Risk Factors Associated with Chemotherapy-Induced Nausea and Vomiting Among Women with Breast Cancer Receiving Highly Emetogenic Chemotherapy: Individual Patient-Based Analysis of Three Prospective Antiemetic Trials.

Purpose: Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified in previous studies, only a few studies have evaluated the risk factors associated with contemporary antiemetic prophylaxis, including olanzapine/aprepitant- or NEPA-containing regimens. This study aimed to identify the risk factors associated with CINV development in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide chemotherapy. Methods: Data from 304 patients enrolled in 3 previously reported prospective antiemetic studies were included. Multivariate logistic regression models were used to predict risk factors associated with CINV occurrence. Additionally, the likelihood of treatment failure in relation to the number of risk factors in individual patients was evaluated. Results: Multivariate analysis of the entire study group revealed that obesity status (defined as body mass index/= 25.0 kg/m2) and the use of olanzapine/aprepitant- or NEPA-containing anti-emetic regimens were associated with a high likelihood, while a history of motion sickness was associated with a lower likelihood, complete response (CR), and "no nausea" in the overall phase. A history of vomiting during pregnancy was also associated with a lower likelihood of an overall CR. Patients with an increasing number of risk factors had a higher likelihood of treatment failure and shorter time to first vomiting. Those who did not achieve CR and "no nausea" in the first cycle were less likely to achieve these parameters in the subsequent cycle of chemotherapy. Conclusion: The present study confirmed previously reported risk factors for CINV in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide. Further optimization of CINV control is required for patients with identifiable risk factors; olanzapine/aprepitant- or NEPA- containing prophylaxis are the preferred contemporary anti-emetics regimens for Chinese breast cancer patients undergoing doxorubicin and cyclophosphamide chemotherapy.

Age-related increases in right hemisphere support for prosodic processing in children.

Language comprehension is a complex process involving an extensive brain network. Brain regions responsible for prosodic processing have been studied in adults; however, much less is known about the neural bases of prosodic processing in children. Using magnetoencephalography (MEG), we mapped regions supporting speech envelope tracking (a marker of prosodic processing) in 80 typically developing children, ages 4-18 years, completing a stories listening paradigm. Neuromagnetic signals coherent with the speech envelope were localized using dynamic imaging of coherent sources (DICS). Across the group, we observed coherence in bilateral perisylvian cortex. We observed age-related increases in coherence to the speech envelope in the right superior temporal gyrus (r = 0.31, df = 78, p = 0.0047) and primary auditory cortex (r = 0.27, df = 78, p = 0.016); age-related decreases in coherence to the speech envelope were observed in the left superior temporal gyrus (r = - 0.25, df = 78, p = 0.026). This pattern may indicate a refinement of the networks responsible for prosodic processing during development, where language areas in the right hemisphere become increasingly specialized for prosodic processing. Altogether, these results reveal a distinct neurodevelopmental trajectory for the processing of prosodic cues, highlighting the presence of supportive language functions in the right hemisphere. Findings from this dataset of typically developing children may serve as a potential reference timeline for assessing children with neurodevelopmental hearing and speech disorders.

Quality of Life Associated with Nausea and Vomiting from Anthracycline-Based Chemotherapy: A Pooled Data Analysis from Three Prospective Trials.

