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Studying the relationships between centre of mass (COM) and centre of pressure (COP) during walking has been shown to be useful in determining movement stability. The aim of the current study was to compare COM-COP separation measures during walking between groups of older adults with no history of falling, and a history of falling due to tripping or slipping. Any differences between individuals who have fallen due to a slip and those who have fallen due to a trip in measures of dynamic balance could potentially indicate differences in the mechanisms responsible for falls. Forty older adults were allocated into groups based on their self-reported fall history during walking. The non-faller group had not experienced a fall in at least the previous year. Participants who had experienced a fall were split into two groups based on whether a trip or slip resulted in the fall(s). A Vicon system was used to collect full body kinematic trajectories. Two force platforms were used to measure ground reaction forces. The COM was significantly further ahead of the COP at heel strike for the trip (14.3 ± 2.7 cm) and slip (15.3 ± 1.1 cm) groups compared to the non-fallers (12.0 ± 2.7 cm). COM was significantly further behind the COP at foot flat for the slip group (-14.9 ± 3.6 cm) compared to the non-fallers (-10.3 ± 3.9 cm). At mid-swing, the COM of the trip group was ahead of the COP (0.9 ± 1.6 cm), whereas for the slip group the COM was behind the COP (-1.2 ± 2.2 cm). These results show identifiable differences in dynamic balance control of walking between older adults with a history of tripping or slipping and non-fallers., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm that exhibits the potential for recurrence and metastasis but rarely involves the oral cavity., Presentation of Case: We report the management and long term follow up of recurrent EHE in a 23- year-old woman. The lesion initially presented as a small area of erythematous gingival swelling with localised bone loss around the lower anterior teeth. It was treated by buccal and lingual stripping of the gingival tissues. The patient suffered local recurrence after 7 years and was treated with a wider surgical excision of the buccal and lingual gingivae, conserving the adjacent teeth and bone with an excellent cosmetic outcome. Over 21 years later, there have been no further recurrences., Discussion: This case highlights the management challenges of EHE and is the only case in the literature to have reported a case of mandibular gingivae with a long review period of 21 years., Conclusion: Oral EHE is an unpredictable lesion with a relatively benign course, unlike non-oral EHE where up to one third of cases may metastasise. Because of the propensity to recur locally after excision and curettage, a wide local excision with close clinical follow has been suggested in the literature as the treatment of choice for oral lesions. However, the lack of metastases from oral lesions, the small size, mandibular site and bland histology in this case suggests that a limited soft tissue excision and bone curettage, with long term follow-up would be appropriate for similar gingival lesions in future., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/Aim: Recently, immune checkpoint inhibitors (ICI) have been added to the treatment of brain metastases. While combining radiotherapy and ICI can enhance therapeutic effects, it might also increase the risk of severe autoimmune adverse events. This retrospective study aims to compare treatment responses and neurotoxicity in patients treated with radiotherapy alone versus those receiving a combination of radiotherapy and ICI. Patients and methods: All patients with brain metastases who received radiotherapy at Hannover Medical School from 2017 to 2019 were included. The medical reports of all study participants were evaluated. Patients who received radiotherapy alone and those who received a combination of radiation and ICI were compared. Results: A total of 248 patients were analyzed, with the most common tumor types being non-small cell lung cancer (NSCLC) and malignant melanoma. Half of the patients received whole-brain radiotherapy (WBRT) and the other half stereotactic radiotherapy (SRT). Of these, 29 patients received concurrent immunotherapy and radiotherapy, 30 completed immunotherapy before radiotherapy, and 29 started ICI after completing radiotherapy. Two cases lacked information on the duration of immunotherapy. Overall survival post-initial tumor diagnosis within the total cohort was 52 months, with significantly worse survival for patients with multiple brain metastases (p = 0.020). No significant differences in survival or incidence of neurological adverse events were observed between patients with or without ICI. Conclusion: Combining radiotherapy and ICI did not significantly increase neurotoxicity or improve survival in this cohort, though the heterogeneity of the subgroups limits the generalizability of these findings. [ABSTRACT FROM AUTHOR]

Introduction: Significant therapeutic changes have recently occurred in the management of melanoma brain metastases (BMs), both in the field of local treatments, with the rise of stereotactic radiotherapy (RT), as well as in systemic ones, with the advent of immunotherapy and targeted therapies (TT). These advances have brought about new challenges, particularly regarding the potential interactions between new TT (notably BRAF/MEK inhibitors) and irradiation. Through a clinical case, we will discuss a side effect not previously described in the literature: ultra-early pseudoprogression (PP) following brain stereotactic radiosurgery (SRS), in a patient treated with dabrafenib-trametinib. Case presentation: A 61-year-old patient with BRAFV600E-mutated melanoma, receiving second-line dabrafenib-trametinib therapy, was referred for SRS on three progressing meningeal implants, without evidence of systemic progression. Four days after the first RT session (1x6 Gy on a fronto-orbital lesion prescribed 5x6 Gy, and 1x20 Gy single fraction on the other lesions), the patient presented with an epileptic seizure. An MRI, compared to the planning MRI ten days earlier, revealed significant progression of the irradiated lesions. The patient's condition improved with dexamethasone and levetiracetam, and RT was halted out of caution. A follow-up MRI at one month demonstrated a size reduction of all treated lesions. Subsequent imaging at five months revealed further shrinking of the two lesions treated with an ablative dose of 20 Gy, while the under-treated fronto-orbital lesion progressed. These dynamics suggest an initial PP in the three irradiated lesions, followed by good response in the ablatively treated lesions and progression in the partially treated lesion. Conclusion: To our knowledge, this represents the first documented case of ultra-early PP following brain SRS in a patient receiving concomitant dabrafenib-trametinib. It highlights the need for particular vigilance when using tyrosine kinase inhibitors (TKIs) with SRS, and warrants further research into potential treatment interactions between RT and novel systemic agents, as well as the optimal treatment sequence of melanoma BMs. [ABSTRACT FROM AUTHOR]

