A cohort profile of children and adolescents who had a suicide-related contact with police or paramedics in Queensland (Australia).

OBJECTIVE: Suicide is a leading cause of death in children and adolescents worldwide and a major public health concern. While suicidal behaviours place a significant demand on mental health and emergency services, data regarding suicide-related contacts with police and paramedics are an underutilised resource. The aim of the present study was to identify the demographic profile of young individuals (aged 5-17) and had a suicide-related contact with police or paramedics in Queensland (Australia). METHODS: The present study utilised a population-wide linked dataset, including data from police and paramedics and health administrative data, between 1 February 2013 and 31 January 2018. RESULTS: The identified cohort of 7929 children had a median age of 15 years and mainly comprised females (63.2%). Over the study period, 64 children died, most by suicide (76.6%). Less than a third of the cohort were responsible for almost two-thirds of the total number of contacts with police or paramedics. CONCLUSION: Findings provide a comprehensive profile of children and adolescents in suicidal crisis and highlight the substantial number of interactions that occur with police and paramedics. Due to the way the linked dataset was constructed, it must be assumed that the number of young persons in suicidal crisis is higher. Findings highlight the value of considering pre-hospital alternatives to presenting to emergency departments (EDs) for this cohort, to reduce impost on EDs and improve outcomes. Further examination of re-presentations by young persons is warranted to inform prevention and intervention strategies.

Our Ways, Your Ways, Both Ways - a multi-disciplinary collaboration to develop, embed and evaluate a model of social and emotional wellbeing care for Aboriginal and Torres Strait Islander young people who experience detention - Phase 1.

The National Strategic Framework for Aboriginal and Torres Strait Islander Peoples' Mental Health and Social and Emotional Wellbeing identifies building a strong Aboriginal and Torres Strait Islander led evidence-base to inform care as a key priority. Aboriginal and/or Torres Strait Islander adolescents in contact with the criminal justice system are a highly vulnerable group of Australians, with substantial unmet needs. There is limited evidence to inform culturally appropriate models of care that meet the social and emotional wellbeing needs of justice-involved Aboriginal and/or Torres Strait Islander adolescents. This project aims to develop, implement and evaluate an in-reach and community transitional model of social and emotional wellbeing care for Aboriginal and/or Torres Strait Islander adolescents (10-17 years old) who experience detention through close engagement with Aboriginal and/or Torres Strait Islander youth, Elders, researchers, practitioners and community members, and by drawing on culturally informed practice and knowledge systems. The project is based on a multi-level mixed methods design, with a strong focus on ongoing project evaluation (based on the Ngaa-bi-nya framework) and co-design. Co-design is facilitated through culturally safe and trauma informed participatory processes based on development of strong partnerships from project initiative, design, implementation and evaluation. Application of the landscape domain of the Ngaa-bi-nya framework for Aboriginal and Torres Strait Islander program evaluation will be explored in Phase one. Aboriginal and Torres Strait Islander adolescents with experience in detention will be engaged through one-on-one interviews with data collection through the Growth and Empowerment Measure (GEM) Youth (which will be adapted from the adult version and validated as part of this study), the Kessler Psychological Distress Scale (K-10), questions around alcohol and drug use, and narrative interviews exploring experience. Qualitative data will be analyzed using an inductive thematic approach, structured within the framework of the Ngaa-bi-nya landscape prompts. Quantitative data will be analyzed using descriptive statistics to provide a profile of the cohort. Findings from Phase one will be used to inform the development of a model of social and emotional wellbeing care that will be implemented and evaluated in Phase two.

Correction: Overall survival of stage IV non-small cell lung cancer patients treated with Viscum album L. in addition to chemotherapy, a real-world observational multicenter analysis.

[This corrects the article DOI: 10.1371/journal.pone.0203058.].

Suicide crisis calls to emergency services: Cohort profile and findings from a data linkage study in Queensland, Australia.

