Chronotype and subjective sleep quality predict white matter integrity in young people with emerging mental disorders.

Protecting brain health is a goal of early intervention. We explored whether sleep quality or chronotype could predict white matter (WM) integrity in emerging mental disorders. Young people (N = 364) accessing early-intervention clinics underwent assessments for chronotype, subjective sleep quality, and diffusion tensor imaging. Using machine learning, we examined whether chronotype or sleep quality (alongside diagnostic and demographic factors) could predict four measures of WM integrity: fractional anisotropy (FA), and radial, axial, and mean diffusivities (RD, AD and MD). We prioritised tracts that showed a univariate association with sleep quality or chronotype and considered predictors identified by ≥80% of machine learning (ML) models as 'important'. The most important predictors of WM integrity were demographics (age, sex and education) and diagnosis (depressive and bipolar disorders). Subjective sleep quality only predicted FA in the perihippocampal cingulum tract, whereas chronotype had limited predictive importance for WM integrity. To further examine links with mood disorders, we conducted a subgroup analysis. In youth with depressive and bipolar disorders, chronotype emerged as an important (often top-ranking) feature, predicting FA in the cingulum (cingulate gyrus), AD in the anterior corona radiata and genu of the corpus callosum, and RD in the corona radiata, anterior corona radiata, and genu of corpus callosum. Subjective quality was not important in this subgroup analysis. In summary, chronotype predicted altered WM integrity in the corona radiata and corpus callosum, whereas subjective sleep quality had a less significant role, suggesting that circadian factors may play a more prominent role in WM integrity in emerging mood disorders.

Youth Perspectives on 'Highly Personalised and Measurement-Based Care': Qualitative Co-Design of Education Materials.

OBJECTIVES: Despite high levels of mental ill-health amongst young people (aged 15-30), this group demonstrates low help-seeking and high drop-out from mental health services (MHS). Whilst shared decision-making can assist people in receiving appropriate and effective health care, young people frequently report that they do not feel involved in treatment decisions. The current study focused on co-design of a clinical education and participant information programme for the Brain and Mind Centre Youth Model of Care. This model, which articulates a youth-focused form of highly personalised and measurement-based care, is designed to promote shared decision-making between young people and clinical service providers. METHODS: We conducted workshops with 24 young people (16-31; MAge = 21.5) who had accessed mental health services. Participants were asked what advice they would give to young people entering services, before giving advice on existing materials. Workshops were conducted and transcripts were coded using thematic analysis by two lived experience researchers and a clinical researcher. RESULTS: Young people found it empowering to be educated on transdiagnostic models of mental illness, namely clinical staging, which gives them a better understanding of why certain treatments may be inappropriate and ineffective, and thus reduce self-blame. Similarly, young people had limited knowledge of links between mental health and other life domains and found it helpful to be educated on multidisciplinary treatment options. Measurement-based care was seen as an important method of improving shared decision-making between young people and health professionals; however, to facilitate shared decision-making, young people also wanted better information on their rights in care and more support to share their expertise in their own needs, values and treatment preferences. CONCLUSIONS: These findings will inform the delivery of the further development and implementation of a youth-specific clinical education and participant information programme for the BMC Youth Model. PATIENT OR PUBLIC CONTRIBUTION: Workshops were facilitated by researchers with lived expertise in mental ill-health (A.H. and/or C.G.) and a clinical researcher (who has expertise as an academic and a clinical psychologist). A.H. and C.G. were also involved in conceptualisation, analysis, interpretation, review and editing of this paper.

Enhancing Research Involvement of Young People With Lived Expertise: Reflecting on Experiences in Digital Mental Health Research.

Given the rapid development of digital mental health technologies and a focus on connecting with youth, there is an urgent need to enhance the engagement of young people with lived expertise in research. Even so, youth with lived experience of accessing mental health services are particularly affected by power imbalances and may receive limited compensation in academic settings. Therefore, an emphasis on how research engagement not only improves the work but can benefit young people themselves is required. Here, 5 young people with lived expertise report on their experience of being employed as researchers at the University of Sydney's Brain and Mind Centre. As such, this team is uniquely placed to offer reflections from their work across multiple stages of research. This led to four key insights, including (1) creating accepting work cultures, (2) providing diverse opportunities for involvement, (3) giving young people agency and flexibility around sharing lived experiences, and (4) creating accommodating work environments for all researchers. We suggest that these insights can support more diverse ways of engaging young people and maximizing the value of participation for both researchers and young people themselves.

