Supporting youth mental health with arts-based strategies: a global perspective.

The devastating impact of youth mental health concerns is increasingly evident on a global scale. This crisis calls for innovative solutions that are sufficiently accessible, scalable, and cost-effective to support diverse communities around the world. One such solution involves engagement in the arts: incorporating and building upon existing local resources and cultural practices to bolster youth mental health. In this article, we describe the global youth mental health crisis and note major gaps in the knowledge and resources needed to address it. We then discuss the potential for arts- and culture-based strategies to help meet this challenge, review the mounting evidence regarding art's ability to support mental health, and call for action to undertake critical research and its translation into accessible community practices. Four steps are suggested: (1) elevate and prioritize youth voice, (2) develop core outcome measures, (3) identify and analyze successful models around the globe, and (4) generate clear funding pathways for research and translational efforts. Worldwide implementation of arts- and culture-based strategies to address youth mental health will provide critical resources to support the health, wellbeing and flourishing of countless youth across the globe.

Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study.

Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual's cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies.

Prevalence of depression and anxiety among adults with vitiligo in a Malaysian tertiary hospital.

INTRODUCTION: Vitiligo is a chronic disorder resulting in skin depigmentation with reported global prevalence of 1-2%. This disease is often accompanied by psychosocial distress owing to the cosmetic disfigurement associated with it. The primary objective of this study was to determine the prevalence of depression and anxiety among adults with vitiligo in a local tertiary hospital. In addition, this study also evaluated the association of depression and anxiety with patients' characteristics. MATERIALS AND METHODS: This cross-sectional study was conducted among vitiligo patients aged 18 years and older in Hospital Klang, Selangor between October 2021 and June 2022. Assessment instruments used were Vitiligo Area Scoring Index (VASI) and Hospital Anxiety and Depression Scale (HADS). Demographic data and clinical characteristics of vitiligo patients were recorded. RESULTS: Of the 100 participants, 12 (12%) and 21 (21%) had depression and anxiety, respectively. The mean depression score (HADS-depression component) was 3.4 (SD 3.4) and mean anxiety score (HADS-anxiety component) was 4.7 (SD 3.9). There were significantly higher number of patients with abnormal HADS-D score in the age group of 35-51 years (p=0.029), single status (p=0.001), with employment (p=0.014) and disease duration <2 years (p=0.004). Patients in the divorced/widowed group had a significant association with anxiety (p=0.011). CONCLUSION: The prevalence of depression was 12% while anxiety was 21% in our cohort. Vitiligo has a significant psychosocial impact, thus clinicians should actively evaluate the mental health of these patients with the use of screening tools such as HADS and provide appropriate referrals and management.

Novel approach to analysis of the immune system using an ungated model of immune surface marker abundance to predict health outcomes.

Traditionally, the immune system is understood to be divided into discrete cell types that are identified via surface markers. While some cell type distinctions are no doubt discrete, others may in fact vary on a continum, and even within discrete types, differences in surface marker abundance could have functional implications. Here we propose a new way of looking at immune data, which is by looking directly at the values of the surface markers without dividing the cells into different subtypes. To assess the merit of this approach, we compared it with manual gating using cytometry data from the Singapore Longitudinal Aging Study (SLAS) database. We used two different neural networks (one for each method) to predict the presence of several health conditions. We found that the model built using raw surface marker abundance outperformed the manual gating one and we were able to identify some markers that contributed more to the predictions. This study is intended as a brief proof-of-concept and was not designed to predict health outcomes in an applied setting; nonetheless, it demonstrates that alternative methods to understand the structure of immune variation hold substantial progress.

Hospital healthcare utilisation among older adults admitted to a university hospital in the last months of life: A retrospective observational study.

