Clades of huge phages from across Earth's ecosystems.

Bacteriophages typically have small genomes1 and depend on their bacterial hosts for replication2. Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystems.

Translating research into practice: outcomes from the Healthy Living after Cancer partnership project.

BACKGROUND: Healthy Living after Cancer (HLaC) was a national dissemination and implementation study of an evidence-based lifestyle intervention for cancer survivors. The program was imbedded into existing telephone cancer information and support services delivered by Australian state-based Cancer Councils (CC). We report here the reach, effectiveness, adoption, implementation, and maintenance of the program. METHODS: In this phase IV study (single-group, pre-post design) participants - survivors of any type of cancer, following treatment with curative intent - received up to 12 nurse/allied health professional-led telephone health coaching calls over 6 months. Intervention delivery was grounded in motivational interviewing, with emphasis on evidence-based behaviour change strategies. Using the RE-AIM evaluation framework, primary outcomes were reach, indicators of program adoption, implementation, costs and maintenance. Secondary (effectiveness) outcomes were participant-reported anthropometric, behavioural and psychosocial variables including: weight; physical activity; dietary intake; quality-of-life; treatment side-effects; distress; and fear of cancer recurrence and participant satisfaction. Changes were evaluated using linear mixed models, including terms for timepoint (0/6 months), strata (Cancer Council), and timepoint x strata. RESULTS: Four of 5 CCs approached participated in the study. In total, 1183 cancer survivors were referred (mostly via calls to the Cancer Council telephone information service). Of these, 90.4% were eligible and 88.7% (n = 791) of those eligible consented to participate. Retention rate was 63.4%. Participants were mostly female (88%), aged 57 years and were overweight (BMI = 28.8 ± 6.5 kg/m2). Improvements in all participant-reported outcomes (standardised effect sizes of 0.1 to 0.6) were observed (p < 0.001). The program delivery costs were on average AU$427 (US$296) per referred cancer survivor. CONCLUSIONS: This telephone-delivered lifestyle intervention, which was feasibly implemented by Cancer Councils, led to meaningful and statistically significant improvements in cancer survivors' health and quality-of-life at a relatively low cost. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12615000882527 (registered on 24/08/2015).

Carboplatin and Pembrolizumab Chemoimmunotherapy Achieves Remission in Recurrent, Metastatic Sebaceous Carcinoma.

A 72-year-old Caucasian woman who had recurrent sebaceous carcinoma of the right orbit with bilateral cervical lymph node involvement 24 months after orbital exenteration was treated with carboplatin (area under the curve of 5) and pembrolizumab (2 mg/kg) for 6 cycles, followed by maintenance pembrolizumab. She obtained a complete pathological remission and remains free of local, regional, and systemic disease at 15 months.

Temperament as a Predictor of Nitrous Oxide Inhalation Sedation Success.

Little is known about implications of temperament for children who receive nitrous oxide inhalation sedation (N2O/O2) for dental care. The aim of this study was to investigate whether child temperament is associated with success in N2O/O2. Child-caregiver dyads were enrolled from patients aged 36-95 months receiving dental care with N2O/O2 at a university-based pediatric dental clinic. To assess child temperament, 48 caregivers completed the Children's Behavior Questionnaire Short Form. Patient behavior was abstracted from Frankl scores recorded in the patient's chart. The overall behavioral failure rate was 15% (n = 7/48). There was no significant difference in sedation outcome associated with sex, health, insurance status, or complexity of treatment provided. Sedation outcome was significantly associated with the broad temperament domain of Effortful Control and its subscales Attentional Focusing and Inhibitory Control. The Negative Affectivity subscales of Frustration, Sadness, and Soothability and the Extraversion/Surgency subscales Activity and Impulsivity were also significantly associated with sedation outcome. The results of this study suggest that Effortful Control is associated with behavior during dental treatment with N2O/O2. The subscales of Attention Focusing, Inhibitory Control, Frustration, Fear, Sadness, Soothability, Activity, and Impulsivity may also be important determinants of child behavior during dental treatment.

Healthy Living after Cancer: a dissemination and implementation study evaluating a telephone-delivered healthy lifestyle program for cancer survivors.

