Retreatment Strategies Research Articles

Protecting the Coastline from the Effects of Climate Change: Adaptive Design for the Coastal Areas of Gangneung, Korea

The purpose of this research is to present design strategies to enable coastal areas to adapt to climate change and maintain the coastlines by addressing the environmental and urban issues. Gangneung is a tourist attraction situated on South Korea’s east coast, and there is an urgent need for integrated research on strategies to prevent the loss of sandy beaches and the damage caused by storm surges and high swell. This research has two objectives: The first is to offer an overview and describe the characteristics of exemplary projects carried out to manage the storm damage while maintaining the coastlines. The second is to propose a design model that can be applied to coastal areas susceptible to climate change by analyzing the design strategies and the current conditions of the Gangneung coastal area. In the case of Gangneung, the damage caused by the storm surges and high swells are more severe compared to inundation caused by sea level rise because of the steep slope and deep water. Therefore, adaptive design strategies are mainly focused on accommodation and retreat strategies that consider these characteristics by moving the coastal roads behind the pine forest and raising the coastal buildings to connect the coast to the forest and to prevent coastal erosion. This research has the potential to be used as an exemplary design adaptation for coastal erosion as well as a basis for regulating the land use policy in areas susceptible to flood by establishing guidelines for publicly funded developments, and preparing long-term relocation plans for the existing coastal developments to create a sustainable and resilient future for the coastal areas.

The emerging mysteries of IgG4-related disease

IgG4-related disease (IgG4-RD) is increasingly recognised in Western societies as a multi-system, inflammatory, fibrosing disease of unknown aetiology that typically, though not exclusively, presents in older men. The clinical manifestations are diverse and almost any organ may be affected. The cardinal histological features are a lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis and an abundance of IgG4+ plasma cells in affected organs. Serum IgG4 levels are elevated in approximately 70% of patients and are a useful biomarker when present. IgG4-RD is frequently misdiagnosed as malignancy. Making the correct diagnosis is important as the disease is usually steroid responsive, although relapse rates are high. Second-line immunosuppressive agents and B-cell depletion therapy have also been used in retreatment strategies. Recent data suggests that the disease is associated with both progressive organ failure and malignancy. The biological mechanisms driving IgG4-RD remain unclear but this is currently an area of intense scientific investigation. Broadly, IgG4+ B cells are thought to exhibit a regulatory phenotype, but it is not known if these are pathogenic or simply represent a bystander effect. Extending our understanding of the role of IgG4 immunoglobulins in health and disease, the assessment of B and T cell immune phenotype, and large genetic studies of IgG4-RD may enhance our understanding of disease pathogenesis. Ultimately it may be that there is not a single, simple unifying aetiology and so careful stratification of disease by clinical phenotype will be required in multi-centre prospective clinical cohorts. These cohorts will also be essential for the study of treatment outcomes with novel therapies.

Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: eastern cooperative oncology group protocol e4402.

In low-tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival when compared with observation. It is not known whether MR provides superior long-term disease control compared with re-treatment rituximab (RR) administered on an as-needed basis. E4402 (RESORT) was a randomized clinical trial designed to compare MR against RR. Eligible patients with previously untreated low-tumor burden FL received four doses of rituximab, and responding patients were randomly assigned to either RR or MR. Patients receiving RR were eligible for re-treatment at each disease progression until treatment failure. Patients assigned to MR received a single dose of rituximab every 3 months until treatment failure. The primary end point was time to treatment failure. Secondary end points included time to first cytotoxic therapy, toxicity, and health-related quality of life (HRQOL). A total of 289 patients were randomly assigned to RR or MR. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years for patients receiving RR and 4.3 years for those receiving MR (P = .54). Three-year freedom from cytotoxic therapy was 84% for those receiving RR and 95% for those receiving MR (P = .03). The median number of rituximab doses was four patients receiving RR and 18 for those receiving MR. There was no difference in HRQOL. Grade 3 to 4 toxicities were infrequent in both arms. In low-tumor burden FL, a re-treatment strategy uses less rituximab while providing disease control comparable to that achieved with a maintenance strategy.

Factors influencing root canal retreatment strategies by general practitioners and specialists in Australia.