Introduction: Childhood cancers as a group affect around 1 in 500 children but each individual diagnosis is a rare disease. While research largely focuses on improving cure rates, the management of side effects of treatment are high priority for clinicians, families and children and young people. Areas covered: The prevention and efficient management of infectious complications, oral mucositis, nausea and vomiting and graft-vs-host disease illustrated with examples of implementation research, translation of engineering to care, advances in statistical methodologies, and traditional bench-to-patient development. The reviews draw from existing systematic reviews and well conducted clinical practice guidelines. Expert opinion: The four areas are driven from patient and family priorities. Some of the problems outlined are ready for proven interventions, others require us to develop new technologies. Advancement needs us to make the best use of new methods of applied health research and clinical trial methodologies. Some of the greatest challenges may be those we're not fully aware of, as new therapies move from their use in adult oncological practice into children. This will need us to continue our collaborative, multi-professional, multi-disciplinary and eclectic approach. [ABSTRACT FROM AUTHOR]

Rationale: Evaluating approaches to reduce treatment burden is a research priority among people with cystic fibrosis on highly effective modulators, including elexacaftor-tezacaftor-ivacaftor (ETI). Objectives: We sought to evaluate the impact of discontinuing both hypertonic saline (HS) and dornase alfa (DA) versus continuing both therapies among a subgroup of participants in the SIMPLIFY study who sequentially participated in trials evaluating the independent clinical effects of discontinuing HS and DA. Methods: SIMPLIFY participants ≥12 years old on ETI and constituting a subgroup using both HS and DA at study entry were randomized to the HS or DA trial and then randomized 1:1 to continue or discontinue the applicable therapy for 6 weeks. After completion of the first trial, eligible participants could enroll in the second trial beginning with a 2-week run-in. Study outcomes were compared across the duration of SIMPLIFY participation between a cohort remaining on both therapies during SIMPLIFY and a cohort that sequentially discontinued both as a result of trial randomizations. Multivariable regression models were used to estimate treatment differences, adjusted for time between trials, trial order, baseline age, sex at birth, and percent predicted forced expiratory volume in 1 second (ppFEV1) at study entry. Results: Forty-three participants discontinued both therapies by the end of SIMPLIFY, and 63 remained on both, with overall average ppFEV1 of 96.7% at study entry and 3.9 months as the average duration of follow-up from beginning of the first trial to completion of the second trial, including time between trials. No clinically meaningful difference in the change in ppFEV1 from baseline to completion of the second trial was observed between those who discontinued and those who remained on both therapies (difference: 0.22% off-on; 95% confidence interval = −1.60, 2.03). Changes in lung clearance index at 2.5% starting concentration, patient-reported outcomes, and safety outcomes were also comparable. Patient-reported treatment burden, as measured by a Cystic Fibrosis Questionnaire–Revised subscale, significantly decreased in those who discontinued both therapies. Conclusions: SIMPLIFY participants who sequentially discontinued both HS and DA experienced no meaningful changes in clinical outcomes and reported decreased treatment burden as compared with those who remained on both therapies. These data continue to inform a new era of postmodulator care of people with cystic fibrosis. [ABSTRACT FROM AUTHOR]

Obesity is a common public health issue worldwide, and its negative impact on lung function has garnered widespread attention. This study sought to investigate the possible association between a new obesity metric, the weight-adjusted waist index (WWI), and lung functions, providing a basis for the monitoring and protection of lung functions. We conducted a cross-sectional evaluation, analyzing data from adults in the U.S. gathered through the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. To explore the correlation between WWIs and lung functions, we utilized a multivariate logistic regression model with appropriate weighting to ensure accuracy. Smooth curve fitting also helped to confirm the linear nature of this relationship. Subgroup analyses were conducted to confirm the uniformity and dependability of the results. Our study included data from 13,805 adults in the United States. Multivariate linear regression analysis revealed that, in the fully adjusted model, higher WWIs were negatively correlated with forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC, peak expiratory flow rate (PEF), and forced expiratory flow rate (FEF) 25%-75% (β = -0.63; 95% confidence interval [CI] [-0.71, -0.55]; β = -0.55; 95% CI [-0.62, -0.48]; β = -0.02; 95% CI [-0.03, -0.01]; β = -1.44; 95% CI [-1.65, -1.23]; β = -0.52; 95% CI [-0.65, -0.39], respectively). Additionally, when analyzing the WWI as a categorical variable, a significant downward trend in the FVC, FEV1, PEF, and FEF 25%-75% was observed from Q2 to Q4 as the WWI increased (trend P < 0.05). Subgroup analysis showed stronger associations between WWI and lung functions, particularly among younger, non-Hispanic white, male participants, and current smokers. Our results indicate that elevated WWI is strongly associated with declining lung functions, demonstrating the importance of long-term monitoring and tracking of WWIs. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Involvement of children and young people in research has a multitude of benefits for children, researchers and the quality of the research itself. Despite the benefits of involvement, this is not always completed or reported in practice. METHODS: This paper looks at the involvement of children and young people during a research study exploring the acceptability of photobiomodulation for mucositis management. It considers the importance of costing involvement into grant funding, and the value of charitable partnerships in conducting research with patient and public involvement. RESULTS: Children and young people with experience of cancer, and their parents, were involved at the stages of grant application, research design, data analysis and dissemination. Involvement of families resulted in changes to inclusion criteria, plain language summaries and participant information documents. They provided insight into data analysis, and designed and filmed co-created video outputs to support acceptability of the treatment, dissemination of the research and research involvement of other children. Involvement was supported both practically and financially by charitable partnership with the Candlelighters children's cancer charity as well as research grant funding from the Royal College of Surgeons of England's Faculty of Dental Surgery. CONCLUSIONS: Child and parent contributors shaped the research project, resulting in changes to the study design, data analysis and co-creation of video resources. Charitable partnership and flexibility of involvement supported diversity in the context of paediatric cancer research. Researchers should consider what they can contribute in return to child contributors and charities who provide support. [ABSTRACT FROM AUTHOR]

