Impact Of Different Treatment Strategies Research Articles

Analysis of the treatment and prognosis of 266 cases of extranodal natural killer/T-cell lymphoma, nasal type in a single medical center.

To assess the impact of different treatment strategies and risk factors on the prognosis of patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL) in a single medical center. The clinical features of 266 patients with ENKTL were retrospectively analyzed, among whom those in stages I and II received sandwich therapy, while those in stages III and IV underwent chemotherapy plus autologous hematopoietic stem cell transplantation. The Kaplan-Meier curves, univariate and multivariate Cox regression analyses were employed for survival and prognosis analysis. Statistical significance was set at P<0.05. Following treatment, the post-intervention outcomes demonstrated a complete remission (CR) rate of 71.05% and a partial remission (PR) rate of 3.76%. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 70.4% and 70.9%, respectively. In addition, the PFS for patients in stage I/II was 79.8%, with an OS of 81.1%, whereas for those in stage III/IV, the PFS was 41.7% and the OS was 40.9%. Notably, the achievement of CR immediately after treatment was an independent prognostic factor (P<0.001). Patients in stage I/II depicted a favorable 5-year OS rate, while those in stage III/IV manifested a less favorable prognosis. Stages of the disease and whether CR was achieved following treatment are important factors determining the survival and prognosis of patients with ENKTL. Further researches focusing on disease onset and mechanisms of drug resistance will contribute to better management of ENKTL.

Analysis of risk factors for post-operative recurrence or progression of intravenous leiomyomatosis

ObjectiveTo analyse the risk factors for post-operative recurrence or progression of intravenous leiomyomatosis and explore the impact of different treatment strategies on patient prognosis.MethodsPatients with intravenous leiomyomatosis who underwent surgery...

Management of Postthyroidectomy Hypoparathyroidism and Its Effect on Hypocalcemia-Related Complications: A Meta-Analysis.

The aim of this Meta-analysis is to evaluate the impact of different treatment strategies for early postoperative hypoparathyroidism on hypocalcemia-related complications and long-term hypoparathyroidism. Embase.com, MEDLINE, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and the top 100 references of Google Scholar were searched to September 20, 2022. Articles reporting on adult patients who underwent total thyroidectomy which specified a treatment strategy for postthyroidectomy hypoparathyroidism were included. Random effect models were applied to obtain pooled proportions and 95% confidence intervals. Primary outcome was the occurrence of major hypocalcemia-related complications. Secondary outcome was long-term hypoparathyroidism. Sixty-six studies comprising 67 treatment protocols and 51,096 patients were included in this Meta-analysis. In 8 protocols (3806 patients), routine calcium and/or active vitamin D medication was given to all patients directly after thyroidectomy. In 49 protocols (44,012 patients), calcium and/or active vitamin D medication was only given to patients with biochemically proven postthyroidectomy hypoparathyroidism. In 10 protocols (3278 patients), calcium and/or active vitamin D supplementation was only initiated in case of clinical symptoms of hypocalcemia. No patient had a major complication due to postoperative hypocalcemia. The pooled proportion of long-term hypoparathyroidism was 2.4% (95% confidence interval, 1.9-3.0). There was no significant difference in the incidence of long-term hypoparathyroidism between the 3 supplementation groups. All treatment strategies for postoperative hypocalcemia prevent major complications of hypocalcemia. The early postoperative treatment protocol for postthyroidectomy hypoparathyroidism does not seem to influence recovery of parathyroid function in the long term.