To evaluate the effect of tooth radiographic features on root canal retreatment strategies used by general dental practitioners and dental specialists in Australia. A descriptive survey study comprising a web-based questionnaire was sent to general dental practitioners and specialists. The questionnaire diagrammatically represented six different clinical scenarios with variables including type of coronal restoration, quality of root filling and the size and presence of a periapical radiolucency. Treatment options included no treatment, orthograde retreatment, periapical surgery and replacement with an implant. For each of the six scenarios, the participant was asked to select a minimum size cut-off point where treatment would be initiated and also indicate the preferred treatment option. A total of 639 questionnaires were submitted online. In teeth without a cast core restoration, the quality of root filling influenced the selection of no treatment as an option (P < 0.001). The presence of a cast post/core restoration influenced both the treatment cut-off point and treatment option, with more practitioners selecting larger lesions as cut-off points (P < 0.001) and more treatment options involving both implant placement (P < 0.001) and periapical surgery (P < 0.001). With more complex treatment planning (i.e. cast post/core restorations and inadequate root filling), general practitioners proposed implant placement more readily compared with specialists (P < 0.001). General practitioners and specialists vary their root canal retreatment strategies according to quality of root filling and type of coronal restoration. Whilst all clinical scenarios could be managed by contemporary endodontic techniques, teeth were still treatment planned for extraction and replacement with an implant. This may be due to the fact that implants are heavily marketed by the dental industry and with more stringent outcome criteria applied to the assessment of root canal treatment compared with implant placement, evidence-based decision-making may be distorted. Future emphasis should be placed on changing practitioners' attitudes towards the retention of salvageable teeth by contemporary endodontic measures.

Re-Treatment with EGFR-TKIs in NSCLC Patients Who Developed Acquired Resistance.

In the era of personalized medicine, epidermal growth factor receptor (EGFR) inhibition with tyrosine kinase inhibitor (TKI) has been a mainstay of treatment for non-small cell lung cancer (NSCLC) patients with an EGFR mutation. Acquired resistance, especially substitution of methionine for threonine at position 790 (T790M), which has accounted for more than half of the cases, developed inevitably in patients who were previously treated with EGFR-TKI. At present, there is no standard treatment for patients who have developed a resistance to EGFR-TKI. Several strategies have been developed or suggested to treat such patients. This article aimsto review the EGFR-TKI re-treatment strategy and the efficacy of different generations of EGFR-TKIs in patients with acquired resistance to prior EGFR-TKI.

FRI0328 Fixed versus On-Flare Retreatment with Rituximab in RA – Results from the Cererra Collaboration

BackgroundThe data on how to optimally retreat patients with RA with rituximab (RTX) have been limited so far.ObjectivesThe aim of this analysis was to compare two common retreatment strategies: A...

Erratum: Monthly OCT monitoring of Ozurdex for macular oedema related to retinal vascular diseases: re-treatment strategy (OCTOME Report 1)

Erratum: Monthly OCT monitoring of Ozurdex for macular oedema related to retinal vascular diseases: re-treatment strategy (OCTOME Report 1)

OP0231 Repeat Cycles on Clinical Relapse for Remission Maintenance in Anca-Associated Vasculitis: Identifying B Cell Biomarkers to Guide Re-Treatment Strategy

BackgroundFollowing remission induction with rituximab (RTX) in ANCA-associated vasculitis (AAV), duration of response is highly variable [1,2]. Repeat cycles may be fixed-interval or on clinical relapse. The former may lead...

When Retreat is the Best Option: Flood Insurance after Biggert-Waters and Other Climate Change Puzzles

Commentators argue, with good reason, that flood risk polices are soft on retreat. We Americans are more interested in fortifying our castles or building them higher than in moving out of harm’s way. And that is despite warnings of rising seas and stronger storms associated with climate change. But the impulse to stay put may be eroding. In particular, the practices and policies of the Federal Emergency Management Agency (FEMA) are gradually encouraging retreat over other alternatives. As one example, FEMA’s current Mitigation Best Practice Database, the agency’s new National Disaster Recovery Framework (NDRF), now contemplates retreat mechanisms. For a while, Congress, too, beat the drums of retreat. The Biggert-Waters Insurance Reform Act of 2012 (BW-12), promised to remove important insurance subsidies for flood-prone homes, forcing some residents to consider relocation as a cost-saving option. Two years later, in response to public backlash, Congress repealed the law’s strongest retreat-based incentives. Congress is expected to reform the insurance program once again by 2017.In this article, we consider retreat as a strategy of hazard-risk reduction, with reference to the developments in FEMA practice and legislation listed above. As the effects of climate increase the risks of floods and other extreme events, we also see FEMA’s evolving retreat strategies as an important part of the nation’s climate adaptation efforts. Unfortunately, initiatives like the new NDRF and Congress’s insurance reforms are developing piecemeal, with blind spots large enough to drive a tornado through. We believe that policy makers would do better to have a set of principles to guide them when considering and implementing strategies that are intended or will have the effect of encouraging retreat. In particular, we think that Congress could have avoided the embarrassing failure of BW-12 if lawmakers had more fully recognized the complex issues at stake in retreat-based policies. One aim of our analysis is to suggest what a successful reform of the NFIP might look like, setting the foundation for more detailed conversations about flood insurance as the 2017 deadline approaches.