Multiple breath washout (MBW) has successfully assessed the silent lung zone particularly in cystic fibrosis lung disease, however, it is limited to the communicating lung only. There are a number of different pulmonary function methods that can assess what is commonly referred to as trapped air, with varying approaches and sensitivity. Twenty-five people with cystic fibrosis (pwCF) underwent MBW, spirometry, body plethysmography, and spirometry-controlled computed tomography (spiro-CT) on the same day. PwCF also performed extensions to MBW that evaluate air trapping, including our novel extension (MBWShX), which reveals the extent of underventilated lung units (UVLU). In addition, we used two previously established 5-breath methods that provide a volume of trapped gas (VTG). We used trapped air % from spiro-CT as the gold standard for comparison. UVLU derived from MBWShX showed the best agreement with trapped air %, both in terms of correlation (RS 0.89, P < 0.0001) and sensitivity (79%). Bland–Altman analysis demonstrated a significant underestimation of the VTG by both 5-breath methods (−249 mL [95% CI −10,796; 580 mL] and −203 mL [95% CI −997; 591 mL], respectively). Parameters from both spirometry and body plethysmography were suboptimal at assessing this pathophysiology. The parameters from MBWShX demonstrated the best relationship with spiro-CT and had the best sensitivity compared with the other pulmonary function methods assessed in this study. MBWShX shows promise to assess and monitor this critical pathophysiological feature, which has been shown to be a driver of lung disease progression in pwCF. NEW & NOTEWORTHY: We consider the term "trapped air" either in the use of imaging or pulmonary function testing, something of a misnomer that can lead to an inaccurate assessment of an important physiological feature. Instead, we propose the term underventilated lung units (UVLU). Of the many pulmonary function methods we used in this study, we found that the use of multiple breath washout with short extension (MBWShX) to be the best nonimaging method. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to evaluate the effectiveness of cryotherapy in preventing oral mucositis in pediatric patients receiving chemotherapy. Methods: An evidence-based practice project utilized a randomized control trial design with two groups (experimental and control groups). Fifty-nine pediatric patients with cancer in Jordan, aged 8–18 years, were randomly assigned to the experimental group (n=29) or the control group (n=30). The intervention was conducted from June 2022 to December 2022. The severity of oral mucositis among pediatric cancer patients was assessed using the World Health Organization oral mucositis grade. Results: There were no significant differences in sex or disease type among the groups. On days 7, 14, and 21, we observed notable between-group differences in treatment responses and the intensity of oral mucositis, highlighting the efficacy of cryotherapy in diminishing the severity of oral mucositis. Conclusion: This study supports the use of cryotherapy as a preventive measure for oral mucositis among pediatric oncology patients in Jordan. The findings suggest that cryotherapy effectively reduces the severity of oral mucositis. Further research is necessary to investigate the broader impacts of cryotherapy. [ABSTRACT FROM AUTHOR]

Background: Early studies indicated that corticosteroids may limit the survival benefit from immunotherapy. We conducted this systematic review to evaluate the effect corticosteroids have on immunotherapy in patients with malignancy, when adjusted for potentially confounding effects of corticosteroids given for palliative indications. Methods: Three electronic databases (PubMed, Embase and Medline) were searched on 1 February 2023. Studies that measured response or survival to immunotherapy in people receiving corticosteroids for non‐cancer indications compared to either no corticosteroids or corticosteroids for cancer‐related indications were included. Studies exclusively evaluating the effect of corticosteroids administered for immune‐related adverse events (irAE) were excluded to avoid immortal time bias. Pooled odds and hazard ratios with 95% confidence intervals (CI) were calculated using a random effects model. Study heterogeneity was assessed using the I2 statistic, and publication bias was evaluated by funnel plot and Egger's regression model. Results: Eight thousand four hundred and twenty‐six titles were identified on our search. Eight studies met our inclusion criteria for meta‐analysis. Administration of corticosteroids does not have a statistically significant effect on survival and response to immunotherapy when administered for non‐cancer‐related indications, with a pooled odds ratio for overall response rate 1.01 (95% CI 0.64–1.60); pooled hazard ratio (HR) for progression free survival 0.87 (95% CI 0.68–1.12); and pooled HR for overall survival 0.79 (95% CI 0.59–1.05). Conclusion: This systematic review indicates that administration of corticosteroids does not affect response to immunotherapy nor survival outcomes, when removing confounding palliative corticosteroid indications. These results are limited by the retrospective nature of the studies included, small sample sizes, lack of information about corticosteroid dosing and the inclusion of irAE in two of the studies which could bias the results. [ABSTRACT FROM AUTHOR]

Background: Recently, the development of advanced, noninvasive methods has allowed the study of respiratory function even in uncooperative infants. To date, there is still little data on the application of this technique in infants with suspected airway obstruction. The aims of our study were: - To evaluate the role of respiratory function testing (PFR) in the diagnosis and follow-up of infants with stridor - To evaluate the differences between patients with inspiratory stridor and expiratory stridor. - To evaluate the concordance between PFR and endoscopy. Methods: We enrolled infants aged < 1 year with a diagnosis of inspiratory and/or expiratory chronic stridor and a group of healthy controls. For each patient we performed PFR at diagnosis (T0) and for cases at follow-up, at 3 months (T1), 6 months (T2), 12 months (T3). At T0, all patients were classified according to a clinical score, and at follow-up, stature-ponderal growth was assessed. When clinically indicated, patients underwent bronchoscopy. Results: We enrolled 48 cases (42 diagnosed with inspiratory stridor and 6 expiratory stridor) and 26 healthy controls. At T0, patients with stridor had increased inspiratory time (p < 0.0001) and expiratory time (p < 0.001) than healthy controls and abnormal curve morphology depending on the type of stridor. At T0, patients with expiratory stridor had a reduced Peak expiratory flow (p < 0.023) and a longer expiratory time (p < 0.004) than patients with inspiratory stridor. We showed an excellent concordance between PFR and endoscopic examination (k = 0.885, p < 0.0001). At follow-up, we showed a progressive increase of the respiratory parameters in line with the growth. Conclusions: PFR could help improve the management of these patients through rapid and noninvasive diagnosis, careful monitoring, and early detection of those most at risk. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the risk factors for delayed chemotherapy–induced vomiting (DCIV) in pediatric oncology patients. We collected data on pediatric patients from a tertiary care pediatric hospital in an Asian urban center. We analyzed the risk factors for DCIV in patients by univariate analysis and logistic regression. Patients were grouped according to age by the Youden index, and differences in clinical features between the high-risk and low-risk groups were calculated. In the univariate analysis, the number of chemotherapy days, pH, and blood glucose levels were significantly associated with DCIV. In the logistic regression analysis, patient age was an independent risk factor (odds ratio [OR] = 1.013, 95% confidence interval [CI] = 1.005-1.021, P =.002). Children in the high-risk group had a higher grade of vomiting (P <.05). Age is an important risk factor for DCIV in pediatric patients, with older children tending to experience more frequent and more severe vomiting. [ABSTRACT FROM AUTHOR]

