Communication partners experiences of communicating with adults with severe/profound intellectual disability through augmentative and alternative communication: A mixed methods systematic review.

People with severe/profound intellectual disability experience challenges in communicating and require their communication partners to adapt to their means of communication. Augmentative and Alternative Communication (AAC) is recognised as a potential means to meet their communication needs. Interventions need to be aimed at both the individual and their communication partners. We conducted a mixed methods systematic review of the literature to synthesise evidence on communication partners experience of communicating with adults with severe/profound intellectual disability through AAC. Eight publications met the inclusion criteria, they underwent thematic synthesis where four themes emerged. A shared commitment to communication partnership is fundamental for the effective and efficient use of AAC. However, there was a disconnect between communication partners perceptions of their roles and responsibilities. This review prompts further research to explore communication partners perceptions of their roles and responsibilities in the use of AAC with people with severe/profound intellectual disabilities.

Acute service and disability service providers experiences of joint working to improve health care experiences of people with an intellectual disability compared to non-joint working: A mixed-method systematic review.

Persons with intellectual disabilities require frequent access to acute services. Many also access disability services within the community. Reports and enquiries have highlighted the sub-optimal healthcare provided to this group when accessing healthcare in acute services. Joint working between acute and disability services has been identified as a measure to improve healthcare for this group. A mixed method systematic review was undertaken to explore current evidence of joint working between both service providers. Twelve publications were included, and the data were analysed using thematic analysis. Confusion around responsibility and limited training in acute services prevented joint working from occurring. Information-sharing is pivotal in promoting joint-working, but measures which facilitated it were not always used. Albeit acute services demonstrated a strong commitment to deliver quality care to those with intellectual disabilities. Much of the available research captures the experiences of staff in acute services. There is a paucity of research available exploring experiences of disability service providers.

Determining the need for a breast cancer awareness educational intervention for women with mild/moderate levels of intellectual disability: A qualitative descriptive study.

OBJECTIVE: Following a review of the existing body of literature, this study aimed to explore the need for a breast cancer awareness intervention specifically targeted at women with mild/moderate levels of intellectual disability (ID) and provide perspectives on the preferred processes and content underpinning an intervention. METHODS: A qualitative, descriptive design using semi-structured, individual (n = 5) and focus group (n = 5) interviews were used to engage with a non-probability, purposive sample of key stakeholders (n = 25) including women with mild/moderate levels of ID, caregivers and healthcare professionals. Data were analysed using qualitative content analysis. RESULTS: Findings highlighted that an educational intervention should focus on breast awareness as opposed to breast cancer awareness. Additionally, findings identified that a combined breast awareness and healthy living intervention could be effective. However, the intervention needs to have a multimodal, hands-on, person-centred approach to learning which is underpinned by theory. Furthermore, integrating the caregivers and healthcare professionals into the intervention is recommended. CONCLUSION: Findings from this study provide a foundation for developing and implementing a theoretically underpinned, multimodal, breast awareness and healthy living educational intervention for women with mild/moderate levels of ID.

Defining breast cancer awareness and identifying barriers to breast cancer awareness for women with an intellectual disability: A review of the literature.

INTRODUCTION: Incidence rates for developing breast cancer are similar for women regardless of intellectual ability. However, women with an intellectual disability present with advanced breast cancers, which often have a poor prognosis. METHOD: A structured narrative review of the literature was performed to explore the concepts of breast awareness and breast cancer awareness and subsequently, identify barriers to breast cancer awareness encountered by women with an intellectual disability. RESULTS: A total of 22 studies involving people with varying levels of intellectual disability informed this review. The barriers to breast cancer awareness encountered by women with an intellectual disability include: lack of their understanding, the role of the carer and literacy issues. CONCLUSION: Identifying the barriers to breast cancer awareness for women with an intellectual disability will help to facilitate breast cancer awareness which has the potential to result in better long-term outcomes through an early diagnosis of breast cancer.

Improved overall survival in melanoma with combined dabrafenib and trametinib.

