Central Venous Access Device-Associated Skin Complications in Adults with Cancer: A Prospective Observational Study.

OBJECTIVES: To identify the prevalence and type of central venous access device-associated skin complications for adult cancer patients, describe central venous access device management practices, and identify clinical and demographic characteristics associated with risk of central venous access device-associated skin complications. METHODS: A prospective cohort study of 369 patients (626 central venous access devices; 7,682 catheter days) was undertaken between March 2017 and March 2018 across two cancer care in-patient units in a large teaching hospital. RESULTS: Twenty-seven percent (n = 168) of participants had a central venous access device-associated skin complication. In the final multivariable analysis, significant (P < .05) risk factors for skin complications were cutaneous graft versus host disease (2.1 times greater risk) and female sex (1.4 times greater risk), whereas totally implanted vascular access device reduced risk for skin complications by two-thirds (incidence risk ratio 0.37). CONCLUSION: Central venous access device-associated skin complications are a significant, potentially avoidable injury, requiring cancer nurses to be aware of high-risk groups and use evidence-based preventative and treatment strategies. IMPLICATIONS FOR PRACTICE: This study has confirmed how common these potentially preventable injuries are. Therefore, the prevalence of these complications could be reduced by focusing on improvements in skin assessment, reductions in central venous access device dressing variation and improving clinician knowledge of this injury.

An mHealth application for chronic vascular access: Consumer led co-creation.

PURPOSE: Children with chronic and complex health conditions frequently need intravenous devices. The current approach to intravenous device selection, insertion, and monitoring is inconsistent, and healthcare consumers are often negatively affected by siloed health information, and poor future planning. Despite child- and family-centred care being recognised as a pillar of paediatric nursing care, limited implementation for vascular access device planning and management is evident. DESIGN AND METHODS: To address this, we conducted a multi-phased approach to co-create, then evaluate, a mobile health (mHealth) application: IV Passport. Co-creation involved a prioritisation survey, followed by a Passport advisory panel consensus meeting. Following confirmation of the required content and features of the Passport, the mHealth application was designed and content validation achieved via survey. RESULTS: The prioritisation survey yielded recommendations for seven features (e.g., graphical presentations of current/past devices). Content for nine device types (e.g., totally implanted ports) was suggested, each with 10 related items (e.g., insertion site). Content items for device-associated complications, future vascular access plans, and educational resources were also suggested. Following design, the application was released through Apple and Android platforms; and adapted to a paper version. Content validation was established; 100% strongly agreed the application was easy to use; 80% agreed/strongly agreed that they would recommend the Passport to others. CONCLUSION: IV Passport embodies effective child- and family-centred care through consumer co-creation to empower patients and families manage vascular access devices. PRACTICE IMPLICATIONS: IV Passport remains active; and can be utilised across many healthcare settings and patient populations.

An mHealth application for chronic vascular access: A multi-method evaluation.

BACKGROUND: Healthcare consumers require diverse resources to assist their navigation of complex healthcare interactions, however, these resources need to be fit for purpose. AIM: In this study, we evaluated the utility, usability and feasibility of children, families and adults requiring long-term intravenous therapy using a recently developed mobile health application (App), intravenous (IV) Passport. DESIGN: Multi-site, parallel, multi-method, prospective cohort study. METHODS: A multi-site, multi-method study was carried out in 2020-2021, with 46 participants (20 adults, 26 children/family) reporting on their experiences surrounding the use of the IV Passport for up to 6 months. RESULTS: Overall, utility rates were acceptable, with 78.3% (N = 36) using the IV Passport over the follow-up period, with high rates of planned future use for those still active in the project (N = 21; 73%), especially in the child/family cohort (N = 13; 100%). Acceptability rates were high (9/10; IQR 6.5-10), with the IV Passport primarily used for documenting new devices and complications. Thematic analysis revealed three main themes (and multiple subthemes) in the qualitative data: Advocacy for healthcare needs, Complexity of healthcare and App design and functionality. CONCLUSION: Several recommendations were made to improve the end-user experience including 'how to' instructions; and scheduling functionality for routine care. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The IV Passport can be safely and appropriately integrated into healthcare, to support consumers. IMPACT: Patient-/parent-reported feedback suggests the Intravenous Passport is a useful tool for record-keeping, and positive communication between patients/parents, and clinicians. REPORTING METHOD: Not applicable. PATIENT CONTRIBUTION: Consumers reported their experiences surrounding the use of the IV Passport for up to 6 months.