Background: Pediatric asthma lacks sensitive objective measures for asthma monitoring. The forced oscillation technique (FOT) offers strong feasibility across the pediatric age range, but relationships between FOT parameter day-to-day variability and pediatric asthma severity and control are unknown., Methods: Day-to-day variability in FOT respiratory system resistance (Rrs) and respiratory system reactance (Xrs) compared with peak expiratory flow (PEF) were defined in 22 children with asthma (mean ± SD age, 10.4 ± 1.1 years) during a 5-day asthma camp. FOT was performed at 6 Hz in triplicate on each test occasion. Relationships between day-to-day FOT variability (expressed as within-subject SD [SDW] and asthma control and severity (defined according to GINA [Global Initiative for Asthma] recommendations) were explored. For comparison, normal baseline FOT values and variability, measured on two occasions, were defined in a separate cohort of 38 healthy children (age, 9.5 ± 1.0 years)., Results: Day-to-day Rrs variability was greater in persistent (n = 16) vs intermittent (n = 6) asthma (mean SDW, 0.69 cm H2O/L/s vs 0.39 cm H2O/L/s; P ≤ .01). Day-to-day Rrs variability was increased in uncontrolled (n = 13) vs partly controlled asthma (n = 9) (mean SDW, 0.75 cm H2O/L/s vs 0.42 cm H2O/L/s; P ≤ .05). PEF variability did not differentiate the groups. Day-to-day variability of Rrs and Xrs but not baseline values were increased in children with asthma vs control children (Rrs mean SDW, 0.61 cm H2O/L/s vs 0.33 cm H2O/L/s [P ≤ .05]; Xrs mean SDW, 0.24 cm H2O/L/s vs 0.15 cm H2O/L/s [P ≤ .05])., Conclusions: Increased day-to-day FOT variability exists in school-aged children with asthma. Day-to-day Rrs variability was associated with asthma severity and asthma control. FOT may be a useful objective monitoring tool in pediatric asthma and warrants further study., Trial Registry: Australian and New Zealand Clinical Trials Registry; No.: ACTRN12614000885695; URL: www.anzctr.org.au.

Imaging studies describe significant ventilation defects across a wide range of cystic fibrosis (CF) related lung disease severity. These are unfortunately poorly reflected by phase III slope analysis-derived Scond and Sacin from multiple-breath washout (MBW). Methodology extending previous two-lung compartment model-based analysis is presented describing size and function of fast- and slow-ventilating lung compartments from nitrogen (N2) MBW and correlation to obstructive lung disease severity. In 37 CF subjects (forced expiratory volume in 1 s [FEV1] mean [SD] 84.8 [19.9] % predicted; abnormal lung clearance index [LCI] in 36/37, range 7.28-18.9) and 74 matched healthy controls, volume and specific ventilation of both fast and slowly ventilated lung compartments were derived from N2-based MBW with commercial equipment. In healthy controls lung emptying was characterized by a large compartment constituting 75.6 (8.4)% of functional residual capacity (FRC) with a specific ventilation (regional alveolar tidal volume/regional lung volume) of 13.9 (3.7)% and a small compartment with high specific ventilation (48.4 [15.7]%). In CF the slowly ventilated lung compartment constituted 51.9(9.1)% of FRC, with low specific ventilation of 5.3 (2.4)%. Specific ventilation of the slowly ventilated lung compartment showed stronger correlation with LCI (r2 = 0.70, P < 0.001) vs. Sacin (r2 = 0.44, P < 0.001) or Scond (no significant correlation). Overventilation of the fast lung compartment was no longer seen in severe CF lung disease. Magnitude and function of under- and overventilated lung volumes can be derived from routine N2 MBW in CF. Reported values agree with previous modelling-derived estimates of impaired ventilation and offer improved correlation to disease severity, compared with SnIII analysis., (Copyright © 2014 the American Physiological Society.)

One of the major complications of Cystic Fibrosis (CF) is CF-Related Diabetes (CFRD), which increases in incidence with age, from 1-2% below the age of 10 years to ∼20% of adolescents and 40-50% of adults. Multiple guidelines have been published over the last few years for the diagnosis and management of CFRD, from the American Diabetes Association (ADA) / US Cystic Fibrosis Foundation, International Society for Pediatric and Adolescent Diabetes (ISPAD) and the Thoracic Society of Australia and New Zealand-Australian Diabetes Society. However, little is published about the particular issues involved in transition of patients with CFRD from paediatric to adult care, nor the issues concerning the development of CFRD during the transition period. This document seeks to provide assistance to physicians, dieticians, nurses, diabetes educators, CF patients and their families by outlining the issues surrounding CFRD during transition from paediatric to adult care., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Obesity has complex and incompletely understood effects upon the respiratory system in childhood, which differs in some aspects to those seen in adults. There is increasing evidence that excess adiposity will impact negatively upon static and dynamic respiratory function as measured through lung volumes, lung compartment mechanics, measures of airway function and exercise capability to varying degrees. Further information is needed to better understand the effects in children, and the importance of onset and duration of obesity on subsequent outcomes. Consensus about how best to express adiposity is also an essential part of this process and fat distribution is another important factor. From a clinical standpoint this creates challenges in distinguishing a deconditioned obese young person from a non-atopic asthmatic because of symptom overlap and lung function testing results, including responses seen during airway challenges. There is evidence to support the role of weight loss in achieving normalisation of lung function parameters, but as always with obesity there are enormous challenges in realising this goal for many subjects., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Accurate discrimination of environmental cues predicting reward, fear, or safety is important for survival. The prelimbic and infralimbic cortices are implicated in regulating reward-seeking and fear behaviors; however, no studies have examined their roles in discriminating among reward, fear, and safety cues. Using a discriminative conditioning task that includes presentations of a reward cue (paired with a reward pellet), fear cue (paired with footshock), and a compound fear+safety cue (no footshock) within the same sessions allowed us to assess the flexibility and precision of fear and reward-seeking behaviors to these cues. We found that fear behavior was appropriately limited to the fear cue in untreated rats, but during infralimbic cortical inactivation, similar levels of fear were seen to the fear and compound fear+safety cues. Reward-seeking behavior was also appropriately limited to the reward cue in untreated rats. Inactivating the prelimbic cortex altered discriminative reward seeking as rats with prelimbic inactivation did not increase their reward seeking behavior during the reward cue to the same degree as saline controls. Our results imply dissociable roles of the two cortical regions: the prelimbic cortex in precise discriminative reward seeking and the infralimbic cortex in discriminating between fear and safety cues. These data suggest that alterations in the balance of activity between areas homologous to the prelimbic and infralimbic cortices may be involved in the processes that go awry in anxiety and addiction disorders.

