to reduce the extra risk of stroke in HF.

Hydroxychloroquine and Risk of Long QT Syndrome in Rheumatoid Arthritis: A Veterans Cohort Study With Nineteen-Year Follow-up.

OBJECTIVE: Recent evidence suggests that hydroxychloroquine use is not associated with higher 1-year risk of long QT syndrome (LQTS) in patients with rheumatoid arthritis (RA). Less is known about its long-term risk, the examination of which was the objective of this study. METHODS: We conducted a propensity score-matched active-comparator safety study of hydroxychloroquine in 8,852 veterans (mean age 64 ± 12 years, 14% women, 28% Black) with newly diagnosed RA. A total of 4,426 patients started on hydroxychloroquine and 4,426 started on another nonbiologic disease-modifying antirheumatic drug (DMARD) and were balanced on 87 baseline characteristics. The primary outcome was LQTS during 19-year follow-up through December 31, 2019. RESULTS: Incident LQTS occurred in 4 (0.09%) and 5 (0.11%) patients in the hydroxychloroquine and other DMARD groups, respectively, during the first 2 years. Respective 5-year incidences were 17 (0.38%) and 6 (0.14%), representing 11 additional LQTS events in the hydroxychloroquine group (number needed to harm 403; [95% confidence interval (95% CI)], 217-1,740) and a 181% greater relative risk (95% CI 11%-613%; P = 0.030). Although overall 10-year risk remained significant (hazard ratio 2.17; 95% CI 1.13-4.18), only 5 extra LQTS occurred in hydroxychloroquine group over the next 5 years (years 6-10) and 1 over the next 9 years (years 11-19). There was no association with arrhythmia-related hospitalization or all-cause mortality. CONCLUSIONS: Hydroxychloroquine use had no association with LQTS during the first 2 years after initiation of therapy. There was a higher risk thereafter that became significant after 5 years of therapy. However, the 5-year absolute risk was very low, and the absolute risk difference was even lower. Both risks attenuated during longer follow-up. These findings provide evidence for long-term safety of hydroxychloroquine in patients with RA.

Assessment of Lung Cancer Risk Among Smokers for Whom Annual Screening Is Not Recommended.

Importance: The US Preventive Services Task Force does not recommend annual lung cancer screening with low-dose computed tomography (LDCT) for adults aged 50 to 80 years who are former smokers with 20 or more pack-years of smoking who quit 15 or more years ago or current smokers with less than 20 pack-years of smoking. Objective: To determine the risk of lung cancer in older smokers for whom LDCT screening is not recommended. Design, Settings, and Participants: This cohort study used the Cardiovascular Health Study (CHS) data sets obtained from the National Heart, Lung and Blood Institute, which also sponsored the study. The CHS enrolled 5888 community-dwelling individuals aged 65 years and older in the US from June 1989 to June 1993 and collected extensive baseline data on smoking history. The current analysis was restricted to 4279 individuals free of cancer who had baseline data on pack-year smoking history and duration of smoking cessation. The current analysis was conducted from January 7, 2022, to May 25, 2022. Exposures: Current and prior tobacco use. Main Outcomes and Measures: Incident lung cancer during a median (IQR) of 13.3 (7.9-18.8) years of follow-up (range, 0 to 22.6) through December 31, 2011. A Fine-Gray subdistribution hazard model was used to estimate incidence of lung cancer in the presence of competing risk of death. Cox cause-specific hazard regression models were used to estimate hazard ratios (HRs) and 95% CIs for incident lung cancer. Results: There were 4279 CHS participants (mean [SD] age, 72.8 [5.6] years; 2450 [57.3%] women; 663 [15.5%] African American, 3585 [83.8%] White, and 31 [0.7%] of other race or ethnicity) included in the current analysis. Among the 861 nonheavy smokers (<20 pack-years), the median (IQR) pack-year smoking history was 7.6 (3.3-13.5) pack-years for the 615 former smokers with 15 or more years of smoking cessation, 10.0 (5.3-14.9) pack-years for the 146 former smokers with less than 15 years of smoking cessation, and 11.4 (7.3-14.4) pack-years for the 100 current smokers. Among the 1445 heavy smokers (20 or more pack-years), the median (IQR) pack-year smoking history was 34.8 (26.3-48.0) pack-years for the 516 former smokers with 15 or more years of smoking cessation, 48.0 (35.0-70.0) pack-years for the 497 former smokers with less than 15 years of smoking cessation, and 48.8 (31.6-57.0) pack-years for the 432 current smokers. Incident lung cancer occurred in 10 of 1973 never smokers (0.5%), 5 of 100 current smokers with less than 20 pack-years of smoking (5.0%), and 26 of 516 former smokers with 20 or more pack-years of smoking with 15 or more years of smoking cessation (5.0%). Compared with never smokers, cause-specific HRs for incident lung cancer in the 2 groups for whom LDCT is not recommended were 10.54 (95% CI, 3.60-30.83) for the current nonheavy smokers and 11.19 (95% CI, 5.40-23.21) for the former smokers with 15 or more years of smoking cessation; age, sex, and race-adjusted HRs were 10.06 (95% CI, 3.41-29.70) for the current nonheavy smokers and 10.22 (4.86-21.50) for the former smokers with 15 or more years of smoking cessation compared with never smokers. Conclusions and Relevance: The findings of this cohort study suggest that there is a high risk of lung cancer among smokers for whom LDCT screening is not recommended, suggesting that prediction models are needed to identify high-risk subsets of these smokers for screening.