Association between parenteral nutrition-containing intravenous lipid emulsion and bloodstream infections in patients with single-lumen central venous access: A secondary analysis of a randomized trial.

BACKGROUND: Distinguishing primary bloodstream infections (BSIs) related to central venous access devices (CVADs) from those that occur through other mechanisms, such as a damaged mucosal barrier, is difficult. METHODS: Secondary analysis was conducted on data from patients with CVADs that were collected for a large, randomized trial. Patients were divided into two groups: those who received parenteral nutrition (PN)-containing intravenous lipid emulsion (ILE) and those who did not have PN-containing ILE. This study investigated the influence of PN-containing ILE (ILE PN) on primary BSIs in patients with a CVAD. RESULTS: Of the 807 patients, 180 (22%) received ILE PN. Most (627/807; 73%) were recruited from the hematology and hematopoietic stem cell transplant unit, followed by surgical (90/807; 11%), trauma and burns (61/807; 8%), medical (44/807; 5%), and oncology (23/807; 3%). When primary BSI was differentiated as a central line-associated BSI (CLABSI) or mucosal barrier injury laboratory-confirmed BSI (MBI-LCBI), the incidence of CLABSI was similar in the ILE PN and non-ILE PN groups (15/180 [8%] vs 57/627 [9%]; P = 0.88) and the incidence of MBI-LCBI was significantly different between groups (31/180 [17%] ILE PN vs 41/627 [7%] non-ILE PN; P < 0.01). CONCLUSION: Our data indicate that twice as many primary BSIs in ILE PN patients are due to MBIs than CVADs. It is important to consider the MBI-LCBI classification, as some CLABSI prevention efforts aimed at CVADs for the ILE PN population may be better directed to gastrointestinal tract protection interventions.

Peripheral intravenous catheters in the care of oncology and haematology patients.

Aim: To determine peripheral intravenous catheter (PIVC) characteristics, complications and risk factors among patients in cancer units. Methods: A secondary analysis of a global, cross-sectional study (127 hospitals in 24 countries). Participants (≥18 years) admitted to cancer units were assessed once for PIVC characteristics and the presence of complications. Variables included patient demographics, device characteristics, treatment details, and device and/or site complications. PIVC characteristics were presented using qualitative descriptors; mixed-effects logistic regression models determined risk factors for PIVC complications. Results: In total, 1,807 participants (1,812 PIVCs) were included; 12% (n=215) of PIVCs presented with complications. Risk factors included: insertion by doctors; insertion in ED and ambulance/other locations; poor PIVC dressing integrity; dwell time ≥49 hours; and administration of colloids/blood products and antiemetics. Conclusions: At least one in ten PIVCs in cancer units present with complications; regular PIVC assessment and improved dressing integrity is likely to reduce risk and improve outcomes.

Evaluating methods for the use and decontamination of needleless connectors: A qualitative inquiry.

BACKGROUND: Needleless connectors (NCs) are essential devices designed to provide safe, needle-free connection between venous access devices, syringes and infusions. There is a variety of designs, and associated decontamination products and practices; the resulting confusion can cause detrimental patient outcomes. This study aimed to explore nurses' attitudes, techniques, and practices around the use and decontamination of NCs in clinical practice. METHODS: Qualitative inquiry was conducted with seven focus groups of 4-6 participants each in the cancer and surgical units of a large tertiary hospital in Australia between January and March 2019. Participants comprised nurses who had taken part in a recent clinical trial of NC decontamination. Focus group sessions were recorded, transcribed and synthesised using content analysis. RESULTS: Seven focus groups were conducted (total, N = 30 participants), lasting 16-20 min. Six major themes were identified surrounding needleless connector use and decontamination: 'safety and utility'; 'terminology and technological understanding'; 'clinical practice determinants'; 'decontamination procedures and influencers'; 'education and culture'; and 'research and innovation'. CONCLUSION: The participants articulated positive attitudes towards needleless connector use for needle-stick and infection prevention, however rationales for care and maintenance practices demonstrated limited understanding of guidelines (e.g., disinfection time) and specific NC function (e.g., positive, negative pressure). The findings indicated the need for targeted, standardised needleless connector education, to enhance staff confidence, improve consistency of care and ensure patient safety.