BACKGROUND: There is limited work on the impact of chemotherapy-induced nausea and vomiting (CINV) on quality of life (QoL) in adriamycin-cyclophosphamide (AC)-treated patients with breast cancer. The objectives of the study were the following: (a) to confirm if symptoms of CINV led to lower QoL during AC; (b) to evaluate the pattern of changes in patients' QoL during multiple cycles of AC; and (c) to assess if the QoL in an earlier cycle affected the QoL in subsequent cycles of AC. MATERIALS AND METHODS: This is a secondary pooled data analysis that included 303 Chinese patients with breast cancer who received 1,177 cycles of adjuvant AC in three prospective antiemetic studies. QoL data were based on Functional Living Index-emesis (FLIE) scored over three to four AC cycles. CINV symptoms assessed included "no significant nausea" (NSN), "significant nausea" (SN), "no vomiting" (NoV), "vomiting" (V), and complete response (CR). RESULTS: Across all AC cycles, the mean scores for the FLIE nausea domain for patients who experienced NSN versus SN were 10.92 versus 53.92, respectively (p < .0001), with lower scores indicating better QoL; the mean scores for the FLIE vomiting domain for patients who experienced NoV versus V were 1.44 versus 19.11, respectively (p < .0001), with similar results across subsequent cycles. Analysis of the effect of the QoL in cycle 1 on the QoL of subsequent cycles revealed the following: for the nausea domain, among patients who had cycle 1 FLIE scores ≥ versus < the mean, the corresponding scores in cycle 2 were 6.87 versus 36.71 (p < .0001); whereas those for cycle 3 were 7.07 versus 36.87 (p < .0001); and those for cycle 4 were 5.92 versus 21.48 (p < .0001). Similar findings were observed for the vomiting domain. Netupitant + palonosetron- or aprepitant/olanzapine-based antiemetics had significantly better QoL outcomes. CONCLUSION: CINV had a significant impact on the QoL of patients with breast cancer treated with AC over multiple cycles. IMPLICATIONS FOR PRACTICE: In this post-hoc analysis of three prospective studies on chemotherapy-induced nausea and vomiting (CINV), quality of life (QoL) using contemporary antiemetic regimens in Chinese breast cancer patients receiving doxorubicin-cyclophosphamide (AC) was evaluated. During the first and subsequent AC cycles, QoL was significantly better for patients who did not experience vomiting or significant nausea. QoL in an earlier cycle affected the QoL in subsequent AC cycles. Furthermore, recent regimens involving olanzapine/aprepitant or netupitant-palonosetron were associated with a positive impact in QoL. Antiemetic guideline-consistent practice and higher clinician awareness of the impact of CINV on QoL can further mitigate the negative effects of CINV on QoL.

Identification of optimal contemporary antiemetic prophylaxis for doxorubicin-cyclophosphamide chemotherapy in Chinese cancer patients: post-hoc analysis of 3 prospective studies.

OBJECTIVE: Chemotherapy-induced nausea and vomiting (CINV) are common with doxorubicin-cyclophosphamide (AC) chemotherapy. Recommended antiemetic regimens incorporate neurokinin-1 receptor antagonist (NK1RA), 5-hydroxytryptamine type-3 receptor antagonist (5HT3RA), corticosteroid, and dopamine antagonists. This post-hoc analysis compared results of 3 prospective antiemetic studies conducted among Chinese breast cancer patients who received (neo)adjuvant AC, in order to identify optimal antiemetic prophylaxis. METHODS: A total of 304 patients were included: Group 1, ondansetron/dexamethasone (D1); Group 2, aprepitant/ondansetron/dexamethasone (D1); Group 3, aprepitant/ondansetron/dexamethasone (D1-3); Group 4, aprepitant/ondansetron/dexamethasone (D1-3)/olanzapine; and Group 5, netupitant/palonosetron/dexamethasone (D1-3). Antiemetic efficacies of Groups 3, 4, and 5 during cycle 1 of AC were individually compared with Group 1. In addition, emesis outcomes of patients in Groups 3 and 5, and those of Groups 2 and 3, were compared. RESULTS: When comparing efficacies of a historical doublet (5HT3RA/dexamethasone) with triplet antiemetic regimens (NK1RA/5HT3RA/dexamethasone) with/without olanzapine, complete response (CR) percentages and quality of life (QOL) in overall phase of cycle 1 AC were compared between Group 1 and the other groups: Group 1 vs. 3, 41.9% vs. 38.3% (P = 0.6849); Group 1 vs. 4, 41.9% vs. 65.0% (P = 0.0107); and Group 1 vs. 5, 41.9% vs. 60.0% (P = 0.0460). Groups 4 and 5 achieved a better QOL. When comparing netupitant-based (Group 3) with aprepitant-based (Group 5) triplet antiemetics, CR percentages were 38.3% vs. 60.0%, respectively (P = 0.0176); Group 5 achieved a better QOL. When comparing 1 day (Group 2) vs. 3 day (Group 3) dexamethasone, CR percentages were 46.8% and 38.3%, respectively (P = 0.3459); Group 3 had a worse QOL. CONCLUSIONS: Aprepitant-containing triplets were non-superior to doublet antiemetics. Netupitant-containing triplets and adding olanzapine to aprepitant-containing triplets were superior to doublets. Netupitant/palonosetron/dexamethasone was superior to aprepitant/ondansetron/dexamethasone. Protracted administration of dexamethasone provided limited additional benefit.

