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Purpose Patients with recurrent glioblastoma (rGBM) have a poor prognosis. Epidermal growth factor receptor (EGFR) gene amplification is present in ~ 50% of glioblastomas (GBMs). Depatuxizumab mafodotin (depatux-m), formerly ABT-414, is an antibody–drug conjugate that preferentially binds cells with EGFR amplification, is internalized and releases a potent antimicrotubule agent, monomethyl auristatin F (MMAF). Here we report the safety, pharmacokinetics, and efficacy of depatux-m monotherapy at the recommended Phase 2 dose (RPTD) in patients with EGFR-amplified, rGBM. Methods M12-356 (NCT01800695) is an open-label study with three escalation and expansion cohorts. Sixty-six patients with EGFR-amplified, rGBM were treated with depatux-m monotherapy at 1.25 mg/kg intravenously every 2 weeks. Adults with measurable rGBM, who were bevacizumab-naïve, with EGFR amplification were eligible. Results Among 66 patients, median age was 58 years (range 35–80). All patients were previously treated with radiotherapy/temozolomide. The most common adverse events (AEs) were eye related (91%), including blurred vision (65%), dry eye (29%), keratitis, and photophobia (27% each). Grade 3/4 AEs occurred in 42% of all patients, and ocular Grade 3/4 AEs occurred in 33% of patients overall. One patient (2%) had a Grade 4 ocular AE. Ocular AEs were manageable and usually resolved once treatment with depatux-m ceased. The objective response rate was 6.8%, the 6-month progression-free survival rate was 28.8%, and the 6-month overall survival rate was 72.5%. Conclusion Depatux-m monotherapy displayed frequent but mostly Grade 1/2 ocular toxicities. A PFS6 of 28.8% was observed in this rGBM population, warranting further study. Electronic supplementary material The online version of this article (doi:10.1007/s00280-017-3451-1) contains supplementary material, which is available to authorized users.

Black men have the highest rate of prostate cancer (PCa) morbidity and mortality in the US, and often receive delayed and/or poorer-quality treatment. This inequity has led many to turn to complementary and alternative medicine/therapies (CAM). However, little is known about the use of these therapies within the Black community. The purpose of this study was to describe types of CAM therapies used, and the reasons behind their use for overall health and PCa treatment and prevention among three groups of Black males, namely African Americans, Caribbean Immigrants and African Immigrants. This study used a mixed-methods design with a quantitative phase (n = 575) followed by a qualitative phase (n = 61) with participants recruited from various parts of the country. Results revealed differences among subgroups in CAM use for overall health and PCa, as well as differences in the types of CAM therapies used and differences in the reasons behind their use. The findings of this study reveal a prevalence of CAM use for overall health and PCa within three different groups of Black men and identifies the specific CAM used. There were significant differences in the types of CAM used by each subgroup for both overall health and PCa. This study also shows that there is value in looking at Black subgroups distinctively, for their rates of CAM use and reasons for use, are distinctly different.

Alzheimer's disease and related dementias (ADRD) often result in communication deficits that can lead to negative health outcomes as well as complications for caregiving and clinical care. Although augmentative and alternative communication (AAC) devices have demonstrated efficacy in assisting persons living with dementia (PLWD) in communicating, few devices offer customization for the person's care preferences (e.g., clothing, food, activities) or are designed for integration into clinical care and caregiving. To address this issue, our research team is developing a novel electronic AAC prototype with a touchscreen to promote communication and personhood for PLWD. The current article describes the development of this technology and uses the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement to describe the clinical trial that is planned to test its efficacy. TARGETS: PLWD and their care partners. INTERVENTION DESCRIPTION: Use of AAC Plus to promote communication and personhood for PLWD. MECHANISMS OF ACTION: AAC Plus will provide PLWD and care partners a way to communicate PLWD's daily preferences and provide clinical data for health care providers. OUTCOMES: Determine whether enhanced communication of daily preferences of PLWD will improve quality of life of PLWD and their care partners. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04571502 (Date of registration October 1, 2020). [ Research in Gerontological Nursing, 14 (5), 225–234.]

Haitian nurses live in a precarious environment, with healthcare disparity and low wages. In the presence of significant politico-social-economic disparities, adverse effects of natural disasters, deleterious infrastructure, challenged self-boundaries, and the burden of caring for high-need patients, the authors sought a better understanding of nurses' perspective of the situation. During qualitative interviews, Haitian nurses in two faith-based hospitals (N = 17) reported feeling powerless yet exhibited resilience and dedication to nursing as a calling. These conditions cry out for support of nurses' self-care needs. Future interventions may help nurses identify better resources to care for themselves and guide their practice.

Objective To review the currently available research into romantic partner involvement during oncology consultations. Methods Studies were identified via database searches plus hand-searching. A narrative review was performed using the principles of Thematic, and Framework syntheses. The search strategy was performed according to the principles of PRISMA. Results From 631 results, 18 studies were included. The findings indicate that romantic partners are most valued by patients when they provide emotional, practical, and informational support. It is also indicated that psychosocial and sexual concerns are rarely discussed. Couples’ self-reported satisfaction with consultations appear related to the extent of romantic partner involvement, the roles that they enacted, and the extent to which psychosocial and sexual concerns were addressed. Conclusion This review indicates that romantic partner involvement during clinical consultations enhances the couple’s experience. However, there are methodological limitations to this body of research, which are discussed in this review. Practice implications Research to date has yet to offer an exploration of the social practices and conversational actions relating to romantic partner involvement during triadic oncology consultations. Future studies that draw upon recordings of these consultations, using methods capable of analysing situated social practices can address this gap.

Background Infertility is a global problem, with high prevalence in India. As a pronatalist society, infertility is particularly problematic in India, causing stigma, shame, and blame especially for women. Infertility consequences for women include discrimination, social exclusion, and abandonment, putting them at high risk for mental health distress. Furthermore, mental health is highly stigmatized and specialized care is largely unavailable. Despite the cultural importance of childbearing, research on infertility distress and resulting mental health sequelae is lacking, particularly among low-income women. The purpose of this study is to assess mental health, using validated scales, among Mumbai slum-dwelling women with a history of infertility. Methods We conducted a mixed-method, cross-sectional study. A focus group discussion with community health workers (n = 7) informed the development of a comprehensive survey. The survey consisted of validated scales whenever possible, in addition to questions pertaining to women's sociodemographic and reproductive history. After rigorous forward and back translation, the surveys were conducted as face-to-face structured interviews due to low literacy levels and the research naivete of our respondents. Interviews were conducted by culturally, linguistically, gender-matched, trained research assistants. Results Mumbai slum-dwelling women of reproductive age suffering from infertility (N = 74) participated. Most (85%) women and their husbands (66%) reported previous infertility testing. Participants had elevated mental health distress (anxiety and depression symptomology) largely explained by general health, length of marriage, and coping strategy employed. Conclusion Women facing the double stigma of mental health and infertility need innovative programs to address their challenges.

BACKGROUND: Intestinal (i.e. “gut”) permeability may be related to cardiovascular disease (CVD) risk, but biomarkers for gut permeability are limited and associations with CVD risk are unknown -particularly among older adults. AIMS: This cross-sectional study aimed to determine if serum biomarkers related to gut permeability [intestinal fatty acid-binding protein (iFABP)] and bacterial toxin clearing [cluster of differentiation 14 (CD14), lipopolysaccharide binding protein (LBP)] are associated with CVD risk among older adults. METHODS: Older adults (n = 74, 69.6 ± 6.5 years old) were stratified by CVD risk category. One-way ANOVAs determined differences in each biomarker by risk category, and associations with risk score were evaluated with Pearson correlations. RESULTS: LBP (p = 0.007), but not iFABP and CD14, was significantly different between CVD risk categories. Post-hoc tests indicated LBP was higher in moderate risk and high-moderate risk compared to the high risk category (p < 0.005). Evaluation of LBP and individual components in the risk score demonstrated a moderate, negative correlation of LBP with age and systolic blood pressure (r = −0.335 and r = −0.297) and a small positive correlation between LBP and total cholesterol and LDL cholesterol (r = 0.204 and r = 0.220). DISCUSSION/CONCLUSION: Lower risk for CVD was associated with higher circulating concentrations of LBP, lower iFABP, and lower systemic inflammation in older adults. Further, there were small positive relationships between total and LDL cholesterol and circulating levels of LBP. These data suggest LBP may be a key component in reducing CVD risk in older adults.