BACKGROUND: Given evidence shows physical activity, a healthful diet and weight management can improve cancer outcomes and reduce chronic disease risk, the major cancer organisations and health authorities have endorsed related guidelines for cancer survivors. Despite these, and a growing evidence base on effective lifestyle interventions, there is limited uptake into survivorship care. METHODS/DESIGN: Healthy Living after Cancer (HLaC) is a national dissemination and implementation study that will evaluate the integration of an evidence-based lifestyle intervention for cancer survivors into an existing telephone cancer information and support service delivered by Australian state-based Cancer Councils. Eligible participants (adults having completed cancer treatment with curative intent) will receive 12 health coaching calls over 6 months from Cancer Council nurses/allied health professionals targeting national guidelines for physical activity, healthy eating and weight control. Using the RE-AIM evaluation framework, primary outcomes are service-level indicators of program reach, adoption, implementation/costs and maintenance, with secondary (effectiveness) outcomes of patient-reported anthropometric, behavioural and psychosocial variables collected at pre- and post-program completion. The total participant accrual target across four participating Cancer Councils is 900 over 3 years. DISCUSSION: The national scope of the project and broad inclusion of cancer survivors, alongside evaluation of service-level indicators, associated costs and patient-reported outcomes, will provide the necessary practice-based evidence needed to inform future allocation of resources to support healthy living among cancer survivors. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR)--ACTRN12615000882527 (registered on 24/08/2015).

The cost of being qualified: Current barriers faced by graduate students in forensic anthropology.

When considering the best ethical practices in forensic anthropology, one must consider how accessible the field is to new students that are responsible for driving the future of research, pedagogy, and the field as a whole. While there is no denying that there are multiple barriers to accessing academia (e.g., racism, sexism, xenophobia, etc.) the cost of a graduate education is a key factor that affects the diversity of people that are able to enter the field. Here, the cost of 24 universities prominent in the education of forensic anthropologists are considered in tandem with the opportunities for funding offered by these institutions and average costs of living for the respective surrounding areas. Demographic data for the universities at the graduate and undergraduate level was additionally compared with the demographics of the cities surrounding the universities. Funding, excluding loans, was shown to be greatly below cost of living in university cities, and often did not match the costs of attendance estimated by institutions. Including the cost of living, the average graduate degree costs over $60,000 per year while the average stipend for graduate students is below $14,000 necessitating the need for loans or out-of-institute support. White individuals were overrepresented in graduate enrollment when compared with surrounding area demographics, even when university demographics were similar to those of the surrounding area. Overall, findings highlight the inaccessibility of pursuing higher education for minority groups and demonstrate the need for institutions to develop funding programs to promote diversity in higher education.

Exploring important service characteristics of telephone cancer information and support services for callers: protocol for a systematic review of qualitative research.

INTRODUCTION: As cancer incidence continues to rise, challenges remain in how to communicate accurate, timely information to people with cancer, their families and healthcare professionals. One option is to provide support and comprehensive, tailored information via a telephone cancer information and support service (CISS). This systematic review aims to summarise the service characteristics of telephone CISS and identify what aspects of services are important from callers' perspectives. METHODS AND ANALYSIS: A comprehensive literature search will be conducted for articles published from database inception to 30 March 2023 (OVID MEDLINE, EMBASE, CINAHL, PsycINFO and SocINDEX). Published, peer-reviewed, articles reporting qualitative research on the service characteristics of telephone CISS important to callers in any language will be included. One researcher will complete the searches, two researchers will independently screen results for eligible studies and a third researcher will resolve any disagreement. A narrative and thematic synthesis of studies will be provided. Study characteristics will be independently extracted by one researcher and checked by a second. Included studies' methodological quality will be evaluated independently by two researchers using the 2022 Critical Appraisal Skills Programme Qualitative Studies Checklist. Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research tool will assess the confidence of the review findings. ETHICS AND DISSEMINATION: Ethics approval is not required for this research as it is a planned systematic review of published literature. Findings will be presented at leading cancer, health economic and supportive care conferences, published in a peer-reviewed journal, and disseminated via websites and social media. PROSPERO REGISTRATION NUMBER: CRD42023413897.

What is the economic and social return on investment for telephone cancer information and support services in Australia? An evaluative social return on investment study protocol.