Thrombus architecture is influenced by the antiplatelet loading treatment in patients with acute myocardial infarction

BackgroundIntracoronary thrombus formation is a main cause of acute myocardial infarction triggered by platelet activation. However, there are no data on the impact of different treatment strategies with antiplatelet agents before percutaneous coronary intervention (PCI) on histological characteristics of thrombus formation. ObjectiveIn this study, we investigate the impact of preinterventional administration of the P2Y12-inhibitors clopidogrel and prasugrel on thrombus composition, highlighting significant changes associated with the antiplatelet pre-treatment. MethodsWe prospectively enrolled 104 consecutive patients with ST-segment elevation myocardial infarction (STEMI) undergoing immediate PCI and thrombus aspiration by immunohistochemical staining along with RNA-sequencing employing Nanostring analysis. Fifty-two patients were treated with either prasugrel loading (60 mg) or clopidogrel loading (600 mg) prior to PCI, respectively. ResultsIn Patients with STEMI, intracoronary thrombus architecture was significantly altered between patients pre-treated with prasugrel when compared to clopidogrel. Fibrin content of thrombi was significantly decreased (41.8 % versus 66.7 %, p = 0.009) after pre-treatment with prasugrel compared to clopidogrel. Furthermore, levels of MPO positive cells in intracoronary thrombi were significantly decreased in patients with prasugrel pre-treatment (90.5 versus 201.1, p = 0.014) indicating an association of antiplatelet pre-treatment and the inflammatory responses during thrombus formation. Most strikingly, we observed significant differences among both pre-treatment groups regarding altered RNA expression and signaling pathways of thrombo-inflammatory processes within the thrombotic material, which were independently associated with antiplatelet strategies. ConclusionsOur study elucidates the impact of antiplatelet pre-treatment on thrombus remodeling and architecture, thereby lowering the risk of recurrent adverse cardiovascular events in prasugrel-treated patients.

P809 The impact of different treatment strategies in newly diagnosed patients with Crohn’s Disease: a multicentre study

Abstract Background The early use of effective therapy may change outcomes in patients with Crohn’s disease (CD). The aim of this study was to compare three different treatment strategies in CD (“top-down”, “accelerated step-up” and “regular step-up” therapy). Methods This was a retrospective multicentre study including patients with incident CD between 2009-2021. Patients were categorized into 3 treatment groups: group 1) “top-down”: anti-TNF ± immunomodulator (IM) within the first year of diagnosis with a maximum interval of 6 months between both drugs; group 2) “accelerated step-up”: IM within the first year of diagnosis followed by anti-TNF 6-12 months later, and group 3) “regular step-up”: IM within the first year of diagnosis with or without the need to further escalate to biologic (&amp;gt;12 months after the beginning of IM). The primary outcome was endoscopic healing (EH; SES-CD&amp;lt;3 and no ulcers) at the end of the follow-up; secondary outcomes were CD-related intestinal resection and hospitalization due to CD-flare. Cox regression analysis was performed and Kaplan-Meier curves were computed for each outcome. Results 156 patients (54% males) were included, with 46% having ileocolonic disease (L3) and 68% an inflammatory phenotype (B1) at diagnosis. Baseline patients’ characteristics in each different treatment strategy are demonstrated in Table 1. Patients were followed for a median of 69 (44-98) months; 12% in group 1 and 19% in group 2 had to switch biologicals (p=0.4); 64% in group 3 escalated to biologicals with a median time since diagnosis of 30 (20-50) months. In group 1, 73% of the patients used concomitant IM. At the end of follow-up, 50% of all patients achieved EH, 20% needed hospitalization and 13% had a CD-related intestinal resection. In a multivariate model adjusted for gender, age at diagnosis, disease location, disease behaviour, perianal disease, and prior surgery, patients in group 3 had a lower probability of achieving EH when compared with patients in group 1 (HR 0.7, 95%CI 0.5-0.96, p=0.02) and group 2 (HR 0.3, 95%CI 0.1-0.8, p=0.01). Kaplan-Meier curves are demonstrated in Figure 1. Using the same model, no differences were found in terms of hospitalization or need for intestinal surgery. Fistulizing disease was a significant predictor for intestinal surgery (HR 2.4, 95%CI 1.5-3.8, p&amp;lt;0.01). Conclusion Introduction of biological therapy within the first two years of diagnosis, either in a “top-down” or “accelerated step-up” approach was associated with a higher probability of achieving EH, as compared to the introduction of an immunomodulator followed by a later introduction of biologic. No differences were found for hospitalization or intestinal surgery. Fistulizing disease was a significant predictor for surgical intervention.