INTRODUCTION: Health needs increase in older age. This translates into higher healthcare utilisation and expenditure compared to any other age group. Much of this is driven by frailty and multimorbidity. Many older people spend their last days in hospital. The aim of this study was to explore the utilisation of healthcare services among older adults admitted to a university hospital in the last 6 months of life. MATERIALS AND METHODS: Patients aged 70 years and over who died on medical wards of a university hospital in 2019 were included based on a stratified sampling approach using three categories. The categories were which medical ward the patient was admitted under, ICD-10 reported cause of death, and gender. The proportion of patients distributed across all three categories was calculated and 200 patients out of 472 deaths in that year were randomly selected to ensure mirrored proportion distributed across these three categories. Data on demographics and healthcare utilisation were collected. Healthcare utilisation parameters included clinical encounters, radiological investigations, and medical procedures undergone. RESULTS: The median age was 83 years with more women (51%) than men. Septicaemia was the commonest cause of death (24.5%), followed by pulmonary disease (21.0%), and cardiovascular disease (19.5%). In the last 6 months before death, median inpatient stay was 9 days. The median number of Emergency Department and outpatient attendance was one episode, respectively, and number of radiology was four investigations. Over one-third of patients had multiple hospital admission. During the terminal admission, the median inpatient stay was 6 days. 45% had a nasogastric tube in-situ. Antibiotics used during the last 24 hours of life and polypharmacy (≥5 medications) were high at 74.5% and 82.5%, respectively. 7% of patients received cardiopulmonary resuscitation. CONCLUSION: This study has provided descriptive evidence of hospital care delivered in the last months of life. The majority had contact with a healthcare team prior to their terminal admission. Many during their terminal admission had healthcare procedures, investigations, antibiotics, and issues of polypharmacy during this time. With an aging population, how care is organised and delivered is important in promoting good care in their later years.

Introduction to the National Cancer Imaging Translational Accelerator (NCITA): a UK-wide infrastructure for multicentre clinical translation of cancer imaging biomarkers.

The National Cancer Imaging Translational Accelerator (NCITA) is creating a UK national coordinated infrastructure for accelerated translation of imaging biomarkers for clinical use. Through the development of standardised protocols, data integration tools and ongoing training programmes, NCITA provides a unique scalable infrastructure for imaging biomarker qualification using multicentre clinical studies.

Effect of SARS and COVID-19 outbreaks on urology practice and training.

INTRODUCTION: The objective was to investigate the changes in urology practice during coronavirus disease 2019 (COVID-19) pandemic with a perspective from our experience with severe acute respiratory syndrome (SARS) in 2003. METHODS: Institutional data from all urology centres in the Hong Kong public sector during the COVID-19 pandemic (1 Feb 2020-31 Mar 2020) and a non-COVID-19 control period (1 Feb 2019-31 Mar 2019) were acquired. An online anonymous questionnaire was used to gauge the impact of COVID-19 on resident training. The clinical output of tertiary centres was compared with data from the SARS period. RESULTS: The numbers of operating sessions, clinic attendance, cystoscopy sessions, prostate biopsy, and shockwave lithotripsy sessions were reduced by 40.5%, 28.5%, 49.6%, 44.8%, and 38.5%, respectively, across all the centres reviewed. The mean numbers of operating sessions before and during the COVID-19 pandemic were 85.1±30.3 and 50.6±25.7, respectively (P=0.005). All centres gave priority to cancer-related surgeries. Benign prostatic hyperplasia-related surgery (39.1%) and ureteric stone surgery (25.5%) were the most commonly delayed surgeries. The degree of reduction in urology services was less than that during SARS (47.2%, 55.3%, and 70.5% for operating sessions, cystoscopy, and biopsy, respectively). The mean numbers of operations performed by residents before and during the COVID-19 pandemic were 75.4±48.0 and 34.9±17.2, respectively (P=0.002). CONCLUSION: A comprehensive review of urology practice during the COVID-19 pandemic revealed changes in every aspect of practice.

Medication use during COVID-19: Review of recent evidence.