Peripheral intravenous catheter failure: A secondary analysis of risks from 11,830 catheters.

BACKGROUND: Peripheral intravenous catheters are an essential medical device which are prone to complications and failure. OBJECTIVES: Identify patient, provider and device risk factors associated with all-cause peripheral intravenous catheter failure as well as individual complications: phlebitis, infiltration/occlusion, and dislodgement to improve patient outcomes. DESIGN: Secondary analysis of twelve prospective studies performed between 2008 and 2020. SETTINGS: Australian metropolitan and regional hospitals including one paediatric hospital. PARTICIPANTS: Participants were from medical, surgical, haematology, and oncology units. METHODS: Multilevel mixed-effects parametric survival regression was used to identify factors associated with all-cause peripheral intravenous catheter failure, phlebitis, occlusion/infiltration, and dislodgement. We studied patient (e.g., age, gender), device (e.g., gauge), and provider (e.g., inserting clinician) variables. Stepwise regression involved clinically and p<0.20 significant variables entered into the multivariable model. Results were expressed as hazard ratios (HRs) and 95% confidence intervals (CI); p<0.01 was considered statistically significant. RESULTS: Of 11,830 peripheral intravenous catheters (8,200 participants) failure occurred in 36% (n = 4,263). Occlusion/infiltration incidence was 23% (n = 2,767), phlebitis 12% (n = 1,421), and dislodgement 7% (n = 779) of catheters. Patient factors significantly associated with failure and complications were: female gender (phlebitis; (HR 1.98, 95% CI 1.72-2.27), (infiltration/occlusion; HR 1.45, 95% CI 1.33-1.58), (failure; HR 1.36, 95% CI 1.26-1.46); and each year increase in age (phlebitis; 0.99 HR, 95% CI 0.98-0.99), (failure; 0.99 HR, 95% CI 0.99-0.99). The strongest provider risk factor was intravenous antibiotics (infiltration/occlusion; HR 1.40, 95% CI 1.27-1.53), (phlebitis; HR 1.36, 95% CI 1.18-1.56), (failure; HR 1.26, 95% CI 1.17-1.36). Catheters inserted by vascular access teams were less likely to dislodge (HR 0.53, 95% CI 0.42-0.67). Device risk factors most associated with all-cause failure were wrist/hand (HR 1.34, 95% CI 1.23-1.46), antecubital fossa peripheral intravenous catheters (HR 1.29, 95% CI 1.16-1.44) and 22/24 gauge (HR 1.27, 95% CI 1.12-1.45) catheters. CONCLUSION: Factors identified, including the protective aspect of vascular access team insertion, and high catheter failure associated with intravenous antibiotic administration, will allow targeted updates of peripheral intravenous catheter guidelines and models of care.

'How many audits do you really need?': Learnings from 5-years of peripheral intravenous catheter audits.

BACKGROUND: Peripheral intravenous catheters (PIVCs) are medical devices used to administer intravenous therapy but can be complicated by soft tissue or bloodstream infection. Monitoring PIVC safety and quality through clinical auditing supports quality infection prevention however is labour intensive. We sought to determine the optimal patient 'number' for clinical audits to inform evidence-based surveillance. METHODS: We studied a dataset of cross-sectional PIVC clinical audits collected over five years (2015-2019) in a large Australian metropolitan hospital. Audits included adult medical, surgical, women's, cancer, emergency and critical care patients, with audit sizes of 69-220 PIVCs. The primary outcome was PIVC complications for one or more patient reported symptom/auditor observed sign of infection or other complications. Complication prevalence and 95% confidence interval (CI) were calculated. We modelled scenarios of low (10%), medium (20%) and high (50%) prevalence estimates against audit sizes of 20, 50, 100, 150, 200, 250, and 300. This was used to develop a decision-making tool to guide audit size. RESULTS: Of 2274 PIVCs evaluated, 475 (21%) had a complication. Complication prevalence per round varied from 7.8% (95% CI, 4.2-12.9) to 39% (95% CI, 32.0-46.4). Precision improved with larger audit size and lower complication rates. However, precision was not meaningfully improved by auditing >150 patients at a complication rate of 20% (95% CI 13.9%-27.3%), nor >200 patients at a complication rate of 50% (95% CI 42.9%-57.1%). CONCLUSION: Audit sizes should be 100 to 250 PIVCs per audit round depending on complication prevalence.