P23 Bayesian Calibration of a Simulation Model of Opioid Use Disorder

Simulation models of opioid use disorder (OUD) evaluate the impact of different treatment strategies on population-level outcomes. Researching Effective Strategies to Prevent Opioid Death (RESPOND) is a dynamic population, state-transition model that simulates the Massachusetts OUD population synthesizing data from multiple sources. Structural complexity and scarcity of available data for opioid modeling pose a special challenge to model calibration. We propose a two-step approach for calibrating RESPOND to OUD outcomes: a naïve empirical calibration (EC) to inform priors of a more rigorous Bayesian calibration method.

Cerebral venous sinus thrombosis in the setting of COVID-19 vaccination: a systematic review and meta-analysis.

Background and PurposeCerebral venous sinus thrombosis (CVST) has been reported as a rare adverse event in association with thrombosis-thrombocytopenia syndrome (TTS) following COVID-19 vaccination.Methods We performed a systematic review and meta-analysis of investigator-initiated registries including confirmed CVST cases, with the aim to calculate (1) the odds ratio of TTS–CVST versus non-TTS–CVST after vector-based vaccines and (2) after non-vector-based vaccines, (3) the in-hospital mortality ratio of TTS–CVST compared to non-TTS–CVST; and (4) the dependency or death at discharge among TTS–CVST compared to non-TTS–CVST cases.ResultsTwo eligible studies were included in the meta-analysis, comprising a total of 211 patients with CVST associated with COVID-19 vaccination. Vector-based COVID-19 vaccination was associated with a higher likelihood of TTS-associated CVST than with non-TTS–CVST (OR: 52.34, 95% CI 9.58–285.98). TTS–CVST was also associated with higher likelihood of in-hospital mortality (OR: 13.29; 95% CI 3.96–44.60) and death or dependency at discharge compared to non-TTS–CVST (OR: 6.70; 95% CI 3.15–14.26). TTS–CVST was recorded with a shorter interval between vaccination and symptom onset [Mean Difference (MD):-6.54 days; 95% CI − 12.64 to − 0.45], affecting younger patients (MD:-9.00 years; 95% CI − 14.02 to − 3.99) without risk factors for thromboses (OR:2.34; 95% CI 1.26–4.33), and was complicated more frequently with intracerebral hemorrhage (OR:3.60; 95% CI 1.31–9.87) and concomitant thromboses in other sites (OR:11.85; 95% CI 3.51–39.98) compared to non-TTS–CVST cases.ConclusionsTTS–CVST following COVID-19 vaccination has distinct risk factor profile, clinical phenotype and prognosis compared to non-TTS–CVST. Further epidemiological data are required to evaluate the impact of different treatment strategies on outcome of TTS–CVST cases following COVID-19 vaccination.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00415-022-11101-2.

A Multi-Institutional Retrospective Analysis of T-Cell Lymphomas with Central Nervous System Relapse

A Multi-Institutional Retrospective Analysis of T-Cell Lymphomas with Central Nervous System Relapse

Tasas de colectomía en colitis ulcerosa 15 años después del diagnóstico. Datos de la cohorte Navarra 2001-2003