Ligand-mediated CsPbBrxI3-x/SiO2quantum dots for red, stable and low-threshold amplify spontaneous emission.

The red-emitting perovskite material has received widespread attention as a long-wavelength optical gain media. But the easy phase change in the air limits its practical application. Herein, red CsPbBrxI3-x/SiO2quantum dots (QDs) are prepared by a ligand-mediated hot injection method in which 3-aminopropyl-triethoxysilane (APTES) is used instead of the usual oleylamine (OAm) ligand. Through the hydrolysis of amino groups, a thin silicon layer is formed on the QD surface, improving the stability and without causing the aggregation of QDs. We find that the ratio of I/Br and the size of QDs can be tuned by adjusting the APTES amount. Moreover, this ligand-mediated synthesis effectively passivates the surface defects, so the photoluminescence quantum yield is remarkably improved, and the carrier lifetime is prolonged. The amplified spontaneous emission is achieved under 532 nm nanosecond laser excitation. Compared with the original CsPbBrI2-OAm QD films, the threshold of CsPbBrxI3-x/SiO2QD films is reduced from 403.5 to 98.7µJ cm-2, and the radiation stability is significantly enhanced. Therefore, this material shows great potential in the random laser field.

In-Hospital Weight Loss and Outcomes in Patients With Heart Failure.

BACKGROUND: Acute decompensation of heart failure (HF) is often marked by fluid retention, and weight loss is a marker of successful diuresis. We examined the relationship between in-hospital weight loss and post-discharge outcomes in patients with HF. METHODS: We conducted a propensity score-matched study of 8830 patients hospitalized for decompensated HF in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, in which 4415 patients in the weight-loss group and 4415 patients in the no-weight-loss group were balanced on 75 baseline characteristics. We defined weight loss as an admission-to-discharge weight loss of 1-30 kilograms, and we defined no weight loss as a weight gain or loss of < 1 kilogram. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with weight loss were estimated. RESULTS: Patients had a mean age of 78 years, 57% were women, and 11% were African American. The median weight loss in the weight-loss group was 3.6 (interquartile range, 2.0-6.0) kilograms. HRs and 95% CIs for 30-day all-cause mortality, all-cause readmission and HF readmission associated with weight loss were 0.75 (0.63-0.90), 0.90 (0.83-0.99) and 0.83 (0.72-0.96), respectively. Respective 60-day HRs (95% CIs) were 0.80 (0.70-0.92), 0.91 (0.85-0.98) and 0.88 (0.79-0.98). These associations were attenuated and lost significance during 6 months of follow-up. CONCLUSIONS: Among older patients hospitalized for decompensated HF, in-hospital weight loss was associated with a lower risk of mortality and hospital readmission. These findings suggest that in-hospital weight loss, a marker of successful diuresis and decongestion, is also a marker of improved clinical outcomes.

Cardiovascular Safety of Hydroxychloroquine in US Veterans With Rheumatoid Arthritis.