BACKGROUND AND AIMS: Police and paramedics play a crucial role in responding to suicide crises in the community. However, little is known about the nature, extent, precipitating factors, pathways and outcomes of a suicide-related call to emergency services and what responses will most effectively and compassionately meet the needs of those in crisis. Partners in Prevention: Understanding and Enhancing First Responses to Suicide Crisis Situations (PiP) was established to address these knowledge gaps. METHODS: This article describes (1) the methodology used to construct the PiP dataset, a population-wide linked dataset that investigates the characteristics and health pathways of individuals in Queensland who were the subject of a suicide-related call to police or paramedics; and (2) preliminary findings on service demand, demographics and health services utilisation. RESULTS: We identified 219,164 suicide-related calls to Queensland Police Service or Queensland Ambulance Service that were made over the 3-year period 1 February 2014 to 31 January 2017. A total of 70,893 individuals were identifiable via records linkage. The cohort linked to more than 7,000,000 health records. We estimated that police or paramedics in Queensland received on average 209 calls per day, with increases year on year over the study period. Analysis of demographic data highlighted the heterogeneous nature of this cohort and important demographic variations between individuals in contact with police versus ambulance services. DISCUSSION: The PiP dataset provides a strong foundation for a multi-modal dataset that can be built on over time, both cross-sectionally and longitudinally. Further linkages to Medicare Benefits Schedule, Pharmaceutical Benefits Scheme and social care datasets are planned. CONCLUSION: Detailed population-level analysis that data linkage can provide is critical to improving understanding and responses to suicide crisis situations. The PiP study is a world first and provides a unique opportunity to improve responses to this public health problem.

Substance use and help-seeking among justice-involved young people in Queensland and Western Australia: A cross-sectional survey of 14-17-year-olds.

INTRODUCTION: This study investigated substance use and help-seeking among justice-involved young people to inform and improve service provision during and after contact with the justice system. METHODS: Young people (14-17 years) in the community with current or prior contact with the justice system were recruited in Queensland and Western Australia, Australia using purposive sampling between 2016 and 2018. A cross-sectional survey was delivered by computer-assisted telephone interview. Information was collected on sociodemographic and health factors; lifetime and frequency of use of alcohol, tobacco and other drugs; and use of health services related to substance use and mental health. RESULTS: Of the 465 justice-involved young people surveyed, most had used alcohol (89%), tobacco (86%) or other drugs (81%). Of the latter, cannabis use was most prevalent (79%), followed by ecstasy (26%) and amphetamine (22%). Young people engaging in higher risk drug use (daily use, injecting use) were more likely to also have an alcohol use disorder, be disengaged from education, unemployed, have attempted suicide and experienced incarceration. Of the cohort, 24% had received treatment at an alcohol and drug service in the past year and 30% had seen a health professional about emotional/behavioural problems. Males and Aboriginal and Torres Strait Islander young people were less likely to have sought professional help. CONCLUSION: The high levels of substance use and disproportionate levels of help-seeking observed in this study illustrate the importance of delivering tailored, comprehensive and coordinated trauma-informed and culturally safe alcohol and drug services to justice-involved young people.

Contact with mental health services in the 12-month period before offending in a cohort of forensic order patients.

There has been limited research examining the details of mental health service contact in the pre-offending period. A retrospective case-note study of the complete cohort of people found not criminally responsible or permanently unfit for trial in Queensland, Australia, was conducted. An electronic clinical database search for seven treatment event types in the 12-months pre-offence was conducted. Of the 123 eligible patients, half were recorded as having experienced at least one treatment event. There was a statistically significant increase in the number of patients experiencing a treatment-related event per month over this 12-month pre-offence period (increase of ∼1.4 patients per month, p < .001). The findings highlight the need for appropriate weight to be placed on both longitudinal and recent factors when undertaking routine clinical review or mental health assessment, or considering changes to a patient's diagnosis and treatment plan. Screening in custody and early intervention are also indicated to ensure appropriate treatment.

Examining the Use of Police and Ambulance Data in Suicide Research.