BACKGROUND: The BRAF inhibitors vemurafenib and dabrafenib have shown efficacy as monotherapies in patients with previously untreated metastatic melanoma with BRAF V600E or V600K mutations. Combining dabrafenib and the MEK inhibitor trametinib, as compared with dabrafenib alone, enhanced antitumor activity in this population of patients. METHODS: In this open-label, phase 3 trial, we randomly assigned 704 patients with metastatic melanoma with a BRAF V600 mutation to receive either a combination of dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) or vemurafenib (960 mg twice daily) orally as first-line therapy. The primary end point was overall survival. RESULTS: At the preplanned interim overall survival analysis, which was performed after 77% of the total number of expected events occurred, the overall survival rate at 12 months was 72% (95% confidence interval [CI], 67 to 77) in the combination-therapy group and 65% (95% CI, 59 to 70) in the vemurafenib group (hazard ratio for death in the combination-therapy group, 0.69; 95% CI, 0.53 to 0.89; P=0.005). The prespecified interim stopping boundary was crossed, and the study was stopped for efficacy in July 2014. Median progression-free survival was 11.4 months in the combination-therapy group and 7.3 months in the vemurafenib group (hazard ratio, 0.56; 95% CI, 0.46 to 0.69; P<0.001). The objective response rate was 64% in the combination-therapy group and 51% in the vemurafenib group (P<0.001). Rates of severe adverse events and study-drug discontinuations were similar in the two groups. Cutaneous squamous-cell carcinoma and keratoacanthoma occurred in 1% of patients in the combination-therapy group and 18% of those in the vemurafenib group. CONCLUSIONS: Dabrafenib plus trametinib, as compared with vemurafenib monotherapy, significantly improved overall survival in previously untreated patients with metastatic melanoma with BRAF V600E or V600K mutations, without increased overall toxicity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT01597908.).

Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma.

BACKGROUND: Combined BRAF and MEK inhibition, as compared with BRAF inhibition alone, delays the emergence of resistance and reduces toxic effects in patients who have melanoma with BRAF V600E or V600K mutations. METHODS: In this phase 3 trial, we randomly assigned 423 previously untreated patients who had unresectable stage IIIC or stage IV melanoma with a BRAF V600E or V600K mutation to receive a combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily) or dabrafenib and placebo. The primary end point was progression-free survival. Secondary end points included overall survival, response rate, response duration, and safety. A preplanned interim overall survival analysis was conducted. RESULTS: The median progression-free survival was 9.3 months in the dabrafenib-trametinib group and 8.8 months in the dabrafenib-only group (hazard ratio for progression or death in the dabrafenib-trametinib group, 0.75; 95% confidence interval [CI], 0.57 to 0.99; P=0.03). The overall response rate was 67% in the dabrafenib-trametinib group and 51% in the dabrafenib-only group (P=0.002). At 6 months, the interim overall survival rate was 93% with dabrafenib-trametinib and 85% with dabrafenib alone (hazard ratio for death, 0.63; 95% CI, 0.42 to 0.94; P=0.02). However, a specified efficacy-stopping boundary (two-sided P=0.00028) was not crossed. Rates of adverse events were similar in the two groups, although more dose modifications occurred in the dabrafenib-trametinib group. The rate of cutaneous squamous-cell carcinoma was lower in the dabrafenib-trametinib group than in the dabrafenib-only group (2% vs. 9%), whereas pyrexia occurred in more patients (51% vs. 28%) and was more often severe (grade 3, 6% vs. 2%) in the dabrafenib-trametinib group. CONCLUSIONS: A combination of dabrafenib and trametinib, as compared with dabrafenib alone, improved the rate of progression-free survival in previously untreated patients who had metastatic melanoma with BRAF V600E or V600K mutations. (Funded by GlaxoSmithKline; Clinical Trials.gov number, NCT01584648.).

Improved survival with MEK inhibition in BRAF-mutated melanoma.