OBJECTIVE: Hydroxychloroquine (HCQ) may prolong the QT interval, a risk factor for torsade de pointes, a potentially fatal ventricular arrhythmia. This study was undertaken to examine the cardiovascular safety of HCQ in patients with rheumatoid arthritis (RA). METHODS: We conducted an active comparator safety study of HCQ in a propensity score-matched cohort of 8,852 US veterans newly diagnosed as having RA between October 1, 2001 and December 31, 2017. Patients were started on HCQ (n = 4,426) or another nonbiologic disease-modifying antirheumatic drug (DMARD; n = 4,426) after RA diagnosis, up to December 31, 2018, and followed up for 12 months after therapy initiation, up to December 31, 2019. RESULTS: Patients had a mean ± SD age of 64 ± 12 years, 14% were women, and 28% were African American. The treatment groups were balanced with regard to 87 baseline characteristics. There were 3 long QT syndrome events (0.03%), 2 of which occurred in patients receiving HCQ. Of the 56 arrhythmia-related hospitalizations (0.63%), 30 occurred in patients in the HCQ group (hazard ratio [HR] associated with HCQ 1.16 [95% confidence interval (95% CI) 0.68-1.95]). All-cause mortality occurred in 144 (3.25%) and 136 (3.07%) of the patients in the HCQ and non-HCQ groups, respectively (HR associated with HCQ 1.06 [95% CI, 0.84-1.34]). During the first 30 days of follow-up, there were no long QT syndrome events, 2 arrhythmia-related hospitalizations (none in the HCQ group), and 13 deaths (6 in the HCQ group). CONCLUSION: Our findings indicate that the incidence of long QT syndrome and arrhythmia-related hospitalization is low in patients with RA during the first year after the initiation of HCQ or another nonbiologic DMARD. We found no evidence that HCQ therapy is associated with a higher risk of adverse cardiovascular events or death.

Time required to review research protocols at 10 Veterans Affairs Institutional Review Boards.

BACKGROUND: Despite perceptions that institutional review boards (IRBs) delay research, little is known about how long it takes to secure IRB approval. We retrospectively quantified IRB review times at 10 large Veterans Affairs (VA) IRBs. METHODS: We collected IRB records pertaining to a stratified random sample of research protocols drawn from 10 of the 26 largest VA IRBs. Two independent analysts abstracted dates from the IRB records, from which we calculated overall and incremental review times. We used multivariable linear regression to assess variation in total and incremental review times by IRB and review level (i.e., exempt, expedited, or full board) and to identify potential targets for efforts to improve the efficiency and uniformity of the IRB review process. RESULTS: In a sample of 277 protocols, the mean review time was 112 d (95% confidence interval [CI]: 105-120). Compared with full-board reviews at IRB 1, average review times at IRBs 3, 8, 9, and 10 were 27 (95% CI: 6-48), 37 (95% CI: 11-63), 45 (95% CI: 20-69), and 24 (95% CI: 2-45) d shorter, and at IRB 6, times were 56 (95% CI: 28-84) d longer. Across all IRBs, expedited reviews were 44 (95% CI: 30-58) d shorter on average than were full-board reviews, with no significant difference between exempt and full-board reviews. However, after subtracting the time required for Research and Development Committee review, exempt reviews were 21 (95% CI: 1-41) d shorter on average than were full-board reviews. CONCLUSIONS: IRB review times differ significantly by IRB and review level. Few VA IRBs approach a consensus panel goal of 60 d for IRB review. The unexpectedly longer review times for exempt protocols in the VA can be attributed to time required for Research and Development Committee review. Prospective, routine collection of key time points in the IRB review process could inform IRB-specific initiatives for reducing VA IRB review times.

Tight glycemic control and use of hypoglycemic medications in older veterans with type 2 diabetes and comorbid dementia.

OBJECTIVE: Older adults with diabetes and dementia are at increased risk for hypoglycemia and other adverse events associated with tight glycemic control and are unlikely to experience long-term benefits. We examined risk factors for tight glycemic control in this population and use of medications associated with a high risk of hypoglycemia in the subset with tight control. RESEARCH DESIGN AND METHODS: This retrospective cohort study of national Veterans Affairs (VA) administrative/clinical data and Medicare claims for fiscal years (FYs) 2008-2009 included 15,880 veterans aged ≥ 65 years with type 2 diabetes and dementia and prescribed antidiabetic medication. Multivariable regression analyses were used to identify sociodemographic and clinical predictors of hemoglobin A1c (HbA1c) control (tight, moderate, poor, or not monitored) and, in patients with tight control, subsequent use of medication associated with a high risk of hypoglycemia (sulfonylureas, insulin). RESULTS: Fifty-two percent of patients had tight glycemic control (HbA1c <7% [53 mmol/mol]). Specific comorbidities, older age, and recent weight loss were associated with greater odds of tight versus moderate control, whereas Hispanic ethnicity and obesity were associated with lower odds of tight control. Among tightly controlled patients, 75% used sulfonylureas and/or insulin, with higher odds in patients who were male, black, or aged ≥ 75 years; had a hospital or nursing home stay in FY2008; or had congestive heart failure, renal failure, or peripheral vascular disease. CONCLUSIONS: Many older veterans with diabetes and dementia are at high risk for hypoglycemia associated with intense diabetes treatment and may be candidates for deintensification or alteration of diabetes medications.

