Two years with GIOIA 'Effects of gliflozins and gliptins on markers of cardiovascular damage in type 2 diabetes': A prospective, multicentre, quasi-experimental study on sodium-glucose cotransporter 2 and dipeptidyl peptidase-4 inhibitors in diabetes clinical practice.

AIM: To assess and compare the metabolic and vascular effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in the clinical practice of patients with type 2 diabetes in Italy. MATERIALS AND METHODS: GIOIA is a 2-year prospective, multicentre, quasi-experimental study that enrolled patients with type 2 diabetes initiating SGLT-2i or DPP-4i for inadequate glycaemic control [glycated haemoglobin (HbA1c) >7%] between March 2018 and March 2021. The primary endpoints were changes in markers of organ damage [carotid intima-media thickness (CIMT), albuminuria, myocardial function] and HbA1c from baseline to year 2. RESULTS: In total, 1150 patients were enrolled in the study (SGLT-2i n = 580, DPP-4i n = 570). Patients initiated on SGLT-2i were younger (about 6 years) and heavier (about 11 kg), had higher HbA1c level (1% more), more albuminuria and cardiovascular events (16% more) than patients initiated on DPP-4i. CIMT and echocardiographic parameters were not significantly different. Propensity score matching yielded two groups, each consisting of 155 patients with diabetes with similar baseline characteristics. Despite a significant similar reduction in HbA1c levels in both groups (-0.8%), more patients on SGLT-2i had regression of CIMT and albuminuria (22% and 10%, respectively, p < .001 vs. DPP-4i); more patients on DPP-4i had progression of CIMT and albuminuria (23% and 28%, respectively, p < .001 vs. SGLT-2i). Left ventricular ejection fraction improved slightly (3%, p = .043) on SGLT-2i only. CONCLUSIONS: In a real-world setting, both SGLT-2i and DPP-4i improve glycaemic control persisting after 2 years of treatment, with a robust effect on both CIMT and albuminuria regression for SGLT-2i as compared with DPP-4i in the propensity score matching.

INSURE: a pooled analysis of ixazomib-lenalidomide-dexamethasone for relapsed/refractory myeloma in routine practice.

Aim: We pooled data from three observational studies (INSIGHT MM, UVEA-IXA and REMIX) to investigate the real-world effectiveness of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory myeloma. Materials & methods: INSIGHT MM was a prospective study conducted in countries across Europe, Asia and North/Latin America while UVEA-IXA and REMIX were multicenter, retrospective/prospective studies conducted in Europe. Patients who had received IRd as ≥2nd line of therapy were analyzed. Primary outcomes were time-to-next treatment (TTNT) and progression-free survival (PFS). Results: Overall, 564 patients were included (median follow-up: 18.5 months). Median TTNT and PFS were 18.4 and 19.9 months; both outcomes were numerically longer for earlier versus later lines. Median treatment duration was 14.0 months. Overall response rate was 64.6%. No new safety concerns were noted. Conclusion: The effectiveness of IRd in routine practice appears similar to the efficacy observed in TOURMALINE-MM1. IRd benefit in earlier versus later lines was consistent with previous reports.

Evaluation of dialectical behavior therapy for adolescents in routine clinical practice: a pre-post study.