OBJECTIVE: To keep health care providers, in response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, informed about the medications that have been proposed to treat the disease and the evidence supporting their use. QUALITY OF EVIDENCE: A narrative review of medications most widely used to treat COVID-19 was conducted, outlining the best available evidence for each pharmacologic treatment to date. Searches were performed in PubMed, EMBASE, and MEDLINE using key words COVID-19 and treatment, as well as related terms. Relevant research studies conducted in human populations and cases specific to patients with COVID-19 were included, as were relevant hand-searched papers and reviews. Only articles in English and Chinese were included. MAIN MESSAGE: While current management of patients with COVID-19 largely involves supportive care, without a widely available vaccine, practitioners have also resorted to repurposing medications used for other indications. This has caused considerable controversy, as many of these treatments have limited clinical evidence supporting their use and therefore pose implications for patient safety, drug access, and public health. For instance, medications such as hydroxychloroquine and chloroquine, lopinavir-ritonavir, nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers gained widespread media attention owing to hype, misinformation, or misinterpretation of research evidence. CONCLUSION: Given the severity of the pandemic and the potential broad effects of implementing safe and effective treatment, this article provides a narrative review of the current evidence behind the most widely used medications to treat COVID-19 in order to enable health care practitioners to make informed decisions in the care of patients with this life-threatening disease.

Febrile neutropenia and its associated hospitalization in breast cancer patients on docetaxel-containing regimen: A retrospective cohort study on duration of prophylactic GCSF administration.

PURPOSE: To compare febrile neutropenia (FN) incidence and hospitalization among breast cancer patients on docetaxel with no granulocyte colony-stimulating factors (GCSF) primary prophylaxis (PP), 4/5-day PP, or 7-day PP. METHODS: We identified 3916 breast cancer patients using docetaxel-cyclophosphamide (TC), doxorubicin-cyclophosphamide then docetaxel (AC-T), fluorouracil-epirubicin-cyclophosphamide then docetaxel (FEC-T), docetaxel-carboplatin-trastuzumab (TJH), or docetaxel-doxorubicin-cyclophosphamide (TAC) from a hospital pharmacy dispensing database in Hong Kong between 2014 and 2016. Patients were offered GCSF within 5 days since administering docetaxel. Outcomes included FN incidence, time to first hospitalization, hospitalization rate, and duration. RESULTS: In TC regimen, FN incidence (with odds ratio, OR) of patients with no PP, 4/5-day PP, and 7-day PP was 21.69%, 7.95% (OR 0.31, p < 0.001), and 5.33% (OR 0.20, p < 0.001), respectively. In TJH regimen, FN incidence of patients with no PP, 4/5-day PP, and 7-day PP was 38.26%, 8.33% (OR 0.15, p < 0.001), and 8.57% (OR 0.15, p < 0.001), respectively. FN incidence of patients on AC-T regimen with no PP and 4/5-day PP was 20.93% and 6.84%, respectively (OR 0.28, p = 0.005); with FEC-T regimen, the incidence was 9.91% and 4.77%, respectively (OR 0.46, p = 0.035). Only 3.27% FN cases were not hospitalized. Mean (±standard deviation, SD) time to first hospitalization was 8.21 ± 2.44 days. Mean (±SD) duration of hospitalization for patients with no PP, 4/5-day PP, and 7-day PP was 4.66 ± 2.60, 4.37 ± 2.85, and 5.12 ± 2.97 days, respectively. CONCLUSION: GCSF prophylaxis in breast cancer patients on docetaxel could reduce FN incidence and hospitalization. 4/5-day PP demonstrated similar efficacy to 7-day PP with superior saving benefits on healthcare expenditure.

HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib.