INTRODUCTION: Over 50% of people affected by cancer report unmet support needs. To address unmet information and psychological needs, non-government organisations such as Cancer Councils (Australia) have developed state-based telephone cancer information and support services. Due to competing demands, evidence of the value of these services is needed to ensure that future investment makes the best use of scarce resources. This research aims to determine the costs and broader economic and social value of a telephone support service, to inform future funding and service provision. METHODS AND ANALYSIS: A codesigned, evaluative social return on investment analysis (SROI) will be conducted to estimate and compare the costs and monetised benefits of Cancer Council Victoria's (CCV) telephone support line, 13 11 20, over 1-year and 3-year benefit periods. Nine studies will empirically estimate the parameters to inform the SROI and calculate the ratio (economic and social value to value invested): step 1 mapping outcomes (in-depth analysis of CCV's 13 11 20 recorded call data; focus groups and interviews); step 2 providing evidence of outcomes (comparative survey of people affected by cancer who do and do not call CCV's 13 11 20; general public survey); step 3 valuing the outcomes (financial proxies, value games); step 4 establishing the impact (Delphi); step 5 calculating the net benefit and step 6 service improvement (discrete choice experiment (DCE), 'what if' analysis). Qualitative (focus groups, interviews) and quantitative studies (natural language processing, cross-sectional studies, Delphi) and economic techniques (willingness-to-pay, financial proxies, value games, DCE) will be applied. ETHICS AND DISSEMINATION: Ethics approval for each of the studies will be sought independently as the project progresses. So far, ethics approval has been granted for the first two studies. As each study analysis is completed, results will be disseminated through presentation, conferences, publications and reports to the partner organisations.

The experience of bereaved cancer carers in rural and regional areas: The impact of the COVID-19 pandemic and the potential of peer support.

BACKGROUND: Caring for someone with cancer during end of life care can be a challenging and complex experience. Those living in rural and regional areas are less likely to have local healthcare services and may be physically isolated. Even where support services such as respite do exist, they may be less likely to be accessed due to the time burden in travelling to services. This was compounded by the COVID-19 pandemic. AIM: To understand the potential benefits of peer support for bereaved carers of people with cancer from rural and regional locations during the COVID-19 period. METHODS: Phone interviews were conducted with bereaved cancer carers living in rural and regional areas in Victoria. Semi-structured interviews were used, and participants were asked about their experience as a carer, bereavement and the potential for peer support. Interviews were audio recorded and transcribed verbatim; transcripts were coded and a thematic analysis was conducted. FINDINGS: 12 interviews were conducted. Carers were mostly female (85%) and were on average 58 years of age (range 42-71). Interviews lasted an average of 58 minutes (range 53-91 minutes). Three themes were derived from the data; 1) Supportive care needs while caring and the impact of COVID-19; 2) Isolation during bereavement compounded by the COVID-19 pandemic; and 3) Peer support requires flexibility to meet diverse needs. CONCLUSION: Peer support has potential to assist bereaved carers of people with cancer. A co-design approach may be beneficial for developing a flexible model for supporting and linking carers together.

Postoperative maxillary sinusitis mimicking tumor recurrence on positron emission tomography.

A significant overlap of standard uptake values occurs in a variety of pathological processes, potentially causing misdiagnosis for tumor recurrence. The authors present a case of acute maxillary sinusitis masquerading as local recurrence of malignancy.

Perspectives of internal medicine physicians regarding medication abortion provision in the primary care setting.

OBJECTIVE: To better understand medication abortion attitudes and interest in future provision among Internal Medicine primary care providers (IM PCPs), and to characterize barriers to provision. STUDY DESIGN: We conducted a survey with IM attendings and trainees at a large academic medical center in Western Pennsylvania. We used descriptive statistics to characterize attitudes towards medication abortion provision, including the belief that it is within their scope of practice and interest in future provision, and to explore perceived barriers to provision. We used logistic regression models to assess factors associated with each of these attitudes. RESULTS: Of 397 eligible attendings and trainees, 121 (30%) completed the survey. Among those surveyed, 44% believed medication abortion is within the scope of practice of IM PCPs with trainees and female-identifying providers being significantly more likely to believe medication abortion is within their scope of practice compared to attending physicians and male physicians (60% vs 30%, p < 0.01 and 53% vs 31%, p = 0.01, respectively). Similarly, 43% endorsed interest in future provision, with trainees (67% vs 23%, p < 0.001) and female providers (54% vs 27%, p = 0.002) being more likely to express interest. The most cited barriers to provision included limited training in residency (70%) and low familiarity with abortion medications (57%). CONCLUSIONS: Many IM providers- particularly trainees- believe medication abortion is within their scope of practice and would like to provide this care. Interventions are needed to provide education and assistance complying with state and federal regulations to enable safe and efficient medication abortion provision by IM providers. IMPLICATIONS: IM departments and residency programs should seek to ensure training is offered to clinicians interested in providing medication abortion as a part of their primary care practice.