Monthly OCT monitoring of Ozurdex for macular oedema related to retinal vascular diseases: re-treatment strategy (OCTOME Report 1)

To evaluate the morphological and functional changes following intravitreal Ozurdex (dexamethasone implant) injections in patients with macular oedema (MO) secondary to retinal vascular diseases. This is a single centre, exploratory phase III, prospective, open-label clinical study. Thirty patients with MO secondary to retinal vascular disorders underwent assessments for best corrected visual acuity, contrast sensitivity, microperimetry, chromatic sensitivity, macular thickness, and morphology using spectral domain optical coherence tomography (SD-OCT) and fluorescein angiography at baseline. They were treated with intravitreal Ozurdex at baseline and monitored monthly with visual acuity and SD-OCT assessments up to 36 weeks. Re-treatment was permitted from 16 to 24 weeks according to pre-defined criteria. All visual function tests were repeated at 24 weeks. The mean change in central sub-field thickness (CST) from baseline was significant at all visits up to 32 weeks. The lowest mean CST was recorded at 8 weeks and the highest mean ETDRS score was achieved at 12 weeks. All visual functions except contrast sensitivity improved significantly by 24 weeks. The study showed that the ideal re-treatment time point based on functional and structural outcomes and known side-effects of Ozurdex treatment is at 20 weeks. Ozurdex therapy has a rapid and dramatic effect on the macula for about 8 weeks followed by a sustained modest effect up to week 32. The optimal re-treatment time point is at 20 weeks.

Repeatability of retinal thickness and volume metrics in neovascular age-related macular degeneration using the Topcon 3DOCT-1000.

Introduction:Optical coherence tomography (OCT) is a commonly used imaging modality that provides detailed cross-sectional retinal images. This has revolutionised management of neovascular age-related macular degeneration. The need for repeated anti-vascular endothelial growth factor injections has led to therapy being delivered using OCT-guided retreatment strategies with both qualitative OCT features of disease activity (e.g. macular fluid) and changes in retinal thickness as triggers for retreatment The purpose of this study is to determine the intra-session repeatability of retinal thickness and volume measurements using the Topcon 3DOCT-1000 spectral-domain optical coherence tomography (SDOCT) device in patients with neovascular age-related macular degeneration (nAMD). This is the largest study to date looking specifically at the Topcon 3DOCT-1000.Materials and Methods:Two SDOCT raster scans were performed by the same blinded observer in the same sitting in consecutive patients attending for nAMD treatment as part of standard validation of a new device. Retrospective analysis was undertaken, with retinal thickness and volume measurements automatically calculated by the onboard software for each Early Treatment of Diabetic Retinopathy Study subfield for each scan. Bland-Altman methods of analysis were used to assess repeatability.Results:Data from the 73 patients were analyzed with a mean age of 78 years (standard deviation 8). The 95% coefficient of repeatability (CR) was 64 μm and 0.050 mm3 for retinal thickness and volume respectively in the central 1 mm macular subfield. The CR did not exceed 85 μm (0.30 mm3) in any subfield. The revised CR for retinal thickness and volume for the subgroup of 37 patients with no segmentation error in the central 1 mm subfield was 53 μm and 0.050 mm3 respectively.Discussion:We report relatively modest intra-sessional repeatability of SDOCT retinal thickness and volume metrics in patients with nAMD in a clinical setting. Though useful in detecting clinical change from measurement variability in clinical practice, these results suggest the precision of macular thickness measurement does not approach the theoretical resolution of SDOCT.