A review of magnetoencephalography use in pediatric epilepsy: an update on best practice.

Introduction: Magnetoencephalography (MEG) is a noninvasive technique that is used for presurgical evaluation of children with drug-resistant epilepsy (DRE).Areas covered: The contributions of MEG for localizing the epileptogenic zone are discussed, in particular in extra-temporal lobe epilepsy and focal cortical dysplasia, which are common in children, as well as in difficult to localize epilepsy such as operculo-insular epilepsy. Further, the authors review current evidence on MEG for mapping eloquent cortex, its performance, application in clinical practice, and potential challenges.Expert opinion: MEG could change the clinical management of children with DRE by directing placement of intracranial electrodes thereby enhancing their yield. With improved identification of a circumscribed epileptogenic zone, MEG could render more patients as suitable candidates for epilepsy surgery and increase utilization of surgery.

Brainstem Associated Somatosensory Evoked Potentials and Response to Vagus Nerve Stimulation: An Investigation of the Vagus Afferent Network.

Despite decades of clinical usage, selection of patients with drug resistant epilepsy who are most likely to benefit from vagus nerve stimulation (VNS) remains a challenge. The mechanism of action of VNS is dependent upon afferent brainstem circuitry, which comprises a critical component of the Vagus Afferent Network (VagAN). To evaluate the association between brainstem afferent circuitry and seizure response, we retrospectively collected intraoperative data from sub-cortical recordings of somatosensory evoked potentials (SSEP) in 7 children with focal drug resistant epilepsy who had failed epilepsy surgery and subsequently underwent VNS. Using multivariate linear regression, we demonstrate a robust negative association between SSEP amplitude (p < 0.01), and seizure reduction. There was no association between SSEP latency and seizure outcomes. Our findings provide novel insights into the mechanism of VNS and inform our understanding of the importance of brainstem afferent circuitry within the VagAN for seizure responsiveness following VNS.

Temporal-plus epilepsy in children: A connectomic analysis in magnetoencephalography.

OBJECTIVE: Seizure recurrence following surgery for temporal lobe (TL) epilepsy may be related to extratemporal epileptogenic foci, so-called temporal-plus (TL+) epilepsy. Here, we sought to leverage whole brain connectomic profiling in magnetoencephalography (MEG) to identify neural networks indicative of TL+ epilepsy in children. METHODS: Clinical and MEG data were analyzed for 121 children with TL and TL+ epilepsy spanning 20 years at the Hospital for Sick Children. Resting-state connectomes were derived using the weighted phase lag index from neuromagnetic oscillations. Multidimensional associations between patient connectomes, TL versus TL+ epilepsy, seizure freedom, and clinical covariates were performed using a partial least squares (PLS) analysis. Bootstrap resampling statistics were performed to assess statistical significance. RESULTS: A single significant latent variable representing 66% of the variance in the data was identified with significant contributions from extent of epilepsy (TL vs TL+), duration of illness, and underlying etiology. This component was associated with significant bitemporal and frontotemporal connectivity in the theta, alpha, and beta bands. By extracting a brain score, representative of the observed connectivity profile, patients with TL epilepsy were dissociated from those with TL+, independent of their postoperative seizure outcome. SIGNIFICANCE: By analyzing 121 connectomes derived from MEG data using a PLS approach, we find that connectomic profiling could dissociate TL from TL+ epilepsy. These findings may inform patient selection for resective procedures and guide decisions surrounding invasive monitoring.

Presurgical Functional Mapping with Magnetoencephalography.

Noninvasive functional brain imaging with magnetoencephalography (MEG) is regularly used to map the eloquent cortex associated with somatosensory, motor, auditory, visual, and language processing before a surgical resection to determine if the functional areas have been reorganized. Most tasks can also be performed in the pediatric population. To acquire an optimal MEG study for any of these modalities, the patient needs to be well rested and attending to the stimulation.

Dataset on chemotherapy-induced nausea and vomiting (CINV) and quality of life (QOL) during multiple chemotherapy cycles among a Chinese breast cancer patient population who were randomized to antiemetic regimens with or without olanzapine.