Editorial Commentary: Diagnosis of Hip Acetabular Retroversion Requires 3-Dimensional Imaging.

Diagnosis of global hip acetabular retroversion requires 3-dimensional imaging. Using anteroposterior pelvis radiographs, the crossover sign has been associated with retroversion. Recent research reports that the ischial spine sign and posterior wall sign also should be considered, yet even taking into account all 3 signs, the false-positive rate for retroversion is reported as greater than 35%. In truth, an anteroposterior radiograph is not sufficient for determination of acetabular retroversion. Retroversion is a 3-dimensional condition, and magnetic resonance imaging or computed tomography-based measurements are required. Thus, before we can determine the efficacy of hip arthroscopy versus periacetabular osteotomy for patients with hip impingement secondary to acetabular retroversion, we need to precisely measure to confirm our diagnosis.

Editorial Commentary: Hip Arthroscopy in Patients With Spine Pain: Outcomes Vary Compared to Patients With Isolated Hip Pathology, but Many Hip-Spine Patients Do Just as Well.

Low back pain present concurrently with hip impingement or labral pathology is frustrating for both patient and surgeon. It is difficult to distinguish true hip pathology from secondary low back symptoms, even with the use of diagnostic injections, cross-sectional imaging, electromyography, and/or nerve conduction studies. In addition, even properly indicated hip arthroscopy can exacerbate sciatic nerve dysfunction, a known complication from traction, and altered gait in the early postoperative period can aggravate sacroiliac and lumbar pathology. Moreover, difficult results vary in these patients after hip arthroscopy and show higher revision rates and less improvement in functional scores compared to patients with isolated hip pathology. Nevertheless, appropriately selected "hip-spine" patients show significant benefit from hip arthroscopy. Provided they have appropriate counseling, many hip-spine patients can undergo hip arthroscopy and experience a satisfying, durable outcome, and improvements at 1 year postoperatively are shown to be maintained at 5 or more years.

Editorial Commentary: Improved Operating Room Efficiency Is the Best Way to Control Orthopaedic Costs.

Current procedural terminology codes and assigned relative value units associated with arthroscopic hip surgery lag behind other joints in accurately describing, and often undervaluing, what surgery entails. Hip arthroscopy is expensive, and, to address inequity, procedural cost drivers require review. Consumable implants and operating room (OR) time drive the costs associated with the procedure. Hospitals, healthcare payors, patients, and surgeons all benefit from increasing OR efficiency and reducing equipment cost. However, the patient loses if financial strategy supersedes care delivery, and it is wrong to cut necessary use of consumables to save money. Fewer anchors is not the answer (yet we should use reusable, nonimplantable supplies when feasible). The greater opportunity to lower costs is improved OR efficiency, requiring a team approach with buy-in from perioperative, anesthesia, surgical staff, and administrators. OR time is a consistent driver of cost across every type of orthopaedic surgery. Studies evaluating strategies for OR efficiency in hip arthroscopy will benefit the field. By leading this effort, surgeons could be best positioned to address inadequate relative value units.

The Effects of Residual Femoral Deformity on Computed Contact Mechanics in Patients Treated With In Situ Fixation for Slipped Capital Femoral Epiphysis.