BACKGROUND: Self-harm and suicidal ideation are prevalent among adolescents, cause physical and psychosocial disability, and have potentially life-threatening consequences. Dialectical behavioral therapy for Adolescents (DBT-A) is an evidence-based intervention for reducing self-harm. However, few studies have investigated the effectiveness of DBT-A when delivered in routine clinical practice. METHODS: A follow-up cohort study, based on data from a quality assessment register of DBT-A in child and adolescent mental health services including seven outpatient clinics. Inclusion criteria were ongoing or a history of self-harming behavior the last 6 months; current suicidal behavior; at least 3 criteria of DSM-IV Borderline personality disorder (BPD), or at least the self-destruction criterion of DSM-IV BPD, in addition to minimum 2 subthreshold criteria; and fluency in Norwegian. Participants received 20 weeks of DBT-A consisting of multifamily skills training groups and individual therapy sessions. Outcomes from 41 participants included frequency of self-harm, suicide attempts and hospitalizations caused by self-harm or suicide attempts, assessed pre-, during, and post-treatment by self-report and reviews of the patient's medical records. Suicidal ideation, urge to self-harm and perceived feelings of happiness and sadness were assessed by the patients' diary cards at week 1, 5, 10, 15 and 20 of the treatment program. RESULTS: Participants attended an average of 17.9 (SD = 4.7) individual sessions, 14.7 (SD = 3.4) group-based skills training sessions and 4.6 (SD = 4.1) brief intersession telephone consultations. Moderate to large within-group effect sizes (ES) were found in self-harm from pre-treatment to 1-5 weeks (d = 0.64), 6-10 weeks (d = 0.84), 11-15 weeks (d = 0.99), 16-20 weeks (d = 1.26) and post-treatment (d = 1.68). Nine participants were admitted to hospitalization during DBT-A, whereas five had attempted suicide, but no suicides were completed. No statistically significant changes were found in suicidal ideation, urge to self-harm or perceived feelings of happiness or sadness from pre to post treatment. CONCLUSION: The findings of the current study are promising as the participants reported considerably reduced self-harm behavior after DBT-A treatment in a child and adolescent mental health outpatient setting.

Clinical Treatment Guidelines for Tafasitamab Plus Lenalidomide in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 24% of new cases of B-cell non-Hodgkin lymphoma in the US each year. Up to 50% of patients relapse or are refractory (R/R) to the standard first-line treatment option, R-CHOP. The anti-CD19 monoclonal antibody tafasitamab, in combination with lenalidomide (LEN), is an NCCN preferred regimen for transplant-ineligible patients with R/R DLBCL and received accelerated approval in the US (July 2020) and conditional marketing authorization in Europe (August 2021) and other countries, based on data from the L-MIND study. The recommended dose of tafasitamab is 12 mg/kg by intravenous infusion, administered in combination with LEN 25 mg for 12 cycles, followed by tafasitamab monotherapy until disease progression or unacceptable toxicity. Tafasitamab + LEN is associated with durable responses in patients with R/R DLBCL. The majority of clinically significant treatment-associated adverse events are attributable to LEN and can be managed with dose modification and supportive therapy. We provide guidelines for the management of patients with R/R DLBCL treated with tafasitamab and LEN in routine clinical practice, including elderly patients and those with renal and hepatic impairment, and advice regarding patient education as part of a comprehensive patient engagement plan. Our recommendations include LEN administration at a reduced dose if required in patients unable to tolerate the recommended dose. No dose modification is required for tafasitamab in special patient populations.

Real-world effectiveness of systemic anticancer therapy for advanced melanoma in the west of Scotland from 2010 to 2018.

Aim: Assess the real-world effectiveness of systemic anticancer therapy in advanced (unresectable or metastatic) melanoma. Methods: This was a retrospective cohort study linking routine healthcare data with systemic anticancer therapy prescriptions for patients starting immunotherapy or targeted treatments between 1 November 2010 and 31 December 2017 in the west of Scotland. Results: Among 362 patients identified, median overall survival varied between 18.5 months (95% CI: 14.4-not estimable) for ipilimumab/nivolumab combination and 5.6 months (95% CI: 4.5-7.3) for dabrafenib, but there were differences in the characteristics of each regimen cohort. Raised lactate dehydrogenase levels and Eastern Cooperative Oncology Group performance status ≥2 negatively impacted overall survival. Conclusion: The patients had a shorter median overall survival than those in pivotal trials. This was expected, given that this real-world cohort included patients with poorer prognostic indicators, typically excluded from trials.

Pomalidomide plus dexamethasone for patients with relapsed or refractory multiple myeloma: Final results of the non-interventional study POSEIDON and comparison with the pivotal phase 3 clinical trials.