This guideline provides an approach to the prevention and treatment of anticipatory chemotherapy-induced nausea and vomiting (CINV) in children. It was developed by an international, inter-professional panel using AGREE II methods and is based on systematic literature reviews. Evidence-based recommendations for pharmacological and non-pharmacological interventions to prevent and treat anticipatory CINV in children receiving antineoplastic agents are provided. Gaps in the evidence used to support the recommendations are identified. The contribution of this guideline to anticipatory CINV control in children requires prospective evaluation., (© 2014 Wiley Periodicals, Inc.)

Maternal immune activation (MIA) during pregnancy is an environmental risk factor for psychiatric illnesses such as schizophrenia and autism in the offspring. Hence, changes in an array of behaviors, including behavioral flexibility, consistent with altered functioning of cortico-limbic circuits have been reported in rodent models of MIA. Surprisingly, previous studies have not examined the effect of MIA on the extinction of fear conditioning which depends on cortico-limbic circuits. Thus, we tested the effects of treating pregnant Long Evans rats with the viral mimetic polyI:C (gestational day 15; 4 mg/kg; i.v.) on fear conditioning and extinction in the male offspring using two different tasks. In the first experiment, we observed no effect of polyI:C treatment on the acquisition or extinction of a classically conditioned fear memory in a non-discriminative auditory cue paradigm. However, polyI:C-treated offspring did increase contextual freezing during the recall of fear extinction in this non-discriminative paradigm. The second experiment utilized a recently developed task to explicitly test the ability of rats to discriminate among cues signifying fear, reward, and safety; a task that requires behavioral flexibility. To our surprise, polyI:C-treated rats acquired the task in a manner similar to saline-treated rats. However, upon subsequent extinction training, they showed significantly faster extinction of the freezing response to the fear cue. In contrast, during the extinction recall test, polyI:C-treated offspring showed enhanced freezing behavior before and after presentation of the fear cue, suggesting an impairment in their ability to regulate fear behavior. These behavioral results are integrated into the literature suggesting impairments in cortico-limbic brain function in the offspring of rats treated with polyI:C during pregnancy.

This guideline provides clinicians with evidence-based recommendations on the use of antifungal prophylaxis in children with cancer and undergoing hematopoietic stem cell transplantation (HSCT). Recommendations are divided into: (1) allogeneic HSCT (2) autologous HSCT (3) acute myeloid leukemia or myelodysplastic syndrome and (4) patients with malignancy and neutropenia for >7 days. A systematic review was conducted and evidence summaries compiled. The quality of evidence and strength of each recommendation was determined using GRADE. Implementation of these recommendations will require adaptation to local context. The contribution of this guideline in the prevention of invasive fungal infections requires prospective evaluation., (© 2013 Wiley Periodicals, Inc.)

Background: Infectious disease physicians may be asked to evaluate and manage a variety of infections in immunocompromised hosts undergoing hematopoietic cell transplant (HCT) and cellular therapies. Over the last decade, several advances in cellular therapy have occurred, with implications for the types of infectious complications that may be seen., Aims: The purpose of this review is to update the infectious disease physician on newer advances in HCT and cellular therapy, including haploidentical transplant, expanding indications for transplant in older individuals and children, and chimeric antigen receptor T-cells. We will review how these advances might influence infectious disease complications following HCT. We will also provide a perspective that infectious disease physicians can use to evaluate the degree of immune suppression in an individual patient to help determine the type of infections that may be encountered., (© 2023 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.)

Chemotherapy-induced nausea and vomiting (CINV) remain the most distressing event in patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). This meta-analysis was conducted to evaluate the efficacy and safety of olanzapine containing regimen in preventing CINV in children on HEC and MEC. We searched PubMed, Embase, and Cochrane central register of controlled trials electronic databases to identify randomized clinical trials that compared 2 groups who either got olanzapine (olanzapine group) or placebo/no olanzapine (control group) for the prevention of CINV in children. The primary outcome was to determine the efficacy of olanzapine (complete response). The secondary outcomes were nausea control, the need for rescue medications, and adverse events of olanzapine. Three randomized clinical trials (n=394 patients) were included in this meta-analysis (olanzapine group, n=194, and placebo/control group, n=200). The pooled analysis of this meta-analysis found that olanzapine had a higher complete response in all phases of emesis in the HEC group and only in the acute phase in HEC/MEC groups compared with the control group. Olanzapine had higher nausea control in all phases of HEC but no nausea control in HEC/MEC. Olanzapine also reduced the need for rescue medications. A significant number of patients in the olanzapine group experienced somnolence (grades 1 and 2), but none of the participants discontinued the study due to side effects. In conclusion, this meta-analysis showed that olanzapine significantly prevented CINV in HEC. There was also a lesser need for rescue medications in the olanzapine group. Somnolence was higher in the olanzapine group, but it was clinically insignificant., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Asthma control remains a significant challenge in the pediatric age range in which ongoing loss of lung function in children with persistent asthma has been reported, despite the use of regular preventer therapy. This has important implications for observed mortality and morbidity during adulthood. Over the past decade, there has been an emergence of other treatment adjuncts, such as anti-Immunoglobulin E (IgE)-directed therapy, low dose theophylline, and the use of macrolide antibiotics, yet their exact role in asthma management remains unclear, despite omalizumab now being incorporated into several international asthma guidelines. As with many aspects of pediatric care, this is driven by a lack of appropriately designed pediatric trials. Extrapolation of data reported in adult studies may be appropriate for adolescent asthma, but is not for younger age groups, in which important pathophysiological differences exist. Novel drugs under development offer potential for benefit in the future, but to date existing data are in most cases limited to adults. Pediatric asthma also offers unique potential to prevent or modify the underlying pathophysiology. Although attempts to do so have been unsuccessful to date, advances may yet come from this approach, as our understanding about the interaction between genetics, environmental factors, and viral illness improve. This review provides an overview of the newer treatment options available for management of pediatric asthma and discusses the merits of other novel therapies in development, as we search to optimize management and improve future outcomes.

