Summary Background The intensity of chemotherapy and need for additional radiotherapy in patients with advanced stage Hodgkin's lymphoma has been unclear. We did a prospective randomised clinical ...trial comparing two reduced-intensity chemotherapy variants with our previous standard regimen. Chemotherapy was followed by PET-guided radiotherapy. Methods In this parallel group, open-label, multicentre, non-inferiority trial (HD15), 2182 patients with newly diagnosed advanced stage Hodgkin's lymphoma aged 18–60 years were randomly assigned to receive either eight cycles of BEACOPPescalated (8×Besc group), six cycles of BEACOPPescalated (6×Besc group), or eight cycles of BEACOPP14 (8×B14 group). Randomisation (1:1:1) was done centrally by stratified minimisation. Non-inferiority of the primary endpoint, freedom from treatment failure, was assessed using repeated CIs for the hazard ratio (HR) according to the intention-to-treat principle. Patients with a persistent mass after chemotherapy measuring 2·5 cm or larger and positive on PET scan received additional radiotherapy with 30 Gy; the negative predictive value for tumour recurrence of PET at 12 months was an independent endpoint. This trial is registered with Current Controlled Trials, number ISRCTN32443041. Findings Of the 2182 patients enrolled in the study, 2126 patients were included in the intention-to-treat analysis set, 705 in the 8×Besc group, 711 in the 6×Besc group, and 710 in the 8×B14 group. Freedom from treatment failure was sequentially non-inferior for the 6×Besc and 8×B14 groups as compared with 8×Besc . 5-year freedom from treatment failure rates were 84·4% (97·5% CI 81·0–87·7) for the 8×Besc group, 89·3% (86·5–92·1) for 6×Besc group, and 85·4% (82·1–88·7) for the 8×B14 group (97·5% CI for difference between 6×Besc and 8×Besc was 0·5–9·3). Overall survival in the three groups was 91·9%, 95·3%, and 94·5% respectively, and was significantly better with 6×Besc than with 8×Besc (97·5% CI 0·2–6·5). The 8×Besc group showed a higher mortality (7·5%) than the 6×Besc (4·6%) and 8×B14 (5·2%) groups, mainly due to differences in treatment-related events (2·1%, 0·8%, and 0·8%, respectively) and secondary malignancies (1·8%, 0·7%, and 1·1%, respectively). The negative predictive value for PET at 12 months was 94·1% (95% CI 92·1–96·1); and 225 (11%) of 2126 patients received additional radiotherapy. Interpretation Treatment with six cycles of BEACOPPescalated followed by PET-guided radiotherapy was more effective in terms of freedom from treatment failure and less toxic than eight cycles of the same chemotherapy regimen. Thus, six cycles of BEACOPPescalated should be the treatment of choice for advanced stage Hodgkin's lymphoma. PET done after chemotherapy can guide the need for additional radiotherapy in this setting. Funding Deutsche Krebshilfe and the Swiss Federal Government.
Abstract Background The Department of Veterans Affairs is the largest US provider of hepatitis C treatment. Although antiviral regimens are becoming simpler, hepatitis C antivirals are not typically ...prescribed by primary care providers. The Veterans Affairs Extension for Community Health Outcomes (VA-ECHO) program was launched to promote primary care–based hepatitis C treatment using videoconferencing-based specialist support. We aimed to assess whether primary care provider participation in VA-ECHO was associated with hepatitis C treatment and sustained virologic response. Methods We identified 4173 primary care providers (n = 152 sites) responsible for 38,753 patients with chronic hepatitis C infection. A total of 6431 patients had a primary care provider participating in VA-ECHO; 32,322 patients had an unexposed primary care provider. Exposure was modeled as a patient-level time-varying covariate. Patients became exposed after primary care provider participation in ≥1 VA-ECHO session. Multivariable Cox proportional hazards frailty modeling assessed the association between VA-ECHO exposure and hepatitis C treatment. Among treated patients, modified Poisson regression assessed the relationship between exposure and sustained virologic response. Results After adjustment, exposed patients received significantly higher rates of antiviral treatment compared with unexposed patients (adjusted hazard ratio, 1.20; 95% confidence interval, 1.10-1.32; P <.01). The rate of primary care provider–initiated antiviral medication was 21.4% among treated patients reviewed on VA-ECHO teleconferences compared with 2.5% among unexposed patients ( P <.01). No difference in adjusted rates of sustained virologic response was observed for patients with exposed primary care providers ( P = .32), with similar crude rates for primary care providers versus specialists. Conclusions National implementation of VA-ECHO was positively associated with hepatitis C treatment initiation by primary care providers, without differences in sustained virologic response.