Inherent and modifiable risk factors for peripheral venous catheter failure during cancer treatment: a prospective cohort study.

PURPOSE: To identify modifiable and non-modifiable risk factors for peripheral intravenous catheter (PIV) failure among patients requiring intravenous treatment for oncology and haematology conditions. METHODS: A single-centre prospective cohort study was conducted between October 2017 and February 2019. Adult in-patients requiring a PIV for therapy were prospectively recruited from two cancer units at a tertiary hospital in Queensland, Australia. The primary outcome was a composite of complications leading to PIV failure (local and bloodstream infection; occlusion; infiltration/extravasation; leakage; dislodgement; and/or phlebitis). Secondary outcomes were (i) PIV dwell time; (ii) insertion and (iii) failure of a CVAD; (iv) adverse events; (v) length of hospital stay. Outcomes were investigated using Bayesian multivariable linear regression modelling and survival analysis. RESULTS: Of 200 participants, 396 PIVs were included. PIV failure incidence was 34.9%; the most common failure type was occlusion/infiltration (n = 74, 18.7%), then dislodgement (n = 33, 8.3%), and phlebitis (n = 30, 7.6%). While several patient and treatment risk factors were significant in univariable modelling, in the final multivariable model, only the use of non-sterile tape (external to the primary dressing) was significantly associated with decreased PIV dislodgement (hazard ratio 0.06, 95% confidence interval 0.01, 0.48; p = 0.008). CONCLUSION: PIV failure rates among patients receiving cancer treatment are high, the sequelae of which may include delayed treatment and infection. Larger studies on risk factors and interventions to prevent PIV failure in this population are needed; however, the use of secondary securements (such as non-sterile tape) to provide further securement to the primary PIV dressing is particularly important. TRIAL REGISTRATION: Study methods were registered prospectively with the Australian New Zealand Clinical Trials Registry on the 27th March 2017 (ACTRN12617000438358); https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372191&isReview=true.

Prophylactic insertion of large bore peripheral intravenous catheters in maternity patients for postpartum haemorrhage: A cohort study.

BACKGROUND: Insertion of a 16 or 18 gauge peripheral intravenous catheter is a potentially painful intervention but one frequently experienced by pregnant women when admitted to hospital. Although the rationale for this practice is 'in case of an emergency bleed', evidence for using large-bore catheters in this population is absent. AIMS: (i) To identify the proportion of 18 gauge or larger peripheral catheters inserted into maternity patients; and (ii) to investigate the proportion of women who require blood products during their perinatal period. MATERIALS AND METHODS: Data from a sub-set of maternity patients who were included in a study of risk factors for peripheral intravenous access failure were analysed using descriptive statistics. RESULTS: One hundred and fourteen catheters were inserted in 95 women. Of the 95 first-inserted catheters, 84 (88.4%) were 16 or 18 gauge and 69 (82.1%) of these were placed in the hand or wrist. Four women (4%) received blood products, all were for non-urgent transfusions. CONCLUSION: Postpartum haemorrhage requiring a blood transfusion remains a relatively rare event. Comprehensive risk assessment should be undertaken before inserting large-bore catheters in perinatal women. Small veins in the hand and wrist should not be used for large bore catheters.

Central venous Access device SeCurement And Dressing Effectiveness for peripherally inserted central catheters in adult acute hospital patients (CASCADE): a pilot randomised controlled trial.