OBJECTIVE: In situ fixation for treatment of slipped capital femoral epiphysis (SCFE) can stabilize the epiphysis and prevent further joint deformation but often leaves residual deformity that may adversely affect intra-articular contact mechanics. The purpose of this study was to investigate the relationship between residual deformity and contact mechanics in the post-SCFE hip. METHODS: Patient-specific hip models were created for 19 patients with SCFE treated with in situ fixation. For each model, discrete element analysis was used to compute cumulative acetabular and femoral contact stress exposure during a walking gait cycle. Slip severity was evaluated for each patient using the two-dimensional Southwick angle and a novel three-dimensional (3D) assessment of multiplanar femoral deformity (3D slip angle). RESULTS: Of the SCFE cases, 2/7 mild (Southwick angle ≤30 degrees) had peak cumulative femoral exposures equivalent to that of severe (Southwick angle ≥60 degrees) cases. Severe SCFE cases had higher peak ( P = 0.015) and mean ( P = 0.028) femoral contact stress exposure and lower cumulative femoral contact area ( P = 0.003) than mild (Southwick angle ≤30 degrees) SCFE cases. Mean femoral contact stress exposure was also higher in severe SCFE cases than in moderate SCFE cases ( P = 0.027). Acetabular and femoral contact mechanics metrics typically demonstrated stronger correlations with 3D slip angle than two-dimensional Southwick angle. CONCLUSIONS: Increased slip severity adversely impacts intra-articular femoral contact mechanics. Contact mechanics metrics demonstrate higher correlations with 3D slip angle, indicating that this novel measurement may better describe global deformity and its relationship to intra-articular mechanics; however, the modest strength of these correlations may also imply that global impingement-generating deformity is not the primary factor driving contact mechanics in the post-SCFE hip. CLINICAL RELEVANCE: Greater slip severity adversely impacts contact mechanics in the post-SCFE hip. However, focal regions of high contact stress were seen even in mild SCFE deformities, suggesting some type of deformity correction should be considered even for mild slips to alleviate secondary impingement, address focal incongruities, and reduce osteoarthritis development/progression.

Does circadian dysrhythmia drive the switch into high- or low-activation states in bipolar I disorder?

OBJECTIVES: Emerging evidence suggests a role of circadian dysrhythmia in the switch between "activation" states (i.e., objective motor activity and subjective energy) in bipolar I disorder. METHODS: We examined the evidence with respect to four relevant questions: (1) Are natural or environmental exposures that can disrupt circadian rhythms also related to the switch into high-/low-activation states? (2) Are circadian dysrhythmias (e.g., altered rest/activity rhythms) associated with the switch into activation states in bipolar disorder? (3) Do interventions that affect the circadian system also affect activation states? (4) Are associations between circadian dysrhythmias and activation states influenced by other "third" factors? RESULTS: Factors that naturally or experimentally alter circadian rhythms (e.g., light exposure) have been shown to relate to activation states; however future studies need to measure circadian rhythms contemporaneously with these natural/experimental factors. Actigraphic measures of circadian dysrhythmias are associated prospectively with the switch into high- or low-activation states, and more studies are needed to establish the most relevant prognostic actigraphy metrics in bipolar disorder. Interventions that can affect the circadian system (e.g., light therapy, lithium) can also reduce the switch into high-/low-activation states. Whether circadian rhythms mediate these clinical effects is an unknown but valuable question. The influence of age, sex, and other confounders on these associations needs to be better characterised. CONCLUSION: Based on the reviewed evidence, our view is that circadian dysrhythmia is a plausible driver of transitions into high- and low-activation states and deserves prioritisation in research in bipolar disorders.

A multidimensional approach for differentiating the clinical needs of young people presenting for primary mental health care.

OBJECTIVES: There is an ongoing necessity to match clinical interventions with the multidimensional needs of young people. A key step toward better service planning and the design of optimal models of care is to use multidimensional assessment to understand the clinical needs of those presenting to primary mental health care. METHODS: 1284 people aged 12-25 years presenting to primary youth mental health services completed an online assessment at service entry. Latent class analysis was conducted for seven scales assessing anxiety, depression, psychosis, mania, functioning (indexed by Work and Social Adjustment Scale), and suicidality. RESULTS: A three-class solution was identified as the optimal solution. Class 1 (n = 305, 23.75%), an early illness stage group, had low and mixed symptomatology with limited functional impairment, class 2 (n = 353, 27.49%) was made up of older persons with established depression and functional impairment, and class 3 (n = 626, 48.75%) had very high and complex needs, with functional impairment, suicidality, and at-risk mental states (psychosis or mania). Additional differentiating characteristics included psychological distress, circadian disturbances, social support, mental health history, eating disorder behaviours, and symptoms of post-traumatic stress disorder. CONCLUSIONS: A large proportion of help-seeking young people present with symptoms and functional impairment that may exceed the levels of care available from basic primary care or brief intervention services. These subgroups highlight the importance of multidimensional assessments to determine appropriate service pathways and care options.