Sustainable tourism, climate change and sea level rise adaptation policies in Barbados

AbstractThe vulnerability of tourism‐dependent communities, coastal tourism facilities, and beaches to climate change demands the use of measures that can urgently minimise vulnerability and in the long term achieve sustainable development. This paper makes policy recommendations to address climate change and sea level rise challenges in small island developing states. Using Barbados as a case study, the paper found that innovations in policies and projects have offset the past ills of mass tourism and fortuitously now serve as pre‐emptive measures in adapting to climate change. The array of methods for combating these changes includes physical planning policies, integrated coastal zone management, and infrastructure projects. Among the key areas for policy innovation are the adoption of protection, accommodation, and retreat strategies, which are informed by rigorous cost‐benefit analysis and stakeholder consultation. Ecosystem‐based adaptation to climate change is also necessary, especially for islands where coral reef protection is urgent. Moreover, policy adjustments are required on building construction, water resources management, sewage treatment, coastal zone management, physical planning, and land management. Institutional constraints, including the lack of capacity to implement, monitor, and enforce measures, must also be addressed if progress is to be made in adapting to climate change. A major conclusion is that the severity of coastal damage, the importance of tourism to sustainable development, and the country's adaptive capacity play a key part in the selection and implementation of climate change adaptation measures.

PGI32 - Comparative Economic Analysis of Retreatment Strategies for HCV Genotype 1 Patients in Russia

PGI32 - Comparative Economic Analysis of Retreatment Strategies for HCV Genotype 1 Patients in Russia

Asset anchoring as a constraint to sea level rise adaptation

It can be argued that there is presently a disparity between the theory of coastal climate change adaptation and the large-scale or mass implementation with respect to adaptation to sea level rise. From a theoretical perspective, rising sea levels will effectively move the coastline landward and hence the most seaward parts of the built environment, which often feature the highest physical asset value and intensity and hence economic density, will become inundated more often and therefore perhaps need to be relocated landward under the guidance of planned retreat policies. By contrast, evidence of active large-scale planned retreat policies being developed and implemented is sparse, and often being rejected in favour of coastal protection strategies. It is argued here that this lack of uptake of coastal retreat strategies is partially a result of a phenomena coined here as ‘asset anchoring’ where major community infrastructure acts to anchor seaside communities in place and inhibit the implementation of coastal retreat strategies.

The ART-strategy: Sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE

Recently, we developed the ART score (assessment for re-treatment with TACE) to guide the decision for a second transarterial chemoembolization (TACE-2) in patients with hepatocellular carcinoma (HCC). Patients with an ART score of 0-1.5 points gained benefit from a second TACE session, while patients with an ART score ≥2.5 points did not. Here, we investigated (1) the prognostic significance of the ART score prior to the third (TACE-3) and fourth TACE (TACE-4), and (2) the feasibility of an ART score guided re-treatment strategy by sequential assessment of the ART score in HCC patients treated with multiple TACE sessions. 109 patients, diagnosed with intermediate stage HCC and treated with ≥3 TACE sessions between January 1999 and December 2009 at the Medical Universities of Vienna and Innsbruck, were included. The ART score prior to each TACE session was assessed in comparison to the TACE naïve liver. The prognostic performance of the ART score before TACE-3 and 4 was evaluated with and without stratification based on the ART score prior to the respective last intervention. The pre-TACE-3 ART score discriminated two groups with different prognosis and remained a valid predictor of OS independent of Child-Pugh score (5-7 points), CRP-levels and tumor characteristics. Even in patients with an initially beneficial ART score (0-1.5 points) before TACE-2, repeated ART score assessment before TACE-3 identified a subgroup of patients with dismal prognosis (median OS: 27.8 vs. 10.8 months, p<0.001). Similar results were observed when the ART score was applied before TACE-4. The sequential assessment of the ART score identifies patients with dismal prognosis prior to each TACE session.

Re-treatment with Highly Purified nIFNα in Mexican Nonresponder Patients with Chronic Genotype 1 Hepatitis C

We undertook this study to evaluate the virological response to and presence of adverse events to natural interferon α (nIFNα; Multiferon®) treatment in previously nonresponsive Mexican patients chronically infected with genotype 1 hepatitis C. Thirty-nine patients received a 4-week induction of 5 days/week of 6 MU nIFNα plus weight-based ribavirin followed by 3 MU of nIFNα three times a week for 44 weeks. The relationship between viral response and incidence of adverse events was analyzed. Early viral response (EVR) was age- and sex-dependent, with older male patients being less responsive. Sustained viral response (SVR) was evaluated according to: a) intention to treat analysis, b) 48-week treatment and 24-week follow-up (16 patients), and c) patients with EVR (11 patients). None of the factors was significantly different in groups a) and b); however, in group c) there was a better response with a marked viral load decline in younger patients and in patients aged 50 years and older. Five of 39 (13%) patients who completed treatment presented with an SVR. The most common adverse effect was asthenia in 27% of patients. nIFNα could be a useful strategy for re-treatment in chronic hepatitis C, genotype 1, in previously nonresponsive patients. Confirmation of these data in a larger population is required.