Improving the physician-patient cardiovascular risk dialogue to improve statin adherence.

BACKGROUND: The purpose of this study was to evaluate the effectiveness of a patient education program developed to facilitate statin adherence. METHODS: A controlled trial was designed to test the effectiveness of a multifaceted patient education program to facilitate statin adherence. The program included a brief, in-office physician counseling kit followed by patient mailings. The primary end point was adherence to filling statin prescriptions during a 120-day period. Patients new to statins enrolled and completed a survey. Data from a national pharmacy claims database were used to track adherence. RESULTS: Patients new to statin therapy exposed to a patient counseling and education program achieved a 12.4 higher average number of statin prescription fill days and were 10% more likely to fill prescriptions for at least 120 days (p = .01). CONCLUSION: Brief in-office counseling on cardiovascular risk followed by patient education mailings can be effective in increasing adherence. Physicians found a one-minute counseling tool and pocket guidelines useful in counseling patients.

Baseline serum C-reactive protein is associated with lipid responses to low-fat and high-polyunsaturated fat diets.

Baseline serum C-reactive protein (CRP) concentrations play a role in the lipid response to diet. This study was a randomized, cross-over, controlled feeding study with 3 phases of 25 d each aimed at determining whether baseline CRP concentrations modulate the serum lipid response to diets differing in fat type and quantity. Participants were adult men and women, age 19-65 y, with LDL-cholesterol concentrations of 3.37-4.66 mmol/L. All participants consumed 3 diets differing in the type of snack, either low or high in fat: low-fat (30.8% of energy), moderate in fat and saturated fat (37.9 and 11.4% of energy, respectively), or moderate in fat and polyunsaturated fat (36.3 and 9.7% of energy, respectively). Using baseline CRP as a continuous variable, CRP x diet interactions on change in serum lipoprotein_a (P = 0.045) and HDL-cholesterol (P = 0.06) were observed. When we used previously established categories to define CRP concentrations (low, <1 mg/L; intermediate, 1-3 mg/L; or high, >3 mg/L), we found a CRP x diet interaction on change in triglyceride concentrations (P = 0.03) and trends for CRP x diet interaction on change in LDL (P = 0.06) and total cholesterol (P = 0.07). If replicated, these results suggest that considering baseline CRP concentrations when prescribing dietary interventions to lower lipid concentrations may be useful. Individuals with high baseline CRP concentrations may benefit from moderate-fat, high polyunsaturated fat diets, whereas those with low baseline CRP concentrations may obtain greater lipid-lowering benefits from low-fat diets.

Changes in environmental tobacco smoke exposure and asthma morbidity among urban school children.

BACKGROUND: Environmental tobacco smoke (ETS) exposure is associated with poor asthma outcomes in children. However, little is known about natural changes in ETS exposure over time in children with asthma and how these changes may affect health-care utilization. This article documents the relationship between changes in ETS exposure and childhood asthma morbidity among children enrolled in a clinical trial of supervised asthma therapy. METHODS: Data for this analysis come from a large randomized clinical trial of supervised asthma therapy in which 290 children with persistent asthma were randomized to receive either usual care or supervised asthma therapy. No smoking cessation counseling or ETS exposure education was provided to caregivers; however, children were given 20 min of asthma education, which incorporated discussion of the avoidance of asthma triggers, including ETS. Asthma morbidity and ETS exposure data were collected from caregivers via telephone interviews at baseline and at the 1-year follow-up. RESULTS: At baseline, 28% of caregivers reported ETS exposure in the home and 19% reported exposure outside of the primary household only. Among children whose ETS exposure decreased from baseline, fewer hospitalizations (p = 0.034) and emergency department (ED) visits (p < or = 0.001) were reported in the 12 months prior to the second interview compared to the 12 months prior to the first interview. Additionally, these children were 48% less likely (p = 0.042) to experience an episode of poor asthma control (EPAC). CONCLUSIONS: This is the first study to demonstrate an association between ETS exposure reduction and fewer EPACs, respiratory-related ED visits, and hospitalizations. These findings emphasize the importance of ETS exposure reduction as a mechanism to improve asthma control and morbidity. Potential policy implications include supporting ETS reductions and smoking cessation interventions for parents and caregivers of children with asthma. Research to identify the most cost-effective strategy is warranted.