To (1) investigate the efficacy of multiple doses of an orally delivered probiotic bacteria Lactobacillus paracasei (LP) modified to express angiotensin (1–7) (LP-A) in altering physiologic parameters relevant to the gut-brain axis in older rats and to (2) compare this strategy with subcutaneous delivery of synthetic Ang(1–7) peptide on circulating Ang(1–7) concentrations and these gut-brain axis parameters. Male 24-month-old F344BN rats received oral gavage of LP-A, or subcutaneous injection of Ang(1–7) for 0×, 1×, 3×, or 7×/week over 4 weeks. Circulating RAS analytes, inflammatory cytokines, and tryptophan and its downstream metabolites were measured by ELISA, electrochemiluminescence, and LC-MS respectively. Microbiome taxonomic analysis of fecal samples was performed via 16S-based PCR. Inflammatory and tryptophan-related mRNA expression was measured in colon and pre-frontal cortex. All dosing regimens of LP-A induced beneficial changes in fecal microbiome including overall microbiota community structure and α-diversity, while the 3×/week also significantly increased expression of the anti-inflammatory species Akkermansia muciniphila. The 3×/week also increased serum serotonin and the neuroprotective analyte 2-picolinic acid. In the colon, LP-A increased quinolinate phosphoribosyltransferase expression (1×/week) and increased kynurenine aminotransferase II (1× and 3×/week) mRNA expression. LP-A also significantly reduced neuro-inflammatory gene expression in the pre-frontal cortex (3×/week: COX2, IL-1β, and TNFα; 7×/week: COX2 and IL-1β). Subcutaneous delivery of Ang(1–7) increased circulating Ang(1–7) and reduced angiotensin II, but most gut-brain parameters were unchanged in response. Oral—but not subcutaneous—Ang(1–7) altered physiologic parameters related to gut-brain axis, with the most effects observed in 3×/week oral dosing regimen in older rats. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11357-020-00196-y) contains supplementary material, which is available to authorized users.

Objective This scoping review will summarize what is known about formal and informal perinatal bereavement care guidelines used in health care facilities before discharge, and map the mental health outcomes of parents against characteristics of the guidelines. Introduction Conflicting evidence for bereavement care guidelines, the lack of randomized controlled trials and experimental studies, and older synthesized information with a limited focus or population make synthesis complex. A scoping review will facilitate the process of determining the breadth and depth of the literature. Inclusion criteria Sources pertaining to bereavement care guidelines used in health care facilities immediately after perinatal loss (miscarriage, stillbirth, or neonatal death) and measuring parents' mental health outcomes will be included. Sources relating to family members other than parents, perinatal loss occurring outside of a health care facility, and physical care guidelines will be excluded. Methods The proposed review will be conducted using JBI methodology for scoping reviews. The team will consider quantitative and qualitative studies, practice guidelines, case reports, expert opinions, systematic reviews, professional organization websites, and gray literature. Major databases to be searched will include CINAHL (EBSCO), PsycINFO (EBSCO), SocINDEX (EBSCO), Cochrane, Embase, MEDLINE (PubMed), and Web of Science. The earliest empirical study found (1976) will serve as the starting date limit. After pilot testing the two-step screening process (titles and abstracts, then full-text articles), data will be extracted, collated, and presented in narrative form as well as in tables and diagrams. The results will provide facilities with a broad view of bereavement care to support grieving parents' mental health.

Background There is a need to improve consultations between patients with persistent musculoskeletal low back pain and orthopaedic spine clinicians when surgery is not indicated. Poor communication and lack of education about self- management in these consultations have been shown to be associated with increased distress and higher subsequent health care seeking. Aim To develop a standardised intervention to improve spine care consultations for patients for whom surgery is not beneficial. Method The intervention was developed in six stages. The first three stages included: interviews with patients, an interactive workshop with clinicians from a mix of disciplines, and interviews with spine clinicians about their perspective of the recommendations, their perceived difficulties and potential improvements. Information from these stages was synthesised by an expert panel, creating a draft intervention structure and content. The main features of the intervention and the materials developed were then reviewed by patients and spine clinicians. Finally, the research team incorporated the recommended amendments to produce the intervention. Results In total, 36 patients and 79 clinicians contributed to the development of the intervention. The final intervention includes three components: a pre-consultation letter with information suggesting that surgery is one possible intervention amongst many, introducing the staff, and alerting patients to bring with them a potted history of interventions tried previously. The intervention includes short online training sessions to improve clinicians’ communication skills, during the consultation, in reference to listening skills, validation of patients’ pain, and use of appropriate language. Clinicians are also supplied with a list of evidence-based sources for advice and further information to share with patients. Finally, post consultation, a follow up letter includes a short summary of the patients’ clinical journey, the results of their examination and tests, and a reminder of recommendations for self-management. Conclusion The intervention includes aspects around patient education and enhanced clinician skills. It was developed with input from a multitude of stakeholders and is based on patients’ perceptions of what they would find reassuring and empowering when surgery is excluded. The intervention has the potential to improve the patients care journey and might lead to changes in practice in spine clinicians.

ObjectiveThis study aimed to explore the perceptions of orthopaedic clinicians about consultations for people with persistent musculoskeletal low back pain (PMLBP) in which surgery is not recommended. Surgery is not recommended for the majority of PMLBP consulting in secondary care settings.SettingSecondary care sector in the UK.ParticipantsSemi-structured qualitative interviews were conducted with 24 orthopaedic team clinicians from 17 different hospitals in the UK and Ireland. Interviews explored clinicians’ perceptions of the challenges in consultations where surgery is not indicated. Interviews were transcribed verbatim and analysed using thematic analysis.ResultsTwo meta-themes, Difficulties and Enablers, each consisting of several subthemes were identified. Difficulties included challenges around the choice of appropriate terminology and labels for PMLBP, managing patients’ expectations, working with mentally vulnerable patients and explaining imaging findings. Enablers included early management of expectations, use of routine imaging, triaging, access to direct referral elsewhere, including other non-surgical practitioners in the team, training to improve communication skills and understanding of psychological issues.ConclusionThe findings highlight clinicians’ perceived need for concordance in messages delivered across the care pathway and training of orthopaedic clinicians to deliver effective reassurance and address patients’ needs in circumstances where surgery is not indicated.

This paper explores how target-audience expectations and generic limitations on modern, mass-culture adaptations of Shakespeare’s comedy Twelfth Night mould the characterization of his officious steward Malvolio, and dictate the degree of centrality that his subplot holds in each different version. A trans-generic application of Shlomith Rimmon-Kenan’s work on characterization will expose how the character of Malvolio is constructed and presented, first in the original play and then in three modern adaptations of Twelfth Night into different popular genres. The works selected for contrastive analysis with the original play each represent different generic fields found on today’s mass-culture market – romance fiction, teen cinema and the web-comic. Respectively, they are: The Madness of Love, a contemporary romance novel by Katharine Davies, published in 2005; She’s the Man, a Hollywood teen film directed by Andy Fickman in 2006; and a web-comic retelling of Twelfth Night by Mya Lixian Gosling, which was published on her website Good Tickle-Brain Shakespeare in 2014.