Background: Police and paramedics are often the first to respond to individuals in suicide crisis and have an important role to play in facilitating optimal care pathways. Yet, little evidence exists to inform these responses. Data linkage provides one approach to examining this knowledge gap. Aim: We identified studies that examined suicide behaviors and linked to police or ambulance data. Method: A systematic search of PubMed and Scopus was undertaken to identify data linkage studies that: (1) examined suicide behaviors, and (2) included police or ambulance data. Studies were reviewed to identify: aims; suicide behaviors examined; how these were measured; how the cohort was defined; topic area; and what datasets were linked. Results: Eight studies met the inclusion criteria. Six studies included police data, and two studies included ambulance data. No study included both. Two topic areas were identified: (1) suicide-related contact with police or ambulance services; and (2) associations between suicidal behaviors and violence, victimization, and criminality. Limitations: Limitations to the review include the potential to have missed studies that investigated or reported on suicidality under the guise of mental health problems; complexities and nuances arising from the role of police data in coronial investigations; and limitations in the number of databases searched. Conclusion: Police and ambulance data represent a currently underutilized source of valuable information relevant to suicide crises, and further research should aim to address this gap.

Exercise for Individuals With Lung Cancer: A Systematic Review and Meta-Analysis of Adverse Events, Feasibility, and Effectiveness.

BACKGROUND: The purpose of this systematic review and meta-analysis was to evaluate the safety (adverse events), feasibility (recruitment, retention, and adherence) and effectiveness of exercise among individuals with lung cancer. DATA SOURCES: Electronic databases (CINAHL, Cochrane, Ebscohost, MEDLINE, Pubmed, ProQuest Health and Medical Complete, ProQuest Nursing and Allied Health Source, Science Direct, and SPORTDiscus) were searched for randomized, controlled, exercise trials involving individuals with lung cancer that were published prior to May 1, 2020. The PEDro scale was used to assess risk of bias, and the Common Terminology Criteria for Adverse Events was used to classify adverse event severity. Feasibility was assessed by computing median (range) recruitment, retention, and exercise attendance rates. Meta-analyses were performed to evaluate adverse event risk between exercise and usual care, and effects on health outcomes. Subgroup effects for exercise mode, supervision, intervention duration, diagnosis or treatment-related factors, and trial quality were assessed. RESULTS: Thirty-two trials (n=2109) involving interventions ranging between 1 and 20 weeks were included. Interventions comprised of aerobic (n=13, 41%), resistance (n=1, 3%), combined aerobic and resistance (n=16, 50%) and other exercise (n=2, 6%). There was no difference in the risk of an adverse event between exercise and usual care groups (exercise: n=64 events; usual care: n=61 events]; risk difference: -0.01 [91% CI = -0.02, 0.01]; P = .31). Median recruitment rate was 59% (9%-97%), retention rate was 86% (50%-100%), and adherence rate was 80% (44%-100%). Significant effects of exercise compared to usual care were observed for quality of life, aerobic fitness, upper-body strength, lower-body strength, anxiety, depression, forced expiratory volume, and sleep (standardized mean difference range=0.20-0.59). Subgroup analyses showed that safety, feasibility, and effect was similar irrespective of exercise characteristics, stage at diagnosis, treatment (surgery and chemotherapy), and trial quality. CONCLUSION: For individuals with lung cancer (stages I-IV), the risk of an adverse event with exercise is low. Exercise can be feasibly undertaken post-diagnosis and leads to improvements in health-related outcomes. Together, these findings add weight behind the importance of integrating exercise into standard cancer care, including for this specific cancer type. IMPLICATIONS FOR NURSING PRACTICE: Exercise should be considered as part of the treatment for all patients with lung cancer at any stage. Exercise has been shown to be low risk and can be feasibly undertaken by patients. The ideal mode, intensity, frequency, or duration of exercise for all patients with lung cancer is not known. Nonetheless, these findings support endorsement of cancer-specific physical activity guidelines, as well as referral to an exercise professional, such as an exercise physiologist or physiotherapist, for those diagnosed with lung cancer.

Exercise and colorectal cancer: a systematic review and meta-analysis of exercise safety, feasibility and effectiveness.

