Outcomes In Routine Clinical Practice Research Articles

Intraocular Pressure Changes and Vascular Endothelial Growth Factor Inhibitor Use in Various Retinal Diseases: Long-Term Outcomes in Routine Clinical Practice: Data from the Fight Retinal Blindness! Registry

To report long-term changes in intraocular pressure (IOP) in eyes receiving vascular endothelial growth factor (VEGF) inhibitors for various retinal conditions over 12 and 24 months in routine clinical practice. Retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Treatment-naïve eyes receiving monotherapy with VEGF inhibitors (ranibizumab [0.5 mg], aflibercept [2 mg], or bevacizumab [1 mg]) with at least 3 injections from December 2013 through December 31, 2018, and at least 12 months of follow-up. Intraocular pressure was measured at each clinical visit for all eyes as part of routine practice. The primary outcome was the mean change in IOP (in millimeters of mercury) at 12 months. The following secondary IOP outcome measures were investigated at 12 and 24 months: (1) mean change in IOP from baseline and (2) proportion of clinically significant IOP increase defined as an elevation of at least 6 mmHg to an IOP of more than 21 mmHg at any point during the follow-up. We identified 3429 treatment-naïve eyes (395 receiving bevacizumab, 1138 receiving aflibercept, and 1896 receiving ranibizumab) with complete IOP data from 3032 patients with 12 months of follow-up data, of which 2125 (62%) had 24 months of follow-up data. The overall mean IOP change was -0.5 mmHg (95% confidence interval CI, -0.6 to -0.3 mmHg) at 12 months and -0.4 mmHg (95% CI, -0.6 to -0.3 mmHg) at 24 months, whereas the proportions of clinically significant IOP increases were 5.6% and 8.8%, respectively. A lower mean IOP change and fewer IOP elevations at 12 and 24 months was observed in eyes receiving aflibercept than in those receiving bevacizumab and ranibizumab (P ≤ 0.01 for both comparisons at each time point and outcome). Eyes with pre-existing glaucoma demonstrated more IOP increases over 12 and 24 months (odds ratio [OR], 2.2 [95% CI, 1.2-3.8; P= 0.012] and 2.1 [95% CI, 1.1-3.8; P= 0.025], respectively). Mean IOP did not change significantly from baseline to 12 and 24 months in eyes receiving VEGF inhibitors, whereas clinically significant IOP elevations occurred in a small proportion of eyes. Aflibercept was associated with fewer clinically significant IOP elevations, whereas eyes with pre-existing glaucoma were at a higher risk.

Real-World Treatment Patterns and Outcomes in Patients Receiving Second-Line Therapy for Advanced/Metastatic Esophageal Squamous Cell Carcinoma.

IntroductionCurrently available second-line (2L) therapies for advanced/metastatic esophageal squamous cell carcinoma (adv/met ESCC) include the taxanes paclitaxel and docetaxel. In clinical trials, such therapies have provided only modest improvements in survival. Few studies have assessed outcomes in routine clinical practice in the USA. We compared real-world clinical outcomes in the US for patients receiving taxane or non-taxane 2L therapy for adv/met ESCC.MethodsThe Flatiron Health database was used to identify patients diagnosed with adv/met ESCC (1 January 2011–31 January 2019) who received 2L therapy; index date was date of adv/met diagnosis. Baseline variables and treatment regimens received were identified. Overall survival (OS; 2L start until death or last recorded medical activity) and duration of therapy (DoT; start of 2L therapy until last administration date of 2L therapy) in patients receiving taxane vs. non-taxane-based therapies in the 2L setting were estimated by Kaplan-Meier method.ResultsThere were no clear differences in baseline characteristics between patients who received 2L taxane therapy (n = 37) and 2L non-taxane therapy (n = 49). Median (95% CI) 2L OS was significantly longer with 2L taxanes (7.3 [5.9–11.5] months) vs. 2L non-taxanes (5.1 [2.9–7.6] months); median (95% CI) 2L DoT was 2.1 (1.8–3.0) months vs. 3.3 (2.6–6.7) months, respectively.ConclusionSurvival was generally poor in patients receiving 2L therapy for adv/met ESCC and was longer in patients receiving 2L taxanes than 2L non-taxane therapy. Efficacious, tolerable therapies for ESCC in the 2L setting are urgently needed.Electronic Supplementary MaterialThe online version of this article (10.1007/s12325-020-01394-y) contains supplementary material, which is available to authorized users.

HANNA: Real-world outcomes from an observational study with nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck in Germany.