BACKGROUND: Effective targeted therapy for non-small-cell lung cancer (NSCLC) patients with human epidermal growth factor receptor 2 (HER2) mutations remains an unmet need. This study investigated the antitumor effect of an irreversible pan-HER receptor tyrosine kinase inhibitor, pyrotinib. PATIENTS AND METHODS: Using patient-derived organoids and xenografts established from an HER2-A775_G776YVMA-inserted advanced lung adenocarcinoma patient sample, we investigated the antitumor activity of pyrotinib. Preliminary safety and efficacy of pyrotinib in 15 HER2-mutant NSCLC patients in a phase II clinical trial are also presented. RESULTS: Pyrotinib showed significant growth inhibition of organoids relative to afatinib in vitro (P = 0.0038). In the PDX model, pyrotinib showed a superior antitumor effect than afatinib (P = 0.0471) and T-DM1 (P = 0.0138). Mice treated with pyrotinib displayed significant tumor burden reduction (mean tumor volume, -52.2%). In contrast, afatinib (25.4%) and T-DM1 (10.9%) showed no obvious reduction. Moreover, pyrotinib showed a robust ability to inhibit pHER2, pERK and pAkt. In the phase II cohort of 15 patients with HER2-mutant NSCLC, pyrotinib 400 mg resulted in a objective response rate of 53.3% and a median progression-free survival of 6.4 months. CONCLUSION: Pyrotinib showed activity against NSCLC with HER2 exon 20 mutations in both patient-derived organoids and a PDX model. In the clinical trial, pyrotinib showed promising efficacy. CLINICAL TRIAL REGISTRATION: NCT02535507.

Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry.

BACKGROUND: Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction. PATIENTS AND METHODS: We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation. RESULTS: We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2). CONCLUSIONS: : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

Symptom clusters of subjective cognitive decline amongst cognitively normal older persons and their utilities in predicting objective cognitive performance: structural equation modelling.

BACKGROUND AND PURPOSE: Prior literature on subjective cognitive decline (SCD) has mostly focused on memory complaints. It is uncertain whether the other non-memory complaints are equally relevant and can be used, alongside memory complaints, to identify populations at high risk of cognitive impairment. How the memory and non-memory complaints of SCD cluster with each other amongst community-dwelling individuals was investigated, and the differential utility of the symptom clusters of SCD in predicting objective cognitive performance was evaluated. METHODS: This study included 736 participants who were ≥60 years and had normal cognition, using the baseline data of an ongoing cohort study. Participants completed baseline assessments which comprised an SCD scale, a global cognitive measure and neuropsychological tests. Symptom clusters of SCD - as identified from exploratory and confirmatory factor analyses - were included in structural equation models to predict baseline changes in neuropsychological tests. RESULTS: The symptoms of SCD were split into two distinct factors, of which factor 1 was reported much more frequently than factor 2. Each standard deviation (SD) increment in factor 1 led to a 0.16-0.50 SD increase in global cognition, immediate memory, visuospatial abilities, language, attention and delayed memory (P < 0.05). In contrast, each SD increment in factor 2 worsened some of the cognitive domains by 0.18-0.37 SD. CONCLUSIONS: The various complaints of SCD can have different implications amongst cognitively normal older persons and may possibly be classified into age-related symptoms and pathological symptoms. The findings highlight the need for caution when selecting SCD measures, and illustrate the potential utility of SCD subtypes to inform on the underlying neurobiology.

Infection control in residential care homes for the elderly in Hong Kong (2005-2014).