Strengthening mental health research outcomes through genuine partnerships with young people with lived or living experience: A pilot evaluation study.

BACKGROUND: Despite increasing support for stakeholder inclusion in research, there is limited evaluative research to guide safe (i.e., youth-friendly) and meaningful (i.e., non-tokenistic) partnerships with young people with lived experience of mental ill-health in research. This paper describes a pilot evaluation and iterative design of a Youth Lived Experience Working Group (LEWG) protocol that was established by the Youth Mental Health and Technology team at The University of Sydney's Brain and Mind Centre, based on the results of two studies. METHODS: Study one consisted of a pilot evaluation of the extent to which youth partners felt empowered to contribute, to qualitatively explore how LEWG processes could be improved. Youth partners completed online surveys, and results were shared over two LEWG meetings in 2021 to empower youth partners to collectively identify actions of positive change regarding LEWG processes. These meetings were audio-recorded and transcripts were subsequently coded using thematic analysis. Study two assessed whether LEWG processes and proposed improvements were acceptable and feasible from the perspective of academic researchers via an online survey in 2022. RESULTS: Quantitative and qualitative data collected from nine youth partners and 42 academic researchers uncovered initial learnings regarding facilitators, motivators, and barriers to partnering with young people with lived experience in research. Implementing clear processes for youth partners and academic researchers on effective partnership strategies, providing training opportunities for youth partners to develop research skills, and providing regular updates on how youth partner contributions led to research outcomes were identified as key facilitators. CONCLUSIONS: This pilot study provides insight into a growing international field on how to optimise participatory processes so that researchers and young people with lived experience can be better supported and engaged to make meaningful contributions to mental health research. We argue that more transparency is needed around participatory research processes so that partnerships with young people with lived experience are not merely tokenistic. CONSUMER CONTRIBUTIONS: Our study has also been approved by and reflects the concepts and priorities of our youth lived experience partners and lived experience researchers, all of whom are authors of this paper.

Dynamic modelling of the impact of community-based acute mental health services for children and adolescents.

OBJECTIVE: To evaluate the potential impact of the recently announced 'Safeguards' initiative on mental health-related emergency department presentation rates for children and adolescents (0-17 years). This state-funded initiative aims to establish 25 Child and Adolescent Acute Response Teams across New South Wales. METHODS: We estimated the effects of the 'Safeguards' initiative using a state-level dynamic model of child and adolescent acute mental health care. Potential reductions in total numbers of mental health-related emergency department presentations and re-presentations (i.e. presentations within 3 months of an initial presentation) were assessed via a series of simulation experiments in which we systematically varied the total number of Child and Adolescent Acute Response Teams and the mean duration of care per patient. RESULTS: Assuming a mean treatment duration of 6 weeks per patient, 25 Child and Adolescent Acute Response Teams are projected to reduce total numbers of mental health-related emergency department presentations and re-presentations over the period 2022-2031 by 15.0% (95% interval, 12.0-18.2%) and 31.7% (26.2-37.8%), respectively. Increasing the total number of Child and Adolescent Acute Response Teams above 25 has minimal additional impact on projected reductions in numbers of emergency department presentations and re-presentations, provided the mean duration of care is no more than 8 weeks. However, where the mean duration of care is greater than 4 weeks, a decrease in the number of Child and Adolescent Acute Response Teams below 25 reduces the potential effectiveness of the 'Safeguards' initiative significantly. CONCLUSION: Our simulation results indicate that full and timely implementation will be critical if the potentially substantial impact of the 'Safeguards' initiative on demand for hospital-based emergency mental health care is to be realised.

Stemming the tide of mental health problems in young people: Challenges and potential solutions.