BACKGROUND: This meta-analysis evaluated the safety, feasibility and effect of exercise among individuals with colorectal cancer. METHODS: A database search (CINAHL, Ebscohost, MEDLINE, Pubmed, ProQuest Health and Medical Complete, ProQuest Nursing, Science Direct) for randomised, controlled, exercise trials involving individuals with colorectal cancer, published before January 1, 2020 was undertaken. Safety (adverse events), feasibility (withdrawal and adherence rates) and effect data (health outcomes including quality of life, QoL) were abstracted. Risk difference (RD) and standardised mean differences (SMD) were calculated to compare safety and effects between exercise and usual care (UC). Subgroup analyses were conducted to assess whether outcomes differed by exercise mode, duration, supervision and treatment. Risk of bias was assessed using the Physiotherapy Evidence Database tool. RESULTS: For the 19 trials included, there was no difference in adverse event risk between exercise and UC (RD = 0.00; 95% CI:-0.01, 0.01, p = 0.92). Median withdrawal rate was 12% (0-22%) and adherence was 86% (42-91%). Significant effects of exercise compared to UC were observed for QoL, fatigue, aerobic fitness, upper-body strength, depression, sleep and reduced body fat (SMD = 0.21-0.66, p < 0.05). Subgroup analyses suggested larger benefits (p < 0.05) for QoL and fatigue for supervised interventions; for QoL, aerobic fitness and reduced body fat for ≥12-week interventions; and for aerobic fitness when interventions were during chemotherapy. CONCLUSION: Although reporting of safety and compliance data was lacking in most trials, findings support that exercise is safe and feasible in colorectal cancer. Further, participation in mixed-mode exercise, including unsupervised exercise, leads to improvements in various health-related outcomes.

A Bioimpedance Spectroscopy-Based Method for Diagnosis of Lower-Limb Lymphedema.

Background: This study aimed at testing whether arm-to-leg ratios of extracellular water (ECW) and ECW normalized to intracellular water (ICW), measured by bioimpedance spectroscopy (BIS), can accurately detect bilateral, lower-limb lymphedema, and whether accounting for sex, age, and body mass index (BMI) improves the diagnostic performance of cut-offs. Methods and Results: We conducted a dual-approach, case-control study consisting of cases of bilateral, lower-limb lymphedema and healthy controls who self-reported absence of lymphedema. The diagnostic performance using normative data-derived cut-offs (i.e., mean + 0.5 standard deviation [SD] to mean + 3 SD; n = 136, 66% controls) and receiver operating characteristic (ROC) curve-derived cut-offs (n = 746, 94% controls) was assessed. The impact of sex, age, and BMI was investigated by comparing stratified and nonstratified normative data-derived cut-offs, and ROC curves generated from adjusted and unadjusted logistic regression models. Arm-to-leg ratios of ECW between mean + 0.5 SD and mean + 1 SD showed fair to good sensitivity (0.73-0.84) and poor to good specificity (0.64 to 0.84). Arm-to-leg ratios of ECW/ICW failed to detect lymphedema (sensitivity <0.5). Stratification by sex, or by sex and age, yielded similar results to nonstratified cut-offs. Cut-offs derived from adjusted ROC curves showed both good sensitivity (0.83-0.89) and specificity (0.8-0.84). Conclusion: These findings represent new BIS criteria for diagnosing lower-limb lymphedema that do not rely on comparison to baseline measures or the presence of a nonaffected, contralateral limb.

Characterization of standardized breath sampling for off-line field use.

Due to several sources of potential variability associated with exhaled breath bag sampling procedures for off-line analysis, the Respiration Collector for in vitro Analysis (ReCIVA) sampler was developed. Although designed to improve upon several pitfalls of sampling with exhaled breath bags, the ReCIVA remains a minimally studied research tool. In this manuscript, several attributes of the ReCIVA sampler are investigated among three individual tests, such as background contamination, control software version, performance of different adsorbent tubes, duplicate sample production, and comparison to exhaled breath bags. The data shows greater than a 58% reduction in background siloxanes can be achieved with submersion of ReCIVA masks in ethyl alcohol or baking the masks at a high temperature (200 °C). The results illustrate the ReCIVA control software version plays a key role in the flow rates applied to thermal desorption (TD) tubes. Using exhaled isoprene as a representative analyte, the data suggest duplicate samples among ReCIVA pump banks can be achieved using two different thermal desorption tubes, Tenax TA and Tenax/Carbograph 5TD, when using an updated control software and manually calibrating the ReCIVA pumps to uniform flow rates (Tenax p = 0.3869, 5TD p = 0.3131). Additionally, using the updated control software and manual ReCIVA flow calibration, the data suggest the ReCIVA can produce statistically similar results among TD tube types (p = 0.3824) and compared to standard exhaled breath bags (p = 0.1534). Collectively, these results establish a method for manually calibrating the flow of the ReCIVA device to allow for the most consistent results. These data support further experimentation into the use of the ReCIVA sampler for exhaled breath research.