INTRODUCTION: This serial cross-sectional survey study aimed to review the trend in various infection control practices in residential care homes for the elderly (RCHEs) in Hong Kong from 2005 to 2014. METHODS: Annual cross-sectional surveys were conducted at all RCHEs in Hong Kong, including self-administered questionnaires, on-site interviews, inspections, and assessments conducted by trained nurses, from 2005 to 2014. In all, 98.5% to 100% of all RCHEs were surveyed each year based on the list of licensed RCHEs in Hong Kong. RESULTS: There was a substantial increase in the proportion of RCHE residents aged ≥85 years, from 40.0% in 2005 to 50.2% in 2014 (P=0.002). The percentage of RCHE residents with special care needs also increased, from 22.3% in 2005 to 32.6% in 2014 for residents with dementia (P<0.001) and from 3.4% in 2005 to 5.0% in 2014 for residents with a long-term indwelling urinary catheter (P<0.001). The proportion of RCHEs with separate rooms for isolation areas ranged from 73.6% to 80% but did not show any significant trend over the study period. The proportion of RCHEs with alcohol hand rub available showed an increasing trend from 25.4% in 2006 to 99.2% in 2014 (P=0.008). The proportion of health or care workers (who were not the designated infection control officers) passing skills tests on hand washing techniques increased from 79.2% in 2006 to 91.5% in 2014 (P=0.02). An increasing trend was also observed for the proportion of infection control officers who were able to prepare properly diluted bleach solution, from 71.5% in 2005 to 92.2% in 2014 (P=0.002). CONCLUSIONS: For infection control practice to continue improving, more effort should be made to enhance and maintain proper practice, and to mitigate the challenge posed by the high turnover rates of healthcare workers in RCHEs. Introduction of self-audits on infection control practices should be considered.

Outcomes of transperineal and transrectal ultrasound-guided prostate biopsy.

OBJECTIVE: To compare the clinical outcomes and pathological findings of transperineal ultrasound-guided prostate biopsy (TPUSPB) and transrectal ultrasound-guided prostate biopsy (TRUSPB) in a secondary referral hospital. METHODS: This was a retrospective study of 100 TPUSPBs and 100 TRUSPBs performed in our centre. Pre-biopsy patient parameters (eg, patient age, clinical staging, serum prostate-specific antigen [PSA] level, prostate size, and PSA density), as well as pathological results and 30-day complication and readmission rates, were retrieved from the patients' medical records and compared between the two groups. RESULTS: One hundred TPUSPBs performed from January 2018 to May 2018 and 100 TRUSPBs performed from January 2016 to April 2016 were included for analysis. Mean age did not significantly differ between the groups. The TPUSPB group had a higher mean PSA level, smaller prostate size, and higher PSA density, compared with the TRUSPB group. The overall prostate cancer detection rate was similar between the TPUSPB and TRUSPB groups (35% vs 25%, P=0.123). There were no significant differences between the groups in prostate cancer detection rates after stratification according to PSA density and clinical staging. With respect to complications, no patients developed fever in the TPUSPB group, while 4% of patients in the TRUSPB group had fever and required at least 1-week admission for intravenous antibiotic administration. CONCLUSION: For prostate biopsy, TPUSPB is safer, with no infection complications, and has similar prostate cancer detection rate compared with TRUSPB.

Effects of backpack and double pack loads on postural stability.

Measurement of postural stability is crucial for identifying predictors of performance, determining the efficacy of physical training and rehabilitation techniques and evaluating and preventing injuries, particularly for heavy load carriage in hikers, mountain search and rescue personnel and soldiers. This study investigated the effect of load distribution on postural stability in an upright stance using backpack and double pack loads under conflicting or impaired somatosensory, visual and vestibular conditions. The sensory organisation tests were conducted on 20 young adults before and after a 10-min level walking exercise. Young adults' ability to use inputs from somatosensory and visual systems to maintain postural stability was significantly reduced following a 10-min walking exercise with a heavy backpack (30% of body weight), whereas no significant changes were observed for double pack carriage. Thus, the distribution of heavy loads to the front and back provides superior balance control compared with back-only loading. Practitioner summary: This study investigated the effects of heavy (30% of body weight) load distribution on postural stability after a 10-min walking exercise. Backpack carriage significantly reduced postural stability, whereas there was no significant effect under double pack loads. Distribution of heavy loads on the front-and-back is desirable for superior balance control.

Skin squames contribute to ammonia and volatile fatty acid production from bacteria colonizing in air-cooling units with odor complaints.