One in five people experience clinically relevant mental health problems before the age of 25 years. Furthermore, in Australia, one in seven children are reported to experience a mental health disorder. Consequently, there has been a steady increase in demand for mental health services for children and young people, and this has been compounded by the COVID-19 pandemic. Unfortunately, currently many children and young people with mental health difficulties are not accessing appropriate and/or timely care, with individuals and families finding it increasingly difficult to access and navigate suitable services. In part, this is related to the fragmented and isolated manner in which child mental health services are operating. To address the current issues in access to appropriate child and adolescent mental health care in Australia, a novel Integrated Continuum of Connect and Care model is proposed to integrate relevant services along a tiered care pathway. The aim of this model is to facilitate timely access to mental health services that meet the specific needs of each child/young person and their family. This model will function within co-located service hubs that integrate health care through a comprehensive assessment followed by a link up to relevant services. The Integrated Continuum of Connect and Care has the potential to pave the way for unifying the fragmented child and youth mental health system in Australia.

Predictive modelling of deliberate self-harm and suicide attempts in young people accessing primary care: a machine learning analysis of a longitudinal study.

PURPOSE: Machine learning (ML) has shown promise in modelling future self-harm but is yet to be applied to key questions facing clinical services. In a cohort of young people accessing primary mental health care, this study aimed to establish (1) the performance of models predicting deliberate self-harm (DSH) compared to suicide attempt (SA), (2) the performance of models predicting new-onset or repeat behaviour, and (3) the relative importance of factors predicting these outcomes. METHODS: 802 young people aged 12-25 years attending primary mental health services had detailed social and clinical assessments at baseline and 509 completed 12-month follow-up. Four ML algorithms, as well as logistic regression, were applied to build four distinct models. RESULTS: The mean performance of models predicting SA (AUC: 0.82) performed better than the models predicting DSH (AUC: 0.72), with mean positive predictive values (PPV) approximately twice that of the prevalence (SA prevalence 14%, PPV: 0.32, DSH prevalence 22%, PPV: 0.40). All ML models outperformed standard logistic regression. The most frequently selected variable in both models was a history of DSH via cutting. CONCLUSION: History of DSH and clinical symptoms of common mental disorders, rather than social and demographic factors, were the most important variables in modelling future behaviour. The performance of models predicting outcomes in key sub-cohorts, those with new-onset or repetition of DSH or SA during follow-up, was poor. These findings may indicate that the performance of models of future DSH or SA may depend on knowledge of the individual's recent history of either behaviour.

Editorial Commentary: Hip Arthroscopy Pain Management With Surgeon-Administered Pericapusular Injection Is Fast, Safe, Inexpensive, and Effective.

Regional pain management after hip arthroscopy is challenging. The hip capsule alone has a complex and highly variable innervation, including contributions from articular branches of the femoral, obturator, accessory obturator, accessory femoral, superior gluteal, accessory superior gluteal, inferior gluteal, sciatic, and posterior femoral cutaneous nerves, nerve to the quadratus femoris, as well as a direct supply from the lumbosacral plexus. Thus, it is unrealistic to expect a traditional peripheral nerve block, including blocks of the proximal lumbar plexus, femoral nerve, and fascia iliaca region to provide thorough hip analgesia without inducing quadriceps weakness that could result in a patient experiencing a fall during the postoperative period. In addition, newer, sensory-only blocks, such as quadratus lumborum or pericapsular nerve group blocks, have not been shown to be superior to simple pericapsular injection (PCI). Hip arthroscopy pain management using surgeon administered PCI is fast, safe, inexpensive, and effective. While not perfect, PCI is the best option among current choices.

Characterising variability in youth mental health service populations: A detailed and scalable approach using digital technology.

OBJECTIVE: This study utilised digital technology to assess the clinical needs of young people presenting for care at headspace centres across Australia. METHOD: 1490 young people (12-25 years) who presented to one of 11 headspace services from four geographical locations (urban New South Wales, urban South Australia, regional New South Wales, and regional Queensland) completed a digital multidimensional assessment at initial presentation. Characteristics were compared between services and geographical locations. RESULTS: We identified major variation in the demographics, and the type and severity of needs across different services. Individuals from regional services were more likely to be younger, of Aboriginal and Torres Strait Islander origin, and present with psychotic-like symptoms and suicidality, while those in urban areas were more likely to have previously sought help and have problematic alcohol use. Further differences in age, distress, depressive symptoms, psychotic-like experiences, trauma, family history, alcohol use, education/employment engagement, and days out of role were identified between different urban sites. CONCLUSIONS: The variability between services provides insight into the heterogeneity of youth mental health populations which has implications for appropriate early intervention and prevention service provisions. We propose that integrating digital technologies has the potential to provide insights for smarter service planning and evaluation.