IntroductionKnowing the natural history of ulcerative colitis (UC) is essential to understand the course of the disease, assess the impact of different treatment strategies and identify poor prognostic factors. One of the most significant matters in this regard is the need for surgery. ObjectivesTo analyse the Colectomy Incidence Rate (CIR) from diagnosis to end of follow-up (31/12/2017) and identify predictive factors for colectomy. Material and methodsA retrospective study enrolling patients with a definitive diagnosis (DD) of UC or Unclassified Colitis (UnC) in the 2001-03 Navarra cohort. ResultsWe enrolled 174 patients with a DD of UC (E2 42.8%; E3 26.6%) and 5 patients with a DD of UnC: 44.1% women, median age 39.2 years (range 7-88) and median follow-up 15.7 years. A total of 8 patients underwent surgery (CIR 3 colectomies/103 patient-years: 3 at initial diagnosis (<1 month), 2 in the first 2 years, 2 at 5 years from diagnosis and 1 at 12 years from diagnosis. All had previously received steroids; 5 had received immunomodulators and 2 had received biologics. In 7 patients (87%), surgery was performed on an emergency basis. The indication was megacolon in 3 (37.5%), severe flare-up in 3 (37.5%) and medical treatment failure in 2 (25%). In 5 cases (62.5%), an ileoanal pouch was made, and in 3 cases, a definitive ileostomy was performed. In the univariate analysis, patients with loss of more than 5 kg at diagnosis and admission at diagnosis had a lower rate of colectomy-free survival. ConclusionsIn our series, colectomy rates are lower than usually reported. Most colectomies were performed in the first 5 years following diagnosis and had an emergency indication.

The strategy and efficacy of prophylaxis against hepatitis B virus recurrence after liver transplantation for HBV-related diseases in the era of potent nucleos(t)ide analogues: A meta-analysis.

This meta-analysis aimed to evaluate the clinical outcome of liver transplant (LT) recipients under potent nucleoside or nucleotide analogue (NA)-based regimens and investigate different prophylactic schemes. We followed PRISMA statement to conduct this study. Two reviewers independently searched relevant literature via PubMed, Embase, Ovid MEDLINE, Web of Science and Insightmeme. Studies were included if they evaluated hepatitis B virus (HBV) recurrence under potent NA-based regimens in patients who received HBV-related LT. Primary and secondary outcomes were HBV recurrence, hepatocellular carcinoma (HCC) recurrence, all-cause and HBV recurrence-related mortality. Incidences with 95% confidence intervals were calculated and assessed by fixed and random effects models. Subgroup analyses were used to examine the impact of different treatment strategies. Altogether 25 studies (N = 2327) were included, with a pooled HBV recurrence rate of 1.01% (95% CI 0.53%-1.59%). HBV viremia or hepatitis D virus superinfection did not influence HBV recurrence significantly (P = 0.23 and 0.71, respectively). The recurrence rate under an indefinite combination of potent NA and hepatitis B immunoglobulin (HBIG) was lower than that under potent NA monotherapy (P = 0.000) and similar to that under NA plus a finite course of HBIG (P = 0.48). The pooled HCC recurrence rate was 5.34% (95% CI 0.78%-12.48%). HBV recurrence-related mortality and all-cause mortality were 0% and 6.95% (95% CI 4.30%-10.08%), respectively. Potent NA-based regimens provide satisfactory HBV antiviral prophylaxis and improve long-term outcomes for LT recipients. A finite combination of potent NA and HBIG is an alternative to life-long dual therapy.

Managing HIV-associated inflammation and ageing in the era of modern ART.

This paper aims to address the concerns around ongoing immune activation, inflammation, and resistance in those ageing with HIV that represent current challenges for clinicians. Presentations at a symposium addressing issues of ageing with HIV infection were reviewed and synthesised. The changing natural history and demographics of human immunodeficiency virus (HIV)-infected individuals means new challenges in contemporary management. In the early years of the epidemic,management was focussed on acute, potentially life-threatening AIDS-related complications. From initial monotherapy with first-generation antiretroviral therapy (ART), the development of combination highly active ART (HAART) allowed HIV control but ART toxicities, treatment adherence and drug resistance emerged as major issues. Today, the availability of potent and tolerable ART has made viral suppression achievable in most people living with HIV (PLHIV), and clinicians are confronted with managing a chronic condition among an ageing population. The combination of diseases of ageing and the co-morbidities associated with HIV-infection, even when well controlled, results in a complex set of challenges for many older PLHIV. There is a growing appreciation that many non-AIDS-related co-morbidities are caused, at least in part, by persistent, low-grade immune activation, inflammation, and hypercoagulability, despite suppressive ART. In order to further improve HIV management, it is important to understand the enduring effects of chronically suppressed HIV infection, the potential contribution of these factors to the ageing process, the possibility of drug resistance, and the impact of different treatment strategies, including early ART initiation.