Background Guidelines recommend cardiac rehabilitation after acute myocardial infarction, yet little is known about the impact of cardiac rehabilitation on medication adherence and clinical outcomes ...among contemporary older adults. The optimal number of cardiac rehabilitation sessions is not clear. Methods We linked patients 65 years or older enrolled in the Acute Coronary Treatment Intervention Outcomes Network Registry-Get With the Guidelines (ACTION Registry-GWTG) from January 2007 to December 2010 to Medicare longitudinal claims data to obtain 1 year follow-up. Results A total of 11,862 patients participated in cardiac rehabilitation after acute myocardial infarction, attending a median number of 26 sessions. Patients attending ≥26 sessions were more likely to be male, had lesser prevalence of comorbid conditions and prior revascularization, and were more likely to present with ST-segment elevation myocardial infarction, compared with patients attending 1 to 25 sessions. Among patients with Medicare Part D prescription coverage, increasing number of cardiac rehabilitation sessions was associated with improvement in adherence to secondary prevention medications such as P2Y12 inhibitors and β-blockers. Each 5-session increase in participation was associated with lower mortality (adjusted hazard ratio HR 0.87, 95% CI 0.83-0.92) and lower overall risk of major adverse cardiac event (adjusted HR 0.69, 95% CI 0.65-0.73) and death/readmission (adjusted HR 0.79, 95% CI 0.76-0.83). Conclusions In this older patient population, number of cardiac rehabilitation sessions attended was associated with improved medication adherence and lower downstream cardiovascular risk in a dose-response relationship. This provides support for the continued use of cardiac rehabilitation for older adults and encourages efforts to maximize attendance.
Objective Hospital readmission after lower extremity bypass is a large cost burden and has become a focal point for policy change directed at disease-specific bundling strategies. The purpose of this ...study was to evaluate rates and predictors of 30-day readmission from a large, multicenter trial data set. Methods We analyzed the PRoject of Ex-Vivo vein graft ENgineering via Transfection III (PREVENT III) data set of 1404 critical limb ischemia (CLI) patients undergoing lower extremity vein graft bypass at 83 North American centers. The primary end point was readmission ≤30 days of discharge. Secondary end points included graft patency and limb salvage evaluated in the context of readmission. The data set was split into a two-thirds derivation set and a one-third validation set for the purposes of creating a risk prediction model. A whole number integer risk score was assigned to independent predictors of readmission. Summary risk scores were collapsed into categories and defined as low (0-1 points), medium (2-5 points), and high (>5 points). Results We analyzed 1356 vein graft bypass patients, of which 23 (1.7%) died in-hospital and were excluded from the readmission analyses. In the derivation data set of 866 patients, 211 (24.4%) were readmitted ≤30 days of discharge. The most common reasons for readmission were wound infection in index leg (39.8%), an additional procedure in the index leg (20.8%), and nonvascular reasons (19%). By multivariable analysis, factors associated with 30-day hospital readmission (odds ratio 95% confidence limits) included female gender (1.5 1.0, 2.1), current smoking (1.6 1.1, 2.4), in-hospital loss of graft patency (1.8 1.0, 3.2), dialysis (2.0 1.2, 3.2), and tissue loss (1.7 1.1, 2.5). In the derivation set, rates of readmission correlated to risk category. The 30-day readmission rates were 15.6% for low-risk patients (0-1 points), 24.1% for moderate-risk (2-5 points) patients, and 38.0% for high-risk (>5 points) patients. Similarly, in the validation set, the rates were 16.5%, 25.4%, and 38.1% for low-, medium-, and high-risk groups, respectively. Thirty-day readmission was not associated with loss of long-term graft patency but was associated with long-term limb loss (hazard ratio, 2.1; 95% confidence interval, 1.4-3.1; P = .0002). Conclusions Readmission after lower extremity bypass for CLI is common (24%). Certain characteristics, such as female gender, current smoking, dialysis-dependence, tissue loss, and in-hospital graft-related events, are associated with increased risk. Readmission is associated with long-term limb loss. These data provide benchmark values for this complex patient population and may prove useful when hospital readmission is used as a quality metric for hospital performance.