BACKGROUND: Activating mutations in serine-threonine protein kinase B-RAF (BRAF) are found in 50% of patients with advanced melanoma. Selective BRAF-inhibitor therapy improves survival, as compared with chemotherapy, but responses are often short-lived. In previous trials, MEK inhibition appeared to be promising in this population. METHODS: In this phase 3 open-label trial, we randomly assigned 322 patients who had metastatic melanoma with a V600E or V600K BRAF mutation to receive either trametinib, an oral selective MEK inhibitor, or chemotherapy in a 2:1 ratio. Patients received trametinib (2 mg orally) once daily or intravenous dacarbazine (1000 mg per square meter of body-surface area) or paclitaxel (175 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to receive trametinib. Progression-free survival was the primary end point, and overall survival was a secondary end point. RESULTS: Median progression-free survival was 4.8 months in the trametinib group and 1.5 months in the chemotherapy group (hazard ratio for disease progression or death in the trametinib group, 0.45; 95% confidence interval [CI], 0.33 to 0.63; P<0.001). At 6 months, the rate of overall survival was 81% in the trametinib group and 67% in the chemotherapy group despite crossover (hazard ratio for death, 0.54; 95% CI, 0.32 to 0.92; P=0.01). Rash, diarrhea, and peripheral edema were the most common toxic effects in the trametinib group and were managed with dose interruption and dose reduction; asymptomatic and reversible reduction in the cardiac ejection fraction and ocular toxic effects occurred infrequently. Secondary skin neoplasms were not observed. CONCLUSIONS: Trametinib, as compared with chemotherapy, improved rates of progression-free and overall survival among patients who had metastatic melanoma with a BRAF V600E or V600K mutation. (Funded by GlaxoSmithKline; METRIC ClinicalTrials.gov number, NCT01245062.).

Factors influencing communication partners of persons with severe/profound intellectual disability use of augmentative and alternative communication: an integrative review.

PURPOSE: To present a synthesis of evidence related to the factors influencing communication partners' use of augmentative and alternative communication with persons with severe/profound intellectual disability. MATERIALS AND METHODS: An integrative review guided by five steps; problem identification, literature search, data evaluation, data analysis and presentation was undertaken. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, nine databases were searched, 1,342 studies were screened against the eligibility criteria, and 15 studies underwent thematic analysis. RESULTS: Two themes emerged; (1) Achieving Meaningful Communication and (2) Communication Partners' Preparedness to Use Augmentative and Alternative Communication. Achieving meaningful communication was central to communication partners' use of augmentative and alternative communication and was two-fold. It involved identifying the persons' communication methods and encouraging them to communicate. Communication partners' preparedness also influenced their use of augmentative and alternative communication. This preparedness was impacted by communication partners' preconceived thoughts about and knowledge of augmentative and alternative communication, nurturing their belief in augmentative and alternative communication, and the interpersonal dynamic between network members. CONCLUSION: Communication partners' use of augmentative and alternative communication is influenced by multiple and complex factors. The findings contribute to the knowledge of the potential factors to be considered to prepare communication partners to use augmentative and alternative communication.

Multiple, complex factors influence communication partners of persons with severe/profound intellectual disability use of augmentative and alternative communication (AAC), which include communication partners' beliefs, attitudes, expectations, knowledge and resources such as training, support and time.To offer individuals with severe/profound intellectual disability opportunities to communicate, communication partners need to recognise their attempts and thus, their ability. Continuously being sensitive to the individuals' communication methods, whilst being cognisant that these methods can change may enhance communication partners' awareness and understanding of the individuals' communication attempts.Communication partners' need to feel prepared to use AAC. To feel prepared, they need to be aware of the potential benefits that AAC can offer the interaction and the long-term outcomes, develop their knowledge, and be surrounded by a supportive team dynamic.

Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial.