BACKGROUND: Peripherally inserted central catheters (PICCs) are commonly used for delivering intravenous therapy. PICC failure is unacceptably high (up to 40%) due to mechanical, infectious and thrombotic complications. Poor securement potentiates all complication types. This randomised controlled trial (RCT) aimed to examine the feasibility of a large RCT of four dressing and securement methods to prevent PICC failure. METHODS: This single-centre pilot RCT included 124 admitted medical/surgical/cancer patients aged ≥ 16 years with a PICC. Interventions were: (i) standard polyurethane dressing and sutureless securement device (SPU + SSD, control); (ii) polyurethane with absorbent lattice pad dressing (PAL + Tape); (iii) combination securement-dressing (CSD); and (iv) tissue adhesive (TA + SPU). All groups except TA + SPU had a chlorhexidine-gluconate (CHG) impregnated disc. Feasibility outcomes were recruitment and safety/acceptability of the interventions. The primary outcome was PICC failure, a composite of PICC removal for local infection, catheter-associated bloodstream infection, dislodgement, occlusion, and/or catheter fracture. Secondary outcomes included individual complications, dressing failure and dwell time, PICC dwell time, skin complications/phlebitis indicators, product costs, and patient and staff satisfaction. Qualitative feedback was also collected. RESULTS: PICC failure incidence was: PAL + CHG + Tape (1/5; 20%; 17.4/1000 days), SPU + SSD + CHG (control) (4/39; 10%; 9.0/1000 days), TA + SPU (3/35; 9%; 9.6/1000 days), and CSD + CHG (3/42; 7%; 9.4/1000 days). Recruitment to PAL + CHG + Tape was ceased after five participants due to concerns of PICC dislodgement when removing the dressing. CSD + CHG, TA + SPU (TA applied only at PICC insertion time), and control treatments were acceptable to patients and health professionals. CONCLUSION: A large RCT of CSD + CHG and TA + SPU (but not PAL + CHG + Tape) versus standard care is feasible. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12616000027415 . Registered on 15 January 2016.

Peripherally InSerted CEntral catheter dressing and securement in patients with cancer: the PISCES trial. Protocol for a 2x2 factorial, superiority randomised controlled trial.

INTRODUCTION: Around 30% of peripherally inserted central catheters (PICCs) fail from vascular, infectious or mechanical complications. Patients with cancer are at highest risk, and this increases morbidity, mortality and costs. Effective PICC dressing and securement may prevent PICC failure; however, no large randomised controlled trial (RCT) has compared alternative approaches. We designed this RCT to assess the clinical and cost-effectiveness of dressing and securements to prevent PICC failure. METHODS AND ANALYSIS: Pragmatic, multicentre, 2×2 factorial, superiority RCT of (1) dressings (chlorhexidine gluconate disc (CHG) vs no disc) and (2) securements (integrated securement dressing (ISD) vs securement device (SED)). A qualitative evaluation using a knowledge translation framework is included. Recruitment of 1240 patients will occur over 3 years with allocation concealment until randomisation by a centralised service. For the dressing hypothesis, we hypothesise CHG discs will reduce catheter-associated bloodstream infection (CABSI) compared with no CHG disc. For the securement hypothesis, we hypothesise that ISD will reduce composite PICC failure (infection (CABSI/local infection), occlusion, dislodgement or thrombosis), compared with SED. SECONDARY OUTCOMES: types of PICC failure; safety; costs; dressing/securement failure; dwell time; microbial colonisation; reversible PICC complications and consumer acceptability. Relative incidence rates of CABSI and PICC failure/100 devices and/1000 PICC days (with 95% CIs) will summarise treatment impact. Kaplan-Meier survival curves (and log rank Mantel-Haenszel test) will compare outcomes over time. Secondary end points will be compared between groups using parametric/non-parametric techniques; p values <0.05 will be considered to be statistically significant. ETHICS AND DISSEMINATION: Ethical approval from Queensland Health (HREC/15/QRCH/241) and Griffith University (Ref. No. 2016/063). Results will be published. TRIAL REGISTRATION: Trial registration number is: ACTRN12616000315415.

Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma.