BACKGROUND: Prognosis of patients with multiple myeloma (MM) who have relapsed on or become refractory to immunomodulators and bortezomib is poor, and treatment options are limited. While pomalidomide plus low-dose dexamethasone (POM/DEX) has demonstrated efficacy in clinical trials, real-world evidence is scarce. PATIENTS AND METHODS: POSEIDON was a prospective non-interventional study designed to evaluate effectiveness, safety and quality of life (QoL) of POM/DEX in patients with relapsed or refractory MM (R/RMM) pretreated with at least two prior therapy lines including both lenalidomide and bortezomib in real world in Germany. Patients received POM/DEX according to physicians' choice. Data were analyzed descriptively. RESULTS: Between 2014 and 2017, 151 patients were enrolled, 144 patients with a median of three prior therapy lines qualified for effectiveness analysis. Median age was 73.2 years. Median progression-free and overall survival were 6.3 months [95% confidence interval (CI) 5.2, 8.6] and 12.9 months [95% CI 10.6, 15.1]. Most frequent grade 3/4 adverse events were leukopenia (8.2%), pneumonia (7.5%) and anemia (5.5%). QoL was maintained after start of POM/DEX. CONCLUSION: The results of POSEIDON support the effectiveness and safety of POM/DEX in R/RMM patients pretreated with lenalidomide and bortezomib and highlight the clinical value of the POM/DEX regimen in the real-world setting. Registered at clinicaltrials.gov (NCT02075996).

A first step towards best practice recommendations for the design and statistical analyses of pragmatic clinical trials: A modified Delphi approach.

AIM: Pragmatic clinical trials (PCTs) are randomized trials implemented through routine clinical practice, where design parameters of traditional randomized controlled trials are modified to increase generalizability. However, this may introduce statistical challenges. We aimed to identify these challenges and discuss possible solutions leading to best practice recommendations for the design and analysis of PCTs. METHODS: A modified Delphi method was used to reach consensus among a panel of 11 experts in clinical trials and statistics. Statistical issues were identified in a focused literature review and aggregated with insights and possible solutions from experts collected through a series of survey iterations. Issues were ranked according to their importance. RESULTS: Twenty-seven articles were included and combined with experts' insight to generate a list of issues categorized into participants, recruiting sites, randomization, blinding and intervention, outcome (selection and measurement) and data analysis. Consensus was reached about the most important issues: risk of participants' attrition, heterogeneity of "usual care" across sites, absence of blinding, use of a subjective endpoint and data analysis aligned with the trial estimand. Potential issues should be anticipated and preferably be addressed in the trial protocol. The experts provided solutions regarding data collection and data analysis, which were considered of equal importance. DISCUSSION: A set of important statistical issues in PCTs was identified and approaches were suggested to anticipate and/or minimize these through data analysis. Any impact of choosing a pragmatic design feature should be gauged in the light of the trial estimand.

Five-year outcomes after intravitreal bevacizumab of treatment-naive eyes with macular edema secondary to CRVO in routine clinical practice: Results of the Pan-American Collaborative Retina Study (PACORES) group.

PURPOSE: The purpose of this study was to report the 5-year outcomes of treatment-naive eyes with cystoid macular edema secondary to central retinal vein occlusion treated with intravitreal bevacizumab in routine clinical practice. METHODS: We conducted multicenter retrospective non-comparative case series of 102 eyes. The main outcome measured was the change in best-corrected visual acuity (BCVA) at 5 years. Secondary outcomes included the number of injections and the change in CMT at 5 years. RESULTS: At 5 years, the mean BCVA improved from 1.22 ± 0.58 (Snellen 20/428) at baseline to 1.00 ± 0.68 logMAR (Snellen 20/200; p < 0.0001). At 5 years, 48 (47%) eyes had a gain of ≥ 3 lines, 41 (40.2%) eyes remained within 3 lines and 13 (12.7%) eyes had a loss of ≥ 3 lines of BCVA. The CMT improved from 740 ± 243 to 322 ± 179 µm (p < 0.0001). At 5 years, 59 (57.8%) eyes had a completely dry SD-OCT. Patients received a total of 10.6 ± 6.1 (range 6-27) injections. Baseline BCVA (p < 0.0001) and the duration of symptoms prior to initial anti-VEGF injection (p = 0.0274) were the only predictive factors for BCVA at 5 years. CONCLUSIONS: After 5 years with an average of 10.6 injections, there was a mean gain of 0.22 logMAR. In addition, more eyes achieved a BCVA of ≥ 20/40, gained ≥ 3 lines and less patients had a BCVA ≤ 20/200. Eyes with a better baseline BCVA and a shorter duration of symptoms were more likely to achieve better BCVA at 5 years.