6532 Background: Nivolumab has demonstrated efficacy in clinical trials of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). As only limited real-world data are available, we describe the use of nivolumab and its outcomes in routine clinical practice. Methods: HANNA is a prospective, observational study of patients with R/M SCCHN treated with nivolumab in 56 hospitals and practices in Germany. In total, 385 patients will be followed for ≤ 5 years from treatment initiation until death, withdrawal of consent, loss of follow-up/record, or end of study. The primary objective is overall survival (OS). Secondary objectives include baseline characteristics, safety profiles, and quality of life (QOL) assessment. Results: By November 2019, data from 311 patients were available. Median follow-up was 3.5 months. Baseline characteristics were male, 81.7%; median age, 63 years; history of smoking, 73.3%; Eastern Cooperative Oncology Group performance status (ECOG PS) 0/1, 60.8%; ECOG PS 2/3, 29.6%. Location of primary tumor was oropharynx, 38.3%; hypopharynx, 20.9%; oral cavity, 22.8%; larynx, 11.6%; others, 6.4%. 55.6% of R/M SCCHN patients progressed ≤ 6 months after platinum-based therapy, whereas 43.4% were platinum-sensitive (progressed > 6 months after platinum-based therapy). Nivolumab was received by 25.1% of patients as first therapy after platinum-based chemo- or radiochemotherapy, by 62.1% as second therapy, and by 12.9% as later line therapy. Median treatment duration was 4.6 months. OS at 1 year was 43.3%. 1-year OS for patients with ECOG PS 0 was 75.9%; ECOG PS 1, 41.2%; and ECOG PS 2, 27.3%. Platinum-sensitive patients had higher 1-year OS probability (51.6%). Drug-related adverse events (grade 1/2) and serious adverse events (grade 3/4) were observed in 28.9% and 10.0% of patients, respectively. Interim QOL data (per FACT-H&N and EQ-5D questionnaire) indicated a tendency toward stabilization or slight improvement. We will present an update of the data with longer follow-up (data cut March 2020). Conclusions: HANNA represents one of the largest real-world datasets for nivolumab in R/M SCCHN and comprises a more diverse set of patients than the phase 3 CheckMate 141 trial, including patients with higher ECOG PS, age, and platinum sensitivity. Outcomes from HANNA show that the improved OS, safety, and QOL seen with nivolumab in the real-world setting are consistent with the outcomes from CheckMate 141. Clinical trial information: NCT03114163 .

Anti-VEGF Treatment of Diabetic Macular Edema: Two-Year Visual Outcomes in Routine Clinical Practice.

Purpose The purpose of this study was to evaluate 2-year visual outcomes in patients with diabetic macular edema (DME) treated with anti-VEGF agents in a routine clinical setting. Methods The medical records of patients treated with ranibizumab or aflibercept due to DME at the Eye Hospital, University Medical Centre Ljubljana, Slovenia, between January 2016 and March 2019 were retrospectively reviewed. After applying inclusion and exclusion criteria, 123 patients (123 eyes) were included in the study. Results Baseline visual acuity (VA) was 60.9 ± 15.2 letters (median 63; range 7–85). Baseline central retinal subfield thickness (CRT) was 440.7 ± 132.5 μm (median 430; range 114–1000). No significant change in VA over 2 years was found (mean change +2.1 ± 16.8 letters (median 2; range −53–52)). However, there was a significant change in VA in the subgroup with baseline VA <70 letters (mean change +5.7 ± 17.9 letters (median 5; range −52–52)). VA gains of ≥15 letters were achieved in 25 eyes (20.3%). Changes in CRT were significant over 2 years. Patients received 4.5 ± 2.1 (median 5, range 1–9) and 2.6 ± 2.3 (median 2, range 0–8) injections in the first and second years, respectively. Conclusions The two-year visual outcomes in this retrospective analysis appear to be comparable to previously reported outcomes in routine clinical practice. Our analysis provides some information about the effectiveness of anti-VEGF treatment in routine clinical practice in Slovenia. More intensive treatment should be implemented in the management of patients in order to achieve better visual outcomes.

Monitoring processes and outcomes in routine clinical practice: A promising approach to plugging the holes of the practice-based evidence colander

The field has struggled with fundamental issues related to evidence-based practice (EBP) implementation and science-practice integration. The development and implementation of routine monitoring and measurement-based care (MBC) strategies in naturalistic psychological service settings has emerged as a promising strategy to address fundamental questions and knowledge gaps. This conceptual paper marks the importance of routine monitoring in real world psychological services. In particular, routine monitoring has facilitated the harnessing of ecologically valid practice-based and patient-focused evidence, which would otherwise be lost to the field. In addition to tracing its historical context, the role and impact of routine monitoring is addressed in the areas of (a) documenting the effectiveness of psychological services, (b) patient-focused research and care, and (c) therapist differences and payment models. Limitations and challenges are also identified. Throughout, the public health significance of routine monitoring as it relates to clinical psychology is highlighted, including its increasingly prominent role in health care systems and mental health care policy. In addition, it is argued that routine monitoring should continue to be a vital transtheoretical and transdiagnostic evidence-based practice.