Retrospectively acquired cohort study to evaluate the long-term impact of two different treatment strategies on disability outcomes in patients with relapsing multiple sclerosis (RE.LO.DI.MS): data from the Italian MS Register.

The increase in disease-modifying drugs (DMDs) allows individualization of treatment in relapsing multiple sclerosis (RMS); however, the long-term impact of different treatment sequences is not well established. This is particularly relevant for MS patients who may need to postpone more aggressive DMD strategies. To evaluate different therapeutic strategies and their long-term outcomes, measured as relapses and confirmed disability progression (CDP), in MS 'real-world' settings. Multicentre, observational, retrospectively acquired cohort study evaluating the long-term impact of different treatment strategies on disability outcomes in patients with RMS in the Italian MS Register. We evaluated 1152 RMS-naïve patients after propensity-score adjustment. Patients included were receiving: interferon beta-1a (IFN-β1a) 44µg switching to fingolimod (FTY; IFN-switchers; n = 97); FTY only (FTY-stayers; n = 157); IFN-β1a only (IFN-stayers; n = 849). CDP and relapses did not differ between FTY-stayers and IFN-switchers [HR (95% CI) 0.99 (0.48-2.04), p = 0.98 and 0.81 (0.42-1.58), p = 0.55, respectively]. However, IFN-stayers showed increased risk of relapses compared with FTY-stayers [HR (95% CI) 1.46 (1.00-2.12), p = 0.05]. The ideal treatment option for MS is becoming increasingly complex, with the need to balance benefit and risks. Our results suggest that starting with FTY affects the long-term disease outcome similarly to escalating from IFN-β1a to FTY.

Obstructive sleep apnoea syndrome and endothelial function: potential impact of different treatment strategies-meta-analysis of prospective studies.

Previous studies have shown an association between obstructive sleep apnoea syndrome (OSAS) and cardiovascular events. Whether this association is mediated by an impairment of endothelial function, which is itself a driver of elevated cardiovascular risk, has yet to be clarified, as it is the eventual protective role of several OSAS treatments. The aim of our meta-analysis is to evaluate the effect of various OSAS treatments on endothelial function calculated by means of flow-mediated dilatation (FMD). We conducted a meta-analysis of prospective studies including patients affected by mild to severe OSAS treated with continuous positive airway pressure (CPAP), surgery, oral appliance and medical treatments. FMD was measured before and after treatment RESULTS: After pooling results from different treatment strategies, OSAS treatment showed a positive impact on endothelial function (Mean Difference [MD] = 2.58; 95% CI 1.95-3.20; p < 0.00001). Our study supports the hypothesis that several modalities of treatment for OSAS positively impact endothelial function. Whether this effect also associates with an improvement of clinical outcomes remains to be ascertained.

Do different treatment strategies influence women’s level of psychosexual distress? Observational cohort study of women with premalignant HPV-associated genital lesions