Codesigning a supportive online resource for Australian cancer carers: a thematic analysis of informal carers' and healthcare professionals' perspectives about carers' responsibilities and content needs.

OBJECTIVE: To gather preliminary qualitative data that will assist in the codesign and development of a new informational and supportive website to assist informal cancer carers in Australia. DESIGN AND SETTING: Utilising a previously tested codesign process, informal carers' experiences and perspectives, including those of healthcare professionals', were examined via focus groups and/or interviews. Data were analysed via thematic analysis. PARTICIPANTS: Rural (n=9) and urban (n=11) carers', and healthcare professionals' (n=8) perspectives were collected. Carers participated in a focus group (n=9) or telephone interview (n=11). Healthcare professionals completed an interview (n=6) or online survey (n=2). RESULTS: Rural and urban carers typically felt ill prepared for their multitudinal caregiving responsibilities. Supporting patient-to-healthcare professional liaisons could especially challenge. Carers' biopsychosocial and fiscal strains were affected by patients' hardships and available informal supports. Rural carers described greater social support than urban carers. Both rural and urban carers also described discontentment related to a carer neglecting healthcare system. Both carers and healthcare professionals endorsed the need for a user-friendly, carer-specific website encompassing practical information and resources, peer-driven advice and evidence-based illness information, tailored to the Australian context. CONCLUSIONS: Carers and healthcare professionals recognise the pressing need for an Australian, cancer carer-specific online resource. Findings will inform the next phase, where a resource will be designed, developed and tested.

Many Parents Would Accept Sexually Transmitted Infection Screening for Their Adolescent at a Pediatric Office Visit.

PURPOSE: Sexually active adolescents are at risk for sexually transmitted infections (STIs), yet screening is infrequently performed during pediatric visits. Lack of parent support and confidentiality are barriers. We explored whether parents of 15- to 17-year-olds would accept chlamydia and gonorrhea screening for their adolescent during a pediatric visit and assessed parental views on the importance of sexual health services. METHODS: A survey of 168 parents of adolescents was conducted during an outpatient pediatric office visit in Western Pennsylvania. RESULTS: Most parents (63%) accept STI screening for their adolescent during a pediatric visit, and 73% think it is important that adolescents spend time alone with their provider. Parents ranked the importance of discussing sexual health as high as other preventive health topics. CONCLUSIONS: Given the burden of STIs among adolescents, pediatricians should use this information to facilitate STI screening during office visits, secure time alone with their patients, and offer sexual health counseling.

Lipid analysis of CO2-rich subsurface aquifers suggests an autotrophy-based deep biosphere with lysolipids enriched in CPR bacteria.

Sediment-hosted CO2-rich aquifers deep below the Colorado Plateau (USA) contain a remarkable diversity of uncultivated microorganisms, including Candidate Phyla Radiation (CPR) bacteria that are putative symbionts unable to synthesize membrane lipids. The origin of organic carbon in these ecosystems is unknown and the source of CPR membrane lipids remains elusive. We collected cells from deep groundwater brought to the surface by eruptions of Crystal Geyser, sequenced the community, and analyzed the whole community lipidome over time. Characteristic stable carbon isotopic compositions of microbial lipids suggest that bacterial and archaeal CO2 fixation ongoing in the deep subsurface provides organic carbon for the complex communities that reside there. Coupled lipidomic-metagenomic analysis indicates that CPR bacteria lack complete lipid biosynthesis pathways but still possess regular lipid membranes. These lipids may therefore originate from other community members, which also adapt to high in situ pressure by increasing fatty acid unsaturation. An unusually high abundance of lysolipids attributed to CPR bacteria may represent an adaptation to membrane curvature stress induced by their small cell sizes. Our findings provide new insights into the carbon cycle in the deep subsurface and suggest the redistribution of lipids into putative symbionts within this community.

"Sutureless" repair of orbital floor and rim fractures.