Chemotherapy-induced nausea and vomiting (CINV) are highly distressing symptoms for cancer patients undergoing cytotoxic chemotherapy. This dataset was obtained from a homogenous group of Chinese breast cancer patients who were uniformly planned to receive a highly emetogenic (neo)adjuvant chemotherapy regimen, consisting of doxorubicin and cyclophosphamide (commonly known as AC). Patients were being randomized to one of the two antiemetic regimens: aprepitant, ondansetron and dexamethasone with (the Olanzapine arm) or without olanzapine (the Standard arm). Patients underwent self-reported diaries and questionnaires to record their nausea and vomiting symptoms, use of rescue medication as well as their quality of life (QOL). The primary and secondary endpoints have focused on efficacy analysis during the first cycle of AC chemotherapy; the results have been reported in The Breast [1]. In this Data in Brief article, we provide outcome of the analysis of data collected during multiple cycles of chemotherapy. The data reported here include the proportion of patients with "Complete Response", "Complete Protection" and "Total Control" of emesis in the acute (0-24 h), delayed (24-120 h) and overall periods (0-120 h), as well as QOL data during all the 4 cycles of AC.

Menopausal symptoms in relationship to breast cancer-specific quality of life after adjuvant cytotoxic treatment in young breast cancer survivors.

INTRODUCTIONS: For young premenopausal breast cancer patients, adjuvant chemotherapy may cause menstrual disruptions and premature menopause, which may in turn impair their quality of life (QoL). In this study among young breast cancer survivors who have undergone adjuvant chemotherapy, the objectives were to assess post-treatment menopausal symptoms and their associated factors, and to correlate these symptoms with breast cancer-specific QoL. METHODS: The study population included premenopausal young Chinese women with early-stage breast cancer who had undergone adjuvant chemotherapy between 3 and 10 years prior to enrolling into this study. At study entry, patients' characteristics and clinical features were collected; each patient had detail menstrual history collected and each filled in MENQOL and FACT-B + 4 questionnaires. RESULTS: Two hundred eighty eligible patients were recruited. For adjuvant chemotherapy, 92% received anthracyclines and 28% received taxanes; 76% received adjuvant tamoxifen. At a median of 5.0 years from initial cancer diagnosis, 49 and 11% had become post- and peri-menopausal respectively. MENQOL at study entry revealed that physical domain score was worse in overweight/obese patients (mean scores for underweight/normal vs overweight/obese: 2.65 vs 2.97, p = 0.0162). Vasomotor domain score was worse in those who received taxanes or tamoxifen (taxane vs non-taxane: 2.91 vs. 2.35, p = 0.0140; tamoxifen vs no tamoxifen: 2.75 vs. 2.34, p = 0.0479). Sexual domain score was worse among those who had become peri/post-menopausal (peri/postmenopausal vs premenopausal: 2.82 vs. 2.29, p = 0.0229). On the other hand, patients who utilized traditional Chinese medicine had significantly worse scores for vasomotor, psychosocial and physical domains. Further, there was a significant association between MENQOL scores and FACT-B + 4 scores; less severe symptoms in the MENQOL domains were associated with better QoL scores in FACT-B + 4 physical, functional, psychosocial and emotional well-being, Breast Cancer Subscale, Arm Subscale and FACT-B total score. CONCLUSION: Among premenopausal breast cancer women who had undergone adjuvant chemotherapy, those who had received taxanes or tamoxifen, were overweight/obese and utilized traditional Chinese medicine had more severe menopausal symptoms. Patients who experienced worse menopausal symptoms were found to have worse breast cancer-specific QoL. Interventional studies with an aim to alleviate menopausal symptoms are warranted to assess if overall QoL of these patients could be improved. TRIAL REGISTRATION: Not applicable.

A randomized study of olanzapine-containing versus standard antiemetic regimens for the prevention of chemotherapy-induced nausea and vomiting in Chinese breast cancer patients.