Background Although β-blockers (BBs) reduce long-term mortality in patients after myocardial infarction (MI), data regarding acute usage are conflicting. Methods We examined acute (≤24 hours) BB use ...in 34,661 patients with ST-elevation MI (STEMI) and non–ST-segment MI (NSTEMI) included in the NCDR® ACTION Registry®-GWTG™ (291 US hospitals) between January 2007 and June 2008. Patients with contraindications or did not receive BBs or with missing data were excluded. We analyzed the use and impact of BB stratified by variables associated with increased risk for shock specified in the recent guidelines: age >70 years, symptoms >12 hours (STEMI patients), systolic blood pressure <120 mm Hg, and heart rate >110 beat/min on presentation. Results Among patients without contraindications, at least 1 high-risk variable was found in 45% of STEMI and 63% of NSTEMI patients. In-hospital complications including cardiogenic shock, mortality, and the composite outcome of shock or mortality were significantly increased with more shock risk factors in both STEMI and NSTEMI patients. Very early use in the emergency department was associated with a significantly increased risk of shock for both STEMI and NSTEMI patients compared to patients treated later but within 24 hours. Conclusions Risk factors for shock are common in STEMI and NSTEMI patients treated with early BBs. Increasing numbers of risk factors were associated with increased risk for shock or death in patients treated with BBs. These results are consistent with current recommendations for avoiding early BB treatment for patients with acute MI.
Background Dabigatran is a novel oral anti-coagulant (NOAC) that reduces risk of stroke in patients with non-valvular atrial fibrillation (NVAF). It does not require routine monitoring with ...laboratory testing which may have an adverse impact on adherence. We aimed to describe adherence to dabigatran in the first year after initiation and assess the association between non-adherence to dabigatran and clinical outcomes in a large integrated healthcare system. Methods We studied a national cohort of 5,376 patients with NVAF, initiated on dabigatran between October-2010 and September-2012 at all Veterans Affairs hospitals. Adherence to dabigatran was calculated as proportion of days covered (PDC) and association between PDC and outcomes was assessed using standard regression techniques. Results Mean age of the study cohort was 71.3 ± 9.7 years; 98.3% were men and mean CHADS2 score was 2.4 ± 1.2 (mean CHA2 DS2 VASc score 3.2 ± 1.4). Median PDC was 94% (IQR 76%-100%; mean PDC 84% ± 22%) over a median follow-up of 244 days (IQR 140-351). A total of 1,494 (27.8%) patients had a PDC <80% and were classified as non-adherent. After multivariable adjustment, lower adherence was associated with increased risk for combined all-cause mortality and stroke (HR 1.13, 95% CI 1.07–1.19 per 10% decrease in PDC). Adherence to dabigatran was not associated with non-fatal bleeding or myocardial infarction. Conclusions In the year after initiation, adherence to dabigatran for a majority of patients is very good. However, 28% of patients in our cohort had poor adherence. Furthermore, lower adherence to dabigatran was associated with increased adverse outcomes. Concerted efforts are needed to optimize adherence to NOACs.