Clinical outcomes in patients with Philadelphia chromosome-positive leukemia treated with ponatinib in routine clinical practice-data from a Belgian registry.

Data on clinical use of ponatinib are limited. This prospective registry aimed to evaluate outcomes of ponatinib treatment in routine practice over 3 years (2016-2019) in Belgium (NCT03678454). Patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) were treated with ponatinib per current label. Fifty patients (33 CML and 17 Ph+ ALL) were enrolled. Fifty-five percent of CML and 29% of Ph+ ALL patients had received ≥3 prior tyrosine kinase inhibitors (TKIs). Reasons for starting ponatinib were intolerance (40%), relapse or refractoriness (28%) to previous TKIs, progression (16%), or T315I mutation (16%). Median follow-up was 15 months for CML and 4.5 months for Ph+ ALL patients. Best response was a major molecular response in 58% of CML and 41% of Ph+ ALL patients. Of 20 patients who started ponatinib due to intolerance to previous TKIs, 9 (64%) CML and 4 (67%) Ph+ ALL achieved a major molecular response. Three-year estimates of overall survival were 85.3% and 85.6%, respectively, in CML and Ph+ ALL patients; estimated progression-free survival was 81.6% and 48.9%. Adverse reactions were reported in 34 patients (68%); rash (26%) and dry skin (10%) were most common. Reported cardiovascular adverse reactions included vascular stenosis (3), arterial hypertension (2), chest pain (1), palpitations (1), and vascular occlusion (1). This Belgian registry confirms results from the PACE clinical trial and supports routine ponatinib use in CML and Ph+ ALL patients who are resistant or intolerant to previous TKIs or with the T315I mutation.

Use of once-weekly semaglutide in patients with type 2 diabetes in routine clinical practice: Results from the SURE Canada multicentre, prospective, observational study.

AIM: To investigate once-weekly (OW) semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D) in routine clinical practice. METHODS: The SURE Canada study was a multicenter, prospective, observational study. Adults with T2D and one or more documented HbA1c values 12 weeks or less before semaglutide initiation were enrolled. The primary endpoint was change in HbA1c from baseline to end of study (EOS; ~30 weeks). Secondary endpoints included change in body weight (BW), waist circumference and patient-reported outcomes (PROs) and the proportion of patients achieving HbA1c of less than 7.0%, weight loss (WL) of 5% or higher, and a composite of HbA1c reduction of 1% or higher and WL of 3% or higher at EOS. Data were analysed and presented for patients on semaglutide at EOS overall and for the following baseline medication subgroups: oral antihyperglycaemic drugs (OADs) only; GLP-1RA experienced; insulin ± OADs without GLP-1RA. RESULTS: In total, 452 patients initiated semaglutide and 356 completed the study on treatment. For the 452 patients, mean baseline HbA1c was 8.1%; 86 (19.0%) patients had HbA1c of less than 7.0%. Mean dose of semaglutide at EOS was 0.76 ± 0.31 mg. Mean HbA1c was reduced by 0.9%-point (95% confidence interval [CI]: 0.97; 0.78). Mean BW was reduced by 4.3 kg (95% CI: 4.79; 3.76). At EOS, 46.9% of patients achieved HbA1c of less than 7.0%, 40.9% achieved WL of 5% or higher and 24.1% achieved the composite endpoint. PROs improved from baseline to EOS. No new safety concerns were reported. CONCLUSIONS: In SURE Canada, patients treated with OW semaglutide in routine clinical practice experienced clinically significant improvements in HbA1c, BW and other outcomes, supporting semaglutide use in routine clinical practice.