Normative Interlimb Impedance Ratios: Implications for Early Diagnosis of Uni- and Bilateral, Upper and Lower Limb Lymphedema.

Background: Bioimpedance spectroscopy detects unilateral lymphedema if the ratio of extracellular fluid (ECF) between arms or between legs is outside three standard deviations (SDs) of the normative mean. Detection of bilateral lymphedema, common after bilateral breast or gynecological cancer, is complicated by the unavailability of an unaffected contralateral limb. The objectives of this work were to (1) present normative values for interarm, interleg, and arm-to-leg impedance ratios of ECF and ECF normalized to intracellular fluid (ECF/ICF); (2) evaluate the influence of sex, age, and body mass index on ratios; and (3) describe the normal change in ratios within healthy individuals over time. Methods: Data from five studies were combined to generate a normative data set (n = 808) from which mean and SD were calculated for interarm, interleg, and arm-to-leg ratios of ECF and ECF/ICF. The influence of sex, age, and body mass index was evaluated using multiple linear regression, and normative change was calculated for participants with repeated measures by subtracting their lowest ratio from their highest ratio. Results: Mean (SD) interarm, interleg, dominant arm-to-leg, and nondominant arm-to-leg ratios were 0.987 (0.067), 1.005 (0.072), 1.129 (0.160), and 1.165 (0.174) for ECF ratios; and 0.957 (0.188), 1.024 (0.183), 1.194 (0.453), and 1.117 (0.367) for ECF/ICF ratios, respectively. Arm-to-leg ratios were significantly affected by sex, age, and body mass index. Mean normative change ranged from 7.2% to 14.7% for ECF ratios and from 14.7% to 67.1% for ECF/ICF ratios. Conclusion: These findings provide the necessary platform for extending bioimpedance-based screening beyond unilateral lymphedema.

Overall survival of stage IV non-small cell lung cancer patients treated with Viscum album L. in addition to chemotherapy, a real-world observational multicenter analysis.

BACKGROUND: Stage IV non-small cell lung cancer (NSCLC) is associated with a five-year survival rate of around 1%. Treatment with Viscum album L. (VA) extracts has been shown to reduce chemotherapy (CTx)-related adverse events, decrease CTx dose reductions and improve quality of life in a number of cancers. Recent data suggest a beneficial effect of add-on treatment with Viscum album L. (VA, European mistletoe) on survival in cancer patients. The objective of this study was to evaluate the effect of VA in addition to chemotherapy on survival in stage IV NSCLC patients. METHODS: The observational study was conducted using data from the Network Oncology clinical registry which is an accredited conjoint clinical registry of German oncological hospitals, practitioners and out-patient centers.Patients were included if they had stage IV NSCLC at diagnosis, lived at least for four weeks post-diagnosis and received chemotherapeutic treatment. Patients with EGFR mutations as well as patients receiving tyrosine kinase inhibitors or immune checkpoint inhibitors were not included. Overall survival and impact on hazard in patients with chemotherapy (CTx) to patients receiving CTx plus VA were compared. To identify factors associated with survival and to address potential sources of bias a multivariate analyses using Cox proportional hazard model was performed. RESULTS: The median age of the population was 64.1 years with 55.7% male patients. The highest proportion of patients had adenocarcinoma (72.2%) and most of the patients were current or past smokers (70.9%). Of 158 stage IV NSCLC patients, 108 received CTx only and 50 additional VA. Median survival was 17.0 months in the CTx plus VA group (95%CI: 11.0-40.0) and was 8.0 months (95%CI: 7.0-11.0) in the CTx only group (χ2 = 7.2, p = .007). Overall survival was significantly prolonged in the VA group (HR 0.44, 95%CI: 0.26-0.74, p = .002). One-year and three-year overall survival rates were greater with CTx plus VA compared to CTX alone (1y: 60.2% vs. 35.5%; 3y: 25.7% vs. 14.2%). CONCLUSION: Our findings suggest that concomitant VA is positively associated with survival in stage IV NSCLC patients treated with standard CTx. These findings complement pre-existing knowldedge of add-on VA's clinical impact, however, results should be interpreted with caution in light of the study's observational character.