Clinical staging and the differential risks for clinical and functional outcomes in young people presenting for youth mental health care.

BACKGROUND: Clinical staging proposes that youth-onset mental disorders develop progressively, and that active treatment of earlier stages should prevent progression to more severe disorders. This retrospective cohort study examined the longitudinal relationships between clinical stages and multiple clinical and functional outcomes within the first 12 months of care. METHODS: Demographic and clinical information of 2901 young people who accessed mental health care at age 12-25 years was collected at predetermined timepoints (baseline, 3 months, 6 months, 12 months). Initial clinical stage was used to define three fixed groups for analyses (stage 1a: 'non-specific anxious or depressive symptoms', 1b: 'attenuated mood or psychotic syndromes', 2+: 'full-threshold mood or psychotic syndromes'). Logistic regression models, which controlled for age and follow-up time, were used to compare clinical and functional outcomes (role and social function, suicidal ideation, alcohol and substance misuse, physical health comorbidity, circadian disturbances) between staging groups within the initial 12 months of care. RESULTS: Of the entire cohort, 2093 young people aged 12-25 years were followed up at least once over the first 12 months of care, with 60.4% female and a baseline mean age of 18.16 years. Longitudinally, young people at stage 2+ were more likely to develop circadian disturbances (odds ratio [OR]=2.58; CI 1.60-4.17), compared with individuals at stage 1b. Additionally, stage 1b individuals were more likely to become disengaged from education/employment (OR=2.11, CI 1.36-3.28), develop suicidal ideations (OR=1.92; CI 1.30-2.84) and circadian disturbances (OR=1.94, CI 1.31-2.86), compared to stage 1a. By contrast, we found no relationship between clinical stage and the emergence of alcohol or substance misuse and physical comorbidity. CONCLUSIONS: The differential rates of emergence of poor clinical and functional outcomes between early versus late clinical stages support the clinical staging model's assumptions about illness trajectories for mood and psychotic syndromes. The greater risk of progression to poor outcomes in those who present with more severe syndromes may be used to guide specific intervention packages.

Predicting the emergence of full-threshold bipolar I, bipolar II and psychotic disorders in young people presenting to early intervention mental health services.

BACKGROUND: Predictors of new-onset bipolar disorder (BD) or psychotic disorder (PD) have been proposed on the basis of retrospective or prospective studies of 'at-risk' cohorts. Few studies have compared concurrently or longitudinally factors associated with the onset of BD or PDs in youth presenting to early intervention services. We aimed to identify clinical predictors of the onset of full-threshold (FT) BD or PD in this population. METHOD: Multi-state Markov modelling was used to assess the relationships between baseline characteristics and the likelihood of the onset of FT BD or PD in youth (aged 12-30) presenting to mental health services. RESULTS: Of 2330 individuals assessed longitudinally, 4.3% (n = 100) met criteria for new-onset FT BD and 2.2% (n = 51) met criteria for a new-onset FT PD. The emergence of FT BD was associated with older age, lower social and occupational functioning, mania-like experiences (MLE), suicide attempts, reduced incidence of physical illness, childhood-onset depression, and childhood-onset anxiety. The emergence of a PD was associated with older age, male sex, psychosis-like experiences (PLE), suicide attempts, stimulant use, and childhood-onset depression. CONCLUSIONS: Identifying risk factors for the onset of either BD or PDs in young people presenting to early intervention services is assisted not only by the increased focus on MLE and PLE, but also by recognising the predictive significance of poorer social function, childhood-onset anxiety and mood disorders, and suicide attempts prior to the time of entry to services. Secondary prevention may be enhanced by greater attention to those risk factors that are modifiable or shared by both illness trajectories.

Response of Leptomeningeal Metastasis of Breast Cancer With a HER2/neu Activating Variant to Tucatinib: A Case Report.