OBJECTIVES: Chemotherapy-induced nausea and vomiting (CINV) are distressing symptoms. This randomized study evaluated the antiemetic efficacies of standard antiemetic regimen with/without olanzapine. PATIENTS AND METHODS: Eligible patients were chemotherapy-naive Chinese breast cancer patients who were planned for (neo)adjuvant doxorubicin/cyclophosphamide. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomized to Olanzapine (with olanzapine) or Standard arms (without olanzapine). Patients filled in self-reported diaries and completed visual analogue scales for nausea, as well as Functional Living Index-Emesis questionnaires. Blood profiles including fasting glucose and lipids were monitored. RESULTS: 120 patients were randomized. In Cycle 1 doxorubicin/cyclophosphamide, the Olanzapine arm had significantly higher rates of "Complete Response" than the Standard arm: 65.0% vs 38.3% in the overall period (p = 0.0035), 70.0% vs 51.7% in the acute period (p = 0.0397) and 92.9% vs 74.2% in the delayed period (p = 0.0254). Olanzapine arm also had significantly higher rates of "No significant nausea" and "No nausea" during all 3 time-frames and better QOL. Similar findings were also revealed throughout multiple cycles. Pre-study abnormalities in glucose and lipids occurred in 39.7% and 34.2% of the studied population respectively; there were no differences in these parameters between the two arms at end-of-study assessment. CONCLUSION: The addition of olanzapine to standard aprepitant-based antiemetic regimen provides clinically meaningful improvement in controlling CINV. This was associated with a positive impact on QOL and tolerable toxicity profiles among Chinese breast cancer patients receiving doxorubicin/cyclophosphamide chemotherapy. Further studies on metabolic profiles of breast cancer patients are warranted.

Bone Health in Premenopausal Chinese Patients after Adjuvant Chemotherapy for Early Breast Cancer.

BACKGROUND: In this cohort study, the objectives were to determine bone mineral density (BMD) and potential associated factors for bone health among young premenopausal patients after adjuvant chemotherapy. METHODS: Eligibility criteria included premenopausal Chinese aged <45 years who had received adjuvant chemotherapy. At study entry, background demographics and menstrual history were collected; BMD was measured. Factors associated with reduced BMD and fracture risk were analyzed. RESULTS: A total of 271 patients entered the study. The median time from breast cancer diagnosis to study entry was 5.0 years. The median ages at breast cancer diagnosis and at study entry were 41 and 47 years, respectively. The median BMDs for femoral neck (FN) and lumbar spine (LS) were 0.72 and 0.91 g/cm2, respectively; 40.2% had abnormal Z-scores (defined as ≤-1) and 50.2% had osteopenia/osteoporosis of either FN or LS. On multivariate analyses, factors that were identified to have a positive association with bone health (higher BMD) included higher family income (OR [95% CI] for LS = 1.573 [1.091-2.268]), taller stature (OR for LS = 2.975 [1.723-5.137]), and higher BMI (OR for FN = 2.156 [1.599-2.907]), while negatively associated factors included longer interval since last adjuvant treatment (OR for LS: 0.435 [0.250-0.757]), peri-/postmenopausal status at study entry (OR for LS = 0.443 [0.255-0.768]; OR for FN = 0.353 [0.205-0.609]), and having received adjuvant tamoxifen (OR for FN = 0.452 [0.243-0.841]). CONCLUSION: About 5 years after breast cancer diagnosis and adjuvant chemotherapy, >50% of premenopausal patients who had received adjuvant chemotherapy were detected to have osteopenia/osteoporosis and 40% had abnormal Z-scores for FN/LS.

Intra-operative cortical motor mapping using subdural grid electrodes in children undergoing epilepsy surgery evaluation and comparison with the conventional extra-operative motor mapping.

OBJECTIVES: The objective of this study was to review our experience with intra-operative "train of five" stimulation using subdural grid for motor mapping in children undergoing epilepsy surgery evaluation. METHODS: Twenty consecutive children below 18-years of age with drug-refractory epilepsy who underwent invasive-EEG monitoring using subdural-grid placement and intra-operative motor mapping using direct cortical stimulation by sub-dural grid electrodes (IODCS-SDG) at our institution between January-2016 and June-2017 were reviewed. Stimulation was delivered through the subdural-grid electrodes using a train-of-five pulses and muscle responses were recorded by motor-evoked-potentials (MEPs). Intra-operative direct cortical stimulation delivered through a ball-tipped probe (IODCS-probe) and extra-operative motor-mapping (EODCS-SDG) were also performed. RESULTS: IODCS-SDG was completed in 20 patients and subsequent EODCS-SDG was done in 17/20 patients. MEP responses were more commonly obtained in the deltoid (19/20), extensor-digitorum-communis (20/20) and first-dorsal-interosseus (19/20). The median thresholds varied between 40 V and 60 V for the six muscle groups. The respective IODCS-probe thresholds tended to be similar. No stimulation-provoked seizures or anaesthesia-related complications were noted during IODCS-SDG. EODCS-SDG could not be completed in 4/17 children and mapping data obtained was frequently inadequate. Nine patients demonstrated 100% concordance between IODCS-SDG and EODCS-SDG for the common mapped body regions. Stimulation-provoked seizures during EODCS-SDG were seen in 6/17 (35.3%) and after-discharges in 7/17 (41.2%) children. CONCLUSIONS: IODCS-SDG could be performed safely in children with drug refractory epilepsy undergoing invasive EEG monitoring. SIGNIFICANCE: IODCS-SDG may be a useful adjunct to EODCS-SDG in motor mapping for children.