This guideline provides an approach to the prevention of acute antineoplastic-induced nausea and vomiting (AINV) in children. It was developed by an international, inter-professional panel using AGREE and CAN-IMPLEMENT methods. Evidence-based interventions that provide optimal AINV control in children receiving antineoplastic agents of high, moderate, low, and minimal emetogenicity are recommended. Recommendations are also made regarding selection of antiemetic agents for children who are unable to receive corticosteroids for AINV control, the role of aprepitant and optimal doses of antiemetic agents. Gaps in the evidence used to support the recommendations were identified. The contribution of this guideline to AINV control in children requires prospective evaluation., (Copyright © 2013 Wiley Periodicals, Inc.)

Objectives: We described previously the development of a set of quality indicators (QIs) of a childhood cancer system in Ontario, Canada. The purpose of this study was to determine the acceptability of the proposed set of QIs among stakeholders of the childhood cancer system., Methods: A modified Delphi method was used to assess stakeholder agreement on the value of the proposed QIs. A QI evaluation survey was mailed to a stakeholder group of 23 multidisciplinary health care providers, survivors, parents, and policymakers who rated each QI on specific criteria. Prior to an in-person consensus meeting, the distribution of scores was provided to panel members. At the meeting, QIs were reevaluated and discussed in three successive rounds. QIs with 80% or more of panel agreement were considered endorsed., Results: Overall, 20 QIs were endorsed by the panel, measuring all seven quality dimensions of Ontario's Cancer System Quality Index framework. Five QIs were endorsed by 100% of the panel as follows: Five-year event-free survival, chemotherapy admission delay, drug availability, sufficient multidisciplinary staff, and parent satisfaction. Although none of the QIs relating to end-of-life or Satellite care were endorsed, panel members emphasized the need to measure these components of the system., Conclusions: Standardized implementation of the 20 pediatric cancer QIs endorsed by the multidisciplinary stakeholder panel will provide ongoing monitoring of various dimensions of system quality and the development of benchmarks over time, greatly augmenting the ability to identify needed system improvements across populations and jurisdictions., (Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objectives: A set of indicators to assess the quality of a childhood cancer system has not been identified in any jurisdiction internationally, despite the movement toward increased accountability and provision of high-quality care with limited health care resources. This study was conducted to develop a set of quality indicators (QIs) of a childhood cancer control and health care delivery system in Ontario, Canada., Methods: A systematic review and targeted gray literature search were conducted to identify potential childhood cancer QIs. A series of investigator focus group sessions followed to review all QIs identified in the literature, and to generate a provisional QI set for a childhood cancer system. QIs were evaluated by three content experts in a sequential selection process on the basis of a series of criteria to select a subset for presentation to stakeholders. Following an appraisal of the relevance of quality assessment frameworks, remaining QIs were mapped onto the Cancer System Quality Index framework., Results: The systematic review yielded few relevant childhood cancer system QIs. Overall, 120 provisional QIs were developed by the investigator group. Based on median QI rating scores, representation across the childhood cancer continuum, and feasibility of data collection, a subset of 33 QIs was selected for stakeholder consideration., Conclusions: The subset of 33 QIs developed on the basis of a systematic literature review and consensus provides the basis for the selection of a set of QIs for ongoing, standardized monitoring of various dimensions of quality in a childhood cancer system., (Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Extrapolation of management strategies based on results from predominantly adult asthma studies frequently occurs in paediatric asthma despite increasing evidence that paediatric asthma and, in particular, pre-school recurrent wheeze are very different disease entities. Response to medications in paediatric subjects is often different from that seen in their older adolescent and adult counterparts. In this update, we discussed recent studies that have had important implications for future paediatric asthma management. The overuse of combination inhaled steroid and long-acting beta2 agonist inhalers in paediatric asthma despite ongoing safety concerns is an increasing trend in paediatric asthma, and recent evidence has helped clarify how they should be used in children. Other aspects discussed include the role of oral corticosteroids in pre-school viral-induced wheeze and the utility of leukotriene receptor antagonists in exercise-induced asthma., (© 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Although pulmonary function testing plays a key role in the diagnosis and management of chronic pulmonary conditions in children under 6 years of age, objective physiologic assessment is limited in the clinical care of infants and children less than 6 years old, due to the challenges of measuring lung function in this age range. Ongoing research in lung function testing in infants, toddlers, and preschoolers has resulted in techniques that show promise as safe, feasible, and potentially clinically useful tests. Official American Thoracic Society workshops were convened in 2009 and 2010 to review six lung function tests based on a comprehensive review of the literature (infant raised-volume rapid thoracic compression and plethysmography, preschool spirometry, specific airway resistance, forced oscillation, the interrupter technique, and multiple-breath washout). In these proceedings, the current state of the art for each of these tests is reviewed as it applies to the clinical management of infants and children under 6 years of age with cystic fibrosis, bronchopulmonary dysplasia, and recurrent wheeze, using a standardized format that allows easy comparison between the measures. Although insufficient evidence exists to recommend incorporation of these tests into the routine diagnostic evaluation and clinical monitoring of infants and young children with cystic fibrosis, bronchopulmonary dysplasia, or recurrent wheeze, they may be valuable tools with which to address specific concerns, such as ongoing symptoms or monitoring response to treatment, and as outcome measures in clinical research studies.