Implementation of Patient-Reported Outcomes (PROMs) from specialist pain clinics in England and Wales: Experience from a nationwide study.

Evaluating outcomes in routine clinical practice is a significant challenge for specialist pain clinics due to the complexity of interventions provided and the subjective nature of pain. This study reports findings from implementation of Patient Reported Outcomes (PROMs) in pain clinics in England and Wales between 2011 and 2013. A paper-based questionnaire was administered at a first appointment in participating centres. This assessed quality of life, experience of health care and health care usage with postal follow-up at 6 and 12months by the research team. Feasibility was assessed in terms of response rates, completion rates and outcomes. Ninety-one (56%) clinics participated, entering 9,588 patients (19% of those eligible). For responders, there was a 92% item completion rate. The dropout rate was high, 46% and 19% returned questions at 6 and 12months, respectively. Quality of life at baseline was low, with a mean EQ5D-3L Time Trade Off value of 0.32. Amongst responders at 12months, 92% continued to experience significant pain. For those with planned discharges 30% achieved the Minimal Important Change for quality of life. Nonetheless, 70% reported positive experiences of care. Patients attending UK pain clinics report an extraordinarily poor quality of life and difficulty with understanding their condition. Problems with PROMs implementation included initial recruitment, follow-up response rates, classification systems and benchmarking. Successful implementation should include use of electronic data capture, feedback and focus on gradual improvement. To achieve this would require extended periods of funding. No nationwide evaluation of the effectiveness of specialist pain clinics had previously been attempted. Comparison of patient outcomes from services enables improvement. This work provides a platform to improve methods of routine PROMs capture in pain clinics, measure clinical effectiveness and identify areas for potential research.

Effect of Interhospital Transfer on Endovascular Treatment for Acute Ischemic Stroke.

Background and Purpose- To assess the effect of inter-hospital transfer on time to treatment and functional outcome after endovascular treatment (EVT) for acute ischemic stroke, we compared patients transferred from a primary stroke center to patients directly admitted to an intervention center in a large nationwide registry. Methods- MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry is an ongoing, prospective, observational study in all centers that perform EVT in the Netherlands. We included adult patients with an acute anterior circulation stroke who received EVT between March 2014 to June 2016. Primary outcome was time from arrival at the first hospital to arterial groin puncture. Secondary outcomes included the 90-day modified Rankin Scale score and functional independence (modified Rankin Scale score of 0-2). Results- In total 821/1526 patients, (54%) were transferred from a primary stroke center. Transferred patients less often had prestroke disability (227/800 [28%] versus 255/699 [36%]; P=0.02) and more often received intravenous thrombolytics (659/819 [81%] versus 511/704 [73%]; P<0.01). Time from first presentation to groin puncture was longer for transferred patients (164 versus 104 minutes; P<0.01, adjusted delay 57 minutes [95% CI, 51-62]). Transferred patients had worse functional outcome (adjusted common OR, 0.75 [95% CI, 0.62-0.90]) and less often achieved functional independence (244/720 [34%] versus 289/681 [42%], absolute risk difference -8.5% [95% CI, -8.7 to -8.3]). Conclusions- Interhospital transfer of patients with acute ischemic stroke is associated with delay of EVT and worse outcomes in routine clinical practice, even in a country where between-center distances are short. Direct transportation of patients potentially eligible for EVT to an intervention center may improve functional outcome.

The management of primary mediastinal B-cell lymphoma: a British Society for Haematology Good Practice Paper.

This Good Practice Paper was compiled according to the British Society for Haematology (BSH) process at http://www.b-s-h.org.uk/guidelines. The BSH produces Good Practice Papers to recommend good practice in areas where there is a limited evidence base but for which a degree of consensus or uniformity is likely to be beneficial to patient care. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org and is also detailed in Table 1.