Quality of life of young Chinese breast cancer patients after adjuvant chemotherapy.

INTRODUCTION: Understanding of quality of life (QoL) of young Chinese breast cancer patients after adjuvant cytotoxic chemotherapy is limited. This study aims to assess the QoL of premenopausal Chinese breast cancer women after receiving adjuvant chemotherapy. PATIENTS AND METHODS: Eligibility criteria included stage I-III breast cancer, premenopausal and age ≤45 years at cancer diagnosis and having received adjuvant chemotherapy within 3-10 years before entry to the present study. Patients' background demographics at the time of breast cancer diagnosis, together with tumor characteristics and anticancer treatments, were collected. At the time of study entry, the menopausal status based on menstrual history, body mass index, and QoL (assessed using Functional Assessment of Cancer Therapy-Breast +4) were recorded. RESULTS: Two hundred and eighty patients were recruited. Ninety-five patients (33.9%) underwent breast-conserving surgery, and nearly all (98.6%) underwent axillary dissection. For adjuvant therapies, 249 patients (88.9%) received anthracycline-containing chemotherapy and 79 (28.2%) received taxane-containing chemotherapy, while 68 (24.3%) received both. One hundred and eighty six patients (66.4%) received adjuvant radiotherapy, and 214 (76.4%) received adjuvant tamoxifen. The median time from breast cancer diagnosis to study entry was 5.01 years. QoL assessment at study entry revealed that older patients had worse social well-being (SWB; mean scores for age ≤40, 41-45, 46-50 and >50 years were 22.0, 19.3, 19.1 and 18.1, respectively, P=0.0442). Patients who underwent axillary dissection had worse scores for breast cancer sub-scale (BCS; mean score 22.2 vs. 28.3, P=0.0212). Patients who underwent taxane-containing chemotherapy had worse scores for arm subscale (mean score 13.8 vs. 15.3, P=0.0053). CONCLUSION: At a median follow-up of 5 years post-diagnosis, patients who were younger had fewer disturbances in their SWB. Patients who had axillary dissection had worse BCS scores, while those who received taxane had worse scores for arm subscale. Further studies are warranted for breast-specific QoL to address the specific issues encountered by breast cancer patients.

Profiles of lipids, blood pressure and weight changes among premenopausal Chinese breast cancer patients after adjuvant chemotherapy.

BACKGROUND: Adjuvant chemotherapy improves outcome of patients with early breast cancer. However, chemotherapy may be associated with long term toxicities. In this retrospective cohort study, the objectives were to determine body weight, body mass index (BMI), blood pressure and fasting lipids levels of young premenopausal Chinese breast cancer patients after adjuvant chemotherapy. Potential factors associated with these parameters were identified. METHODS: Eligibility criteria include premenopausal Chinese patients who were diagnosed to have stage I-III breast cancer within 3-10 years, age < 45 and having received adjuvant chemotherapy at the time of breast cancer diagnosis. Information at initial breast cancer diagnosis were retrieved from patients' medical records and include age at diagnosis, tumor characteristics, anti-cancer treatments, blood pressure and body weight and height. At study entry, all patients had additional background demographics collected, as well as blood pressure, body weight and fasting serum lipid profiles measured. Incidence of chemotherapy-related amenorrhoea (CRA) and menopause were determined. Factors associated with weight gain, hypertension and dyslipidaemias were analyzed. RESULTS: Two hundred and eighty patients were studied. The median age at breast cancer diagnosis was 41 years (range: 24-45). The median time from breast cancer diagnosis to study entry was 5.0 years. The median age at study entry was 46.5 years (range: 28-54). 91.1% developed CRA; 48.9% had become menopausal and 10% were peri-menopausal. Between initial breast cancer diagnosis and the time of study entry, the median weight gain was 1.8 kg; 63.2% gained weight by >2%; 52.1% were overweight/obese; 30.7% had hypertension. Abnormal total-cholesterol and LDL-cholesterol occurred in 34.3% and 56.1% respectively. On multivariate analyses, older age was associated with reduced risk while occurrence of CRA and having received taxane-containing regimens were associated with increased risk of weight gain. Oestrogen-receptor positivity was associated with reduced risk while overweight/obese statuses were associated with increased risk of hypertension. Use of tamoxifen was associated with reduced risk of abnormal LDL-cholesterol. Weight gain, overweight/obese, older age, progression to post/peri-menopausal status at study entry, having received corticosteroid premedication before adjuvant chemotherapy and having received taxane-containing adjuvant chemotherapy were associated with increased risk of dyslipidaemias. CONCLUSION: Among young premenopausal Chinese breast cancer patients who had received adjuvant chemotherapy, the current study has revealed that although there was only a median weight gain of 1.8 kg, there was a nearly 60% increase in abnormal BMI. Further, a significant proportion of patients were detected to have hypertension and dyslipidaemias. Interventional studies with lifestyle modifications are warranted.