Metastatic breast cancer demonstrates HER2/neu amplification approximately 15% of the time. However, HER2 mutations, which often stimulate tumor growth, occur in only 3% to 5% of patients, and are seen more frequently in metastatic versus primary tumors. They are more frequent in lobular carcinoma, including triple-negative lobular cancer. Many of these variants are resistant to trastuzumab and lapatinib. However, neratinib can be efficacious, and recent data suggest that antibody-drug conjugates (ADCs) such as ado-trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan may also be helpful. Laboratory and clinical data raise the possibility that simultaneous treatment with ADCs plus neratinib may be even more efficacious. Tucatinib, which has demonstrated significant activity in the central nervous system, has also been shown in vitro to be active against a number of these HER2 variants. This report describes a patient with metastatic estrogen receptor-positive, HER2-nonamplified breast cancer with an activating HER2 mutation whose tumor became resistant to neratinib as well as capecitabine, but whose subsequent leptomeningeal disease had a dramatically successful response to tucatinib plus capecitabine. As the frequency of HER2 mutations increases during the evolution of metastatic breast cancer, it is important to obtain genomic evaluation on these tumors with either repeat tissue or liquid biopsy as they progress over time.

Social and occupational outcomes for young people who attend early intervention mental health services: a longitudinal study.

OBJECTIVE: To identify trajectories of social and occupational functioning in young people during the two years after presenting for early intervention mental health care; to identify demographic and clinical factors that influence these trajectories. DESIGN: Longitudinal, observational study of young people presenting for mental health care. SETTING: Two primary care-based early intervention mental health services at the Brain and Mind Centre (University of Sydney), 1 June 2008 - 31 July 2018. PARTICIPANTS: 1510 people aged 12-25 years who had presented with anxiety, mood, or psychotic disorders, for whom two years' follow-up data were available for analysis. MAIN OUTCOME MEASURES: Latent class trajectories of social and occupational functioning based on growth mixture modelling of Social and Occupational Assessment Scale (SOFAS) scores. RESULTS: We identified four trajectories of functioning during the first two years of care: deteriorating and volatile (733 participants, 49%); persistent impairment (237, 16%); stable good functioning (291, 19%); and improving, but late recurrence (249, 16%). The less favourable trajectories (deteriorating and volatile; persistent impairment) were associated with physical comorbidity, not being in education, employment, or training, having substance-related disorders, having been hospitalised, and having a childhood onset mental disorder, psychosis-like experiences, or a history of self-harm or suicidality. CONCLUSIONS: Two in three young people with emerging mental disorders did not experience meaningful improvement in social and occupational functioning during two years of early intervention care. Most functional trajectories were also quite volatile, indicating the need for dynamic service models that emphasise multidisciplinary interventions and measurement-based care.

Quantifying pathogen infection risks from household laundry practices.

AIMS: Contaminated laundry can spread infections. However, current directives for safe laundering are limited to healthcare settings and not reflective of domestic conditions. We aimed to use quantitative microbial risk assessment to evaluate household laundering practices (e.g., detergent selection, washing and drying temperatures, and sanitizer use) relative to log10 reductions in pathogens and infection risks during the clothes sorting, washer/dryer loading, folding and storing steps. METHODS AND RESULTS: Using published data, we characterized laundry infection risks for respiratory and enteric pathogens relative to a single user contact scenario and a 1.0 × 10-6 acceptable risk threshold. For respiratory pathogens, risks following cold water wash temperatures (e.g. median 14.4℃) and standard detergents ranged from 2.2 × 10-5 to 2.2 × 10-7 . Use of advanced, enzymatic detergents reduced risks to 8.6 × 10-8 and 2.2 × 10-11 respectively. For enteric pathogens, however, hot water, advanced detergents, sanitizing agents and drying are needed to reach risk targets. SIGNIFICANCE AND IMPACT OF THE STUDY: Conclusions provide guidance for household laundry practices to achieve targeted risk reductions, given a single user contact scenario. A key finding was that hand hygiene implemented at critical control points in the laundering process was the most significant driver of infection prevention, additionally reducing infection risks by up to 6 log10 .