A Systematic Review and Meta-Analysis of the Safety, Feasibility, and Effect of Exercise in Women With Stage II+ Breast Cancer.

OBJECTIVE: To systematically evaluate the safety, feasibility, and effect of exercise among women with stage II+ breast cancer. DATA SOURCES: CINAHL, Cochrane, Ebscohost, MEDLINE, Pubmed, ProQuest Health and Medical Complete, ProQuest Nursing and Allied Health Source, Science Direct and SPORTDiscus were searched for articles published before March 1, 2017. STUDY SELECTION: Randomized, controlled, exercise trials involving at least 50% of women diagnosed with stage II+ breast cancer were included. DATA EXTRACTION: Risk of bias was assessed and adverse event severity was classified using the Common Terminology Criteria. Feasibility was evaluated by computing median (range) recruitment, withdrawal, and adherence rates. Meta-analyses were performed to evaluate exercise safety and effects on health outcomes only. The influence of intervention characteristics (mode, supervision, duration and timing) on exercise outcomes were also explored. DATA SYNTHESIS: There were no differences in adverse events between exercise and usual care (risk difference: <0.01 ([95% CI: -0.01, 0.01], P=0.38). Median recruitment rate was 56% (1%-96%), withdrawal rate was 10% (0%-41%) and adherence rate was 82% (44%-99%). Safety and feasibility outcomes were similar, irrespective of exercise mode, supervision, duration, or timing. Effects of exercise for quality of life, fitness, fatigue, strength, anxiety, depression, body mass index and waist circumference compared with usual care were significant (standardized mean difference range: 0.17-0.77, P<0.05). CONCLUSION: The findings support the safety, feasibility, and effects of exercise for those with stage II+ breast cancer, suggesting that national and international exercise guidelines appear generalizable to women with local, regional, and distant breast cancer.

Implementation of an Integrative Oncological Concept in the Daily Care of a German Certified Breast Cancer Center.

BACKGROUND: In recent decades the concept of integrative medicine has attracted growing interest in patients and professionals. At the Gemeinschaftskrankenhaus Havelhöhe (GKH), a hospital specialized in anthroposophical medicine, a breast cancer center (BCC) has been successfully certified for more than 5 years. The objective of the present study was to analyze how integrative strategies were implemented in the daily care of primary breast cancer patients. METHODS: Clinical, demographic, and follow-up data as well as information on non-pharmacological interventions were analyzed. In addition, BCC quality measures were compared with data of the National Breast Cancer Benchmarking Report 2016. RESULTS: Between 2011 and 2016, 741 primary breast cancer patients (median age 57.4 years) were treated at the GKH BCC. 91.5% of the patients showed Union for International Cancer Control (UICC) stage 0, I, II, or III and 8.2% were in UICC stage IV. 97% of the patients underwent surgery, 53% radiation, 38% had hormone therapy, and 25% received cytostatic drugs. 96% of the patients received non-pharmacological interventions and 32% received Viscum album L. THERAPY: Follow-up was performed in up to 93% of the patients 2 years after first diagnosis. Compared to nationwide benchmarking BCCs, the GKH BCC met the requirements in central items. CONCLUSIONS: The results of the present study show that integrative therapies offered by the concept of anthroposophical medicine can be implemented in the daily care and treatment of a certified BCC. However, as national guidelines on integrative concepts in oncology are missing, further studies are needed for a systematic evaluation of integrative treatment and care concepts in this field.

Safety of Combined Treatment With Monoclonal Antibodies and Viscum album L Preparations.

Combination strategies involving chemotherapy and monoclonal antibodies (mAb) are commonly used in attempts to produce better clinical outcomes. This practice has led to new and ongoing toxicities that may lead to reductions in dose or noncompliance, limiting the effectiveness of treatment. Viscum album L (VA) preparations are widely used in Europe as additive therapy and have been associated with reduced chemotherapy-related adverse reactions and increased health-related quality of life. Concomitant VA therapy might also reduce toxicity related to mAb. This retrospective study investigated the safety of combined treatment with VA and mAb in cancer patients. A total of 43 patients had combined therapy (474 exposures); 12 had VA without mAb (129 exposures), and 8 had mAb without VA (68 exposures). Most patients (89.3%) received concomitant chemotherapy or supportive therapies. A total of 34 patients (60.7%) experienced 142 adverse events (AEs). Leucopenia (14.1% of all events), acneiform rash (8.5%), and stomatitis (6.3%) occurred most frequently. Longitudinal logistic regression analysis suggested a nearly 5 times higher odds of experiencing an AE following treatment with mAb compared with mAb plus VA (95% CI = 1.53-16.14). Our results, together with theoretical consideration of potential botanical-drug interactions, suggest that combined treatment with VA and mAb is safe.