Results from a Prospective Real World Study Show Strong Efficacy of Idelalisib in CLL, Including High-Risk CLL, and Provide Evidence That Pjp Prophylaxis Positively Impacts on Overall Survival

Introduction: Idelalisib is a first-in-class PI3Kδ-inhibitor. In clinical studies idelalisib demonstrated significant efficacy in patients with CLL, including patients with TP53 aberrations (del17p and/or TP53m). On this basis national and international guidelines in Europe recommend idelalisib as one treatment option in this high-risk CLL patient population. However, it is unclear how efficacy reported in clinical studies translates into real world experience. Considering the importance of such data, we initiated a real world study soon after market authorization of idelalisib in the European Union prospectively investigating efficacy and safety of idelalisib in routine clinical practice. Concomitant PJP prophylaxis is a risk minimization measure that was introduced after market authorization of idelalisib. Nevertheless, the impact on patient outcomes in routine clinical practice has not been studied in detail. We therefore also analyzed the impact of PJP prophylaxis on overall survival (OS) within this real world cohort.Methods: A prospective, two-cohort, multicenter, non-interventional post-authorization safety study (PASS) reporting real world safety and efficacy data on the use of idelalisib in Germany. Inclusion of patients was based on the physician's decision to initiate treatment with idelalisib in accordance with the European Summary of Product Characteristics. Descriptive statistics were used for data analysis.Results: This analysis included 84 CLL patients with a median age of 74 years. 88% of patients were older than 65 years, 70% were male and 86% presented with one or more co-morbidities. Binet stage A, B, C was reported in 25%, 33% and 37% of patients, respectively. The median time from diagnosis to start of idelalisib therapy was 89.5 months and patients received a median number of two prior lines of therapy, including treatment with the BTK inhibitor ibrutinib in 11 patients (13%). With a median observation time of 11.5 months the median overall survival (OS) for the entire CLL patient population was not reached. Our CLL cohort included 24 patients (29%) that did not receive PJP prophylaxis for idelalisib therapy. We therefore compared OS in patients with and without concomitant PJP prophylaxis. In patients receiving PJP prophylaxis survival rates were higher in the first 6-12 months of therapy, with 6-month and 12-month survival rates in patients with vs without PJP prophylaxis of 98% vs 76% and 84% vs 76%, respectively (Figure 1). 19% of CLL patients (n=16) had documented TP53 aberrations, including five patients that received idelalisib as first-line treatment. In patients with TP53 aberrations the overall response rate (ORR) was 77% compared to 67% in patients without TP53 aberrations. Importantly, the 12-month survival rates for patients with and without TP53 aberrations were similar with 81% and 83%, respectively. Median OS was not reached for either patient population (Figure 2).Conclusion: This prospective real world study started collecting data on the efficacy and safety of idelalisib in routine clinical practice soon after market authorization of idelalisib in Europe. Results demonstrate similar efficacy of idelalisib irrespective of the patients' TP53 status confirming the efficacy previously reported in pivotal clinical studies. Additionally, our results provide evidence that PJP prophylaxis is an effective risk minimization measure impacting on survival. [Display omitted] DisclosuresHoechstetter:Hexal: Other: Travel Grants; Abbvie: Other: Travel Grants; Gilead Sciences: Consultancy, Other: Travel Grants. Eissmann:Gilead Sciences: Employment. Hucke:Gilead Sciences: Employment. van Troostenburg:Gilead Sciences: Employment. Ramroth:Gilead Sciences: Employment. Knauf:Celgene: Consultancy, Honoraria; Gilead Sciences: Consultancy; Janssen: Consultancy; Mundipharma: Consultancy; Roche: Consultancy; Amgen: Consultancy, Honoraria; AbbVie: Consultancy.

Pyogenic Spondylodiscitis: Risk Factors for Adverse Clinical Outcome in Routine Clinical Practice.

We aimed to describe the clinical features and outcomes of pyogenic spondylodiscitis and to identify factors associated with an unfavourable clinical outcome (defined as death, permanent disability, spinal instability or persistent pain). In our tertiary centre, 91 cases were identified prospectively and a retrospective descriptive analysis of clinical records was performed prior to binary regression analysis of factors associated with an unfavourable outcome. A median 26 days elapsed from the onset of symptoms to diagnosis and 51% of patients had neurological impairment at presentation. A microbiological diagnosis was reached in 81%, with Staphylococcus aureus most commonly isolated. Treatment involved prolonged hospitalisation (median stay 40.5 days), long courses of antibiotics (>6 weeks in 98%) and surgery in 42%. While this was successful in eradicating infection, only 32% of patients had a favourable clinical outcome and six patients (7%) died. Diabetes mellitus, clinical evidence of neurological impairment at presentation, a longer duration of symptoms and radiological evidence of spinal cord or cauda equina compression were independent factors associated with an unfavourable outcome. Our data indicate that spondylodiscitis is associated with significant morbidity and suggest that adverse outcomes may be predicted to an extent by factors present at the time of diagnosis.