Background Ageing may cause impairments in executing bilateral movement control. This study investigated age-related changes in interlimb force coordination across multiple trials by quantifying bilateral motor synergies based on the uncontrolled manifold hypothesis. Participants completed the trials with and without visual feedback. Methods Twenty healthy individuals (10 older adults and 10 young adults) performed 12 isometric force control trials for the two vision conditions at 5% of maximal voluntary contraction. All dependent variables were analyzed in two-way mixed model (Group × Vision Condition; 2 × 2) ANOVAs with repeated measures on the last factor. Results The analyses revealed that older adults had greater mean force produced by two hands in both vision conditions (i.e., yes and no visual feedback). Across both vision conditions, the older adult group showed greater asymmetrical force variability (i.e., standard deviation of non-dominant hand > standard deviation of dominant hand) and revealed more positive correlation coefficients between forces produced by two hands as compared with the young adult group. Finally, an index of bilateral motor synergies was significantly greater in young adults than older adults when visual feedback was available. Conclusion The current findings indicate that deficits in interlimb force coordination across multiple trials appeared in older adults.

Background Physical exercise is associated with decreased cardiovascular disease (CVD) risk, but recent large-scale trials suggest that exercise alone is insufficient to reduce CVD events in high-risk older adults. Purpose This pilot randomized clinical trial aimed to collect critical data on feasibility, safety, and protocol integrity necessary to design a fully powered randomized controlled trial (RCT) and evaluate the impact of combining structured exercise with an intervention designed to enhance non-exercise physical activity (EX+NEPA) compared to EX alone. Methods Forty participants aged ≥60 years with moderate-to-high risk of coronary heart disease events were randomly assigned to either the EX+NEPA or EX groups and followed for 20 weeks. Both groups underwent a twice-weekly, 8-week center-based exercise intervention with aerobic and resistance exercises. EX+NEPA group also received a wearable activity tracking device along with behavioral monitoring and feedback throughout the study. Study outcomes were evaluated at 8 and 20 weeks. Results Data are presented as adjusted mean change of the differences over time with 95% confidence intervals at 20 weeks. Relative to EX, the change in steps/day at 20 weeks was 1994 (-40.27, 4028) higher for EX+NEPA. For sedentary time at close-out, the EX+NEPA group was -6.8 (-45.2, 31.6) min/day relative to EX. The between-group differences for systolic and diastolic blood pressure were -9.9 (-19.6, -0.3) and -1.8 (-6.9, 3.3) mmHg, respectively. Conclusion The addition of wearable technology intervention appeared to positively influence daily activity patterns and changes in blood pressure - potentially improving risk factors for CVD. A fully powered randomized trial is needed to ultimately test this hypothesis.

Background Over the past decade, there has been an increase in the use of information technologies to educate and support people with dementia and their family caregivers. At the same time, chatbot technologies have become increasingly popular for use by the public and have been identified as having benefits for health care delivery. However, little is known about how chatbot technologies may benefit people with dementia and their caregivers. Objective This study aims to identify the types of current commercially available chatbots that are designed for use by people with dementia and their caregivers and to assess their quality in terms of features and content. Methods Chatbots were identified through a systematic search on Google Play Store, Apple App Store, Alexa Skills, and the internet. An evidence-based assessment tool was used to evaluate the features and content of the identified apps. The assessment was conducted through interrater agreement among 4 separate reviewers. Results Of the 505 initial chatbots identified, 6 were included in the review. The chatbots assessed varied significantly in terms of content and scope. Although the chatbots were generally found to be easy to use, some limitations were noted regarding their performance and programmed content for dialog. Conclusions Although chatbot technologies are well established and commonly used by the public, their development for people with dementia and their caregivers is in its infancy. Given the successful use of chatbots in other health care settings and for other applications, there are opportunities to integrate this technology into dementia care. However, more evidence-based chatbots that have undergone end user evaluation are needed to evaluate their potential to adequately educate and support these populations.

ObjectivesContextual components of treatment previously associated with patient outcomes include the environment, therapeutic relationship and expectancies. Questions remain about which components are most important, how they influence outcomes and comparative effects across treatment approaches. We aimed to identify significant and strong contextual predictors of patient outcomes, test for psychological mediators and compare effects across three treatment approaches.DesignProspective cohort study with patient-reported and practitioner-reported questionnaire data (online or paper) collected at first consultation, 2 weeks and 3 months.SettingPhysiotherapy, osteopathy and acupuncture clinics throughout the UK.Participants166 practitioners (65 physiotherapists, 46 osteopaths, 55 acupuncturists) were recruited via their professional organisations. Practitioners recruited 960 adult patients seeking treatment for low back pain (LBP).Primary and secondary outcomesThe primary outcome was back-related disability. Secondary outcomes were pain and well-being. Contextual components measured were: therapeutic alliance; patient satisfaction with appointment systems, access, facilities; patients’ treatment beliefs including outcome expectancies; practitioners’ attitudes to LBP and practitioners’ patient-specific outcome expectancies. The hypothesised mediators measured were: patient self-efficacy for pain management; patient perceptions of LBP and psychosocial distress.ResultsAfter controlling for baseline and potential confounders, statistically significant predictors of reduced back-related disability were: all three dimensions of stronger therapeutic alliance (goal, task and bond); higher patient satisfaction with appointment systems; reduced patient-perceived treatment credibility and increased practitioner-rated outcome expectancies. Therapeutic alliance over task (ηp2=0.10, 95% CI 0.07 to 0.14) and practitioner-rated outcome expectancies (ηp2=0.08, 95% CI 0.05 to 0.11) demonstrated the largest effect sizes. Patients’ self-efficacy, LBP perceptions and psychosocial distress partially mediated these relationships. There were no interactions with treatment approach.ConclusionsEnhancing contextual components in musculoskeletal healthcare could improve patient outcomes. Interventions should focus on helping practitioners and patients forge effective therapeutic alliances with strong affective bonds and agreement on treatment goals and how to achieve them.

Objective: This review examined the effectiveness of telemonitoring versus usual care on self-care behaviors among community-dwelling adults with heart failure. Introduction: Heart failure is a global health crisis. There is a body of high-level evidence demonstrating that telemonitoring is an appropriate and effective therapy for many chronic conditions, including heart failure. The focus has been on traditional measures such as rehospitalizations, length of stay, cost analyses, patient satisfaction, quality of life, and death rates. What has not been systematically evaluated is the effectiveness of telemonitoring on self-care behaviors. Involving patients in self-care is an important heart failure management strategy. Inclusion criteria: This review included studies on adult participants (18 years and older), diagnosed with heart failure (New York Heart Association Class I – IV), who used telemonitoring in the ambulatory setting. Studies among pediatric patients with heart failure, adult patients with heart failure in acute care settings, or those residing in a care facility were excluded. Methods: Eight databases, including CINAHL, Cochrane Central Register of Controlled Trials, Embase, MEDLINE, Epistemonikos, ProQuest Dissertations and Theses, PsycINFO, and Web of Science were systematically searched for English-language studies between 1997 and 2019. Studies selected for retrieval were assessed by two independent reviewers for methodological quality using critical appraisal checklists appropriate to the study design. Those meeting a priori quality standards of medium or high quality were included in the review. Results: Twelve publications were included in this review (N = 1923). Nine of the 12 studies were randomized controlled trials and three were quasi-experimental studies. Based on appropriate JBI critical appraisal tools, the quality of included studies was deemed moderate to high. In a majority of the studies, a potential source of bias was related to lack of blinding of treatment assignment. Telemonitoring programs ranged from telephone-based support, interactive websites, and mobile apps to remote monitoring systems and devices. Self-care outcomes were measured with the European Heart Failure Self-care Behaviour Scale in nine studies and with the Self-care of Heart Failure Index in three studies. Telemonitoring improved self-care behaviors across 10 of these studies, achieving statistical significance. Clinical significance was also observed in nine of the 12 studies. All studies utilized one of two validated instruments that specifically measure self-care behaviors among patients with heart failure. However, in some studies, variation in interpretation and reporting was observed in the use of one instrument. Conclusions: Overall, telemonitoring had a positive effect on self-care behavior among adult, community-dwelling patients with heart failure; however, there is insufficient and conflicting evidence to determine how long the effectiveness lasts. Longitudinal studies are needed to determine the sustained effect of telemonitoring on self-care behaviors. In addition, the limitations of the current studies (eg, inadequate sample size, study design, incomplete statistical reporting, self-report bias) should be taken into account when designing future studies. This review provides evidence for the use of telemonitoring, which is poised for dramatic expansion given the current clinical environment encouraging reduced face-to-face visits. Systematic review registration number: PROSPERO CRD42019131852