Heavy-Load Lifting: Acute Response in Breast Cancer Survivors at Risk for Lymphedema.

PURPOSE: Despite a paucity of evidence, prevention guidelines typically advise avoidance of heavy lifting in an effort to protect against breast cancer-related lymphedema. This study compared acute responses in arm swelling and related symptoms after low- and heavy-load resistance exercise among women at risk for lymphedema while receiving adjuvant taxane-based chemotherapy. METHODS: This is a randomized, crossover equivalence trial. Women receiving adjuvant taxane-based chemotherapy for breast cancer who had undergone axillary lymph node dissection (n = 21) participated in low-load (60%-65% 1-repetition maximum, two sets of 15-20 repetitions) and heavy-load (85%-90% 1-repetition maximum, three sets of 5-8 repetitions) upper-extremity resistance exercise separated by a 1-wk wash-out period. Swelling was determined by bioimpedance spectroscopy and dual-energy x-ray absorptiometry, with breast cancer-related lymphedema symptoms (heaviness, swelling, pain, tightness) reported using a numeric rating scale (0-10). Order of low- versus heavy-load was randomized. All outcomes were assessed before, immediately after, and 24 and 72 h after exercise. Generalized estimating equations were used to evaluate changes over time between groups, with equivalence between resistance exercise loads determined using the principle of confidence interval inclusion. RESULTS: The acute response to resistance exercise was equivalent for all outcomes at all time points irrespective of loads lifted, with the exception of extracellular fluid at 72 h after exercise with less swelling after heavy loads (estimated mean difference, -1.00; 95% confidence interval, -3.17 to 1.17). CONCLUSIONS: Low- and heavy-load resistance exercise elicited similar acute responses in arm swelling and breast cancer-related lymphedema symptoms in women at risk for lymphedema receiving adjuvant taxane-based chemotherapy. These represent important preliminary findings, which can be used to inform future prospective evaluation of the long-term effects of repeated exposure to heavy-load resistance exercise.

Clinical safety of combined therapy of immune checkpoint inhibitors and Viscum album L. therapy in patients with advanced or metastatic cancer.

BACKGROUND: Despite improvement of tumour response rates in patients with progressive and metastatic cancer, immune checkpoint inhibitors (ICM) induce toxicities in cancer patients. Viscum album L. (VA, mistletoe) extracts are applied as add-on cancer therapy especially in German speaking countries and within integrative and anthroposophical concepts with the goal to improve quality of life. The primary objective of this pilot observational cohort study was to determine the rate of adverse events (AE) related to ICM therapy with and without VA in patients with advanced or metastatic cancer in a certified Cancer Center. METHODS: ICM or combined ICM/VA therapies were applied in patients with progressive or metastatic cancer. AE rates of both therapy groups were compared. RESULTS: A total of sixteen cancer patients were treated with ICM: nivolumab (75%), ipilimumab (19%) or pembrolizumab (6%). The median age of the study population was 64 years (IQR 57.8; 69.3); 44% were male. Of the sixteen patients receiving ICM, nine patients received additional VA (56%; ICM/VA group) and seven did not (44%; ICM group). No statistically significant differences were seen between groups with respect to AE-rates (67% ICM/VA versus 71% ICM). Adjusted multivariate regression analysis revealed that concomitant application of VA did not alter the AE rate in ICM treated patients. 85% of AEs were expected ICM reactions. No AEs of grade 3 or greater were documented for the total study cohort. CONCLUSIONS: This is the first study evaluating the clinical safety profile of ICM in combination with VA in patients with advanced or metastatic cancer. The overall AE rate of the study cohort is comparable to AE rates of ICM treatment in the literature. Our data indicate a first impression that concomitant VA application may not alter ICM-induced AE rates. However, the nature of this study does not allow excluding possible immunological interactions between ICM and VA. Further prospective trials in larger study cohorts should focus on the assessment of safety aspects, clinical efficacy and health related quality of life in patients with combined ICM/VA therapy. TRIAL REGISTRATION: DRKS00013335 , retrospectively registered (November 27th, 2017) at the German Clinical Trials Register ( www.drks.de ).