B-cell-targeted therapies in systemic lupus erythematosus and ANCA-associated vasculitis: current progress

B cells play a central role in the pathogenesis of systemic lupus erythematosus and anti-neutrophil cytoplasmic antibody-associated vasculitis. There are various strategies for targeting B cells including depletion, inhibition of survival factors, activation and inhibition of co-stimulatory molecules. Controlled trials in systemic lupus erythematosus have shown positive results for belimumab, promising results for epratuzumab and negative results for rituximab. The failure of rituximab in controlled trials has been attributed to trial design, sample size and outcome measures rather than true inefficacy. In anti-neutrophil cytoplasmic antibody-associated vasculitis, rituximab is effective for remission induction and in relapsing disease. However, the optimal long-term re-treatment strategy remains to be determined. Over the next 5 years, evidence will be available regarding the clinical efficacy of these novel therapies, biomarkers and their long-term safety.

A risk model to describe the behaviours of actors in the houses falling into the sea problem

The long-term solution to managing the impacts of sea-level rise is through the development and application of planning provisions and public policy, especially with regards to new developments in the coastal zone. By contrast, imposing new planning provisions, such as enforced retreat strategies, on legacy or existing private assets that are exposed to erosion and sea-level rise will impact on private property rights. In many cases this will incentivise rights-holders to pursue alternative recourse pathways. It is argued here that the behaviour of the key actors in this legacy assets problem are not well described in the models commonly proposed in the literature, and a new risk-based model framework is proposed that better explains the observed behaviours.

Mo1358 Occurrence of Stricturing and Penetrating Complications Is Diminished in Crohn's Disease Patients Treated by Immunomodulatory and/or Anti-TNF Therapy Within the First Two Years of Disease Duration When Corrected for Diagnostic Delay

perianal (n = 18) and other fistulating disease (n = 3). The median duration of anti-TNF therapy was 18 months (range 12 78). 62 patients (87.3%) continued on immunomodulator therapy following anti-TNF withdrawal. Relapse rates after 90 days, 180 days and 365 days were 3/71 (4.2%), 5/67 (7.5%), 12/56 (21.4%) respectively. Of those with perianal disease, the relapse rate was 6/18 (33%) at 365 days. All 6 patients who had dose escalation in the 6 months before withdrawal relapsed. Twenty-five relapsed patients were retreated with anti-TNF agents (9 ADA; 16 IFX), with a response rate of 80% when retreated with same agent as had been withdrawn. 5 patients where IFX was withdrawn responded when retreated with ADA. The overall recapture of response with use of either agent was 84%. Assessment practice changed after NICE guidance was issued in May 2010; before this 6 of 15 (40%) patients stopping anti-TNF therapy had clinical assessment alone. Only 3 of 56 patients (5.3%) were assessed after that date by clinical assessment alone. Conclusions: Relapse rates following withdrawal of antiTNF therapy are lower than previously reported, with a high response rate on retreatment. Patients requiring dose escalation in the 6 months prior to withdrawal may be at higher risk of relapse. We have demonstrated increased endoscopic and radiological assessment prior to withdrawal of anti-TNF therapy. Prospective evaluation of a withdrawal and retreatment strategy for anti-TNF treatment in a larger cohort of Crohn’s patients is required.

Visual Performance in Patients with Neovascular Age-Related Macular Degeneration Undergoing Treatment with Intravitreal Ranibizumab

Purpose. To assess visual function and its response to serial intravitreal ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (nv-AMD). Methods. Forty-seven eyes of 47 patients with nv-AMD, and corrected distance visual acuity (CDVA) logMAR 0.7 or better, undergoing intravitreal injections of ranibizumab, were enrolled into this prospective study. Visual function was assessed using a range of psychophysical tests, while mean foveal thickness (MFT) was determined by optical coherence tomography (OCT). Results. Group mean (±sd) MFT reduced significantly from baseline (233 (±59)) to exit (205 (±40)) (P = 0.001). CDVA exhibited no change between baseline and exit visits (P = 0.48 and P = 0.31, resp.). Measures of visual function that did exhibit statistically significant improvements (P < 0.05 for all) included reading acuity, reading speed, mesopic and photopic contrast sensitivity (CS), mesopic and photopic glare disability (GD), and retinotopic ocular sensitivity (ROS) at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal ranibizumab injections exhibit improvements in many parameters of visual function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not only be considered in the design of studies investigating nv-AMD, but also in treatment and retreatment strategies for patients with the condition.