Lisa R Roberts,1 Solomon J Renati,2 Shreeletha Solomon,3 Susanne Montgomery4 1School of Nursing, Loma Linda University, Loma Linda, CA, 92350, USA; 2Psychology Department, Veer Wajekar A. S. & C. College, University of Mumbai, Navi Mumbai, 400702, India; 3Martin Luther Christian University, Shillong, Meghalaya, 793006, India; 4School of Behavioral Health, Director of Research, Behavioral Health Institute, Loma Linda University, Loma Linda, CA, 92350, USACorrespondence: Lisa R RobertsLoma Linda University School of Nursing, 11262 Campus Street, Loma Linda, CA, 92350, USAEmail lroberts@llu.eduPurpose: Given the pressures surrounding women’s reproductive role in India, and persistent high rates of perinatal death, the purpose of this study is to describe and compare poor rural and urban Indian women’s experiences of perinatal grief.Participants and Methods: Two cross-sectional studies were compared on shared quantitative variables. Poor rural (N = 217) and urban, slum-dwelling (N = 149) Central Indian women with a history of stillbirth, and/or infant death were recruited with the aid of local community health workers. Trained, local, gender, and linguistically matched research assistants conducted the structured interviews. Shared quantitative variables include demographics, Social Provision Scale, Shortened Ways of Coping-Revised, Perinatal Grief Scale, social norms and autonomy.Results: While similar with respect to SES, age, number of living sons and perinatal loss experiences, these samples of poor women differed significantly across many variables, most notably women’s household position, joint family living, number of live daughters, religious coping, autonomy, and degrees of perinatal grief. While perinatal grief was significantly associated with many variables bi-variably, most lost their relative influence in our stepwise multivariable modeling within site (rural/urban), with only social norms and social support remaining significant for rural (31% of variance) and wishful thinking and social norms for urban participants (38.4% of variance). In the combined sample household position, social support and social norms remained significant and explained 53.6% of the adjusted variance.Conclusion: In both samples, perinatal grief was high following perinatal loss. Both groups of women with perinatal loss have increased risk of mental health sequelae. Notably, the context affected how they experienced perinatal grief, with rural women’s grief being higher and more affected by their societal pressures and isolation. Such nuances are important considerations for much-needed tailored approaches to future interventions.Keywords: stillbirth, infant death, bereavement, maternal, mental health risk

Background India has the highest number of stillbirths and the highest neonatal death rate in the world. In the context of its pronatalist society, women who experience perinatal loss often encounter significant social repercussions on top of grief. Furthermore, even when pregnancy outcomes were favorable, adverse life circumstances put some women at risk for postnatal depression. Therefore, perinatal loss and postnatal depression take a heavy toll on women’s mental health. The purpose of this study is to assess mental health among a sample of Mumbai slum-dwelling women with a history of recent childbirth, stillbirth, or infant death, who are at risk for perinatal grief, postnatal depression, or mental health sequelae. Methods We conducted a mixed method, cross-sectional study. A focus group discussion informed the development of a comprehensive survey using mainly internationally validated scales. After rigorous forward and back-translation, surveys were administered as face-to-face structured interviews due to low literacy and research naiveté among our respondents. Interviews were conducted by culturally, linguistically, gender-matched, trained research assistants. Results Of our reproductive age (N = 260) participants, 105 had experienced stillbirth, 69 had a history of infant death, and 25 had experienced both types of loss. Nearly half of the sample met criteria for postnatal depression, and 20% of these women also met criteria for perinatal grief. Anxiety and depression varied by subgroup, and was highest among women desiring an intervention. Conclusions Understanding factors contributing to women’s suffering related to reproductive challenges in this pronatalist context is critically important for women’s wellbeing.

Introduction There is an increasing affinity for remote health consultations (including telephone and virtual platforms), enabling new models of accessing services to evolve. Whilst many key skills are transferable from traditional to remote consultations, there is even greater emphasis on verbal communication skills during these interactions. Purpose This masterclass considers the communication skills required for delivering remote health care consultations, in particular focussing on: 12 interactional features in an opening sequence of a remote call; active listening; how to offer advice using the Ask-Offer-Ask framework; and subtleties in phrasing and prosody when closing a call that may indicate a level of satisfaction (or otherwise). Implications In planning for digitally-enabled services to become mainstream, the differences in communication between remote and face-to-face consultations must be recognised and embraced., Highlights • This paper describes 12 interactional features in opening a virtual consultation. • Offering, rather than giving advice, can help build a two-way conversation. • Subtleties in phrasing and prosody when closing a call may indicate satisfaction. • Different communication is needed in remote and face-to-face consultations.

ObjectivesAmid a political agenda for integrated, high-value care, the UK is implementing its Low Back and Radicular Pain Pathway. To align care with need, it is imperative to understand the patients’ perspective. The purpose of this study was, therefore, to explore how people experience being managed for sciatica within an National Health Service (NHS) pathway.DesignQualitative interpretative study.SettingMusculoskeletal Service in an NHS, Primary Care Trust, UK.ParticipantsThe sample comprised 14 people aged ≥18 years with a clinical presentation of sciatica, who were currently under the care of a specialist physiotherapist (the specialist spinal triage practitioner), had undergone investigations (MRI) and received the results within the past 6 weeks. People were excluded if they had previously undergone spinal surgery or if the suspected cause of symptoms was cauda equina syndrome or sinister pathology. Participants were sampled purposively for variation in age and gender. Data were collected using individual semi-structured interviews (duration: 38–117 min; median: 82.6 min), which were audio-recorded and transcribed verbatim. Data were analysed thematically.ResultsA series of problems with the local pathway (insufficient transparency and information; clinician-led decisions; standardised management; restricted access to specialist care; and a lack of collaboration between services) made it difficult for patients to access the management they perceived necessary. Patients were therefore required to be independent and proactive or have agency. This was, however, difficult to achieve (due to the impact of sciatica and because patients lacked the necessary skills, funds and support) and together with the pathway issues, this negated patients’ capability to manage sciatica.ConclusionsThis novel paper explores how patients experience the process of being managed within a sciatica pathway. While highlighting the need to align with recommended best practice, it shows the need to be more person-centred and to support and empower patient agency.Trial registration numberClinicalTrials.gov reference (UOS-2307-CR); Pre-results.

Acute interstitial nephritis is a well-known cause of acute kidney injury, but its association with cocaine use is extremely rare. In this article, we chronicle the case of a patient who developed acute interstitial nephritis secondary to cocaine insufflation. Furthermore, we conducted a systematic literature search of MEDLINE, Cochrane, Embase, and Scopus databases regarding cocaine-induced acute interstitial nephritis. A comprehensive review of the search results yielded a total of 7 case reports only. The data on patient characteristics, clinical features, biochemical profiles, treatment, and outcomes were collected and analyzed. This paper illustrates that acute interstitial nephritis may be added to the list of differentials in patients with acute kidney injury and a history of cocaine use. The therapeutic approach for cocaine-related kidney disease may be different than other etiologies responsible for acute renal insult. Prompt recognition of this entity is crucial because such patients may ultimately develop severe deterioration in renal function.