PURPOSE: To report on the surgical outcomes of patients undergoing orbital fracture repair without periosteal or conjunctival closure. DESIGN: Retrospective interventional case series. PARTICIPANTS: Eighty-two patients (85 eyes) who underwent transconjunctival repair of isolated floor (n = 38) or complex orbital fracture (n = 47) without conjunctival closure. METHODS: A transconjunctival incision below the tarsus provides preseptal access to the inferior orbital rim, after which the periosteum is incised for exploration and repair of orbital floor fractures. Forced ductions are performed after release of entrapped tissue and placement of an orbital floor implant, and the conjunctiva is reapproximated with forceps and draped into the inferior fornix. MAIN OUTCOME MEASURES: Incidence of postoperative complications, including orbital implant exposure, infection, and migration. RESULTS: Patients were followed for an average of 318 days postoperatively (range 82-978 days). One patient experienced a pyogenic granuloma at the conjunctival incision that resolved with steroid drops. Other complications included lateral canthal dystopia or pyogenic granuloma at the lateral canthotomy site, when used. There were no cases of postoperative implant exposure, infection, or migration. CONCLUSIONS: Forgoing closure of the periorbita and conjunctiva after transconjunctival orbital floor and rim fracture repair is associated with a low incidence of postoperative complications. This technique is applicable in the repair of both isolated floor fractures and complex orbital fractures. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any material discussed in this article.

Ewing sarcoma presenting as a subconjunctival mass.

A 14-year-old previously healthy boy presented for evaluation of a subconjunctival mass that had been present for 2 to 3 years, but had recently started to enlarge. Imaging demonstrated an anterior orbital lesion that enhanced with gadolinium. An excisional biopsy was performed and revealed highly malignant-appearing small, blue, round tumor cells. Immuohistochemical stains were strongly reactive with CD99 (MIC2 and O13), CD56, and retained INI-1 reactivity. The EWS-FLI1 chimeric fusion gene transcript was also detected by reverse transcription-polymerase chain reaction analysis, confirming Ewing sarcoma. Full-body CT, bone scan, and bone marrow biopsy were all negative, proving this to be a premetastatic, primary orbital tumor arising from soft tissue.

Expanding the phenotype of a neurofibromatosis type 1-like syndrome: a patient with a SPRED1 mutation and orbital manifestations.

A 4-year-old child with no medical history presented for evaluation of a small, palpable nodule near the left inferolateral rim. The lesion had a bluish hue and had been slowly enlarging over the course of several months. MRI of the orbits revealed a heterogenous and infiltrative preseptal and extraconal mass which enhanced with gadolinium, and sphenoid wing dysplasia on the left. A complete ophthalmic and physical examination failed to reveal any other stigmata of neurofibromatosis type 1 (NF1) or neurofibromatosis type 2 (NF2). An incisional biopsy of the palpable mass revealed a plexiform neurofibroma. Molecular sequencing of the NF1 and NF2 genes did not reveal causative mutations. Further investigation revealed a loss of function mutation in SPRED1 on chromosome 15. Although loss of function mutations in the SPRED1 gene are known to cause several dermatologic changes associated with the NF1-like phenotype, to our knowledge, this is the first description of a SPRED1 gene mutation resulting in ophthalmic abnormalities.

Orbital burkitt lymphoma in immunocompetent patients: a report of 3 cases and a review of the literature.

PURPOSE: To describe a series of 3 immunocompetent patients with the sporadic form of orbital Burkitt lymphoma and review the outcomes of such patients reported in the scientific literature. METHODS: Retrospective review of medical records and the literature. Cases of orbital Burkitt lymphoma in immunocompromised and African patients were excluded from the review. Measured parameters included gender, age, ocular signs, imaging results, the range of systemic involvement, and treatment. RESULTS: Current cases and review of the scientific literature resulted in 16 immunocompetent patients with sporadic orbital Burkitt lymphoma. The median age at presentation was 12 years. Most common ocular signs at presentation were proptosis (13/16), external ophthalmoplegia (9/16), and eyelid edema (7/16). Optic neuropathy was noted in 5 of 16 patients. Concomitant paranasal sinus involvement was present in 8 of 16 patients. Fourteen (88%) of the patients had systemic involvement, of which the most common locations were central nervous system (6/16), lymphatics (6/16), bone marrow (6/16), and liver (4/16). Survival data were available for 13 patients. Seven patients (54%) died within 12 months of presentation. CONCLUSIONS: Sporadic orbital Burkitt lymphoma occurs in immunocompetent individuals with a wide age range. Fifty percent presented with adjacent paranasal sinus involvement. Concurrent or eventual systemic involvement is common. The large number of patients with central nervous system involvement in our review of the literature supports the role of lumbar puncture and neuroimaging in the workup of all patients with orbital Burkitt lymphoma. Prognosis remains guarded, with significant mortality within 1 year of presentation.