Impact of fingolimod on clinical and magnetic resonance imaging outcomes in routine clinical practice: A retrospective analysis of the multiple sclerosis, clinical and MRI outcomes in the USA (MS-MRIUS) study

BackgroundThe effectiveness of fingolimod on clinical and magnetic resonance imaging (MRI) outcomes in patients with multiple sclerosis (MS) has been well established in trials and, to a lesser extent, in the real world. ObjectiveTo evaluate clinical and MRI outcomes in patients with relapsing MS receiving fingolimod in US clinical practice. MethodsClinical and MRI data from 590 patients initiating fingolimod treatment at 33 MS centers in the USA were retrospectively analyzed. Clinical data were obtained from medical records. MRI data were systematically quantified at a centralized imaging facility. Patients had an index (within 6 months before and 1 month after starting fingolimod) and post-index (9–24 months after starting fingolimod) MRI scan; 184 individuals had a pre-index scan (9–24 months before starting fingolimod). ResultsIn the index to post-index period, mean annualized relapse rates decreased from 0.36 to 0.13 and disability progression occurred in 18.5% of patients. Median T2, T1 and gadolinium-enhancing lesion volume changed by 1.15%, 2.36%, and –100% between the index and post-index scans, respectively, and median annualized percentage changes in brain volume and lateral ventricular volume were –0.32% and +0.66%, respectively. For patients with pre-index scans, MRI outcomes were unchanged or improved during treatment. Outcomes were generally comparable with those in fingolimod phase 3 trials. ConclusionThis real-world study highlights the effectiveness of fingolimod and the feasibility of quantifying clinical and MRI data collected from multiple centers during routine clinical practice on a group level using a systematic, quantitative methodology.

Brief coping strategy enhancement for distressing voices: Predictors of engagement and outcome in routine clinical practice.

Cognitive behaviour therapy is recommended internationally as a treatment for psychosis (targeting symptoms such as auditory hallucinations, or "voices"). Yet mental health services are commonly unable to offer such resource-intensive psychological interventions. Brief, symptom-specific and less resource-intensive therapies are being developed as one initiative to increase access. However, as access increases, so might the risk of offering therapy to clients who are not optimally disposed to engage with and benefit from therapy. Thus, it is important to identify who is most/least likely to engage with and benefit from therapy, and when. In the current study, 225 clients were assessed for suitability for a brief, 4-session, manualized, cognitive behaviour therapy-based intervention for voices (named coping strategy enhancement therapy) and 144 commenced therapy, at a transdiagnostic voices clinic based in Sussex, UK. This article reports on the value of depression, anxiety, stress, insight into the origin of voices, length of voice hearing, and demographics in the prediction of engagement and outcomes. The study found that higher levels of baseline depression, anxiety, and stress were significantly associated with poorer outcomes, especially if clients also had high levels of voice-related distress. The engagement analyses showed that levels of voice-related distress at baseline predicted dropout. These findings highlight the importance of assessing negative affect and voice-related distress prior to commencing therapy for distressing voices, to help determine if the client is suitable or ready for brief-coping strategy enhancement.

PCV2 - Characterizing Patients Treated With Macitentan For Pulmonary Arterial Hypertension (PAH) In The U.S. Opsumit Users Registry (OPUS)

Health plans look beyond randomized controlled trials (RCTs) in making formulary decisions. There are three approved endothelin receptor antagonists, but no head-to-head trials. Real world evidence (RWE) informs the application of RCT results to healthcare decision making by assessing care and patient outcomes in routine clinical practice. RWE is derived from registries, medical records, pragmatic trials, and claims databases. OPUS registry (NCT02126943) is a US-based, multi-center, longitudinal, observational drug registry of newly treated macitentan patients. The objective of this analysis is to describe clinical characteristics, co-morbidities, and treatment of PAH patients with macitentan. Patients newly treated with macitentan (initiated < 30 days prior to enrollment visit) were included in the registry, regardless of prior or concomitant PAH therapy. Planned observation period was at least one year. Data collected at enrollment or follow-up included: demographics, clinical characteristics, outcomes, adverse events, macitentan treatment and registry discontinuation. As of June 2017, 1136 patients with PAH had follow-up data--74.2% females and 25.8% males. Of this cohort, 44.5% of patients were > 65 years of age; 57.9% patients had idiopathic PAH, and 24.9%, PAH associated with connective tissue disease. Common baseline comorbidities included: hypertension (52.6%), edema (24.5%), signs of right heart failure (15.8%), and diabetes mellitus (22.5%). Median exposure to macitentan was 9.6 months. Macitentan was initiated as monotherapy in 41.7%, and double or triple combination therapy in 58.2% of patients. Most common adverse events were dyspnea (18.0%) and peripheral edema (8.9%). 12.4% of patients experienced ≥1 PAH-related hospitalization. OPUS reports macitentan use and safety in real world clinical settings. Reported comorbidities are consistent with other large registries and claims analyses. Macitentan is initiated most commonly as double or triple combination therapy. PAH related hospitalizations were lower than previously reported in both claims analysis and registries.

