Treatment preferences towards thrombopoietin-receptor agonists for immune thrombocytopenia and experience of disease (TRAPeze): Italy cohort

Objective: Identify patient preference towards thrombopoietin-receptor agonists (TPO-RAs) and determine the clinical and social impact of immune thrombocytopenia (ITP) in Italy.Methods: The Thrombopoietin-Receptor Agonist Patient experience (TRAPeze) survey collected responses from Italian residents from 17th January to 28th February 2022. TRAPeze utilized a discrete choice experiment (DCE) to elicit patient preferences towards TPO-RA attributes and a patient burden survey (PBS) to determine ITP disease characteristics and social impact.Results: Seventy-six respondents completed the DCE, of which 69 completed both the DCE and PBS (mean [range] age 45 [18.0-73.0] years, 80% female). TPO-RA attributes with the greatest influence over respondent choice were method of administration (odds ratio [OR] 2.96; 95% confidence interval [CI] 2.16-4.06), drug-food interactions (OR 1.48; 95% CI 1.17-1.86) and frequency of dosing (OR 1.32; 95% CI 1.15-1.52). Respondents were more likely to prefer therapies administered orally over subcutaneous injection (OR 3.76; 95% CI 2.51-5.63), once weekly over once daily (OR 1.83; 95% CI 1.26-2.65), and therapies without food restrictions over with restrictions (OR 1.58; 95% CI 1.17-2.14).The most frequently reported symptoms were bruising (82%), petechiae (65%) and fatigue (64%). Most respondents (84%) felt ITP impacted familial relationships and 71% of employed respondents reported fatigue influencing their ability to work, with 31% reducing working hours.The most frequently reported symptoms were bruising (82%), petechiae (65%) and fatigue (64%). Most respondents (84%) felt ITP impacted familial relationships and 71% of employed respondents reported fatigue influencing their ability to work, with 31% reducing working hours.Conclusion: Although responses indicated a moderate perception of general health, ITP clearly impacted respondent work and social life. Our findings demonstrate respondents preferred TPO-RAs delivered orally, with less frequent dosing and without food restrictions

Registries in immune thrombocytopenia (ITP) in Europe: the European Research Consortium on ITP (ERCI) network

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Long-term treatment with rilzabrutinib in patients with immune thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune disease associated with autoantibodymediated platelet destruction and impaired platelet production, resulting in thrombocytopenia and a predisposition to bleeding. The ongoing, global phase 1/2 study showed that rilzabrutinib, a Bruton tyrosine kinase inhibitor specifically developed to treat autoimmune disorders, could be an efficacious and well-tolerated treatment for ITP. Clinical activity, durability of response, and safety were evaluated in 16 responding patients who continued rilzabrutinib 400 mg twice daily in the long-term extension (LTE) study. At LTE entry, the median platelet count was 87 × 109/L in all patients, 68 × 109/L in those who had rilzabrutinib monotherapy (n = 5), and 156 × 109/L in patients who received concomitant ITP medication (thrombopoietin-receptor agonists and/or corticosteroids, n = 11). At a median duration of treatment of 478 days (range, 303-764), 11 of 16 patients (69%) continued to receive rilzabrutinib. A platelet count of =50 × 109/L was reported in 93% of patients for more than half of their monthly visits. The median percentage of LTE weeks with platelet counts =30 × 109/L and =50 × 109/L was 100% and 88%, respectively. Five patients discontinued concomitant ITP therapy and maintained median platelet counts of 106 × 109/L at 3 to 6 months after stopping concomitant ITP therapy. Adverse events related to treatment were grade 1 or 2 and transient, with no bleeding, thrombotic, or serious adverse events. With continued rilzabrutinib treatment in the LTE, platelet responses were durable and stable over time with no new safety signals.</p

Physical function endpoints in cancer cachexia clinical trials: Systematic Review 1 of the cachexia endpoints series