One of the most notable Indoor Air Quality problems is odor emission. This study investigated the potential contribution of skin squames to the production of ammonia (NH3 ) and volatile organic acids (VFAs) by 7 bacteria isolated from air-cooling (AC) units with complaints of urine and body odors. Our previous study showed that keratinolytic activity is higher in AC units with odor complaints than those without. In the offices where these units are located, the most likely source of keratins is from human skin squames. Most bacteria can produce NH3 and VFAs in the skin squame culture. Some correlations between the levels of NH3 , NH4+, VFAs, and keratinolytic activity were found. The odor production pathway with skin squames was proposed. Staphylococcus haemolyticus was abundant in the AC units with odor problems and had a high level of keratinolytic activity in addition to odor production. For long-term odor control, it is important to reduce the level of skin squames entering the AC units.

Efficacy and tolerability of trastuzumab emtansine in advanced human epidermal growth factor receptor 2-positive breast cancer.

INTRODUCTION: The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has changed dramatically with the introduction and widespread use of HER2-targeted therapies. There is, however, relatively limited real-world information about the effectiveness and safety of trastuzumab emtansine (T-DM1) in Hong Kong Chinese patients. We assessed the efficacy and toxicity profiles among local patients with HER2-positive advanced breast cancer who had received T-DM1 therapy in the second-line setting and beyond. METHODS: This retrospective study involved five local centres that provide service for over 80% of the breast cancer population in Hong Kong. The study period was from December 2013 to December 2015. Patients were included if they had recurrent or metastatic histologically confirmed HER2+ breast cancer who had progressed after at least one line of anti-HER2 therapy including trastuzumab. Patients were excluded if they received T-DM1 as first-line treatment for recurrent or metastatic HER2+ breast cancer. Patient charts including biochemical and haematological profiles were reviewed for background information, T-DM1 response, and toxicity data. Adverse events were documented during chemotherapy and 28 days after the last dose of medication. RESULTS: Among 37 patients being included in this study, 28 (75.7%) had two or more lines of anti-HER2 agents and 26 (70.3%) had received two or more lines of palliative chemotherapy. Response assessment revealed that three (8.1%) patients had a complete response, eight (21.6%) a partial response, 11 (29.7%) a stable disease, and 12 (32.4%) a progressive disease; three patients could not be assessed. The median duration of response was 17.3 (95% confidence interval, 8.4-24.8) months. The clinical benefit rate (complete response + partial response + stable disease, ≥12 weeks) was 37.8% (95% confidence interval, 22.2%-53.5%). The median progression-free survival was 6.0 (95% confidence interval, 3.3- 9.8) months and the median overall survival had not been reached by the data cut-off date. Grade 3 or 4 toxicities included thrombocytopaenia (13.5%), raised alanine transaminase (8.1%), anaemia (5.4%), and hypokalaemia (2.7%). No patient died as a result of toxicities. CONCLUSIONS: In patients with HER2-positive advanced breast cancer who have been heavily pretreated with anti-HER2 agents and cytotoxic chemotherapy, T-DM1 is well tolerated and provided a meaningful progression-free survival of 6 months and an overall survival that has not been reached. Further studies to identify appropriate patient subgroups are warranted.

Gender Differences in Energy Expenditure During Walking With Backpack and Double-Pack Loads.

OBJECTIVE: To investigate gender differences in energy expenditure during walking with backpack and double-pack loads. BACKGROUND: Studies have reported that energy expenditure during walking with double-pack loads is lower compared with backpack carriage. However, the effect of gender on energy expenditure while walking with these two load distribution systems has not been investigated. METHOD: Thirty healthy young adults (15 female and 15 male participants) walked on a treadmill with backpack and double-pack loads weighing 30% of their body weight at a speed of 0.89 m/s for 10 min. The energy expenditure in terms of oxygen consumption (VO2) and respiratory exchange ratio (RER) were continuously monitored using a portable gas analyzer throughout each walking exercise. A mixed-design analysis of variance model was adopted to test the effects of gender, pack, and time on VO2 and RER. RESULTS: No time effect was observed on VO2. However, significant gender, pack, and interaction effects were observed. The lowest VO2 was found in female participants under double-pack carriage. No significant gender or pack differences existed in RER. However, RER significantly and incrementally increased in time from the 4th through 6th, 8th, and 10th min. CONCLUSION: This study revealed that heavy double-pack load carriage for healthy young female participants had significantly lower energy expenditure (normalized by the entire system weight, i.e., the participant's weight plus the weight of the pack) than that of the male participants in a 10-min walking exercise. APPLICATION: The findings of this study indicated that healthy young female participants carried a heavy double-pack with less energy cost (normalized by the entire system weight, i.e., the participant's weight plus the weight of the pack) compared with their male counterparts during a 10-min walking exercise.