Pulmonary Metastasectomy for Colorectal Cancer: Predictors of Survival in Routine Surgical Practice

Resection of lung metastases is considered standard treatment for patients with metastatic colorectal cancer. We describe surgical management, prognostic factors, and outcomes in routine clinical practice. All cases of colorectal cancer lung metastases in Ontario, Canada, resected during 2002 to 2009 were identified using the Ontario Cancer Registry and linked electronic records. Pathology reports were reviewed to identify extent of disease. The study population included 420 patients (60% male). Median age was 64 years. A solitary metastasis was present in 61% (256 of 420). Mean size of the largest metastasis was 2.4 cm. Lymph nodes were resected in 63% (263 of 420) of patients. The 5-year cancer-specific survival (CSS) and overall survival (OS) was 42% (95% confidence interval [CI], 37% to 47%) and 40% (95% CI, 35% to 45%), respectively. On adjusted analyses, greater number (p < 0.001) and size (p= 0.001) of lesions and lymph node involvement (p < 0.001) were associated with inferior CSS and OS. Lymph node positivity was strongly associated with survival (adjusted CSS hazard ratio, 2.19 [95% CI, 1.48 to 3.25]; adjusted OS hazard ratio, 2.08 [95% CI, 1.41 to 3.07]). Unadjusted 5-year CSS/OS was 49%/47% for node-negative disease and 19%/19% for node-positive disease. The negative prognostic effect of size (>2 cm) and number (>1) of lesions was additive: 5-year CSS/OS ranged from 57%/55% (single lesion <2 cm) to 24%/20% (multiple lesions, largest lesion>2 cm). Long-term survival of patients with resected colorectal cancer lung metastases in routine practice is comparable to outcomes reported in institutional case series. Lymph node positivity is strongly associated with reduced survival. Combining size and number of metastatic lesions in advance of the operation may facilitate treatment decision making.

Measuring Use of Evidence Based Psychotherapy for Posttraumatic Stress Disorder in a Large National Healthcare System.

To derive a method of identifying use of evidence-based psychotherapy (EBP) for post-traumatic stress disorder (PTSD), we used clinical note text from national Veterans Health Administration (VHA) medical records. Using natural language processing, we developed machine-learning algorithms to classify note text on a large scale in an observational study of Iraq and Afghanistan veterans with PTSD and one post-deployment psychotherapy visit by 8/5/15 (N = 255,968). PTSD visits were linked to 8.1million psychotherapy notes. Annotators labeled 3467 randomly-selected psychotherapy notes (kappa = 0.88) to indicate receipt of EBP. We met our performance targets of overall classification accuracy (0.92); 20.2% of veterans received ≥ one session of EBP over the study period. Our method can assist with identifying EBP use and studying EBP-associated outcomes in routine clinical practice.

Abstract 114: Aspects versus Perfusion in the Trevo Retriever Registry: Defining the Core on the Largest Scale to Date

Background: Routine use of advanced imaging versus ASPECTS for imaging triage of endovascular thrombectomy candidates has not been evaluated on a large scale to date. Ischemic core may be defined by ASPECTS or perfusion imaging, yet these variable definitions likely reflect different pathophysiology as perfusion may fluctuate and ASPECTS lesions may be time-dependent. Methods: The Trevo Retriever Registry was a prospective, open-label, consecutive enrollment, multicenter, international registry with more than 65 enrolling sites worldwide. The Imaging and Angiography Core Lab systematically adjudicated more than 1,500 subjects, scoring ASPECTS and separately processing perfusion imaging. Ischemic core volume on perfusion imaging was defined as rrCBF&lt;30% (CTP) and analyzed with respect to ASPECTS. Results: 488 subjects (68.3±14.4 years; 53.3% women; baseline NIHSS median 15 (10-19) with anterior circulation occlusions were evaluated with both ASPECTS and perfusion imaging prior to thrombectomy. Arterial occlusions included 87/487 (17.9%) ICA and 296/487 (60.8%) proximal M1 MCA, treated with thrombectomy at median 4.7 (3.3-7.9) hours from time last known well (TLKW). ASPECTS was median 8 (7-9) with ischemic core lesions of median 18 (4.9-39.2) cc. At-risk hypoperfusion (Tmax&gt;6s) lesions were median 109.8 (62-156.9) cc. TLKW was associated with ASPECTS (r=-0.18, p&lt;0.001) yet no time relationship was noted with either ischemic core or at-risk hypoperfusion on perfusion imaging. ASPECTS correlated modestly with perfusion imaging-derived ischemic core (r=-0.35, p&lt;0.001) and at-risk hypoperfusion (r=-0.24, p&lt;0.001). Post-procedure mTICI≥2b occurred in 448/488 (91.8%). Each increment in baseline ASPECTS was associated with an adjusted OR of 1.21 (95%CI (1.05-1.39), p&lt;0.008 for good clinical outcomes (day 90 mRS 0-2), whereas the perfusion lesion volume for ischemic core and at-risk hypoperfusion did not predict outcomes. Conclusions: Largescale, systematic evaluation of ASPECTS and perfusion imaging prior to thrombectomy reveals discrepancy in the definition of ischemic core and the prediction of clinical outcomes after revascularization. ASPECTS is time-dependent, yet reliably predicts outcomes in routine clinical practice.