Ixazomib-lenalidomide-dexamethasone in routine clinical practice: effectiveness in relapsed/refractory multiple myeloma.

Aim: To evaluate the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma in routine clinical practice. Patients & methods: Patient-level data from the global, observational INSIGHT MM and the Czech Registry of Monoclonal Gammopathies were integrated and analyzed. Results: At data cut-off, 263 patients from 13 countries were included. Median time from diagnosis to start of IRd was 35.8 months; median duration of follow-up was 14.8 months. Overall response rate was 73%, median progression-free survival, 21.2 months and time-to-next therapy, 33.0 months. Ixazomib/lenalidomide dose reductions were required in 17%/36% of patients; 32%/30% of patients discontinued ixazomib/lenalidomide due to adverse events. Conclusion: The effectiveness and safety of IRd in routine clinical practice are comparable to those reported in TOURMALINE-MM1. Clinical trial registration: NCT02761187 (ClinicalTrials.gov).

Lay abstract Proteasome inhibitors are drugs used in multiple myeloma (MM), a blood cancer that develops from cells in the bone marrow. Ixazomib is the first oral proteasome inhibitor to be approved for use in MM, when given in combination with two other oral drugs, lenalidomide and dexamethasone, to adult patients who have received one prior therapy. Our study, which was conducted in routine clinical practice, found that the effectiveness and safety of ixazomib + lenalidomide + dexamethasone in previously treated MM patients were similar to those seen in the Phase III clinical trial on which approval was based. These findings are important because they suggest that MM patients in everyday practice can achieve the same benefits from this treatment as patients in clinical trials, despite often being in poorer health.

VISUAL OUTCOMES IN PATIENTS WITH DIABETIC MACULAR EDEMA TREATED WITH DEXAMETHASONE IMPLANT IN ROUTINE CLINICAL PRACTICE.

The aim was to evaluate visual outcomes of the real-life usage of dexamethasone (DEX) implants in diabetic macular edema (DME) patients and evaluate the possible additional visual acuity (VA) gain with combined treatment. We retrospectively reviewed medical records of DME patients treated with DEX implants. The mean best-corrected visual acuity (BCVA) and mean central retinal thickness (CRT) at baseline and one year were compared. BCVA improved from 58.4±14.9 letters at baseline to 62.4±14.5 letters at one-year evaluation (p=0.002). The mean change in BCVA was 5.2±11.1 letters. CRT decreased from 485.7±146.3 µm at baseline to 391.5±129.0 µm at one year (p<0.001). The mean change in CRT was -89.6±143.3 µm. Patients received a mean of 2.0±0.7 DEX implants. Study eyes were also divided into a group receiving DEX implant monotherapy and a group receiving DEX implant and vascular endothelial growth factor inhibitor (anti-VEGF) therapy. Changes in BCVA and CRT and the number of DEX implant injections were compared between the two groups. No difference in VA gain was found between the eyes receiving monotherapy and the eyes receiving combined treatment. In conclusion, DEX implant therapy was effective in gaining vision in DME patients. No additional VA gain was achieved with combined treatment.

Induction therapy with the MATRix regimen in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system - an international study of feasibility and efficacy in routine clinical practice.

The MATRix chemoimmunotherapy regimen is highly effective in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL). However, nothing is known about its feasibility and efficacy in everyday practice, where patients are more often older/frailer than those enrolled in clinical trials. We conducted a retrospective study addressing tolerability/efficacy of MATRix in 156 consecutive patients with newly diagnosed PCNSL treated outside a clinical trial. Median age and ECOG Performance Status of considered patients were 62 years (range 28-78) and 2 (range 0-4). The overall response rate after MATRix was 79%. Nine (6%) treatment-related deaths were recorded. After a median follow-up of 27.4 months (95% confidence interval [CI] 24.4-31.9%), the two-year progression-free and overall survival were 56% (95% CI 48.4-64.9%) and 64.1% (95% CI 56.7-72.5%) respectively. Patients not eligible for the IELSG32 trial were treated with lower dose intensity and had substantially worse outcomes than those fulfilling inclusion criteria. This is the largest series of PCNSL patients treated with MATRix outside a trial and recapitulates the IELSG32 trial outcomes in the non-trial setting for patients who fit the trial criteria. These data underscore the feasibility and efficacy of MATRix as induction treatment for fit patients in routine practice.