In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6-min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group-Performance Status [ECOG-PS]) or patient-reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ-C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise-based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG-PS (16 vs. 9 trials), and patient-reported EORTC QLQ-C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia

Physical Function Endpoints in Cancer Cachexia Trials; Systematic Review 1 of the Cachexia Endpoints Series

Abstract In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990–2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6‐min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group‐Performance Status [ECOG‐PS]) or patient‐reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ‐C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise‐based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG‐PS (16 vs. 9 trials), and patient‐reported EORTC QLQ‐C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia

Internal validation of STRmix™ – A multi laboratory response to PCAST

We report a large compilation of the internal validations of the probabilistic genotyping software STRmix™. Thirty one laboratories contributed data resulting in 2825 mixtures comprising three to six donors and a wide range of multiplex, equipment, mixture proportions and templates. Previously reported trends in the LR were confirmed including less discriminatory LRs occurring both for donors and non-donors at low template (for the donor in question) and at high contributor number. We were unable to isolate an effect of allelic sharing. Any apparent effect appears to be largely confounded with increased contributor number

Appetite and dietary intake endpoints in cancer cachexia clinical trials: Systematic Review 2 of the cachexia endpoints series

There is no consensus on the optimal endpoint(s) in cancer cachexia trials. Endpoint variation is an obstacle when comparing interventions and their clinical value. The aim of this systematic review was to summarize and evaluate endpoints used to assess appetite and dietary intake in cancer cachexia clinical trials. A search for studies published from 1 January 1990 until 2 June 2021 was conducted using MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Eligible studies examined cancer cachexia treatment versus a comparator in adults with assessments of appetite and/or dietary intake as study endpoints, a sample size ≥40 and an intervention lasting ≥14 days. Reporting was in line with PRISMA guidance, and a protocol was published in PROSPERO (2022 CRD42022276710). This review is part of a series of systematic reviews examining cachexia endpoints. Of the 5975 articles identified, 116 were eligible for the wider review series and 80 specifically examined endpoints of appetite (65 studies) and/or dietary intake (21 studies). Six trials assessed both appetite and dietary intake. Appetite was the primary outcome in 15 trials and dietary intake in 7 trials. Median sample size was 101 patients (range 40–628). Forty-nine studies included multiple primary tumour sites, while 31 studies involved single primary tumour sites (15 gastrointestinal, 7 lung, 7 head and neck and 2 female reproductive organs). The most frequently reported appetite endpoints were visual analogue scale (VAS) and numerical rating scale (NRS) (40%). The appetite item from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30/C15 PAL (38%) and the appetite question from North Central Cancer Treatment Group anorexia questionnaire (17%) were also frequently applied. Of the studies that assessed dietary intake, 13 (62%) used food records (prospective registrations) and 10 (48%) used retrospective methods (24-h recall or dietary history). For VAS/NRS, a mean change of 1.3 corresponded to Hedge's g of 0.5 and can be considered a moderate change. For food records, a mean change of 231 kcal/day or 11 g of protein/day corresponded to a moderate change. Choice of endpoint in cachexia trials will depend on factors pertinent to the trial to be conducted. Nevertheless, from trials assessed and available literature, NRS or EORTC QLQ C30/C15 PAL seems suitable for appetite assessments. Appetite and dietary intake endpoints are rarely used as primary outcomes in cancer cachexia. Dietary intake assessments were used mainly to monitor compliance and are not validated in cachexia populations. Given the importance to cachexia studies, dietary intake endpoints must be validated before they are used as endpoints in clinical trials