Mirabegron improves quality-of-life, treatment satisfaction, and persistence in patients with overactive bladder: a multi-center, non-interventional, real-world, 12-month study

Objective: Observational studies can provide evidence about patient outcomes in routine clinical practice. This prospective, non-interventional study (BELIEVE) is the largest real-world European study to date to assess quality-of-life, treatment satisfaction, resource utilization, and persistence in patients with overactive bladder (OAB) who were prescribed mirabegron as part of routine clinical practice.Methods: The primary objective was to evaluate change from baseline in quality-of-life based on overactive bladder questionnaire (OAB-q) sub-scales. Secondary objectives included evaluation of treatment persistence, patient satisfaction, healthcare resource utilization and adverse events (AEs). Follow-up was for 12 months with visit windows at 2–4 and 10–12 months. Median change from baseline in total OAB-q and its sub-scales (Health-related quality-of-life [HRQoL] and symptom bother scale) were assessed.Results: Overall, 862 patients were enrolled from eight European countries. In the Full Analysis Set (FAS), 73.7% were female, mean age was 61.2 years; 47.7% ≥65 years. At baseline, 41.3% had switched from other OAB treatments, 42.2% were treatment naïve, 10.1% were lapsed, and 6.4% were on combination treatment. Symptom bother and HRQoL total scores improved from baseline to 2–4 and 10–12 months. There was a notable improvement in dry rate, increasing from 34.9% at baseline to 43.7% at 10–12 months in the FAS, and a reduction in pad use. Persistence was high, with 53.8% of FAS patients remaining on mirabegron at 10–12 months. Overall, no unexpected safety issues were observed and AEs were consistent with the known safety profile of mirabegron.Conclusion: Patients receiving mirabegron in a real-world setting reported meaningful improvements in QoL and health status, with a persistence rate of 53.8% at 12 months for the FAS. No unexpected safety issues were observed, and AEs were consistent with the known safety profile of mirabegron.

Real-world effectiveness of 8-week treatment with ledipasvir/sofosbuvir in chronic hepatitis C

Ledipasvir/sofosbuvir (LDV/SOF) for 8 to 24 weeks is approved for the treatment of chronic hepatitis C virus infection (HCV). In the ION-3 study, 8 weeks of LDV/SOF was non-inferior to 12 weeks in previously untreated genotype 1 (GT1) patients without cirrhosis. According to the Summary of Product Characteristics (SmPC), 8-week treatment may be considered in naïve non-cirrhotic GT1-patients. However, there are only limited data on the effectiveness of an 8-week regimen of LDV/SOF under real-world conditions. The aim of the present study was to characterise patients receiving 8 weeks of LDV/SOF compared to those receiving 12 weeks of LDV/SOF, and to describe therapeutic outcomes in routine clinical practice. The German Hepatitis C-Registry is a large national real-world cohort that analyses effectiveness and safety of antiviral therapies in chronic HCV. This data set is based on 2,404 patients. Treatment with SOF/LDV (without RBV) for 8 or 12 weeks was initiated on or before September 30, 2015. Overall, 84.6% (2,034/2,404) of the safety population (intention-to-treat-1 [ITT1]) and 98.2% (2,029/2,066) of the per protocol (PP) population achieved sustained virological response at week 12 (SVR12). In the 8-week group, 85.1% (824/968) of ITT1 and 98.3% (821/835) of PP patients achieved SVR12, while in the 12-week group, 85.5% (1,210/1,415) of ITT1, and 98.1% (1,208/1,231) of PP patients achieved SVR12. When treated according to the SmPC, 98.7% (739/749) of the patients achieved SVR12 (PP). Relapse was observed in 9.5% (2/21) of cirrhotic patients treated for 8 weeks (PP). Under real-world conditions a high proportion of eligible patients receiving 8-week LDV/SOF treatment achieved SVR12. Relapse occurred more frequently in patients who did not meet the selection criteria according to the SmPC. In a large real-world cohort of patients mainly treated by physicians in private practice in Germany, shorter HCV treatment (8-week) resulted in equivalent cure rates to 12-week treatment in genotype 1 HCV-infected patients. Thus, shorter treatment can be recommended in these patients which would substantially reduce costs of therapy. Clinical Trial number: DRKS00009717 (German Clinical Trials Register, DRKS).