ObjectiveTo examine the impact of different treatment strategies - surgical treatment or watchful waiting- on sexual activity, psychosocial distress, and fear of progression in women with Human Papillomavirus (HPV)-associated premalignant genital lesions. Study designObservational cohort study of women diagnosed with HPV-associated premalignant lesions of the cervix, vagina or vulva. Patients were stratified into two groups depending on the severity of their premalignancy: surgical treatment or watchful waiting. Validated patient administered questionnaires, i.e. Fear of Progression questionnaire (FoP-Q), Cervical Dysplasia Distress Questionnaire (CDDQ), and Sexual Activity Questionnaire (SAQ) were completed after clinical evaluation (baseline), at 6- and 12-months follow-ups. Results209 women treated with surgery (N = 125) were compared with women who were monitored in regular intervals (N = 82). During an observational period of 12 months there were no significant differences in fear of progression, psychosocial distress, and sexual activity (p > 0.05). The level of concerns and anxiety about the future, and fear of progression were present, mostly at baseline. While there was a small increase of tension from visit to visit in both groups, patients generally were able to cope with their clinical situation quite well. ConclusionsFear of progression, psychosocial distress and sexual activity in women with precancerous HPV- associated premalignant genital lesions seem to be independent from type of treatment. Both treatment strategies may be applied without major psychological sequelae, as long as adequate information is provided.

Not type of induction therapy but consolidation with allogeneic hematopoietic cell transplantation determines outcome in older AML patients: A single center experience of 355 consecutive patients

Therapeutic decision making is often challenging in older AML patients. We collected retrospective data of 355 consecutive AML patients (≥60 years) who were treated with intensive chemotherapy (IC) (n = 155), hypomethylating agents (HMA) (n = 83), or best supportive care (BSC) (n = 117) between 2002 and 2017. Overall survival (OS) and response rates after therapy were analyzed. Multivariate Cox regression was performed to analyze the impact of different treatment strategies on survival. The median OS was not significantly different between patients treated with IC or HMA (14.9 vs 10.9 months; HR = 1.32, p = 0.076)), despite a difference in complete remission rate (59% after IC vs 35% after HMA). Patients who received a allogeneic hematopoietic cell transplantation (allo HCT) after treatment with IC or HMA had a significant survival benefit compared to patient who didn’t proceed to allo HCT (median OS 65 vs 8 months, respectively, p < 0.001). The type of induction therapy (i.e. IC or HMA) did not impact on survival after allo HCT (48 vs 65 months, respectively, p = 0.440). In conclusion, consolidation with an allo HCT provides a significant benefit for older AML patients independent of upfront treatment with IC or HMA. Our data suggest that more older patients should be considered for an allo HCT.

Assessing the benefits of five years of different approaches to treatment of urogenital schistosomiasis: A SCORE project in Northern Mozambique.

BackgroundIn Mozambique, schistosomiasis is highly endemic across the whole country. The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) coordinates a five-year study that has been implemented in various African countries, including Mozambique. The overall goal of SCORE was to better understand how to best apply preventive chemotherapy with praziquantel (PZQ) for schistosomiasis control by evaluating the impact of alternative treatment approaches.MethodsThis was a cluster-randomised trial that compared the impact of different treatment strategies in study areas with prevalence among school children of ≥21% S. haematobium infection by urine dipstick. Each village was randomly allocated to one of six possible combinations of community-wide treatment (CWT), school-based treatment (SBT), and/or drug holidays over a period of four years, followed by final data collection in the fifth year. The most intense intervention arm involved four years of CWT, while the least intensive arm involved two years of SBT followed by two consecutive years of PZQ holiday. Each study arm included 25 villages randomly assigned to one of the six treatment arms. The primary outcome of interest was change in prevalence and intensity of S. haematobium among 100 children aged 9-to-12-years that were sampled each year in every village. In addition to children aged 9-to-12 years, 100 children aged 5–8 years in their first-year of school and 50 adults (aged 20–55 years) were tested in the first and final fifth year of the study. Prevalence and intensity of S. haematobium infection was evaluated by two filtrations, each of 10mL, from a single urine specimen.Principal findingsIn total, data was collected from 81,167 individuals across 149 villages in ten districts of Cabo Delgado province, Northern Mozambique. Overall PZQ treatment resulted in a significant reduction in the prevalence of S. haematobium infection from Year 1 to Year 5, where the average prevalence went from 60.5% to 38.8%, across all age groups and treatment arms. The proportion of those heavily infected also reduced from 17.6% to 11.9% over five years. There was a significantly higher likelihood of males being infected than females at baseline, but no significant difference between the sexes in their response to treatment. The only significant response based on a study arm was seen in both the 9-to-12-year-old and first-year cross sections, where two consecutive treatment holidays resulted in a significantly higher final prevalence of S. haematobium than no treatment holidays. When the arms were grouped together, four rounds of treatment (regardless of whether it was CWT or SBT), however, did result in a significantly greater reduction in S. haematobium prevalence than two rounds of treatment (i.e. with two intermittent or consecutive holiday years) over a five-year period.ConclusionsAlthough PC was successful in reducing the burden of active infection, even among those heavily infected, annual CWT did not have a significantly greater impact on disease prevalence or intensity than less intense treatment arms. This may be due to extremely high starting prevalence and intensity in the study area, with frequent exposure to reinfection, or related to challenges in achieving high treatment coverage More frequent treatment had a greater impact on prevalence and intensity of infection when arms were grouped by number of treatments, however, cost efficiency was greater in arms only receiving two treatments. Finally, a significant reduction in prevalence of S. haematobium was seen in adults even in the SBT arms implying the rate of transmission in the community had been decreased, even where only school children have been treated, which has significant logistical and cost-saving implications for a national control programme in justifying CWT.