Background Patients with glioblastoma (GBM) have a dismal prognosis. Nearly all will relapse with no clear standard of care for recurrent disease (rGBM). Approximately 50% of patients have tumors harboring epidermal growth factor receptor (EGFR) amplification. The antibody–drug conjugate depatuxizumab mafodotin (depatux-m) binds cells with EGFR amplification, is internalized, and releases a microtubule toxin, killing the cell. Here we report efficacy, safety and pharmacokinetics (PK) of depatux-m + temozolomide (TMZ) in patients with EGFR-amplified rGBM. Methods M12-356 (NCT01800695) was an open-label study encompassing patients with newly diagnosed or rGBM across 3 treatment arms. Results are reported for adults with EGFR-amplified, measurable rGBM who received depatux-m (0.5–1.5 mg/kg) on days 1 and 15, and TMZ (150–200 mg/m2) on days 1–5 in a 28-day cycle. Patients were bevacizumab and nitrosourea naïve. Results There were 60 patients, median age 56 years (range, 20–79). Fifty-nine patients previously received TMZ. Common adverse events (AEs) were blurred vision (63%), fatigue (38%), and photophobia (35%). Grades 3/4 AEs were split between ocular and non-ocular AEs, occurring in 22% of patients each. Systemic PK exposure of depatux-m was dose proportional. The objective response rate was 14.3%, the 6-month progression-free survival rate was 25.2%, and the 6-month overall survival rate was 69.1%. Conclusions Depatux-m + TMZ displayed an AE profile similar to what was described previously. Antitumor activity in this TMZ-refractory population was encouraging. Continued study of depatux-m in patients with EGFR-amplified, newly diagnosed, or recurrent GBM is ongoing in 2 global, randomized trials (NCT02573324, NCT02343406).

Background Epidermal growth factor receptor (EGFR) alterations are associated with multiple cancers. Current EGFR-directed therapies have led to increased efficacy but are associated with specific side effects. The antibody-drug conjugate depatuxizumab mafodotin (depatux-m) targets EGFR with a monoclonal antibody linked to a cytotoxin, and is highly tumor-specific. Methods This phase 1/2 study evaluated the safety, pharmacokinetics, and efficacy of depatux-m in patients who had advanced solid tumors with known wild-type EGFR overexpression, amplification, or mutated EGFR variant III. A 3 + 3 dose escalation was used, and 2 dosing schedules were evaluated. Depatux-m also was manufactured under an alternate process to reduce the drug load and improve the safety profile, and it was tested at the maximum tolerated dose (MTD). In another cohort, prolonged infusion time of depatux-m was evaluated; and a cohort with confirmed EGFR amplification also was evaluated at the MTD. Results Fifty-six patients were treated. The MTD and the recommended phase 2 dose for depatux-m was 3.0 mg/kg. Common adverse events (AEs) were blurred vision (48%) and fatigue (41%). A majority of patients (66%) experienced 1 or more ocular AEs. Grade 3 or 4 AEs were observed in 43% of patients. One patient with EGFR-amplified, triple-negative breast cancer had a partial response. Stable disease was observed in 23% of patients. Pharmacokinetics revealed that depatux-m exposures were approximately dose-proportional. Conclusions Depatux-m resulted in infrequent nonocular AEs but increased ocular AEs. Patient follow-up confirmed that ocular AEs were reversible. Lowering the drug-antibody ratio did not decrease the number of ocular AEs. A partial response in 1 patient with EGFR-amplified disease provides the opportunity to study depatux-m in diseases with a high incidence of EGFR amplification. Cancer 2018;124:2174-83. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Background:Clinical guidelines recommend that investigations, such as magnetic resonance imaging, are offered only when likely to change management. Meanwhile, the optimal process of diagnosing radiculopathy remains uncertain and, in clinical practice, differences of opinion can occur between patient and clinician regarding the perceived importance of investigations.Objectives:To explore peoples' experiences of investigations and the effect of concordance between clinical presentation and investigation findings.Methods:In this qualitative study, 14 participants who had recently undergone investigations for a clinical presentation of radiculopathy were purposively recruited from an NHS, Primary Care Service in the United Kingdom. Based on the principles of interpretative phenomenological analysis, individual, semi-structured interviews were recorded and transcribed verbatim. Data were managed using a framework approach and analysed thematically.Findings:Although people reported wanting investigations to understand the cause of symptoms and inform management, access to them was reported to be difficult and protracted. When investigations revealed potentially relevant findings, people experienced relief, validation, empowerment and decisive decision-making. Disappointment emerged, however, regarding treatment options and waiting times, and long-term prognosis. When investigations failed to identify relevant findings, people were unable to make sense of their symptoms, relinquish their search to identify the cause, or to move forward in their management.Conclusions:This study provides the first reported in-depth interpretation of peoples' experience of undergoing investigations specifically for radiculopathy. Important implications have been identified for: investigation referral criteria; shared-decision-making; information sharing and managing expectations and disappointment.

Background: back pain guidelines endorse giving advice to enable people to self-manage and continue normal activities. Little is known however, about the content of advice that clinicians give and this project aimed to identify the advice given by clinicians to patients with back pain at their initial consultation. Methods: a secondary analysis was conducted with 25 audio-recordings and transcriptions of consultations between patients with back pain and physiotherapists in a primary care outpatients department. Using a Framework approach, the data were coded and analysed to identify the content of advice given and mode of delivery. Results: the mean duration of consultation was 38 min 59 s (range 26:21–53:16). Advice was given in 88% (n = 22/25) of consultations and 96% included additional exercise instruction. Cognitive reassurance was evident, focussing on getting people confident to ‘move your back’ despite pain and encouraging active lifestyle changes. Beyond reassurance and discussion to enhance confidence, the key topics of advice given were: activity promotion; postural changes; practical self-help advice regarding ways to sit; pain-management advice including medication and using heat. Gaps were identified in the advice given, most notably there was a lack of specificity relating to the frequency and duration of recommended tasks and activities. Conclusions: advice and reassurance are integral to enabling people to self-manage their back pain. It is important to avoid contradictory and unhelpful messages. Despite its importance, little is known about the advice offered by clinicians during initial back pain consultations highlighting the need for guidance to be patient-centred and tailored.

BackgroundDevelopmental dysplasia of the hip (DDH) is a very common congenital disorder, and late-presenting cases often require surgical treatment. Surgical reduction of the hip may be complicated by avascular necrosis (AVN), which occurs as a result of interruption to the femoral head blood supply during treatment and can result in long-term problems. Some surgeons delay surgical treatment until the ossific nucleus (ON) has developed, whereas others believe that the earlier the reduction is performed, the better the result. Currently there is no definitive evidence to support either strategy.ObjectivesTo determine, in children aged 12 weeks to 13 months, whether or not delayed surgical treatment of a congenitally dislocated hip reduces the incidence of AVN at 5 years of age. The main clinical outcome measures were incidence of AVN and the need for a secondary surgical procedure during 5 years’ follow-up. In addition, to perform (1) a qualitative evaluation of the adopted strategy and (2) a health economic analysis based on NHS and societal costs.DesignPhase III, unmasked, randomised controlled trial with qualitative and health economics analyses. Participants were randomised 1 : 1 to undergo either early or delayed surgery.SettingPaediatric orthopaedic surgical centres in the UK.ParticipantsChildren aged 12 weeks to 13 months with DDH, either newly diagnosed or following failed splintage, and who required surgery. We had a target recruitment of 636 children.InterventionsSurgical reduction of the hip performed as per the timing allocated at randomisation.Main outcome measuresPrimary outcome – incidence of AVN at 5 years of age (according to the Kalamchi and MacEwen classification). Secondary outcomes – need for secondary surgery, presence or absence of the ON at the time of primary treatment, quality of life for the main carer and child, and a health economics and qualitative analysis.ResultsThe trial closed early after reaching LimitationsOveroptimistic estimates of numbers of eligible patients seen at recruiting centres during the planning of the trial, as well as an overestimation of the recruitment rate, may have also contributed to unrealistic expectations on achievable patient numbers.Future workThere may be scope for investigation using routinely available data.ConclusionsHip ’Op has highlighted the importance of accurate advance information on numbers of available eligible patients, as well as support from all participating investigators when conducting surgical research. Despite substantial consultation with parents of children in the planning stage, the level of non-participation experienced during recruitment was much higher than anticipated. The qualitative work has emphasised the need for appropriate advice and robust support for parents regarding the ‘real-life’ aspects of managing children with DDH.Trial registrationCurrent Controlled Trials ISRCTN76958754.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 21, No. 63. See the NIHR Journals Library website for further project information.