Abstract Objective To identify medical practices that offer no net benefits. Methods We reviewed all original articles published in 10 years (2001-2010) in one high-impact journal. Articles were ...classified on the basis of whether they addressed a medical practice, whether they tested a new or existing therapy, and whether results were positive or negative. Articles were then classified as 1 of 4 types: replacement, when a new practice surpasses standard of care; back to the drawing board, when a new practice is no better than current practice; reaffirmation, when an existing practice is found to be better than a lesser standard; and reversal, when an existing practice is found to be no better than a lesser therapy. This study was conducted from August 1, 2011, through October 31, 2012. Results We reviewed 2044 original articles, 1344 of which concerned a medical practice. Of these, 981 articles (73.0%) examined a new medical practice, whereas 363 (27.0%) tested an established practice. A total of 947 studies (70.5%) had positive findings, whereas 397 (29.5%) reached a negative conclusion. A total of 756 articles addressing a medical practice constituted replacement, 165 were back to the drawing board, 146 were medical reversals, 138 were reaffirmations, and 139 were inconclusive. Of the 363 articles testing standard of care, 146 (40.2%) reversed that practice, whereas 138 (38.0%) reaffirmed it. Conclusion The reversal of established medical practice is common and occurs across all classes of medical practice. This investigation sheds light on low-value practices and patterns of medical research.
Summary Background Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is used to treat patients with non-Hodgkin lymphoma. Interval decrease from 3 weeks of treatment (CHOP-21) to 2 ...weeks (CHOP-14), and addition of rituximab to CHOP-21 (R-CHOP-21) has been shown to improve outcome in elderly patients with diffuse large B-cell lymphoma (DLBCL). This randomised trial assessed whether six or eight cycles of R-CHOP-14 can improve outcome of these patients compared with six or eight cycles of CHOP-14. Methods 1222 elderly patients (aged 61–80 years) were randomly assigned to six or eight cycles of CHOP-14 with or without rituximab. Radiotherapy was planned to sites of initial bulky disease with or without extranodal involvement. The primary endpoint was event-free survival; secondary endpoints were response, progression during treatment, progression-free survival, overall survival, and frequency of toxic effects. Analyses were done by intention to treat. The trial is registered on National Cancer Institute website, number NCT00052936 and as EU-20243. Findings 3-year event-free survival was 47·2% after six cycles of CHOP-14 (95% CI 41·2–53·3), 53·0% (47·0–59·1) after eight cycles of CHOP-14, 66·5% (60·9–72·0) after six cycles of R-CHOP-14, and 63·1% (57·4–68·8) after eight cycles of R-CHOP-14. Compared with six cycles of CHOP-14, the improvement in 3-year event-free survival was 5·8% (−2·8–14·4) for eight cycles of CHOP-14, 19·3% (11·1–27·5) for six cycles of R-CHOP-14, and 15·9% (7·6–24·2) for eight cycles of R-CHOP-14. 3-year overall survival was 67·7% (62·0–73·5) for six cycles of CHOP-14, 66·0% (60·1–71·9) for eight cycles of CHOP-14, 78·1% (73·2–83·0) for six cycles of R-CHOP-14, and 72·5% (67·1–77·9) for eight cycles of R-CHOP-14. Compared with treatment with six cycles of CHOP-14, overall survival improved by −1·7% (−10·0–6·6) after eight cycles of CHOP-14, 10·4% (2·8–18·0) after six cycles of R-CHOP-14, and 4·8% (−3·1–12·7) after eight cycles of R-CHOP-14. In a multivariate analysis that used six cycles of CHOP-14 without rituximab as the reference, and adjusting for known prognostic factors, all three intensified regimens improved 3-year event-free survival (eight cycles of CHOP-14: RR relative risk 0·76 0·60–0·95, p=0·0172; six cycles of R-CHOP-14: RR 0·51 0·40–0·65, p<0·0001; eight cycles of R-CHOP-14: RR 0·54 0·43–0·69, p<0·0001). Progression-free survival improved after six cycles of R-CHOP-14 (RR 0·50 0·38–0·67, p<0·0001), and eight cycles of R-CHOP-14 (RR 0·59 0·45–0·77, p=0·0001). Overall survival improved only after six cycles of R-CHOP-14 (RR 0·63 0·46–0·85, p=0·0031). In patients with a partial response after four cycles of chemotherapy, eight cycles were not better than six cycles. Interpretation Six cycles of R-CHOP-14 significantly improved event-free, progression-free, and overall survival over six cycles of CHOP-14 treatment. Response-adapted addition of chemotherapy beyond six cycles, though widely practiced, is not justified. Of the four regimens assessed in this study, six cycles of R-CHOP-14 is the preferred treatment for elderly patients, with which other approaches should be compared.