BACKGROUND: Dabrafenib, an inhibitor of mutated BRAF, has clinical activity with a manageable safety profile in studies of phase 1 and 2 in patients with BRAF(V600)-mutated metastatic melanoma. We studied the efficacy of dabrafenib in patients with BRAF(V600E)-mutated metastatic melanoma. METHODS: We enrolled patients in this open-label phase 3 trial between Dec 23, 2010, and Sept 1, 2011. This report is based on a data cutoff date of Dec 19, 2011. Patients aged 18 years or older with previously untreated, stage IV or unresectable stage III BRAF(V600E) mutation-positive melanoma were randomly assigned (3:1) to receive dabrafenib (150 mg twice daily, orally) or dacarbazine (1000 mg/m(2) intravenously every 3 weeks). Patients were stratified according to American Joint Committee on Cancer stage (unresectable III+IVM1a+IVM1b vs IVM1c). The primary endpoint was investigator-assessed progression-free survival and was analysed by intention to treat; safety was assessed per protocol. This study is registered with ClinicalTrials.gov, number NCT01227889. FINDINGS: Of the 733 patients screened, 250 were randomly assigned to receive either dabrafenib (187 patients) or dacarbazine (63 patients). Median progression-free survival was 5·1 months for dabrafenib and 2·7 months for dacarbazine, with a hazard ratio (HR) of 0·30 (95% CI 0·18-0·51; p<0·0001). At data cutoff, 107 (57%) patients in the dabrafenib group and 14 (22%) in the dacarbazine group remained on randomised treatment. Treatment-related adverse events (grade 2 or higher) occurred in 100 (53%) of the 187 patients who received dabrafenib and in 26 (44%) of the 59 patients who received dacarbazine. The most common adverse events with dabrafenib were skin-related toxic effects, fever, fatigue, arthralgia, and headache. The most common adverse events with dacarbazine were nausea, vomiting, neutropenia, fatigue, and asthenia. Grade 3-4 adverse events were uncommon in both groups. INTERPRETATION: Dabrafenib significantly improved progression-free survival compared with dacarbazine. FUNDING: GlaxoSmithKline.

Can standardized diagnostic assessment be a useful adjunct to clinical assessment in child mental health services? A randomized controlled trial of disclosure of the Development and Well-Being Assessment to practitioners.

PURPOSE: While research demands standardized diagnostic assessments as an indication of sufficient methodological rigour, there is debate about their application to clinical practice. The Development and Well-Being Assessment (DAWBA) provides a structured assessment of psychiatric disorder. Since it can be completed on-line, it could be used by Child and Adolescent Mental Health Services with few additional demands on staff. Access to the standardized diagnostic information as an adjunct to clinical assessment could reduce the number of appointments spent on assessment, free up practitioner time to work on engagement and improve clinical outcomes by increasing the accuracy of assessment and thus access to the appropriate evidence-based treatment. METHOD: Randomized controlled trial of the disclosure of the DAWBA to the assessing practitioner (n = 117) versus assessment at normal (n = 118) and analysed by "intention to disclose". RESULTS: Exposure to the DAWBA may increase agreement between the DAWBA and practitioners about some anxiety disorders, but detected no other statistically significant increased agreement for other disorders, nor a reduced need for further assessment, the number of difficulties recognised or influence on outcomes. CONCLUSIONS: The results may be explained by the inadequacy of the DAWBA, lack of statistical power to detect any effects that were present or a reluctance of some practitioners to use the DAWBA in their assessment. Future research might benefit from exploring the use of the DAWBA or similar assessments as a referral rather than an assessment tool, and exploring how practitioners and parents experience and use the DAWBA and what training might optimise the utility of the DAWBA to clinical practice.

[The work placement for developing skills]. / Le parcours de stage pour développer ses compétences.

The implementation of the reform of nursing studies is a strategic part of the 2009-2013 care project of Millau General Hospital as it has modified the supervision of students on work placements and the organisation of caregivers. In order to make the ten-week work placements a rich learning experience, the teams of the hospital and nurse training institute have designed work placements and tools to provide the best possible support for the students and help them construct a professional identity.

Prognostic or predictive plasma cytokines and angiogenic factors for patients treated with pazopanib for metastatic renal-cell cancer: a retrospective analysis of phase 2 and phase 3 trials.

