Evaluation of Lay Support in Pregnant women with Social risk (ELSIPS): a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Maternal, neonatal and child health outcomes are worse in families from black and ethnic minority groups and disadvantaged backgrounds. There is little evidence on whether lay support improves maternal and infant outcomes among women with complex social needs within a disadvantaged multi-ethnic population in the United Kingdom (UK).</p> <p>Method/Design</p> <p>The aim of this study is to evaluate a lay Pregnancy Outreach Worker (POW) service for nulliparous women identified as having social risk within a maternity service that is systematically assessing social risks alongside the usual obstetric and medical risks. The study design is a randomised controlled trial (RCT) in nulliparous women assessed as having social risk comparing standard maternity care with the addition of referral to the POW support service.</p> <p>The POWs work alongside community midwifery teams and offer individualised support to women to encourage engagement with services (health and social care) from randomisation (before 28 weeks gestation) until 6 weeks after birth.</p> <p>The primary outcomes have been chosen on the basis that they are linked to maternal and infant health. The two primary outcomes are engagement with antenatal care, assessed by the number of antenatal visits; and maternal depression, assessed using the Edinburgh Postnatal Depression Scale at 8-12 weeks after birth. Secondary outcomes include maternal and neonatal morbidity and mortality, routine child health assessments, including immunisation uptake and breastfeeding at 6 weeks. Other psychological outcomes (self efficacy) and mother-to-infant bonding will also be collected using validated tools.</p> <p>A sample size of 1316 will provide 90% power (at the 5% significance level) to detect increased engagement with antenatal services of 1.5 visits and a reduction of 1.5 in the average EPDS score for women with two or more social risk factors, with power in excess of this for women with any social risk factor. Analysis will be by intention to treat.</p> <p>Qualitative research will explore the POWs' daily work in context. This will complement the findings of the RCT through a triangulation of quantitative and qualitative data on the process of the intervention, and identify other contextual factors that affect the implementation of the intervention.</p> <p>Discussion</p> <p>The trial will provide high quality evidence as to whether or not lay support (POW) offered to women identified with social risk factors improves engagement with maternity services and reduces numbers of women with depression.</p> <p>MREC number</p> <p>10/H1207/23</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN35027323">ISRCTN35027323</a></p

Factors predicting toxicity and response following isolated limb infusion for melanoma: An international multi-centre study

Available online 13 July 2020Introduction: Isolated limb infusion (ILI) is a minimally-invasive procedure for delivering high-dose regional chemotherapy to treat melanoma in-transit metastases confined to a limb. The aim of this international multi-centre study was to identify predictive factors for toxicity and response. Methods: Data of 687 patients who underwent a first ILI for melanoma in-transit metastases confined to the limb between 1992 and 2018 were collected at five Australian and four US tertiary referral centres. Results: After ILI, predictive factors for increased limb toxicity (Wieberdink grade III/IV limb toxicity, n = 192, 27.9%) were: female gender, younger age, procedures performed before 2005, lower limb procedures, higher melphalan dose, longer drug circulation and ischemia times, and increased tissue hypoxia. No patient experienced grade V toxicity (necessitating amputation). A complete response (n = 199, 28.9%) was associated with a lower stage of disease, lower burden of disease (BOD) and thinner Breslow thickness of the primary melanoma. Additionally, an overall response (combined complete and partial response, n = 441, 64.1%) was associated with female gender, Australian centres, procedures performed before 2005, lower limb procedures and lower actinomycin-D doses. On multivariate analysis, higher melphalan dose remained a predictive factor for toxicity, while lower stage of disease and lower BOD remained predictive factors for overall response. Conclusion: ILI is safe and effective to treat melanoma in-transit metastases. Predictive factors for toxicity and response identified in this study will allow improved patient selection and optimization of intra-operative parameters to increase response rates, while keeping toxicity low.Timothy J. Kenyon-Smith, Hidde M. Kroon, John T. Miura, Jüri Teras, Georgia M. Beasley, Dean Mullen, Norma E. Farrow, Paul J. Mosca, Michael C. Lowe, Clara R. Farley, Aishwarya Potdar, Hala Daou, James Sun, Jeffrey M. Farma, Michael A. Henderson, David Speakman, Jonathan Serpell, Keith A. Delman, B. Mark Smithers, Andrew Barbour, Brendon J. Coventry, Douglas S. Tyler, Jonathan S. Zager, John F. Thompso

International Multicenter Experience of Isolated Limb Infusion for In-Transit Melanoma Metastases in Octogenarian and Nonagenarian Patients