A controlled trial of the effectiveness of internet continuing medical education.

BACKGROUND: The internet has had a strong impact on how physicians access information and on the development of continuing medical education activities. Evaluation of the effectiveness of these activities has lagged behind their development. METHODS: To determine the effectiveness of a group of 48 internet continuing medical education (CME) activities, case vignette surveys were administered to US physicians immediately following participation, and to a representative control group of non-participant physicians. Responses to case vignettes were analyzed based on evidence presented in the content of CME activities. An effect size for each activity was calculated using Cohen's d to determine the amount of difference between the two groups in the likelihood of making evidence-based clinical decisions, expressed as the percentage of non-overlap, between the two groups. Two formats were compared. RESULTS: In a sample of 5621 US physicians, of the more than 100,000 physicians who participated in 48 internet CME activities, the average effect size was 0.75, an increased likelihood of 45% that participants were making choices in response to clinical case vignettes based on clinical evidence. This likelihood was higher in interactive case-based activities, 51% (effect size 0.89), than for text-based clinical updates, 40% (effect size 0.63). Effectiveness was also higher among primary care physicians than specialists. CONCLUSION: Physicians who participated in selected internet CME activities were more likely to make evidence-based clinical choices than non-participants in response to clinical case vignettes. Internet CME activities show promise in offering a searchable, credible, available on-demand, high-impact source of CME for physicians.

Testing for differences in distribution tails to test for differences in 'maximum' lifespan.

BACKGROUND: Investigators are actively testing interventions intended to increase lifespan and wish to test whether the interventions increase maximum lifespan. Based on the fact that one cannot be assured of observing population maximum lifespans in finite samples, in previous work, we constructed and validated several tests of difference in the upper parts of lifespan distributions between a treatment group and a control group by testing whether the probabilities that observations are above some threshold defining 'old' or being in the tail of the survival distribution are equal in the two groups. However, a limitation of these tests is that they do not consider how much above the threshold any particular observation is. METHODS: In this article we propose new methods which improve upon our previous tests by considering not only whether an observation is above some threshold, but also the magnitudes by which observations exceed the threshold. RESULTS: Simulations show that the new methods control type I error rates quite well and that the power of the new methods is usually higher than that of the tests we previously proposed. In illustrative analyses of two real datasets involving rodents, when setting the threshold equal to 110 (100) weeks for the first (second) datasets, the new methods detected differences in 'maximum lifespan' between groups at nominal alpha levels of 0.01 (0.05) for the first (second) datasets and provided more significant results than competitor tests. CONCLUSION: The new methods not only have good performance in controlling the type I error rates but also improve the power compared with the tests we previously proposed.

Sexual risk behaviors and sexually transmitted infection prevalence in an outpatient psychiatry clinic.

BACKGROUND: Nearly 3% of Americans experience severe and persistent mental illness (SPMI) and behaviors that place affected individuals at risk for sexually transmitted infections (STIs) are common. Few data describe the prevalence of risk behaviors or STI among persons with SPMI. We aim to quantitate STI/human immunodeficiency virus risk and determine the STI prevalence amongst outpatient psychiatric clinic attendees. METHODS: Psychiatric outpatients were approached to participate in an interviewer-administered survey collecting data on their sexual history, psychiatric history, and risk behaviors. Females submitted self-collected vaginal swabs, whereas males submitted urine to be tested for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis (women only). RESULTS: The prevalence of N. gonorrhoeae was 1%, C. trachomatis 3.3% and T. vaginalis 15.7%. Exchanging sex for drugs was the only behavior independently associated with having an STI in this population. CONCLUSIONS: Taking a sexual history in persons with SPMI is important. Those engaging in high-risk behavior should be routinely screened for STI/human immunodeficiency virus allowing for detection, treatment, and preventive education.

Fibrillation in patients subjected to coronary artery bypass grafting.