Mediterranean grassland soil C-N compound turnover is dependent on rainfall and depth, and is mediated by genomically divergent microorganisms.

Soil microbial activity drives the carbon and nitrogen cycles and is an important determinant of atmospheric trace gas turnover, yet most soils are dominated by microorganisms with unknown metabolic capacities. Even Acidobacteria, among the most abundant bacteria in soil, remain poorly characterized, and functions across groups such as Verrucomicrobia, Gemmatimonadetes, Chloroflexi and Rokubacteria are understudied. Here, we have resolved 60 metagenomic and 20 proteomic data sets from a Mediterranean grassland soil ecosystem and recovered 793 near-complete microbial genomes from 18 phyla, representing around one-third of all microorganisms detected. Importantly, this enabled extensive genomics-based metabolic predictions for these communities. Acidobacteria from multiple previously unstudied classes have genomes that encode large enzyme complements for complex carbohydrate degradation. Alternatively, most microorganisms encode carbohydrate esterases that strip readily accessible methyl and acetyl groups from polymers like pectin and xylan, forming methanol and acetate, the availability of which could explain the high prevalence of C1 metabolism and acetate utilization in genomes. Microorganism abundances among samples collected at three soil depths and under natural and amended rainfall regimes indicate statistically higher associations of inorganic nitrogen metabolism and carbon degradation in deep and shallow soils, respectively. This partitioning decreased in samples under extended spring rainfall, indicating that long-term climate alteration can affect both carbon and nitrogen cycling. Overall, by leveraging natural and experimental gradients with genome-resolved metabolic profiles, we link microorganisms lacking prior genomic characterization to specific roles in complex carbon, C1, nitrate and ammonia transformations, and constrain factors that impact their distributions in soil.

Implementing Systematic Screening and Structured Care for Distressed Callers Using Cancer Council's Telephone Services: Protocol for a Randomized Stepped-Wedge Trial.

BACKGROUND: Structured distress management, comprised a 2-stage screening and referral model, can direct supportive care resources toward individuals who are most likely to benefit. This structured approach has yet to be trialed in Australian community-based services such as Cancer Council New South Wales (NSW) and Victoria Cancer Information and Support (CIS) 13 11 20 lines who care for a large community of cancer patients and caregivers. OBJECTIVE: The aim of this study was to evaluate the effectiveness of structured screening and referral in (1) increasing the proportion of distressed CIS callers who accept supportive care referrals and (2) reducing distress levels at 6-month follow-up. METHODS: In this stepped-wedge trial, Cancer Council NSW and Victoria CIS consultants are randomized to deliver structured care during inbound 13 11 20 calls in accordance with 3 intervention periods. Eligible callers are patients or caregivers who score 4 or more on the Distress Thermometer; NSW or Victorian residents; aged 18 years or older; and English proficient. Study data are collected via computer-assisted telephone interviews (CATIs) at 3- and 6-month follow-up and CIS record audit. CATIs include demographic and service use items and the General Health Questionnaire (GHQ-28) to assess distress. An economic analysis of the structured care model will be completed. RESULTS: The structured care model was developed by guideline review and identification of service characteristics to guide mapping decisions; place-card methodology; and clinical vignettes with think-aloud methodology to confirm referral appropriateness. The model includes an additional screening tool (Patient Health Questionnaire-4) and a referral model with 16-20 CIS services. Descriptive statistics will be used to assess referral uptake rates. Differences between GHQ-28 scores for structured and usual care callers will be tested using a generalized linear mixed model with fixed effects for intervention and each time period. The trial will recruit 1512 callers. The sample size will provide the study with approximately 80% power to detect a difference of 0.3 SD in the mean score of the GHQ-28 at an alpha level of .05 and assuming an intra-cluster correlation of .04. A random sample of recorded calls will be reviewed to assess intervention fidelity and contamination. To date, 1835 distressed callers have been invited to participate with 60.71% (1114/1835) enrolled in the study. A total of 692 participants have completed 6-month CATIs. Recruitment is anticipated to end in late 2019. CONCLUSIONS: This trial is among the first to rigorously test the outcomes of a community-based structured approach to distress management. The model is evidence-informed, practice-ready, and trialed in a real-world setting. The study outcomes will advance the understanding of distress management internationally for both patients and caregivers. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12617000352303; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372105&isReview=true (Archived by WebCite on http://www.webcitation.org/78AW0Ba09). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12473.