Millennium Development Goal 4, to reduce child mortality, can only be achieved by reducing stillbirths globally. A confluence of medical and sociocultural factors contribute to the high stillbirth rates in India. The psychosocial aftermath of stillbirth is a well-documented public health problem, though less is known of the experience for men, particularly outside of the Western context. Therefore, men's perceptions and knowledge regarding reproductive health, as well as maternal-child health are important.Key informant interviews (n = 5) were analyzed and 28 structured interviews were conducted using a survey based on qualitative themes.Qualitative themes included men's dual burden and right to medical and reproductive decision making power. Wives were discouraged from expressing grief and pushed to conceive again. If not successful, particularly if a son was not conceived, a second wife was considered a solution. Quantitative data revealed that men with a history of stillbirths had greater anxiety and depression, perceived less social support, but had more egalitarian views towards women than men without stillbirth experience. At the same time fathers of stillbirths were more likely to be emotionally or physically abusive. Predictors of mental health, attitudes towards women, and perceived support are discussed.Patriarchal societal values, son preference, deficient women's autonomy, and sex-selective abortion perpetuate the risk for future poor infant outcomes, including stillbirth, and compounds the already higher risk of stillbirth for males. Grief interventions should explore and take into account men's perceptions, attitudes, and behaviors towards reproductive decision making.

Prior evidence suggests that the choice of antihypertensive medication may influence functional status among older adults with hypertension, particularly in conjunction with exercise. In particular, angiotensin converting enzyme (ACE) inhibitors have shown potential to positively influence function. However, randomized, controlled trials are needed to confirm this hypothesis. This paper outlines an RCT designed to determine if choice of first-line antihypertensive medication influences functional and cardiovascular risk factor responses to exercise among older adults with hypertension. Two hundred and thirteen inactive, community-dwelling adults ≥60 years of age with hypertension and functional limitations will be recruited to engage in a 32-week intervention study. Participants will be randomized to one of three first-line antihypertensive agents: (1) the ACE inhibitor perindopril, (2) the AT1 receptor antagonist losartan, or (3) the thiazide diuretic hydrochlorothiazide (HCTZ). Six weeks after randomization, participants will begin a 20-week structured aerobic exercise intervention. Participants will perform two 45-min center-based sessions coupled with 60 min of home-based walking per week. The primary aim is to determine if perindopril improves self-paced gait speed when compared with losartan and HCTZ. The secondary aim is to determine the relative effect of perindopril on secondary outcomes such as: (a) exercise capacity, (b) body mass and composition, and (c) circulating indices of cardiovascular risk. This RCT is expected to identify differential effects of first-line antihypertensive medications when combined with physical exercise thus have potential implications for antihypertensive prescription guidelines for older adults. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03295734.

Losatuxizumab vedotin (formerly ABBV-221) is a second-generation antibody-drug conjugate targeting epidermal growth factor receptor (EGFR). In this multicenter phase 1 study, eligible patients with EGFR-dependent solid tumors received losatuxizumab vedotin (3 + 3 design) intravenously at starting dose of 0.3 mg/kg over 3 h per 21-day cycle, with alternate dosing schedules utilized (2 weeks on/1 week off or weekly) to mitigate infusion reactions. Forty-five patients received ≥1 doses of losatuxizumab vedotin (13 colon, 6 non-small cell lung cancer, 5 head and neck [HNC], 5 glioblastoma multiforme, 2 breast, 14 other). Tumor samples were evaluated for EGFR protein expression by immunohistochemistry, EGFR and EGFR ligand mRNA expression by RNAseq, and results compared with outcome. Most common adverse events were infusion-related reaction (22/45; 49%) and fatigue (20/45; 44%). While most infusion reactions were grade ≤ 2, four patients experienced grade ≥3 infusion reactions. Several infusion reaction mitigation strategies were explored. Because of the high incidence of infusion reactions, the trial was stopped and the maximum tolerated dose was not reached. The last cleared dose: 6 mg/kg/cycle. Nineteen patients (42%) had stable disease; 4 remained on study >6 months. One HNC patient with increased levels of EGFR and EGFR ligands (amphiregulin, epiregulin) achieved a confirmed partial response. Pharmacokinetic analysis of losatuxizumab vedotin showed exposures appeared to be approximately dose-proportional. The high frequency of infusion reactions necessitated early closure of this trial. The detailed mitigation strategies used in this protocol for infusion-related reactions may provide beneficial information for trial design of agents with high infusion reaction rates.

Objective We explored patients’ experiences of using Internet-based self-management support for low back pain (LBP) in primary care, with and without physiotherapist telephone guidance. Design Exploratory descriptive qualitative study using thematic analysis, nested within a randomized feasibility trial. Methods Patients with LBP who participated in a feasibility trial of the SupportBack Internet intervention (ISRCTN: 31034004) were invited to take part in semistructured telephone interviews after the three-month intervention period (a convenience sample from within the trial population). Fifteen participants took part (age range = 36–87 years, 66.7% female, characteristics representative of the trial population). Data were analyzed thematically. Results Analysis resulted in the development of six themes (subthemes in parentheses): Perceptions of SupportBack’s design (Clarity and ease of use, Variety and range of information provided, Need for specificity and flexibility), Engaging with the SupportBack intervention, Promoting positive thought processes (Reassurance, Awareness of self-management), Managing behavior with SupportBack (Motivation and goal setting, Using activity as a pain management strategy, Preferences for walking or gentle back exercises), Feeling supported by telephone physiotherapists (Provision of reassurances and clarity, Physiotherapists are motivating), Severity and comorbidity as barriers (Preexisting condition or severity acting as a barrier, Less useful for mild low back pain). Conclusions The Internet intervention SupportBack appeared to feasibly support self-management of LBP. Reassurance and ongoing support to implement behavioral changes were central to reported benefits. The addition of physiotherapist telephone support further enhanced the patient experience and the potential utility of the intervention.

Objective This systematic review seeks to synthesize evidence to determine the effect of telemonitoring on self-care behaviors of adults with heart failure. Introduction There is a high-level body of evidence demonstrating that telemonitoring is an appropriate and effective therapy for many chronic conditions and, specifically, for patients with heart failure. However, the effect of telemonitoring on self-care behaviors in the adult population with heart failure is unknown. Inclusion criteria This review will include studies on adult participants (18 years and over) diagnosed with heart failure who use telemonitoring in the ambulatory setting. Studies of pediatric heart failure patients, and adult heart failure patients in acute care settings or in a care facility, will be excluded. Methods The search for studies will include English language studies published from 1997. Search terms will include heart failure, telemonitoring, self-care, and outpatient/ambulatory care, and will be used in three key sources: CINAHL, Embase, and PubMed. For the full review, Epistomonikos, ProQuest, PsycINFO, and Web of Science will also be searched. Using inclusion/exclusion criteria, two reviewers will select studies based on a three-step process. Methodological quality will be determined using critical appraisal checklists appropriate to the study design. Data extraction will include populations, study designs and methods, interventions, and outcomes related to self-care behaviors. Pooled studies will allow calculation of meta-analysis, while calculated effect sizes and confidence intervals will inform impact and precision of effect. Systematic review registration number PROSPERO CRD42019131852.

Declining cognitive functions in older individuals have enormous emotional, clinical, and public health consequences. Thus, therapeutics for preserving function and keeping older adults living independently are imperative. Aging is associated dysbiosis, defined as a loss of number and diversity in gut microbiota, which has been linked with various aspects of cognitive functions. Therefore, the gut microbiome has the potential to be an important therapeutic target for symptoms of cognitive impairment. In this review, we summarize the current literature regarding the potential for gut-targeted therapeutic strategies for prevention/treatment of the symptoms of cognitive impairment. Specifically, we discuss four primary therapeutic strategies: wild-type and genetically modified probiotics, fecal microbiota transplantation, physical exercise, and high-fiber diets and specifically link these therapies to reducing inflammation. These strategies may hold promise as treatment paradigm symptoms related to cognitive impairment.