From Structure to Circuits: The Contribution of MEG Connectivity Studies to Functional Neurosurgery.

New advances in structural neuroimaging have revealed the intricate and extensive connections within the brain, data which have informed a number of ambitious projects such as the mapping of the human connectome. Elucidation of the structural connections of the brain, at both the macro and micro levels, promises new perspectives on brain structure and function that could translate into improved outcomes in functional neurosurgery. The understanding of neuronal structural connectivity afforded by these data now offers a vista on the brain, in both healthy and diseased states, that could not be seen with traditional neuroimaging. Concurrent with these developments in structural imaging, a complementary modality called magnetoencephalography (MEG) has been garnering great attention because it too holds promise for being able to shed light on the intricacies of functional brain connectivity. MEG is based upon the elemental principle of physics that an electrical current generates a magnetic field. Hence, MEG uses highly sensitive biomagnetometers to measure extracranial magnetic fields produced by intracellular neuronal currents. Put simply then, MEG is a measure of neurophysiological activity, which captures the magnetic fields generated by synchronized intraneuronal electrical activity. As such, MEG recordings offer exquisite resolution in the time and oscillatory domain and, as well, when co-registered with magnetic resonance imaging (MRI), offer excellent resolution in the spatial domain. Recent advances in MEG computational and graph theoretical methods have led to studies of connectivity in the time-frequency domain. As such, MEG can elucidate a neurophysiological-based functional circuitry that may enhance what is seen with MRI connectivity studies. In particular, MEG may offer additional insight not possible by MRI when used to study complex eloquent function, where the precise timing and coordination of brain areas is critical. This article will review the traditional use of MEG for functional neurosurgery, describe recent advances in MEG connectivity analyses, and consider the additional benefits that could be gained with the inclusion of MEG connectivity studies. Since MEG has been most widely applied to the study of epilepsy, we will frame this article within the context of epilepsy surgery and functional neurosurgery for epilepsy.

Chemotherapy-Related Amenorrhea and Menopause in Young Chinese Breast Cancer Patients: Analysis on Incidence, Risk Factors and Serum Hormone Profiles.

PURPOSE: In this prospective cross-sectional study on young premenopausal breast cancer patients, the objectives were to: determine the incidences of chemotherapy-related amenorrhea (CRA) and menopause (CRM); identify associated factors; and assess plasma levels of estradiol (E2) and follicular stimulating hormone (FSH) among patients who developed menopause. METHODS: Eligibility criteria include Chinese stage I-III breast cancer patients, premenopausal, age ≤45 at breast cancer diagnosis, having received adjuvant chemotherapy, within 3-10 years after breast cancer diagnosis. Detailed menstrual history prior to and after adjuvant treatment was taken at study entry. Patients' background demographics, tumor characteristics and anti-cancer treatments were collected. The rates of CRA and CRM were determined. Analysis was conducted to identify factors associated with CRM. For postmenopausal patients, levels of E2 and FSH were analyzed. RESULTS: 286 patients were recruited; the median time from breast cancer diagnosis to study entry was 5.0 years. 255 patients (91.1%) developed CRA. Of these, 66.7% regained menstruation. At the time of study entry, 137 (48.9%) had developed CRM, amongst whom 84 were age ≤45. On multivariate analysis, age was the only associated factor. Among patients with CRM, the median FSH was 41.0 IU/L; this was significantly lower in those who were taking tamoxifen compared to those who were not (20.1 vs. 59.7 IU/L, p<0.0001). The E2 level was <40 pmol/L; there was no difference between those who were still on tamoxifen or not. CONCLUSION: After adjuvant chemotherapy, the majority of young Chinese breast cancer patients developed CRA; ~50% developed CRM, with 61% at age ≤45. Age at diagnosis is the only factor associated with CRM. FSH level may be affected by tamoxifen intake.