Presented here are the 5-year end-of-study results from the pivotal phase 2 trial of brentuximab vedotin in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) after failed hematopoietic autologous stem cell transplantation. At 5 years, the overall patient population (N = 102) had an estimated overall survival (OS) rate of 41% (95% confidence interval [CI]: 31-51) and progression-free survival (PFS) rate of 22% (95% CI: 13-31). Patients who achieved a complete response (CR) to brentuximab vedotin (N = 34) had estimated OS and PFS rates of 64% (95% CI: 48-80%) and 52% (95% CI: 34-69%), respectively. The median OS and PFS were not reached in CR patients, with 13 patients (38% of all CR patients) remaining in follow-up and in remission at study closure. Of the 13 patients, 4 received consolidative hematopoietic allogeneic stem cell transplant, and 9 (9% of all enrolled patients) remain in sustained CR without receiving any further anticancer therapy after treatment with brentuximab vedotin. Of the patients who experienced treatment-emergent peripheral neuropathy, 88% experienced either resolution (73%) or improvement (14%) in symptoms. These 5-year follow-up data demonstrate that a subset of patients with R/R HL who obtained CR with single-agent brentuximab vedotin achieved long-term disease control and may potentially be cured. The trial was registered at www.clinicaltrials.gov as #NCT00848926.

Response assessment in lymphoma: Concordance between independent central review and local evaluation in a clinical trial setting.

BACKGROUND: Independent central review of clinical imaging remains the standard for oncology clinical trials with registration potential. A limited independent central review strategy has been proposed for solid tumor trials based on concordance between central and local evaluation of response. Concordance between independent central review and local evaluation of response in hematological malignancies is not known. METHODS: We retrospectively evaluated concordance between prospectively performed central and local assessments of response using the Revised Response Criteria for Malignant Lymphoma across two international, open-label, single-arm, registration studies of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma (N = 102) or systemic anaplastic large-cell lymphoma (N = 58). RESULTS: Overall objective response rates were similar between assessors for both the trial in Hodgkin lymphoma (75% independent central review, 72% local evaluation) and the trial in anaplastic large-cell lymphoma (86% independent central review, 83% local evaluation). Patient-specific objective response concordance was also substantial (Hodgkin lymphoma: kappa = 0.68; anaplastic large-cell lymphoma: kappa = 0.74). Median progression-free survival was similar between assessors for patients with anaplastic large-cell lymphoma (14.3 months by independent central review (95% confidence interval: 6.9, -); 14.5 months by local evaluation (95% confidence interval: 9.4, -)), but longer by local evaluation in patients with Hodgkin lymphoma (5.8 months by independent central review (95% confidence interval: 5.0, 9.0); 9.0 months by local evaluation (95% confidence interval: 7.1, 12.0)). Median duration of response was longer by local evaluation in both malignancies, which was primarily attributable to earlier computed tomography and positron emission tomography-based scoring of progression by independent central review. CONCLUSION: A limited independent review audit strategy for clinical trials of some lymphomas appears feasible and practical based on substantial concordance in assessments of overall objective response by central and local evaluation in two international, prospective, registration trials in lymphoma. Some variability between assessors in the time-to-event endpoints was observed, which appeared attributable to earlier assignments of progression by independent central review compared with local evaluation.

Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: High-dose therapy followed by autologous stem-cell transplantation is standard of care for patients with relapsed or primary refractory Hodgkin's lymphoma. Roughly 50% of patients might be cured after autologous stem-cell transplantation; however, most patients with unfavourable risk factors progress after transplantation. We aimed to assess whether brentuximab vedotin improves progression-free survival when given as early consolidation after autologous stem-cell transplantation. METHODS: We did this randomised, double-blind, placebo-controlled, phase 3 trial at 78 sites in North America and Europe. Patients with unfavourable-risk relapsed or primary refractory classic Hodgkin's lymphoma who had undergone autologous stem-cell transplantation were randomly assigned, by fixed-block randomisation with a computer-generated random number sequence, to receive 16 cycles of 1·8 mg/kg brentuximab vedotin or placebo intravenously every 3 weeks, starting 30-45 days after transplantation. Randomisation was stratified by best clinical response after completion of salvage chemotherapy (complete response vs partial response vs stable disease) and primary refractory Hodgkin's lymphoma versus relapsed disease less than 12 months after completion of frontline therapy versus relapse 12 months or more after treatment completion. Patients and study investigators were masked to treatment assignment. The primary endpoint was progression-free survival by independent review, defined as the time from randomisation to the first documentation of tumour progression or death. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01100502. FINDINGS: Between April 6, 2010, and Sept 21, 2012, we randomly assigned 329 patients to the brentuximab vedotin group (n=165) or the placebo group (n=164). Progression-free survival by independent review was significantly improved in patients in the brentuximab vedotin group compared with those in the placebo group (hazard ratio [HR] 0·57, 95% CI 0·40-0·81; p=0·0013). Median progression-free survival by independent review was 42·9 months (95% CI 30·4-42·9) for patients in the brentuximab vedotin group compared with 24·1 months (11·5-not estimable) for those in the placebo group. We recorded consistent benefit (HR <1) of brentuximab vedotin consolidation across subgroups. The most frequent adverse events in the brentuximab vedotin group were peripheral sensory neuropathy (94 [56%] of 167 patients vs 25 [16%] of 160 patients in the placebo group) and neutropenia (58 [35%] vs 19 [12%] patients). At time of analysis, 28 (17%) of 167 patients had died in the brentuximab vedotin group compared with 25 (16%) of 160 patients in the placebo group. INTERPRETATION: Early consolidation with brentuximab vedotin after autologous stem-cell transplantation improved progression-free survival in patients with Hodgkin's lymphoma with risk factors for relapse or progression after transplantation. This treatment provides an important therapeutic option for patients undergoing autologous stem-cell transplantation. FUNDING: Seattle Genetics and Takeda Pharmaceuticals International.

Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma.

We present response and survival outcomes of a pivotal phase 2 trial of the antibody-drug conjugate brentuximab vedotin in patients with relapsed/refractory Hodgkin lymphoma following autologous stem cell transplant (N = 102) after a median observation period of approximately 3 years. Median overall survival and progression-free survival were estimated at 40.5 months and 9.3 months, respectively. Improved outcomes were observed in patients who achieved a complete remission (CR) on brentuximab vedotin, with estimated 3-year overall survival and progression-free survival rates of 73% (95% confidence interval [CI]: 57%, 88%) and 58% (95% CI: 41%, 76%), respectively, in this group (medians not reached). Of the 34 patients who obtained CR, 16 (47%) remain progression-free after a median of 53.3 months (range, 29.0 to 56.2 months) of observation; 12 patients remain progression-free without a consolidative allogeneic stem cell transplant. Younger age, good performance status, and lower disease burden at baseline were characteristic of patients who achieved a CR and were favorable prognostic factors for overall survival. These results suggest that a significant proportion of patients who respond to brentuximab vedotin can achieve prolonged disease control. The trial was registered at www.clinicaltrials.gov as #NCT00848926.

Re-examining the evidence in radiation dermatitis management literature: an overview and a critical appraisal of systematic reviews.

PURPOSE: To provide an overview and a critical appraisal of systematic reviews (SRs) of published interventions for the prevention/management of radiation dermatitis. METHODS AND MATERIALS: We searched Medline, CINAHL, Embase, and the Cochrane Library. We also manually searched through individual reference lists of potentially eligible articles and a number of key journals in the topic area. Two authors screened all potential articles and included eligible SRs. Two authors critically appraised and extracted key findings from the included reviews using AMSTAR (the measurement tool for "assessment of multiple systematic reviews"). RESULTS: Of 1837 potential titles, 6 SRs were included. A number of interventions have been reported to be potentially beneficial for managing radiation dermatitis. Interventions evaluated in these reviews included skin care advice, steroidal/nonsteroidal topical agents, systemic therapies, modes of radiation delivery, and dressings. However, all the included SRs reported that there is insufficient evidence supporting any single effective intervention. The methodological quality of the included studies varied, and methodological shortfalls in these reviews might create biases to the overall results or recommendations for clinical practice. CONCLUSIONS: An up-to-date high-quality SR in the prevention/management of radiation dermatitis is needed to guide practice and direction for future research. We recommend that clinicians or guideline developers critically evaluate the information of SRs in their decision making.

Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma.