BACKGROUND:Isolated limb infusion (ILI) is used to treat in-transit melanoma metastases confined to an extremity. However, little is known about its safety and efficacy in octogenarians and nonagenarians (ON). PATIENTS AND METHODS:ON patients (≥ 80 years) who underwent a first ILI for American Joint Committee on Cancer seventh edition stage IIIB/IIIC melanoma between 1992 and 2018 at nine international centers were included and compared with younger patients (< 80 years). A cytotoxic drug combination of melphalan and actinomycin-D was used. RESULTS:Of the 687 patients undergoing a first ILI, 160 were ON patients (median age 84 years; range 80-100 years). Compared with the younger cohort (n = 527; median age 67 years; range 29-79 years), ON patients were more frequently female (70.0% vs. 56.9%; p = 0.003), had more stage IIIB disease (63.8 vs. 53.3%; p = 0.02), and underwent more upper limb ILIs (16.9% vs. 9.5%; p = 0.009). ON patients experienced similar Wieberdink limb toxicity grades III/IV (25.0% vs. 29.2%; p = 0.45). No toxicity-related limb amputations were performed. Overall response for ON patients was 67.3%, versus 64.6% for younger patients (p = 0.53). Median in-field progression-free survival was 9 months for both groups (p = 0.88). Median distant progression-free survival was 36 versus 23 months (p = 0.16), overall survival was 29 versus 40 months (p < 0.0001), and melanoma-specific survival was 46 versus 78 months (p = 0.0007) for ON patients compared with younger patients, respectively. CONCLUSIONS:ILI in ON patients is safe and effective with similar response and regional control rates compared with younger patients. However, overall and melanoma-specific survival are shorter.Jüri Teras, Hidde M. Kroon, John T. Miura, Tim Kenyon-Smith, Georgia M. Beasley, Dean Mullen, Norma E. Farrow, Paul J. Mosca, Michael C. Lowe, Clara R. Farley, Aishwarya Potdar, Hala Daou, James Sun, Michael Carr, Jeffrey M. Farma, Michael A. Henderson, David Speakman, Jonathan Serpell, Keith A. Delman, B. Mark Smithers, Andrew Barbour, Douglas S. Tyler, Brendon J. Coventry, Jonathan S. Zager, and John F. Thompso

Factors predicting toxicity and response following isolated limb infusion for melanoma: An international multi-center analysis

Poster presentation #P204H.M. Kroon, T. Kenyon-Smith, J.T. Miura, J. Teras, G.M. Beasley, D. Mullen, N.E. Farrow, P. Mosca, M.C. Lowe, C.R. Farley, Y. Kim, S.M. Naqvi, A. Potdar, H. Daou, J. Sun, J.M. Farma, M.A. Henderson, D. Speakman, J. Serpell, K.A. Delman, M. Smithers, B.J. Coventry, D.S. Tyler, J.S. Zager, J.F. Thompso

International multicenter experience of isolated limb infusion for in-transit melanoma metastases in octogenarian and nonagenarian patients

Background: Isolated limb infusion (ILI) is used to treat in-transit melanoma metastases confined to an extremity. However, little is known about its safety and efficacy in octogenarians and nonagenarians (ON). Patients and Methods: ON patients (≥ 80\ua0years) who underwent a first ILI for American Joint Committee on Cancer seventh edition stage IIIB/IIIC melanoma between 1992 and 2018 at nine international centers were included and compared with younger patients (< 80\ua0years). A cytotoxic drug combination of melphalan and actinomycin-D was used. Results: Of the 687 patients undergoing a first ILI, 160 were ON patients (median age 84\ua0years; range 80–100\ua0years). Compared with the younger cohort (n = 527; median age 67\ua0years; range 29–79\ua0years), ON patients were more frequently female (70.0% vs. 56.9%; p = 0.003), had more stage IIIB disease (63.8 vs. 53.3%; p = 0.02), and underwent more upper limb ILIs (16.9% vs. 9.5%; p = 0.009). ON patients experienced similar Wieberdink limb toxicity grades III/IV (25.0% vs. 29.2%; p = 0.45). No toxicity-related limb amputations were performed. Overall response for ON patients was 67.3%, versus 64.6% for younger patients (p = 0.53). Median in-field progression-free survival was 9\ua0months for both groups (p = 0.88). Median distant progression-free survival was 36 versus 23\ua0months (p = 0.16), overall survival was 29 versus 40\ua0months (p < 0.0001), and melanoma-specific survival was 46 versus 78\ua0months (p = 0.0007) for ON patients compared with younger patients, respectively. Conclusions: ILI in ON patients is safe and effective with similar response and regional control rates compared with younger patients. However, overall and melanoma-specific survival are shorter

Factors predicting toxicity and response following isolated limb infusion for melanoma: an international multi-centre study

Introduction: Isolated limb infusion (ILI) is a minimally-invasive procedure for delivering high-dose regional chemotherapy to treat melanoma in-transit metastases confined to a limb. The aim of this international multi-centre study was to identify predictive factors for toxicity and response. Methods: Data of 687 patients who underwent a first ILI for melanoma in-transit metastases confined to the limb between 1992 and 2018 were collected at five Australian and four US tertiary referral centres. Results: After ILI, predictive factors for increased limb toxicity (Wieberdink grade III/IV limb toxicity, n = 192, 27.9%) were: female gender, younger age, procedures performed before 2005, lower limb procedures, higher melphalan dose, longer drug circulation and ischemia times, and increased tissue hypoxia. No patient experienced grade V toxicity (necessitating amputation). A complete response (n = 199, 28.9%) was associated with a lower stage of disease, lower burden of disease (BOD) and thinner Breslow thickness of the primary melanoma. Additionally, an overall response (combined complete and partial response, n = 441, 64.1%) was associated with female gender, Australian centres, procedures performed before 2005, lower limb procedures and lower actinomycin-D doses. On multivariate analysis, higher melphalan dose remained a predictive factor for toxicity, while lower stage of disease and lower BOD remained predictive factors for overall response. Conclusion: ILI is safe and effective to treat melanoma in-transit metastases. Predictive factors for toxicity and response identified in this study will allow improved patient selection and optimization of intra-operative parameters to increase response rates, while keeping toxicity low