Effect of adding GLP-1RA on mortality, cardiovascular events, and metabolic outcomes among insulin-treated patients with type 2 diabetes: A large retrospective UK cohort study

Combining a GLP-1 receptor agonist (GLP-1RA) with insulin is often an effective treatment strategy for overweight patients with type 2 diabetes (T2D), but little is known about the longer-term effects on cardiovascular and mortality outcomes in routine clinical practice in the United Kingdom. We therefore compared the times to a major nonfatal cardiovascular (CV) event and all-cause mortality among overweight patients with T2D treated with insulin alone versus insulin+GLP-1RA in a large UK database. A retrospective cohort study was conducted in 18,227 patients with insulin-treated T2D from UK General Practices using The Health Improvement Network database. The 5-year risk of mortality and a 3-point composite of all-cause mortality and nonfatal CV outcomes (myocardial infarction or stroke) was compared between a propensity score-matched cohort of those on insulin alone (n=1,793) and insulin+GLP-1RA (n=1,793), irrespective of other diabetes therapies, providing a total of 12,682 person-years of follow-up. Cox proportional hazard models were used to estimate the hazard ratios of the outcomes. Hemoglobin A1c reduction was similar between both groups (-0.42 vs -0.33%, P=.089 at 12 months). Overall, 3-point composite events of all-cause mortality and CV events (major adverse cardiovascular even) were 98 versus 55 for the insulin alone versus insulin+GLP-1RA groups, respectively (14.7 vs 9.2 per 1,000 person-years; adjusted hazard ratio [aHR]: 0.64; 95% CI: 0.42-0.98; P=.038). Corresponding composite nonfatal CV events were 33 versus 28 (6.0 vs 5.6 per 1,000 person-years; aHR: 0.76; 95% CI: 0.41-1.42; P=.393), whereas all-cause mortality events were 49 versus 13 (6.9 vs 2.0 per 1,000 person-years; aHR: 0.35; 95% CI: 0.17-0.73; P=.005). Based on a large UK cohort in routine clinical practice, adding a GLP-1RA to insulin therapy is associated with a reduction in risk of composite CV events and all-cause mortality but a nonsignificant higher risk of hospitalization for heart failure in overweight patients with T2D.

HbA1c Outcomes in Patients Treated With Canagliflozin Versus Sitagliptin in US Health Plans

PurposeClinical trial evidence supports greater glycemic control with canagliflozin than with sitagliptin. The objective of this study was to provide real-world evidence comparing outcomes in routine clinical practice among patients initiating each medication. MethodsWith the use of a health care administrative database, patients initiating canagliflozin were compared with patients initiating sitagliptin (first prescription fill as index date). Baseline (6 months before index date) demographic and clinical (eg, comorbidities and diabetes-related complications) characteristics were compared, and propensity score matching was used to control for baseline differences between cohorts. Outcomes included change in glycosylated hemoglobin (HbA1c) and persistence with medication over a 9-month period after index date. FindingsBefore matching, the canagliflozin cohort (N = 3993) was younger than the sitagliptin cohort (N = 12,153) and was composed of fewer women and Medicare Advantage enrollees, with lower mean baseline comorbidity scores (all p < 0.001). Before matching, the canagliflozin cohort (valid n = 1482) had a significantly (p < 0.001) higher baseline HbA1c (8.60) than the sitagliptin cohort (valid n = 3697; HbA1c, 8.32). After matching (n = 1472 per cohort), patients were well balanced on baseline characteristics, and HbA1c values were not significantly different (p = 0.634) between the cohorts. Patients initiating canagliflozin had greater reductions in HbA1c than patients in the sitagliptin cohort (−0.93% versus −0.57%, respectively; p = 0.004), with similar mean (median) time from index date to follow-up HbA1c of 185.4 (199.0) and 184.3 (190.5) days, respectively (p = 0.802). Only 29.8% of canagliflozin patients discontinued during follow-up compared with 41.5% of sitagliptin patients (p < 0.001); the average days of persistence on index therapy was longer for canagliflozin patients (152 days) than for sitagliptin patients (139 days; p < 0.001). ImplicationsIn this observational study, patients initiating canagliflozin had greater reduction in HbA1c and longer persistence with medication than did patients who initiated sitagliptin, over a 9-month period. Better understanding of antihyperglycemic treatment, HbA1c results, and differences among patients in demographic/clinical characteristics as well as persistence with treatment will inform optimal diabetes treatment choice in routine practice.