Introduction: Various functional residual capacity (FRC) repeatability criteria have been proposed for lung clearance index (LCI) measurement by multiple breath washout (MBW). Adult guidelines recommend three technically acceptable tests with FRC values within 10%, whilst preschool guidelines recommend two such tests. Feasibility of and need for recommendations in children is unclear., Methods: Retrospective analysis of MBW data was undertaken in healthy control (n = 90) and cystic fibrosis (CF) subjects (n = 108) encompassing infancy, pre-school and school age ranges. Feasibility of FRC repeatability recommendations was investigated in those with three technically acceptable tests. Validity of mean LCI from the first two tests alone (vs. all three) was investigated by comparing mean data and sensitivity to detect abnormal peripheral airway function in CF., Results: LCI coefficient of variation (CoV) was related to FRC CoV (P < 0.001) and disease category (P = 0.002). Application of adult repeatability criteria decreased LCI CoV (4.7 vs. 8.5%, P < 0.001), but had poor feasibility beyond infancy (62/150, 41%). Preschool recommendations increased feasibility but only to 70% overall. There was no difference in mean LCI (All three minus 1st two tests) in healthy controls [mean (95% CI) difference: 0.02 (-0.01, 0.06; P = 0.15)], this difference being statistically but not clinically significant in CF subjects [0.07 (0.00,0.13; P = 0.04)]. Sensitivity in CF subjects was unaffected., Conclusion: Adult FRC repeatability recommendations improved LCI repeatability in pediatric subjects, but poor feasibility limited utility. In an experienced pediatric MBW center, recent preschool recommendations can be extended to two technically acceptable tests, irrespective of FRC repeatability, without significantly affecting mean LCI or compromising sensitivity., (Copyright © 2012 Wiley Periodicals, Inc.)

Inert gas washout tests, performed using the single- or multiple-breath washout technique, were first described over 60 years ago. As measures of ventilation distribution inhomogeneity, they offer complementary information to standard lung function tests, such as spirometry, as well as improved feasibility across wider age ranges and improved sensitivity in the detection of early lung damage. These benefits have led to a resurgence of interest in these techniques from manufacturers, clinicians and researchers, yet detailed guidelines for washout equipment specifications, test performance and analysis are lacking. This manuscript provides recommendations about these aspects, applicable to both the paediatric and adult testing environment, whilst outlining the important principles that are essential for the reader to understand. These recommendations are evidence based, where possible, but in many places represent expert opinion from a working group with a large collective experience in the techniques discussed. Finally, the important issues that remain unanswered are highlighted. By addressing these important issues and directing future research, the hope is to facilitate the incorporation of these promising tests into routine clinical practice.

As survival improves after lung and heart-lung transplants, the long term detrimental impact of current management on renal function becomes more apparent as the number of non-renal solid organ transplant recipients on renal transplant waiting lists increases. Progressive chronic kidney disease (CKD) is a significant cause of morbidity and mortality in the transplant population. In this review we discuss the specific problems prior to lung or heart-lung transplant that predispose to CKD, as well as potential renal complications encountered during the peri- and post-transplant period. Significant acute and chronic nephrotoxicity is caused by calcineurin inhibitors (CNI). Mechanisms to decrease CNI exposure exist but have yet to be adopted in routine clinical care. Modifiable risk factors and the current screening and management approach taken at our institution are described. Pediatric nephrologists should be involved from an early stage. Future work will need to focus on identifying more accurate measures of renal function, given the limitations of current glomerular filtration rate estimation equations in a population where nutritional status may rapidly change post transplant. Multicentre studies of CNI minimisation strategies are required to guide future therapy that aims to minimise CKD development and progression in this vulnerable population.

Allergic bronchopulmonary aspergillosis [ABPA] complicates cystic fibrosis in around 10% of teenagers. Systemic corticosteroids are the mainstay of treatment but with on-going use are associated with significant side effects prompting consideration of steroid sparing therapies. The clinical courses over ten years of two children with CF complicated by steroid dependent chronic ABPA and its successful treatment with monthly omalizumab are reported., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The assessment of standing turning performance is proposed to predict fall risk in older adults. This study investigated differences in segmental coordination during a 360° standing turn task between older community-dwelling fallers and non-fallers., Methods: Thirty-five older adults age mean (SD) of 71 (5.4) years performed 360° standing turns. Head, trunk and pelvis position relative to the laboratory and each other were recorded using a Vicon motion analysis system. Fall incidence was monitored by monthly questionnaire over the following 12 months and used to identify non-faller, single faller and multiple faller groups., Results: Multiple fallers were found to have significantly different values, when compared to non-fallers, for pelvis onset (p=0.002); mean angular separation in the transverse plane between the head and trunk (p=0.018); peak angular separation in the transverse plane between the trunk and pelvis (p=0.013); and mean angular separation between the trunk and pelvis (p<0.001)., Conclusions: Older adults who subsequently experience multiple falls show a simplified turning pattern to assist in balance control. This may be a predictor for those at increased risk of falling., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Forced oscillation technique (FOT) parameters are less repeatable than spirometry, and the impact of technical factors, such as data acquisition and data filtering, are unknown. FOT was performed, in triplicate, on 48 children (8-11 years) and repeated two weeks later. We examined the separate effects of monitoring tidal volume (V(T)) prior to measurement and length of data acquisition on measurement repeatability. We compared the effects on repeatability of a filtering technique in which complete breaths containing respiratory artefact were rejected and statistical filters in which outlying data points were rejected. Within- and between-session repeatability of respiratory system resistance (Rrs) and reactance (Xrs) were assessed using coefficient of variation (CV) and intra-class correlation coefficient (ICC). Longer data acquisition reduced CV of Rrs and Xrs (60s vs. shorter durations, p ≤ 0.001). Monitoring V(T) reduced CV of Rrs (p = 0.05). Complete breath filtering improved CV and ICC for both Rrs and Xrs. The repeatability of FOT measurements can be improved by optimising data acquisition and filtering., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Question: What evidence is available regarding the use of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), surgical resection or chemotherapy for the treatment of recurrent/progressive brain metastases?, Target Population: This recommendation applies to adults with recurrent/progressive brain metastases who have previously been treated with WBRT, surgical resection and/or radiosurgery. Recurrent/progressive brain metastases are defined as metastases that recur/progress anywhere in the brain (original and/or non-original sites) after initial therapy., Recommendation: Level 3 Since there is insufficient evidence to make definitive treatment recommendations in patients with recurrent/progressive brain metastases, treatment should be individualized based on a patient's functional status, extent of disease, volume/number of metastases, recurrence or progression at original versus non-original site, previous treatment and type of primary cancer, and enrollment in clinical trials is encouraged. In this context, the following can be recommended depending on a patient's specific condition: no further treatment (supportive care), re-irradiation (either WBRT and/or SRS), surgical excision or, to a lesser extent, chemotherapy. Question If WBRT is used in the setting of recurrent/progressive brain metastases, what impact does tumor histopathology have on treatment outcomes? No studies were identified that met the eligibility criteria for this question.