Scheduled Telephone Support for Internet Cognitive Behavioral Therapy for Depression in Patients at Risk for Dropout: Pragmatic Randomized Controlled Trial.

BACKGROUND: Therapist-supported, internet-delivered cognitive behavioral therapy (iCBT) is efficient in the treatment of depression. However, the optimal mode and intensity of therapist support remain to be identified. Scheduled telephone support (STS) may improve adherence and outcomes but, as it is time- and resource-consuming, should be reserved for patients for whom the usual support may be insufficient. OBJECTIVE: This paper aims to reveal whether add-on STS for patients at risk of dropping out improves treatment adherence and symptoms in iCBT for depression. METHODS: Among patients participating in an ongoing large observational routine clinical practice study of iCBT for depression delivered nationwide by Helsinki University Hospital (HUS-iCBT), those demonstrating a ≥14-day delay in initiation of treatment received invitations to this subsidiary STS study. A total of 100 consenting patients were randomly allocated to either HUS-iCBT as usual (control group, n=50) or HUS-iCBT plus add-on STS (intervention group, n=50). Proportions of those reaching midtreatment and treatment end point served as the primary outcome; secondary outcomes were change in Beck Depression Inventory (BDI)-measured depressive symptoms and time spent in treatment. RESULTS: Add-on STS raised the proportion of patients reaching midtreatment compared with HUS-iCBT as usual (29/50, 58% vs 18/50, 36%; P=.045) and treatment end point (12/50, 24% vs 3/50, 6%; P=.02). Change in BDI score also favored add-on STS (3.63 points vs 1.1 points; P=.049), whereas duration of treatment did not differ. CONCLUSIONS: Add-on STS enhances adherence and symptom improvement of patients at risk of dropping out of iCBT for depression in routine clinical practice. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) 55123131; http://www.isrctn.com/ISRCTN55123131.

Development of an International Standard Set of Value-Based Outcome Measures for Patients With Chronic Kidney Disease: A Report of the International Consortium for Health Outcomes Measurement (ICHOM) CKD Working Group.

Value-based health care is increasingly promoted as a strategy for improving care quality by benchmarking outcomes that matter to patients relative to the cost of obtaining those outcomes. To support the shift toward value-based health care in chronic kidney disease (CKD), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international working group of health professionals and patient representatives to develop a standardized minimum set of patient-centered outcomes targeted for clinical use. The considered outcomes and patient-reported outcome measures were generated from systematic literature reviews. Feedback was sought from patients and health professionals. Patients with very high-risk CKD (stages G3a/A3 and G3b/A2-G5, including dialysis, kidney transplantation, and conservative care) were selected as the target population. Using an online modified Delphi process, outcomes important to all patients were selected, such as survival and hospitalization, and to treatment-specific subgroups, such as vascular access survival and kidney allograft survival. Patient-reported outcome measures were included to capture domains of health-related quality of life, which were rated as the most important outcomes by patients. Demographic and clinical variables were identified to be used as case-mix adjusters. Use of these consensus recommendations could enable institutions to monitor, compare, and improve the quality of their CKD care.

Prophylaxis of chemotherapy-induced neutropenia and febrile neutropenia with lipegfilgrastim in patients with non-Hodgkin lymphoma (NADIR study).