OBJECTIVE: Atrial fibrillation is the most frequently encountered postoperative arrhythmic complication after coronary artery bypass grafting. Ischemic preconditioning has proved a potent endogenous factor in suppressing ischemia-reperfusion-induced arrhythmias. The protective effect of ischemic preconditioning on atrial fibrillation after coronary artery bypass grafting has not been studied. The purpose of the present study was to investigate whether ischemic preconditioning had an effect on postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting. METHODS: Eighty-five patients undergoing coronary artery bypass grafting were randomized into ischemic preconditioning and control groups. Holter data from 24-hour electrocardiography were collected 1 day before the operation to the second postoperative day. Atrial fibrillation was registered as positive if any atrial fibrillation event occurred. RESULTS: The overall incidence of postoperative atrial fibrillation and sustained atrial fibrillation was 34.1% and 27.1%, respectively. The occurrence of atrial fibrillation was significantly lower in the ischemic preconditioning group (21.4% in patients undergoing ischemic preconditioning and 46.5% in control subjects, P =.015). Preoperative recent unstable angina did not influence the incidence of atrial fibrillation. Patients with atrial fibrillation had longer intensive care unit stays and compromised postoperative hemodynamic outcomes. Binary logistic regression analysis showed that ischemic preconditioning, preoperative mean heart rate, and postoperative pulmonary capillary wedge pressure were the independent predictors of atrial fibrillation. CONCLUSIONS: Postcoronary artery bypass grafting atrial fibrillation is associated with more complicated postoperative outcome. Higher preoperative heart rate and postoperative pulmonary capillary wedge pressure were the independent predictors of atrial fibrillation. Recent unstable angina is not related to the occurrence of postcoronary artery bypass grafting atrial fibrillation. Ischemic preconditioning significantly suppresses postcoronary artery bypass grafting atrial fibrillation, suggesting that ischemic preconditioning can be used as an effective prophylactic method for postoperative atrial fibrillation.

Antitumor efficacy of TRA-8 anti-DR5 monoclonal antibody alone or in combination with chemotherapy and/or radiation therapy in a human breast cancer model.

PURPOSE: A monoclonal antibody (TRA-8) has been developed that binds to death receptor 5 (DR5), one of two death receptors bound by tumor necrosis factor-related apoptosis-inducing ligand. The purpose of this study was to evaluate in vitro the binding and cytotoxicity of TRA-8 to human breast cancer cell lines. The antitumor efficacy of TRA-8 was evaluated in a xenograft human breast cancer murine model, as a single agent and in combination with chemotherapy or radiation therapy. Anti: The binding of TRA-8 to a panel of nine human breast cancer cell lines was evaluated by indirect immunofluorescence and flow cytometry. Cytotoxicity of TRA-8 alone and in the presence of Adriamycin or paclitaxel was measured in vitro using the ATP-lite assay. Antitumor efficacy was determined by treatment of nude mice bearing well-established s.c. DR5-positive 2LMP human breast cancer xenografts with TRA-8 alone or in combination with Adriamycin or paclitaxel. Tumor size and regression rates were determined. In addition, a study was carried out with TRA-8 and Adriamycin in combination with 3 Gy (60)Co irradiation of 2LMP xenografts on days 9 and 17. RESULTS: All nine human breast cancer cell lines expressed DR5 with TRA-8 reactivity varying from strongly to weakly positive. Four cell lines were sensitive to TRA-8 cytotoxicity with IC(50) of 17-299 ng/ml, whereas other cell lines had weak cytotoxicity or were resistant. In vivo studies demonstrated significant inhibition of growth of 2LMP xenografts by TRA-8 treatment alone. The combination of TRA-8 + Adriamycin or paclitaxel produced significant inhibition of tumor growth as compared with controls or either agent alone. An aggregate analysis of all 166 animals studied demonstrated that TRA-8 alone or in combination with Adriamycin, paclitaxel, or radiation produced a significant increase in tumor doubling time compared with any modality alone with mean doubling time in days of 12 (untreated), 14 (radiation), 17 (Adriamycin), 25 (paclitaxel), 39 (Adriamycin + radiation), 47 (TRA-8), 65 (TRA-8 + radiation), 71 (TRA-8 + paclitaxel), 81 (TRA-8 + Adriamycin), and >140 (TRA-8 + Adriamycin and radiation). Complete tumor regressions occurred in 1 of 42 untreated animals, 1 of 54 animals receiving chemotherapy and/or radiation, and 28 of 68 animals receiving TRA-8 alone or TRA-8 combination regimens. Fourteen of those 28 complete regressions did not relapse over periods of follow-up between 99 and 171 days, with a mean of 146 +/- 24 days. CONCLUSIONS: The TRA-8 anti-DR5 antibody alone or in combination with chemotherapy and/or radiation has striking antitumor efficacy in breast cancer xenograft models. Additional studies with other tumor types and chemotherapy agents are warranted. These studies support the generation of a humanized TRA-8 for introduction into early clinical trials.