Question: Do prophylactic anticonvulsants decrease the risk of seizure in patients with metastatic brain tumors compared with no treatment?, Target Population: These recommendations apply to adults with solid brain metastases who have not experienced a seizure due to their metastatic brain disease., Recommendation: Level 3 For adults with brain metastases who have not experienced a seizure due to their metastatic brain disease, routine prophylactic use of anticonvulsants is not recommended. Only a single underpowered randomized controlled trial (RCT), which did not detect a difference in seizure occurrence, provides evidence for decision-making purposes.

Target Population: This recommendation applies to adults with newly diagnosed brain metastases; however, the recommendation below does not apply to the exquisitely chemosensitive tumors, such as germinomas metastatic to the brain., Recommendation: Should patients with brain metastases receive chemotherapy in addition to whole brain radiotherapy (WBRT)? Level 1 Routine use of chemotherapy following WBRT for brain metastases has not been shown to increase survival and is not recommended. Four class I studies examined the role of carboplatin, chloroethylnitrosoureas, tegafur and temozolomide, and all resulted in no survival benefit. Two caveats are provided in order to allow the treating physician to individualize decision-making: First, the majority of the data are limited to non small cell lung (NSCLC) and breast cancer; therefore, in other tumor histologies, the possibility of clinical benefit cannot be absolutely ruled out. Second, the addition of chemotherapy to WBRT improved response rates in some, but not all trials; response rate was not the primary endpoint in most of these trials and end-point assessment was non-centralized, non-blinded, and post-hoc. Enrollment in chemotherapy-related clinical trials is encouraged.

Question: Should patients with newly-diagnosed metastatic brain tumors undergo open surgical resection versus whole brain radiation therapy (WBRT) and/or other treatment modalities such as radiosurgery, and in what clinical settings?, Target Population: These recommendations apply to adults with a newly diagnosed single brain metastasis amenable to surgical resection., Recommendations: Surgical resection plus WBRT versus surgical resection alone Level 1 Surgical resection followed by WBRT represents a superior treatment modality, in terms of improving tumor control at the original site of the metastasis and in the brain overall, when compared to surgical resection alone. Surgical resection plus WBRT versus SRS + or - WBRT Level 2 Surgical resection plus WBRT, versus stereotactic radiosurgery (SRS) plus WBRT, both represent effective treatment strategies, resulting in relatively equal survival rates. SRS has not been assessed from an evidence-based standpoint for larger lesions (>3 cm) or for those causing significant mass effect (>1 cm midline shift). Level 3 Underpowered class I evidence along with the preponderance of conflicting class II evidence suggests that SRS alone may provide equivalent functional and survival outcomes compared with resection + WBRT for patients with single brain metastases, so long as ready detection of distant site failure and salvage SRS are possible. Note The following question is fully addressed in the WBRT guideline paper within this series by Gaspar et al. Given that the recommendation resulting from the systematic review of the literature on this topic is also highly relevant to the discussion of the role of surgical resection in the management of brain metastases, this recommendation has been included below.

Question: Should patients with newly-diagnosed metastatic brain tumors undergo stereotactic radiosurgery (SRS) compared with other treatment modalities? Target population These recommendations apply to adults with newly diagnosed solid brain metastases amenable to SRS; lesions amenable to SRS are typically defined as measuring less than 3 cm in maximum diameter and producing minimal (less than 1 cm of midline shift) mass effect. Recommendations SRS plus WBRT vs. WBRT alone Level 1 Single-dose SRS along with WBRT leads to significantly longer patient survival compared with WBRT alone for patients with single metastatic brain tumors who have a KPS > or = 70.Level 1 Single-dose SRS along with WBRT is superior in terms of local tumor control and maintaining functional status when compared to WBRT alone for patients with 1-4 metastatic brain tumors who have a KPS > or =70.Level 2 Single-dose SRS along with WBRT may lead to significantly longer patient survival than WBRT alone for patients with 2-3 metastatic brain tumors.Level 3 There is class III evidence demonstrating that single-dose SRS along with WBRT is superior to WBRT alone for improving patient survival for patients with single or multiple brain metastases and a KPS<70 [corrected].Level 4 There is class III evidence demonstrating that single-dose SRS along with WBRT is superior to WBRT alone for improving patient survival for patients with single or multiple brain metastases and a KPS < 70. SRS plus WBRT vs. SRS alone Level 2 Single-dose SRS alone may provide an equivalent survival advantage for patients with brain metastases compared with WBRT + single-dose SRS. There is conflicting class I and II evidence regarding the risk of both local and distant recurrence when SRS is used in isolation, and class I evidence demonstrates a lower risk of distant recurrence with WBRT; thus, regular careful surveillance is warranted for patients treated with SRS alone in order to provide early identification of local and distant recurrences so that salvage therapy can be initiated at the soonest possible time. Surgical Resection plus WBRT vs. SRS +/- WBRT Level 2 Surgical resection plus WBRT, vs. SRS plus WBRT, both represent effective treatment strategies, resulting in relatively equal survival rates. SRS has not been assessed from an evidence-based standpoint for larger lesions (>3 cm) or for those causing significant mass effect (>1 cm midline shift). Level 3: Underpowered class I evidence along with the preponderance of conflicting class II evidence suggests that SRS alone may provide equivalent functional and survival outcomes compared with resection + WBRT for patients with single brain metastases, so long as ready detection of distant site failure and salvage SRS are possible. SRS alone vs. WBRT alone Level 3 While both single-dose SRS and WBRT are effective for treating patients with brain metastases, single-dose SRS alone appears to be superior to WBRT alone for patients with up to three metastatic brain tumors in terms of patient survival advantage.