Evaluation of an asthma education programme delivered in an antenatal clinic

Severe and poorly controlled asthma may lead to adverse outcomes for mothers and their babies. An asthma management and education programme was established in the Antenatal Clinic (ANC) of John Hunter Hospital to optimise asthma management in pregnant women with asthma. Aim: The aim of this study was to evaluate the effect of the Asthma Management Service in the John Hunter Hospital ANC. Design: Longitudinal analytic survey. Method: Women were enrolled in their first trimester and underwent an initial assessment of asthma severity, treatment and management skills. Deficits were corrected by skills education, medical assessment and treatment. Records were reviewed of pregnant women with asthma who attended the Asthma Management Service between January 1998 and December 1999. Results: 83 women were enrolled and 72 patients attended between 2 and 8 visits during pregnancy, depending upon asthma severity. Conclusion: After structured asthma education, there were significant improvements in asthma knowledge and management skills. The antenatal clinic is a opportune setting for asthma education among pregnant women with asthma. Asthma Control Visit 1 After Education p Value Night Symptoms 53% 42% 0.15 Morning Symptoms 66% 46% 0.01 Activity Limitation 35% 30% 0.65 Asthma Skills pMDI: Inadequate 13% 0% 0.001 Spacer: Inadequate 2% 0% 0.50 Medication Knowledge 47% 88% 0.0001 Action Plan 13% 78% 0.0001 Peak Flow Monitoring 8% 78% 0.0001

A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura

The safety and efficacy of weekly rituximab 375 mg/m(2) (x4), given within 3 days of acute TTP admission, with standard therapy (PEX and steroids) was evaluated. Clinical outcomes were compared to historical controls (n = 40) who had not received rituximab. Within the trial group, 15 of 40 required ICU admission and 15% of all cases with the highest troponin T levels on admission were ventilated. Before the second rituximab infusion, 68% of cases had a platelet count > 50 x 10(9)/L and 38% > 150 x 10(9)/L. Fewer PEX were required in whites compared to nonwhite in the rituximab group (mean 14 vs 21, P = .0095). Inpatient stay was reduced by 7 days in the non-ICU trial cases compared to historical controls (P = .04), especially in whites, with a mean reduction of 7 days (P = .05). Ten percent of trial cases relapsed, median, 27 months (17-31 months), compared to 57% in historical controls, median 18 months (3-60 months; P = .0011). There were no excess infections or serious adverse events with rituximab. In conclusion, rituximab appears a safe and effective therapy. Inpatient stay and relapse are significantly reduced in the rituximab cohort. Rituximab should be considered in conjunction with standard therapy on acute presentation of TTP. This study was registered at www.clinicaltrials.gov as NCT009-3713. (Blood. 2011; 118(7): 1746-1753

Barriers to racial/ethnic minority application and competition for NIH research funding.

BACKGROUND: Despite recognition of the need to increase the pool of racial/ethnic minority investigators, racial/ethnic minority representation among National Institutes of Health (NIH)-funded investigators remains low. Racial/ethnic minority investigators bring unique perspectives and experiences that enhance the potential for understanding factors that underlie racial/ethnic variation in health and health status. Identification of barriers to successful minority competition for NIH funding and suggestions for strategies to overcome them were obtained from a concept mapping project and a meeting of minority investigators and investigators at minority-serving institutions. METHODS: Concept mapping, a mixed-methods planning approach that integrates common data collection processes with multivariate statistical analyses, was used in this exploratory project. The concept mapping approach generated a series of related "concept maps" that were used for data interpretation and meeting discussions. RESULTS: Barriers to minority investigator competition for NIH funding identified by concept mapping participants include: (1) inadequate research infrastructure, training and development; (2) barriers to development as independent researchers; (3) inadequate mentoring; (4) insensitivity, misperceptions and miscommunication about the specific needs of investigators involved in research with minority communities; (5) institutional bias in NIH policies; (6) unfair competitive environment; (7) lack of institutional support; (8) lack of support for research topics/methods relevant to research with minority communities; and (9) social, cultural and environmental barriers. DISCUSSION: Data from both the concept mapping and the meeting discussions suggest the need to use a multilevel approach to increase minority representation among funded NIH investigators. Specifically, the NIH should use strategies that overcome barriers at the home institution, within NIH and at the investigator level