Cost-effectiveness analysis of use of a polypill versus usual care or best practice for primary prevention in people at high risk of cardiovascular disease

BackgroundClinical trials suggest that use of fixed-dose combination therapy (‘polypills’) can improve adherence to medication and control of risk factors of people at high risk of cardiovascular disease (CVD) compared to usual care, but cost-effectiveness is unknown.ObjectiveTo determine whether a polypill is cost-effective compared to usual care and optimal guideline-recommended treatment for primary prevention in people already on statins and/or blood pressure lowering therapy.MethodsA Markov model was developed to perform a cost-utility analysis with a one year time cycle and a 10 year time horizon to compare the polypill with usual care and optimal implementation of NICE Guidelines, using patient level data from a retrospective cross-sectional study. The model was run for ten age (40 years+) and gender-specific sub-groups on treatment for raised CVD risk with no history of CVD. Published sources were used to estimate impact of different treatment strategies on risk of CVD events.ResultsA polypill strategy was potentially cost-effective compared to other strategies for most sub-groups ranging from dominance to up to £18,811 per QALY depending on patient sub-group. Optimal implementation of guidelines was most cost-effective for women aged 40–49 and men aged 75+. Results were sensitive to polypill cost, and if the annual cost was less than £150, this approach was cost-effective compared to the other strategies.ConclusionsFor most people already on treatment to modify CVD risk, a polypill strategy may be cost-effective compared with optimising treatment as per guidelines or their current care, as long as the polypill cost is sufficiently low.

Impact of treatment and outcomes for patients with posttransplant drug-associated thrombotic microangiopathy.

Drug-induced transplant-associated thrombotic microangiopathy (DTA-TMA) is a rare but serious complication that can occur after hematopoietic cell transplantation (HCT) or solid organ transplantation (SOT) without guidelines for optimal management of this condition. Given the ambiguity surrounding the treatment for DTA-TMA, we conducted a retrospective review to evaluate the impact of different treatment strategies in DTA-TMA patients. Our primary endpoint was to determine the overall response rate (ORR) for DTA-TMA based on the type of treatment modality chosen while secondary endpoints included the time to response, relapse rates, and overall survival for DTA-TMA cases. There were a total of 14 DTA-TMA patients of whom nine were post-HCT and five were post-SOT. Most of the DTA-TMA cases were due to tacrolimus (n = 11) with a minority related to sirolimus (n = 3). A total of nine of 14 patients demonstrated response and five had no response to therapy. The ORR among the DTA-TMA patients after HCT and SOT who received plasma exchange (PLEX) were 25 and 100%, respectively. The ORRs among the patients (includes HCT and SOT) who received rituximab (n = 3) and eculizumab (n = 5) were 67 and 60%, respectively. There were two relapses noted in our study and both were in the HCT group. While discontinuation of the offending agent may be sufficient for treatment of DTA-TMA after HCT, PLEX may be a reasonable option for DTA-TMA after SOT. Although the results are encouraging with rituximab and eculizumab in the treatment of DTA-TMA, larger prospective studies are needed to validate our findings.