OBJECTIVE: The prospective non-interventional study (NIS) NADIR was designed to evaluate both effectiveness and safety of prophylactic use of lipegfilgrastim (Lonquex® ), a glycopegylated granulocyte colony-stimulating factor, in cancer patients with different tumor entities undergoing chemotherapy in routine clinical practice. The primary objective was incidence of severe neutropenia, febrile neutropenia (FN), and neutropenia-associated complications. METHOD: NADIR was a national, multicenter, prospective NIS. RESULTS: Here, we present the data on patients with non-Hodgkin lymphoma (NHL). Final analysis comprised 337 NHL patients having received ≥1 administration of lipegfilgrastim. Primary prophylaxis with lipegfilgrastim was documented in 78.7% of patients with high risk to develop FN. In total, ≥1 severe neutropenia (grade 3/4) was reported in 115 (34.1%) patients and ≥1 event of FN documented in 15 (4.5%) patients. Grade 3/4 infections were reported in 22 (6.5%) patients overall. Most frequently reported adverse events (AEs) related to lipegfilgrastim in total were bone pain (5.4%), leukocytosis (2.1%), back pain (1.8%), platelet count decreased (1.2%), and myalgia (1.2%). Fatal serious AEs were documented in 9 (2.7%) patients; none were attributable to lipegfilgrastim. CONCLUSION: Prophylaxis or therapeutic intention with lipegfilgrastim in NHL patients in routine clinical practice showed similar effectiveness and safety as demonstrated in the pivotal trials.

Factors associated with second-line triplet therapy in routine care in relapsed/refractory multiple myeloma.

WHAT IS KNOWN AND OBJECTIVE: Second-line therapy (SLT) trials in relapsed/refractory multiple myeloma (RRMM) report superior outcomes with triplet combinations. We sought to determine factors associated with triplet SLT in routine practice. METHODS: A retrospective cohort with claims for MM between 01/01/2008 and 03/31/2015 was grouped by 1-2 ("doublet") or 3+ ("triplet") agent therapy. Charlson comorbidity index (CCI) and disability status; CRAB symptoms (hypercalcaemia, renal/bone disease, anaemia); and relapse risk were determined. RESULTS: Among 623 patients, the triplet group (n=146 [23%]) was younger (65.2 vs 69.8 years) and more likely to have high-risk relapse (67% vs 50%), CRAB symptoms (94.5% vs 81.1%), triplet first-line treatment (75% vs 51%) and frontline stem cell transplant (38% vs 20%) (P<0.001 for all). In multivariate analyses, CRAB symptoms (OR: 3.22, 95% CI: 1.47, 7.10), high-risk relapse (OR: 1.71, 95% CI: 1.12, 2.62) and prior triplet therapy (OR: 2.16, 95% CI: 1.38, 3.40), but neither CCI nor disability, were associated with triplet SLT. A trend towards triplets among younger patients (<65 vs >75 years, OR: 1.73, 95% CI: 0.99, 3.04) was observed. WHAT IS NEW AND CONCLUSION: The majority of patients did not receive triplet regimens. Treatment selection with triplet therapy for RRMM should carefully consider comorbidities and patient-specific characteristics.

Non-Invasive Prenatal Testing for Sex Chromosome Aneuploidy in Routine Clinical Practice.

OBJECTIVES: To assess the accuracy of non-invasive prenatal testing (NIPT) for sex chromosome aneuploidy (SCA) in routine clinical practice and to review counselling and sonographic issues arising in SCA cases. METHODS: Three specialist Australian obstetric ultrasound and prenatal diagnosis practices offering NIPT after 10 weeks' gestation participated in this study. NIPT was reported for chromosomes 21, 18, 13, X, and Y. RESULTS: NIPT screening was performed in 5,267 singleton pregnancies. The odds of being affected given a positive screening result (OAPR) was lowest for SCAs, most notably for monosomy X (20%). Fewer women underwent invasive prenatal testing when counselled regarding a high risk for SCA (65.5%) compared with those who had a high risk for another aneuploidy (85%). The positive screening rate of NIPT including SCA was 2.3%, but 1.2% if only the autosomal trisomies were included in the panel. CONCLUSION: The addition of SCA testing to NIPT doubles the positive screening rate. The OAPR for SCAs (most notably for monosomy X) is reduced compared with the autosomal trisomies. Clinicians need a more extensive discussion with women prior to the inclusion of the X and Y chromosomes in the NIPT panel, given the complexity in counselling regarding further management and the additional anxiety that these abnormal results may cause. A benefit of sex chromosome analysis is an improvement in antenatal diagnosis of some disorders of sexual development.