Immune-related and adverse drug reactions to low versus high initial doses of Viscum album L. in cancer patients.

BACKGROUND: Immune-related adverse drug reactions (ADRs) to immunotherapy agents have been associated with beneficial clinical outcomes in oncology. Viscum album L. (VA, European mistletoe) is frequently used as an immunomodulatory agent alongside conventional cancer treatment in Europe. VA has been associated with improved quality of life and a reduction in chemotherapy-related ADRs. Beneficial effects of VA are believed to be related to its immunomodulatory properties. Current guidelines recommend commencing with a low dose and increasing slowly overtime, however, off-label prescribing of high initial doses is common. PURPOSE: We investigated ADR profiles related to subcutaneous VA therapy commencing with low, recommended doses versus higher than recommended doses. STUDY DESIGN: Retrospective cohort study. METHODS: Medical records of 1361 cancer patients treated between 2003 and 2013 were assessed. Patients were divided into two groups based on whether the dose of their first VA injection adhered to current guidelines. Patient characteristics and suspected VA-related ADRs were compared between dose groups. RESULTS: Of 1361 cancer patients, 516 (38%) started with a recommended, low dose of VA(≤0.02 mg) and 845 (62%) started with a higher dose(>0.02 mg). Groups did not differ by age or gender, but significant differences were observed for type (p < 0.001) and stage of cancer (p = 0.05). Starting with a high dose of VA was significantly associated with a higher incidence of VA-related ADRs compared to starting with a low dose (20.7% versus 0.8%, p < 0.001). Adjusting for age, gender, tumour type and stage of disease, produced an odds ratio of 37.5 (95% CI = 15.7-122.8, p < .001). Almost all ADRs, irrespective of the initial VA dose, were of mild or moderate intensity. Most ADRs were immune-related, general disorders and administration site conditions, many of which are desired reactions, such as pyrexia and local reactions. Overall, no serious ADRs occurred. CONCLUSIONS: Starting VA therapy with a higher than recommended dose was associated with a high frequency of ADRs, however, nearly all ADRs were expected, of mild to moderate intensity and most were desired reactions. Future research is necessary to investigate whether higher incidences of immune-related events are indicators of beneficial immunomodulation and better clinical outcomes.

Lymphedema following gynecological cancer: Results from a prospective, longitudinal cohort study on prevalence, incidence and risk factors.

OBJECTIVE: Cancer-related lymphedema is a debilitating condition that adversely influences function, health and quality of life. The purpose of this study was to assess the prevalence, incidence, and risk factors of lower-limb lymphedema pre- through to 24months post-surgery for gynecological cancer. METHODS: A clinic-based sample of women (n=408) with gynecological cancer participated in a prospective, longitudinal study (2008-2011) using self-reported measures (swelling in one or both legs) and objectively measured lymphedema (bioimpedance spectroscopy) at baseline (pre-surgery), six weeks-three months, 6-12months, and 15-24months post-surgery. RESULTS: At pre-surgery, 15% of women self-reported lymphedema and 27% had measurable evidence of lymphedema. By 24months post-surgery, incidence of new self-reported or measured lymphedema was 45% and 37%, respectively. Three-quarters of these new cases presented by 12-months post-treatment. While lymphedema was transient for some women, 60% had persistent lymphedema. More extensive lymph node dissection, receipt of chemotherapy and radiation therapy, increasing body mass index, insufficient levels of physical activity, diagnosis of vulvar/vaginal cancer and presence of pre-treatment lymphedema were identified as potential risk factors (p<0.05). CONCLUSION: Findings support the need for integration of pre-surgical assessment, and prospective, post-treatment surveillance of lymphedema into gynecological cancer care. Future research exploring the role of maintaining healthy body weight, regular physical activity and education about early detection of lymphedema to improve gynecological cancer survivorship is warranted.