BACKGROUND: Several targeted drugs are approved for treatment of patients with metastatic renal-cell cancer, but no validated biomarkers are available for prediction of clinical outcome. We aimed to assess the prognostic and predictive associations of pretreatment plasma concentrations of cytokine and angiogenic factors (CAFs) with data from a phase 2 and a phase 3 trial of pazopanib treatment. METHODS: We used a three-step approach for screening, confirmation, and validation of prospective CAF biomarkers. We screened 17 CAFs in 129 patients who had the greatest or least tumour shrinkage in a phase 2 trial of 215 patients treated with pazopanib. We confirmed associations of candidate CAFs (those identified in the screening and from previous studies) with tumour response and progression-free survival (PFS) in 215 patients from this phase 2 trial with an independent analytical platform. We validated confirmed markers in 344 patients from a randomised, placebo-controlled, phase 3 clinical study of pazopanib. FINDINGS: Five candidate markers emerged from initial screening-interleukin 6, interleukin 8, hepatocyte growth factor (HGF), tissue inhibitor of metalloproteinases (TIMP)-1, and E-selectin. Confirmatory analyses identified associations of interleukin 6, interleukin 8, VEGF, osteopontin, E-selectin, and HGF with continuous tumour shrinkage or PFS in patients treated with pazopanib. In the validation set of samples from the phase 3 trial, patients treated with pazopanib who had high concentrations (relative to median) of interleukin 8 (p=0·006), osteopontin (p=0·0004), HGF (p=0·010), and TIMP-1 (p=0·006) had shorter PFS than did those with low concentrations. In the placebo group, high concentrations of interleukin 6 (p<0·0001), interleukin 8 (p=0·002), and osteopontin (p<0·0001) were all prognostically associated with shorter PFS. These factors were stronger prognostic markers than were standard clinical classifications (Eastern Cooperative Oncology Group, Memorial Sloan-Kettering Cancer Center, and Heng criteria). High concentrations of interleukin 6 were predictive of improved relative PFS benefit from pazopanib compared with placebo (p(interaction)=0·009); standard clinical classifications were not predictive of PFS benefit. INTERPRETATION: CAF profiles could provide prognostic information beyond that of standard clinical classification and identify markers predictive of pazopanib benefit in patients with metastatic renal-cell carcinoma. Further studies of the predictive effects of these markers in different populations and with different drugs (eg, mTOR inhibitors) are warranted. FUNDING: GlaxoSmithKline.

Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial.

BACKGROUND: Brain metastases are common in patients with metastatic melanoma and median overall survival from their diagnosis is typically 17-22 weeks. We assessed dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain. METHODS: We undertook a multicentre, open-label, phase 2 trial in 24 centres in six countries. We enrolled patients with histologically confirmed Val600Glu or Val600Lys BRAF-mutant melanoma and at least one asymptomatic brain metastasis (≥5 mm and ≤40 mm in diameter). Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had adequate organ function. Patients were split into two cohorts: those in cohort A had not received previous local treatment for brain metastases and those in cohort B had progressive brain metastases after previous local treatments. Patients received 150 mg oral dabrafenib twice a day until disease progression, death, or unacceptable adverse events. The primary endpoint was the proportion of patients with Val600Glu BRAF-mutant melanoma who achieved an overall intracranial response, which was defined as a complete response or partial response assessed with a modified form of Response Evaluation Criteria in Solid Tumors (RECIST 1.1). We included patients who received at least one dose of dabrafenib in efficacy and safety analyses. This study is registered with ClinicalTrials.gov, number NCT01266967. FINDINGS: Between Feb 2, 2011, and Aug 5, 2011, we enrolled 172 patients: 89 (52%) in cohort A and 83 (48%) in cohort B. 139 (81%) had Val600Glu BRAF-mutant melanoma. 29 (39·2%, 95% CI 28·0-51·2) of 74 patients with Val600Glu BRAF-mutant melanoma in cohort A achieved an overall intracranial response, as did 20 (30·8%, 19·9-43·4) of 65 in cohort B. One (6·7%, 0·2-31·9) of 15 patients with Val600Lys BRAF-mutant melanoma achieved an overall intracranial response in cohort A, as did four (22·2%, 6·4-47·6) of 18 such patients in cohort B. Treatment-related adverse events of grade 3 or worse occurred in 38 (22%) patients. Eleven (6%) patients developed squamous-cell carcinoma (five [6%] patients in cohort A, of whom one also had keratoacanthoma; six [7%] in cohort B). Four grade 4 treatment-related adverse events occurred in cohort A: one blood amylase increase, one convulsion, one lipase increase, and one neutropenia. Two grade 4 events occurred in cohort B: one agranulocytosis and one intracranial haemorrhage. 51 (30%) patients had a serious adverse event. The three most frequent serious adverse events were pyrexia (ten [6%] patients), intracranial haemorrhage (ten [6%]; one treatment-related), and squamous-cell carcinoma (11 [6%]). INTERPRETATION: Dabrafenib has activity and an acceptable safety profile in patients with Val600Glu BRAF-mutant melanoma and brain metastases irrespective of whether they are untreated or have been previously treated but have progressed. FUNDING: GlaxoSmithKline.