Real-World Effectiveness and Safety of Oral Combination Antiviral Therapy for Hepatitis C Virus Genotype 4 Infection.

Patients with hepatitis C virus (HCV) genotype 4 infection are poorly represented in clinical trials of second-generation direct-acting antiviral agents (DAAs). More data are needed to help guide treatment decisions. We investigated the effectiveness and safety of DAAs in patients with genotype 4 infection in routine practice. In this cohort study, HCV genotype 4-infected patients treated with ombitasvir/paritaprevir/ritonavir (OMV/PTVr) + ribavirin (RBV) (n=122) or ledipasvir/sofosbuvir (LDV/SOF) ± RBV (n=130) included in a national database were identified and prospectively followed up. Demographic, clinical and virologic data and serious adverse events (SAEs) were analyzed. Differences between treatment groups mean that data cannot be compared directly. Overall sustained virologic response at Week 12 post treatment (SVR12) was 96.2% with OMV/PTVr+RBV and 95.4% with LDV/SOF±RBV. In cirrhotic patients, SVR12 was 91.2% with OMV/PTVr+RBV and 93.2% with LDV/SOF±RBV. There was no significant difference in SVR12 according to degree of fibrosis in either treatment group (P = .243 and P = .244, respectively). On multivariate analysis, baseline albumin <3.5 g/dL (OMV/PTVr) and bilirubin >2 mg/dL (both cohorts) were significantly associated with failure to achieve SVR (P < .05). Rates of SAEs and SAE-associated discontinuation were 5.7% and 2.5%, respectively, in the OMV/PTVr subcohort and 4.6% and 0.8%, respectively, in the LDV/SOF subcohort. DAA-based regimens returned high rates of SVR12, comparable to limited data from clinical trials, in cirrhotic and non-cirrhotic HCV genotype 4 patients managed in a realworld setting. Safety profiles of both regimens were good and comparable to those reported for other HCV genotypes.

Childhood immune thrombocytopenia: A nationwide cohort study on condition management and outcomes.

OBJECTIVES: Nationwide prospective cohort study exploring (i) the factors associated with treatment initiation (vs. watchful waiting) in children with primary immune thrombocytopenia (ITP) followed in routine clinical practice and (ii) the predictors of chronicity at 12 months. PROCEDURE: Between 2008 and 2013, 23 centers throughout France consecutively included 257 children aged 6 months-18 years and diagnosed with primary ITP over a 5-year period. Data on ITP clinical features along with medical management were collected at baseline and 12 months. Multivariate logistic regressions were used to determine (i) and (ii) as defined above, providing odds ratio (OR) with 95% confidence interval (95% CI). RESULTS: One hundred thirty-seven (53%) children were males, median age was 4.6 years, median platelet count was 7 × 109/l, and 214 (81%) patients initiated medication. Factors independently associated with treatment initiation included platelet counts <10 × 109/l (P < 0.0001) and mucocutaneous bleeding symptoms at baseline (P < 0.001). At 12 months, data were available for 211 (82%) children, of whom 160 (74%) had recovered. Predictors of chronicity included female gender (OR = 2.2; 95% CI = 1.0-4.8), age ≥10 years (OR = 2.6; 95% CI = 1.1-6.0), and platelet counts ≥10 × 109 /l (OR = 3.2; 95% CI = 1.5-6.9). CONCLUSIONS: In routine clinical practice, the decision to apply a watchful waiting strategy seems to be driven by platelet counts even in the absence of bleeding symptoms, resulting in treatment being initiated in more than 80% of the children surveyed. Overall, younger children with ITP showed good prognosis, with lower platelet counts and, to a lesser extent, male gender predicting more favorable outcomes.