PURPOSE: Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. In phase I studies, brentuximab vedotin demonstrated significant activity with a favorable safety profile in patients with relapsed or refractory CD30-positive lymphomas. PATIENTS AND METHODS: In this multinational, open-label, phase II study, the efficacy and safety of brentuximab vedotin were evaluated in patients with relapsed or refractory Hodgkin's lymphoma (HL) after autologous stem-cell transplantation (auto-SCT). Patients had histologically documented CD30-positive HL by central pathology review. A total of 102 patients were treated with brentuximab vedotin 1.8 mg/kg by intravenous infusion every 3 weeks. In the absence of disease progression or prohibitive toxicity, patients received a maximum of 16 cycles. The primary end point was the overall objective response rate (ORR) determined by an independent radiology review facility. RESULTS: The ORR was 75% with complete remission (CR) in 34% of patients. The median progression-free survival time for all patients was 5.6 months, and the median duration of response for those in CR was 20.5 months. After a median observation time of more than 1.5 years, 31 patients were alive and free of documented progressive disease. The most common treatment-related adverse events were peripheral sensory neuropathy, nausea, fatigue, neutropenia, and diarrhea. CONCLUSION: The ADC brentuximab vedotin was associated with manageable toxicity and induced objective responses in 75% of patients with relapsed or refractory HL after auto-SCT. Durable CRs approaching 2 years were observed, supporting study in earlier lines of therapy.

Early age-related macular degeneration, cognitive function, and dementia: the Cardiovascular Health Study.

OBJECTIVE: To describe the association of cognitive function and dementia with early age-related macular degeneration (AMD) in older individuals. METHODS: This population-based study included 2,088 persons aged 69 to 97 years who participated in the Cardiovascular Health Study. The AMD was assessed from retinal photographs based on a modified Wisconsin AMD grading system. Cognitive function was assessed using the Digit Symbol Substitution Test (DSST) and the Modified Mini-Mental State Examination. Participants were also evaluated for dementia using detailed neuropsychological testing. RESULTS: After controlling for age, sex, race, and study center, persons with low DSST scores (lowest quartile of scores, < or =30) were more likely to have early AMD (odds ratio, 1.38; 95% confidence interval, 1.03-1.85) than were persons with higher DSST scores. In analyses further controlling for education, systolic blood pressure, total cholesterol level, diabetes mellitus, smoking status, and apolipoprotein E genotype, this association was stronger (odds ratio, 2.00; 95% confidence interval, 1.29-3.10). There was no association of low Modified Mini-Mental State Examination scores, dementia, or Alzheimer disease with early AMD. CONCLUSIONS: In this older population, cognitive impairment may share common age-related pathogenesis and risk factors with early AMD.

Apolipoprotein E gene and retinal microvascular signs in older people: the Cardiovascular Health Study.

PURPOSE: To examine the association between apolipoprotein E (APOE) gene polymorphism and retinal microvascular signs in an older population. METHODS: Retinal photographs were taken of 2,152 participants (1,831 whites, and 321 African-Americans), aged 69-96 years, who were participating in a population-based study of four United States communities. We used standardized protocols to assess photographs for the presence of retinal microvascular signs (retinopathy, arterio-venous nicking, and focal arteriolar narrowing) and a computer-assisted method to measure retinal vessel diameters. We analyzed DNA extracted from blood samples of participants for common allelic variants of the APOE gene. RESULTS: After adjusting for age, gender, systolic blood pressure, smoking, total serum cholesterol, and other risk factors, we found white participants carrying the epsilon2 and epsilon4 alleles were more likely to have arterio-venous nicking than the epsilon3/epsilon3 homozygotes, with odds ratio (OR) of 1.70 and confidence interval (CI) 95% (1.03-2.83) for the epsilon2 carriers and OR 1.74 (95% CI 1.06-2.84) for the epsilon4 carriers. Among white participants without hypertension, the associations remained significant for the epsilon4 carriers (OR 2.32, 95% CI 1.18-4.57). Whites, normotensive carriers of the epsilon2 allele had significantly narrower retinal arteriolar diameters (adjusted mean arteriolar diameter of 163.5 mum, 95% CI 160.1-167.0, p=0.03) compared to the epsilon3/epsilon3 homozygotes (167.8 mum, 95% CI 166.0-169.6). APOE gene polymorphism was not associated with retinopathy, focal narrowing, or retinal venular diameters in white participants. There were insufficient numbers of African-Americans for separate multivariate analysis. CONCLUSIONS: This study provides little evidence that the APOE gene polymorphism plays a significant role in the pathogenesis of retinal microvascular changes in the general population. In the older white population, APOE epsilon2 and epsilon4 allele carriers were more likely to have arterio-venous nicking. Other retinal signs, however, were not related to APOE gene polymorphism.