Epidermal growth factor receptor (EGFR) amplification has been reported to occur in ~ 50% of glioblastomas (GBMs). We are conducting several global studies that require central testing for EGFR amplification during screening, representing an opportunity to confirm the frequency of amplification in GBM in a large cohort and to evaluate whether EGFR amplification differs by region of the world. EGFR amplification was measured by fluorescence in situ hybridization during screening for therapeutic trials of an EGFR antibody–drug conjugate: two Phase 2/3 global trials (INTELLANCE-1, INTELLANCE-2), and a Japanese Phase 1/2 trial (INTELLANCE-J). We evaluated the proportion of tumor tissue samples harboring EGFR amplification among those tested and differences in amplification frequency by geography. EGFR was amplified in 54% of 3150 informative cases screened for INTELLANCE-1 and -2, consistent with historic controls, but was significantly lower in patients from Asia versus the rest of the world (35% vs. 56%, P

Guatemalan maternal and infant mortality rates remain high, particularly among indigenous populations. In remote areas, traditional birth attendants (TBAs), without formal midwifery education, are frequently the only maternal care providers. We conducted a mixed methods study to evaluate knowledge, skills, and attitudes of 26 TBAs in western Guatemala. The purposes of this study were to evaluate the efficacy of a community-based midwifery training program and to determine how the knowledge, skills, and attitudes of TBAs influence the care provided to indigenous mothers and infants. Themes from 5 key informant interviews included survival of mother and baby, facilitating referrals, and community pressure not to refer. We offered a 2-week simulation-based training designed for low resource settings. Participants completed pre- and posttests and demonstrated midwifery skills. Knowledge scores and objectively measured skills improved significantly. Attitude outcomes included increased endorsement regarding importance of pre- and postnatal visits, recognizing risk/complications, and partnering with medical providers. Potential effects discussed include safe TBA practice, training value, and intent to disseminate learnings in their communities.

Stillbirth is a significant global health problem that frequently results in perinatal grief with compound negative psychosocial impact. In low-resource settings with exceedingly high stillbirth rates, such as rural Chhattisgarh, India, it is vital to utilize low-cost, effective interventions. Mindfulness-based stress reduction is an evidence-based intervention utilized for a broad range of physical and mental health problems, and is adaptable to specific populations. The objective of this study was to explore the sustained effectiveness of a shortened, culturally adapted mindfulness-based intervention (MBI) designed to address complex grief after stillbirth. We used an observational, mixed-methods pre-post study design with 6-week and 12-month follow-up assessments among women with a history of stillbirth (N = 22). Analyses explored study outcomes and continued use of mindfulness skills. Pretest results showed elevated psychological symptoms and high levels of perinatal grief. General linear modeling repeated measures was used to explore 6-week and 12-month follow-up changes from baseline, controlling for significantly correlated demographic variables. Longitudinal results indicated significant reductions in perinatal grief and psychological symptoms; four of the five facets of mindfulness changed in the desired direction; and resilience scores indicated thriving. The shortened, culturally adapted, MBI pilot brought about sustained, significant reductions of perinatal grief and mental health symptoms, and participants reported use of mindfulness skills in day-to-day life. This study shows that the significant mental health needs among rural women of various castes and ethnicities in Chhattisgarh following stillbirth were successfully addressed by a promising MBI with potential scalability and sustainability.

Commonalities are presented from the experiences of U.S. nurse researchers who conducted studies in India, Jordan, Aotearoa/New Zealand, and Trinidad and Tobago. While planning research, it is important to engage collaborators who are members of the culture to be studied to understand what are culturally appropriate aims and methods. It is also vital to observe cultural etiquette, especially while gaining entrée and collecting data. Issues related to data collection include timing it around local holidays and events, and adapting individualist methods for obtaining consent and data to be more respectful for those in a collectivist culture. Care must be taken to give back, to sharing findings, and insure sustainability for future research in the host culture. Based on these and other reflections, recommendations are offered to support investigators planning research in a culture that is not their own.

Purpose To evaluate the safety and feasibility of combining exercise (EX) and resveratrol to treat older adults with physical function limitations. Methods Three-arm, two-site pilot randomized, controlled trial (RCT) for community-dwelling adults (N = 60), 71.8 ± 6.3 years of age with functional limitations. Participants were randomized to receive either 12 weeks of (1) EX + placebo [EX0], (2) EX + 500 mg/day resveratrol [EX500], or (3) EX + 1000 mg/day resveratrol [EX1000]. EX consisted of two sessions a week for 12 weeks of center-based walking and whole-body resistance training. Safety was assessed through adverse events and feasibility through exercise session and supplement (placebo, or resveratrol) protocol adherence. Outcome measures included a battery of indices of physical function as well as skeletal muscle mitchondrial function. Data were adjusted for age and gender using the Intent-To-Treat approach. Results Adverse event frequency and type were similar between groups (n = 8 EX0, n = 12 EX500, and n = 7 EX1000). Overall, 85% of participants met the supplement adherence via pill counts while 82% met the exercise session adherence. Adjusted within group mean differences (95% confidence interval) from week 0 to 12 for gait speed ranged from −0.04 (EX0: −0.1, 0.03) m/s to 0.04 (EX1000: −0.02, 0.11) and the six-minute walk test mean differences were 9.45 (EX0: −9.02, 27.7), 22.9 (EX500: 4.18, 41.6), and 33.1 (EX1000: 13.8, 52.4) meters. Unadjusted mean differences for citrate synthase were −0.80 (EX0: −15.45, 13.84), −1.38 (EX500: −12.16, 9.39), and 7.75 (EX1000: −4.68, 20.18) mU/mg. COX activity mean within group changes ranged from −0.05 (EX0) to 0.06 (EX500) k/s/mg. Additional outcomes are detailed in the text. Conclusion The pilot RCT indicated that combined EX + resveratrol was safe and feasible for older adults with functional limitations and may improve skeletal muscle mitochondrial function and mobility-related indices of physical function. A larger trial appears warranted and is needed to formally test these hypotheses.

IntroductionSelf-management and remaining physically active are first-line recommendations for the care of patients with low back pain (LBP). With a lifetime prevalence of up to 85%, novel approaches to support behavioural self-management are needed. Internet interventions may provide accessible support for self-management of LBP in primary care. The aim of this randomised controlled trial is to determine the clinical and cost-effectiveness of the ‘SupportBack’ internet intervention, with or without physiotherapist telephone support in reducing LBP-related disability in primary care patients.Methods and analysisA three-parallel arm, multicentre randomised controlled trial will compare three arms: (1) usual primary care for LBP; (2) usual primary care for LBP and an internet intervention; (3) usual primary care for LBP and an internet intervention with additional physiotherapist telephone support. Patients with current LBP and no indicators of serious spinal pathology are identified and invited via general practice list searches and mailouts or opportunistic recruitment following LBP consultations. Participants undergo a secondary screen for possible serious spinal pathology and are then asked to complete baseline measures online after which they are randomised to an intervention arm. Follow-ups occur at 6 weeks, 3, 6 and 12 months. The primary outcome is physical function (using the Roland and Morris Disability Questionnaire) over 12 months (repeated measures design). Secondary outcomes include pain intensity, troublesome days in pain over the last month, pain self-efficacy, catastrophising, kinesophobia, health-related quality of life and cost-related measures for a full health economic analysis. A full mixed-methods process evaluation will be conducted.Ethics and disseminationThis trial has been approved by a National Health Service Research Ethics Committee (REC Ref: 18/SC/0388). Results will be disseminated through peer-reviewed journals, conferences, communication with practices and patient groups. Patient representatives will support the implementation of our full dissemination strategy.Trial registration numberISRCTN14736486.