Introduction
Music is so widely available and inexpensive in the modern world; it is a common option for stress reduction, comfort and enjoyment. Silent disco headphones are used among young people; ...however, no study has yet investigated whether it is feasible to use these headphones to support mental health and well-being among older people with dementia in hospital settings.
Objective
The study’s main objective is to explore whether music delivered by silent disco headphones was feasible and acceptable to a sample of inpatients staying in an older adult mental health unit of a large urban hospital.
Methods
We employed a video-ethnographic design in data collection, including conversational interviews and observations with video recording among ten patient participants in a hospital unit. A focus group was conducted with ten hospital staff on the unit.
Results
Our analysis identified three themes that represented experiences of patients and staff: (1) perceived usefulness, (2) perceived ease of use, and (3) attitude. Patient participants reported the music delivered by the headphones brought positive benefits. Witnessing the positive effects on patients influenced the staff’s view of how music could be used in the clinical setting to support patients’ well-being.
Conclusions
The music delivered by the silent disco headphones in an older adult mental health unit was found to be an acceptable and feasible intervention for patients. Leadership support is identified as an enabling factor in supporting technology adoption in the clinical setting. The findings can be used to inform practice development and future research.
Objective End-stage renal disease (ESRD) imparts a significant survival disadvantage to individuals undergoing lower extremity revascularization; however, the influence of lesser degrees of renal ...impairment remains unclear. This study examined the prognostic significance of the chronic kidney disease (CKD) classification on survival, limb salvage, and graft patency in patients undergoing lower extremity arterial reconstruction. Methods A prospective registry was evaluated for consecutive patients between January 31, 1995, and December 21, 2004, undergoing first-time, lower extremity vein bypass surgery. Glomerular filtration rate (GFR) was estimated with the Modification of Diet in Renal Disease equation using each patient’s preoperative creatinine concentration. CKD categories were taken from current National Kidney Foundation Kidney Disease Outcomes Quality Initiative staging criteria. Results The cohort included 456 subjects, with a mean (± SD) age of 68.1 ± 10.8 years. There were 274 men (60%) and 378 Caucasians (82.5%). Comorbidities included diabetes mellitus in 270 (59.0%), hypertension in 333 (72.7%), coronary artery disease in 242 (52.8%), and dyslipidemia in 203 (44.5%). The surgical indication was critical limb ischemia in 384 (83.8%). Among the variables examined, diabetes and critical ischemia as the indication for bypass were significantly skewed toward higher CKD classifications ( P < .001). The 5-year survival rates by CKD class were, CKD 1 and 2, 57%; CKD 3, 46%; CKD 4, 23%; and CKD 5, 9.5%. On univariate analysis, age, coronary artery disease, diabetes mellitus, hypertension, critical ischemia, and CKD were significant predictors of mortality. After adjustment, however, only age (hazard ratio HR, 1.05, 95% confidence interval CI, 1.03 to 1.06) and CKD stages 4 (HR, 4.23; 95% CI, 2.04 to 8.75) and 5 (HR, 3.27; 95% CI, 1.96 to 5.45) retained significance. Subjects within the CKD 5 classification were more likely to have a major amputation ( P = .018) compared with all other CKD classes. Notably, no relationship was detected between CKD category and graft patency. Conclusion CKD staging adequately differentiates survival curves and risk for major amputation among patients with renal impairment who are undergoing lower extremity bypass surgery. This may help in clinical decision analysis as well as in the refinement of stratification in future clinical trial design where survival is an end point.
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