Targeting the IL1ß Pathway for Cancer Immunotherapy Remodels the Tumor Microenvironment and Enhances Antitumor Immune Responses.

High levels of IL1ß can result in chronic inflammation, which in turn can promote tumor growth and metastasis. Inhibition of IL1ß could therefore be a promising therapeutic option in the treatment of cancer. Here, the effects of IL1ß blockade induced by the mAbs canakinumab and gevokizumab were evaluated alone or in combination with docetaxel, anti-programmed cell death protein 1 (anti-PD-1), anti-VEGFα, and anti-TGFß treatment in syngeneic and humanized mouse models of cancers of different origin. Canakinumab and gevokizumab did not show notable efficacy as single-agent therapies; however, IL1ß blockade enhanced the effectiveness of docetaxel and anti-PD-1. Accompanying these effects, blockade of IL1ß alone or in combination induced significant remodeling of the tumor microenvironment (TME), with decreased numbers of immune suppressive cells and increased tumor infiltration by dendritic cells (DC) and effector T cells. Further investigation revealed that cancer-associated fibroblasts (CAF) were the cell type most affected by treatment with canakinumab or gevokizumab in terms of change in gene expression. IL1ß inhibition drove phenotypic changes in CAF populations, particularly those with the ability to influence immune cell recruitment. These results suggest that the observed remodeling of the TME following IL1ß blockade may stem from changes in CAF populations. Overall, the results presented here support the potential use of IL1ß inhibition in cancer treatment. Further exploration in ongoing clinical studies will help identify the best combination partners for different cancer types, cancer stages, and lines of treatment.

Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors.

BACKGROUND: Numerous efficacious chemotherapy regimens may cause thrombocytopenia. Thrombopoietin receptor (TPO-R) agonists, such as eltrombopag, represent a novel approach for the treatment of chemotherapy-induced thrombocytopenia. The TPO-R MPL is expressed on megakaryocytes and megakaryocyte precursors, although little is known about its expression on other tissues. METHODS: Breast, lung, and ovarian tumor samples were analyzed for MPL expression by microarray and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and for TPO-R protein expression by immunohistochemistry (IHC). Cell line proliferation assays were used to analyze the in vitro effect of eltrombopag on breast, lung, and ovarian tumor cell proliferation. The lung carcinoma cell lines were also analyzed for TPO-R protein expression by Western blot. RESULTS: MPL mRNA was not detectable in 118 breast tumors and was detectable at only very low levels in 48% of 29 lung tumors studied by microarray analysis. By qRT-PCR, low but detectable levels of MPL mRNA were detectable in some normal (14-43%) and malignant (3-17%) breast, lung, and ovarian tissues. A comparison of MPL to EPOR, ERBB2, and IGF1R mRNA demonstrates that MPL mRNA levels were far lower than those of EPOR and ERBB2 mRNA in the same tissues. IHC analysis showed negligible TPO-R protein expression in tumor tissues, confirming mRNA analysis. Culture of breast, lung, and ovarian carcinoma cell lines showed no increase, and in fact, showed a decrease in proliferation following incubation with eltrombopag. Western blot analyses revealed no detectable TPO-R protein expression in the lung carcinoma cell lines. CONCLUSIONS: Multiple analyses of breast, lung, and ovarian tumor samples and/or cell lines show no evidence of MPL mRNA or TPO-R protein expression. Eltrombopag does not stimulate growth of breast, lung, or ovarian tumor cell lines at doses likely to exert their actions on megakaryocytes and megakaryocyte precursors.

Non-verbal communication between Registered Nurses Intellectual Disability and people with an intellectual disability: an exploratory study of the nurse's experiences. Part 2.

This is the second of two articles presenting the findings of a qualitative study which explored the experiences of Registered Nurses Intellectual Disability (RNIDs) of communicating with people with an intellectual disability who communicate non-verbally. While Part 1 outlined the study background, context and methodology along with the overarching, multi-dimensional category of 'familiarity/knowing the person', the current article critically discusses the themes and subthemes encapsulated in this category. Each theme is considered in the light of current policies, strategies and philosophies shaping the provision of services to people with an intellectual disability in Ireland. The results suggest that the RNID is ideally located and key to supporting the implementation of these policies and strategies due to their highly developed and proficient skill set as well as experience of communicating with people with an intellectual disability who communicate non-verbally.