Examining progression-free survival in first- and second-line treatment for BRAF-mutant metastatic colorectal cancer (CRC).

728 Background: BRAF mutated (BRAFm) CRC represents ~10% of all CRC and is associated with significantly poorer prognosis. However, responses to chemotherapy do still occur. Some data suggest that the poor prognosis associated with BRAFm CRC is dominated by substantially poorer second line PFS (PFS2), whereas first line PFS (PFS1) was similar for both BRAFm and BRAF wildtype (BRAFwt) CRC. Using a large multicenter dataset, our study aimed to examine PFS1 and PFS2 in BRAFm versus BRAFwt CRC. Methods: Prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) database was interrogated. PFS was calculated and compared in patients with BRAFm versus BRAFwt CRC. Median survival was determined by the Kaplan-Meier method and compared using the log rank test. Results: TRACC identified 523 CRC patients with known BRAF mutation status, who received first-line chemotherapy: 53 (10%) were BRAFm, while 470 (90%) were BRAFwt. At the time of data analysis, only 231 (44%) CRC patients had received second-line chemotherapy, of which 21 (9%) were BRAFm and 210 (91%) were BRAFwt. PFS1 analyses demonstrated significantly poorer survival in the BRAFm population (Median 7.8mo versus 11.5mo, HR 1.72, p = 0.0026). PFS2 analyses revealed similar findings for the BRAFm population, albeit non-significant due to smaller numbers (Median 5.5mo versus 7.7mo, HR1.26, p = 0.44). Conclusions: Our study demonstrated that BRAFm CRC was associated with poorer PFS in both first- and second-line settings. Additional analyses will be performed to examine the impact of different treatment strategies and other clinicopathological features.

Are targeted treatment recommendations in chronic hepatitis C tailored to diagnostic methods of fibrosis?

The progression of chronic HCV infection varies significantly depending on patient characteristics. The goal of the present study was to evaluate the consequences of targeted and universal therapy for HCV-related morbidity-mortality based on the use of non-invasive diagnostic tests in France, Italy and the UK. A country-specific Markov model was used to predict clinical outcomes in patients with chronic HCV mono-infection over 5years. Therapeutic strategies used in the three countries analysed: no treatment, targeted therapy based on stage of fibrosis (F2- or F3-scenario), treatment regardless of stage of fibrosis (universal analysis), base-case analysis and yearly assessments. Universal therapy is the most effective strategy and reduced the 5-year incidence of cirrhosis by 12.0-17.7, liver complications by 4.2-5.3 and liver deaths by 3.7-4.7, vs. no treatment. In base-case analysis, the F2-scenario using FibroScan or patented blood biomarkers reduces the 5-year incidence of cirrhosis by 2.7-4.0, liver complications by 3.5-3.7 and liver deaths by 3.3-3.7, vs. no treatment. The results of the F3-scenario are poor for the incidence of cirrhosis, and moderately effective for the liver complications. The alternative analysis with a yearly assessment of fibrosis improves the impact of targeted therapy. By quantifying the impact of different strategies of targeted therapy and universal therapy, this study could help health agencies and experts to draft therapeutic guidelines for HCV-related fibrosis. The impact of different treatment strategies was evaluated in three countries, France, Italy and UK, using a mathematical model. This analysis showed that: i) A prioritization strategy of HCV treatment for patients with advanced disease would decrease the overall impact of treatment on morbidity and mortality; and ii) A strategy initiating HCV treatment to all would already show a benefit in reducing 5-year morbidity and mortality.