In a pilot randomized clinical trial, participants aged &ge, 60 years (n = 35) with physical limitations and symptomatic knee osteoarthritis (OA) were randomized to 12 weeks of lower-body low-load resistance training with blood-flow restriction (BFR) or moderate-intensity resistance training (MIRT) to evaluate changes in muscle strength, pain, and physical function. Four exercises were performed three times per week to volitional fatigue using 20% and 60% of one repetition maximum (1RM). Study outcomes included knee extensor strength, gait speed, Short Physical Performance Battery (SPPB) performance, and pain via the Western Ontario and McMaster Universities OA Index (WOMAC). Per established guidance for pilot studies, primary analyses for the trial focused on safety, feasibility, and effect sizes/95% confidence intervals of dependent outcomes to inform a fully-powered trial. Across three speeds of movement, the pre- to post-training change in maximal isokinetic peak torque was 9.96 (5.76, 14.16) Nm while the mean difference between groups (BFR relative to MIRT) was &minus, 1.87 (&minus, 10.96, 7.23) Nm. Most other directionally favored MIRT, though more spontaneous reports of knee pain were observed (n = 14) compared to BFR (n = 3). BFR may have lower efficacy than MIRT in this context&mdash, though a fully-powered trial is needed to definitively address this hypothesis.

We explored potential barriers and facilitators for prostate cancer screening choices among high-risk Black men. In our sample of 264 Black men over 45 years of age living in the U.S. who met the American Cancer Society criteria for screening, we found that only 49.6% had ever been screened. We investigated potential barriers including screening intention, access to care, medical mistrust, and fatalism. Potential facilitating factors investigated were provider-patient conversations encompassing the pros and cons of screening, ethnicity taken into account, insurance, and previous prostate cancer screening. Recommendations and resources are suggested to increase screening of high-risk Black men.

BACKGROUND: Depatuxizumab mafodotin (depatux-m, formerly ABT-414) is an EGFR-directed antibody-drug conjugate being developed for treatment of EGFR-amplified glioblastoma (GBM). As therapeutic pressure engenders tumor adaptations, it is important to understand the stability of biomarkers targeted by precision medicine approaches such as depatux-m. Therefore, we assessed EGFR amplification (amp) and expression in longitudinally-sampled GBMs from patients (pts) treated +/- depatux-m to explore biomarker stability. MATERIAL AND METHODS: Formalin-fixed, paraffin embedded GBM tumor tissue was analyzed from 68 patients who underwent at least 2 surgeries; EGFR amp was detected by in situ hybridization (e.g., FISH) or next-generation sequencing in all samples. Fifty-six pts did not receive depatux-m; among 12 pts who did, EGFR expression was also evaluated by RNA sequencing. RESULTS: Of 56 pts who did not receive depatux-m, 31 (55%) had tumors harboring EGFR amp at 1st surgery (initial diagnosis); among those, EGFR amp was maintained at re-operation in 27 (87%), and not maintained in 4 (13%). None of the 25 cases without baseline EGFR amp acquired it at the 2nd surgery. Of 12 pts treated with depatux-m between surgeries, 9 cases harbored EGFR amp at baseline which was maintained in 4 (44%) at the 2(nd) surgery, all 4 of which had the highest levels of EGFR expression at baseline. Of the 3 cases without EGFR amp at baseline, none acquired amplification at the 2(nd) surgery, and all 3 had the lowest levels of EGFR expression at study start. CONCLUSION: The presence of EGFR amp in GBM tissue at baseline was maintained at 2(nd) surgery in 87% of pts who received treatment other than depatux-m, and in 44% following depatux-m exposure. Therefore, depatux-m exposure appears to reduce EGFR amp maintenance (p=0.0159 by Fisher’s exact test); accordingly, the therapeutic approach may influence EGFR status. In no case was EGFR amp acquired at recurrence, regardless of depatux-m therapy. Ongoing analyses of additional tumor samples will increase power and further examine concordance among EGFR amp assays.

Background Patients with radicular symptoms can experience high levels of pain and disability with at least a third experiencing on-going symptoms 12 months after onset. Aims To explore ‘what matters’ about living with radicular symptoms at the point of seeing a spinal specialist and to consider how care can be aligned to best address need. Methods In this qualitative study, based on the principles of interpretative phenomenological analysis, 14 participants with a clinical presentation of radicular symptoms were purposively recruited from an NHS, Musculoskeletal Service in the UK. Individual, semi-structured interviews were undertaken, audio-recorded and transcribed verbatim. Data were managed using a Framework approach and analysed thematically. Findings Radicular symptoms were experienced as a protracted journey of acute exacerbations of symptoms that were difficult to make sense of. Adversely affecting almost all aspects of life, participants struggled to maintain their physical and functional independence; their important relationships; social networks and the roles and activities that provided joy and purpose. The impact of radicular symptoms was a ‘life on hold’ and an uncertain future, and 3/14 reported suicidal thoughts. Conclusions This paper, the first to focus on the lived experience of radicular symptoms at the point of seeing a spinal specialist, reveals the severity and devastating impact of radicular symptoms. Important implications have been identified regarding the need for clinicians to legitimise the symptoms and impact of radicular symptoms; to identify early those patients who might benefit from injection/surgery; and to signpost appropriate patients to sources of psychological support.

To evaluate the rates and characteristics of musculoskeletal disorders (MSDs) in physical therapists (PTs) according to their specialty and setting.Participants completed an online questionnaire including 15 demographic questions, 7 work-related and 8 injury-related questions for 9 different body parts.Complete responses were obtained from 121 PTs; 96% reported MSD symptoms during the previous 12 months, 64% affecting at least 3 body parts. The body parts with the highest prevalence of symptoms were the low back (66%) and the neck (61%). For PTs specialized in acute care, geriatrics and pediatrics, the body part most commonly affected was the low back, while for PTs specialized in orthopedics and neurology, the body part most commonly affected was the neck. Regarding work settings, the low back was the most commonly affected for PTs working in skilled nursing facilities, outpatient clinics and hospitals, and the neck in PTs working in academic and home health settings.MSDs are common among PTs; the body parts most often affected were the low back and neck. The prevalence and body parts affected varied by practice setting and specialty area. The findings can help informing the design of evidence-based rehabilitation, prevention, training and educational programs.Rehabilitation of injured physical therapists needs to address the symptoms of the multiple body parts that are usually affected (e.g. back, wrists and hands). Rehabilitation of injured physical therapists needs to take into consideration their job demands, practice setting and specialty area. The findings can inform the design of rehabilitation, prevention, training and educational programs for physical therapists.

Background Ilorasertib (ABT-348) is a novel inhibitor of Aurora kinase, vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptors, and the Src families of tyrosine kinases. Ilorasertib alone or in combination with azacitidine demonstrated activity in preclinical models in various hematological malignancies, indicating that pan-Aurora kinase and multiple kinase inhibition may have preferential antileukemic activity. This phase 1 trial determined the safety, pharmacokinetics, and preliminary antitumor activity of ilorasertib alone or combined with azacitidine in advanced hematologic malignancies. Patients and methods Fifty-two patients (median age, 67 years; 35 % with >4 prior regimens) with acute myelogenous leukaemia (AML; n = 38), myelodysplastic syndrome (n = 12), or chronic myelomonocytic leukaemia (n = 2) received 3 or 6 doses of ilorasertib per 28-day cycle and were assigned to arm A (once-weekly oral), B (twice-weekly oral), C (once-weekly oral plus azacitidine), or D (once-weekly intravenous) treatment. Results Maximum tolerated doses were not determined; the recommended phase 2 oral monotherapy doses were 540 mg once weekly and 480 mg twice weekly. The most common grade 3/4 adverse events were hypertension (28.8 %), hypokalemia (15.4 %), anemia (13.5 %), and hypophosphatemia (11.5 %). Oral ilorasertib pharmacokinetics appeared dose proportional, with a 15-hour half-life and no interaction with azacitidine. Ilorasertib inhibited biomarkers for Aurora kinase and VEGF receptors, and demonstrated clinical responses in 3 AML patients. Conclusions Ilorasertib exhibited acceptable safety and pharmacokinetics at or below the recommended phase 2 dose, displayed evidence of dual Aurora kinase and VEGF receptor kinase inhibition, and activity in AML.