Successful targeting of the NRG1 pathway indicates novel treatment strategy for metastatic cancer.

BACKGROUND: NRG1 fusion-positive lung cancers have emerged as potentially actionable events in lung cancer, but clinical support is currently limited and no evidence of efficacy of this approach in cancers beyond lung has been shown. PATIENTS AND METHODS: Here, we describe two patients with advanced cancers refractory to standard therapies. Patient 1 had lung adenocarcinoma and patient 2 cholangiocarcinoma. Whole-genome and transcriptome sequencing were carried out for these cases with select findings validated by fluorescence in situ hybridization. RESULTS: Both tumors were found to be positive for NRG1 gene fusions. In patient 1, an SDC4-NRG1 gene fusion was detected, similar gene fusions having been described in lung cancers previously. In patient 2, a novel ATP1B1-NRG1 gene fusion was detected. Cholangiocarcinoma is not a disease type in which NRG1 fusions had been described previously. Integrative genome analysis was used to assess the potential functional significance of the detected genomic events including the gene fusions, prioritizing therapeutic strategies targeting the HER-family of growth factor receptors. Both patients were treated with the pan HER-family kinase inhibitor afatinib and both displayed significant and durable response to treatment. Upon progression sites of disease were sequenced. The lack of obvious genomic events to describe the disease progression indicated that broad transcriptomic or epigenetic mechanisms could be attributed to the lack of prolonged response to afatinib. CONCLUSION: These observations lend further support to the use of pan HER-tyrosine kinase inhibitors for the treatment of NRG1 fusion-positive in both cancers of lung and hepatocellular origin and indicate more broadly that cancers found to be NRG1 fusion-positive may benefit from such a clinical approach regardless of their site of origin. CLINICAL TRIAL INFORMATION: Personalized Oncogenomics (POG) Program of British Columbia: Utilization of Genomic Analysis to Better Understand Tumour Heterogeneity and Evolution (NCT02155621).

Occurrence, Distribution, and Fate of Organic UV Filters in Coral Communities.

Organic ultraviolet (UV) filters are widely used in personal care products and occur ubiquitously in the aquatic environment. In this study, concentrations of seven commonly used organic UV filters were determined in seawater, sediment and five coral species collected from the eastern Pearl River Estuary of South China Sea. Five compounds, benzophenone-1, -3, and -8 (BP-1, -3, and -8), octocrylene (OC) and octyl dimethyl-p-aminobenzoic acid (ODPABA), were detected in the coral tissues with the highest detection frequencies (>65%) and concentrations (31.8 ± 8.6 and 24.7 ± 10.6 ng/g ww, respectively) found for BP-3 and BP-8. Significantly higher concentrations of BP-3 were observed in coral tissues in the wet season, indicating that higher inputs of sunscreen agents could be attributed to the increased coastal recreational activities. Accumulation of UV filters was only observed in soft coral tissues with bioaccumulation factors (log10-values) ranging from 2.21 to 3.01. The results of a preliminary risk assessment indicated that over 20% of coral samples from the study sites contained BP-3 concentrations exceeding the threshold values for causing larval deformities and mortality in the worst-case scenario. Higher probabilities of negative impacts of BP-3 on coral communities are predicted to occur in wet season.