A psychological intervention for smoking cessation delivered as treatment for smokers with chronic obstructive pulmonary disease: Multiple needs of a complex group and recommendations for novel service development.

This pilot study investigated the benefits of adjunctive psychological intervention for smokers accessing standard smoking cessation interventions. Chronic obstructive pulmonary disease (COPD) smokers attending a smoking cessation service were offered up to 12 adjunctive clinical psychology sessions. Baseline data included demographics, smoking history, and disease severity. Outcomes included attendance and quit rate. In all, 59 patients with moderate COPD were referred. Of the 20 patients who attended training sessions, 7 (35%) were relapse prevention referrals and 13 (65%) were current smokers. Of the seven relapse prevention referrals, six (86%) maintained their quit, 2 of 13 (15%) of the current smoker group maintained a 28-day quit and 3 of 13 (23%) of current smokers reduced their tobacco intake. For COPD smokers with a heavy smoking history and multiple past quit attempts, there was insufficient evidence to show that additional psychological intervention leads to higher quit rates. Significant barriers to quitting and complex medical and psychosocial needs were identified in this group, suggesting that the current 'one-size-fits-all' approach to smoking cessation may not be sufficient to meet the needs of such a complex group.

Occipital lobe lesions result in a displacement of magnetoencephalography visual evoked field dipoles.

PURPOSE: The pattern-reversal visual evoked potential measured electrically from scalp electrodes is known to be decreased, or absent, in patients with occipital lobe lesions. We questioned whether the measurement and source analysis of the neuromagnetic visual evoked field (VEF) might offer additional information regarding visual cortex relative to the occipital lesion. METHODS: We retrospectively examined 12 children (6-18 years) with occipital lesions on MRI, who underwent magnetoencephalography and ophthalmology as part of their presurgical assessment. Binocular half-field pattern-reversal VEFs were obtained in a 151-channel whole-head magnetoencephalography. Data were averaged and dipole source analyses were performed for each half-field stimulation. RESULTS: A significant lateral shift (P < 0.02) in the dipole location was observed in the lesional hemisphere compared with those in the nonlesional hemisphere, regardless of the lesion location. No differences were observed in latency, strength (moment), and residual errors of VEF dipoles between the lesional and nonlesional hemispheres. CONCLUSIONS: Magnetoencephalography demonstrated the mass effect on the dipole location of VEF in children with occipital lesions. Magnetoencephalography may be useful as a screening test of visual function in young patients. We discuss potential explanations for this lateral shift and emphasize the utility of adding the magnetoencephalography pattern-reversal visual evoked field protocol to the neurologic work-up.

Neuromagnetic vistas into typical and atypical development of frontal lobe functions.

The frontal lobes are involved in many higher-order cognitive functions such as social cognition executive functions and language and speech. These functions are complex and follow a prolonged developmental course from childhood through to early adulthood. Magnetoencephalography (MEG) is ideal for the study of development of these functions, due to its combination of temporal and spatial resolution which allows the determination of age-related changes in both neural timing and location. There are several challenges for MEG developmental studies: to design tasks appropriate to capture the neurodevelopmental trajectory of these cognitive functions, and to develop appropriate analysis strategies to capture various aspects of neuromagnetic frontal lobe activity. Here, we review our MEG research on social and executive functions, and speech in typically developing children and in two clinical groups - children with autism spectrum disorder and children born very preterm. The studies include facial emotional processing, inhibition, visual short-term memory, speech production, and resting-state networks. We present data from event-related analyses as well as on oscillations and connectivity analyses and review their contributions to understanding frontal lobe cognitive development. We also discuss the challenges of testing young children in the MEG and the development of age-appropriate technologies and paradigms.