Non-verbal communication between Registered Nurses Intellectual Disability and people with an intellectual disability: an exploratory study of the nurse's experiences. Part 1.

This is the first of two articles presenting the findings of a qualitative study which explored the experiences of Registered Nurses Intellectual Disability (RNIDs) of communicating with people with an intellectual disability who communicate non-verbally. The article reports and critically discusses the findings in the context of the policy and service delivery discourses of person-centredness, inclusion, choice and independence. Arguably, RNIDs are the profession who most frequently encounter people with an intellectual disability and communication impairment. The results suggest that the communication studied is both complicated and multifaceted. An overarching category of 'familiarity/knowing the person' encompasses discrete but related themes and subthemes that explain the process: the RNID knowing the service-user; the RNID/service-user relationship; and the value of experience. People with an intellectual disability, their families and disability services are facing a time of great change, and RNIDs will have a crucial role in supporting this transition.

Correction: Phase II Study Evaluating 2 Dosing Schedules of Oral Foretinib (GSK1363089), cMET/VEGFR2 Inhibitor, in Patients with Metastatic Gastric Cancer.

[This corrects the article DOI: 10.1371/journal.pone.0054014.].

Human epidermal growth factor receptor 2 (HER2) extracellular domain levels are associated with progression-free survival in patients with HER2-positive metastatic breast cancer receiving lapatinib monotherapy.

BACKGROUND: Changes in serum human epidermal growth factor receptor 2 (HER2) levels associated with clinical outcomes, including objective response rate, progression-free survival (PFS), and overall survival have been reported in patients with metastatic breast cancer (MBC) receiving trastuzumab and chemotherapy. This study investigated whether baseline or changes in serum HER2 correlated with overall response rate (ORR) and/or PFS in patients with MBC receiving first-line lapatinib monotherapy. METHODS: The EGF20009 study investigated lapatinib monotherapy in 138 HER2-positive patients with MBC previously untreated for their metastatic disease. Serum was collected and assessed at baseline and every 4 weeks for 16 weeks after treatment initiation. Disease assessment was performed at weeks 8 and 12 and every 12 weeks thereafter. A ≥ 20% decrease or increase in serum HER2 was defined as a significant change. RESULTS: Seventy-nine percent of patients had elevated baseline serum HER2. Baseline serum HER2 was associated with ORR (P = .043) but not PFS. Patients with a ≥ 20% decrease from baseline of serum HER2 at weeks 4, 8, 12, and 16 had a significantly increased ORR and prolonged PFS. Conversely, those with a ≥ 20% increase from baseline had a significantly lower ORR and shorter PFS. CONCLUSION: Significant decreases in serum HER2 levels during the first 16 weeks of lapatinib monotherapy were associated with better clinical outcome (longer PFS and increased ORR) in HER2-positive MBC patients.

Lapatinib plus capecitabine in treating HER2-positive advanced breast cancer: efficacy, safety, and biomarker results from Chinese patients.

Overexpression of human epidermal growth factor receptor-2 (HER2) in metastatic breast cancer (MBC) is associated with poor prognosis. This single-arm open-label trial (EGF109491; NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), time to response (TTR), duration of response (DoR), central nervous system (CNS) as first site of relapse, and safety. The results showed that there were 23 patients with partial responses and 7 patients with stable disease, resulting in a CBR of 57.7%. The median PFS was 6.34 months (95% confidence interval, 4.93-9.82 months). The median TTR and DoR were 4.07 months (range, 0.03-14.78 months) and 6.93 months (range, 1.45-9.72 months), respectively. Thirteen (25.0%) patients had new lesions as disease progression. Among them, 2 (3.8%) patients had CNS disease reported as the first relapse. The most common toxicities were palmar-plantar erythrodysesthesia (59.6%), diarrhea (48.1%), rash (48.1%), hyperbilirubinemia (34.6%), and fatigue (30.8%). Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample, baseline PIK3CA mutation status was not associated with CBR (P = 0.639) or PFS (P = 0.989). These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC, irrespective of PIK3CA status.