Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040.

BACKGROUND: Patients with advanced hepatocellular carcinoma (aHCC) have a poor prognosis and high mortality. Nivolumab monotherapy demonstrated clinical benefit with an acceptable safety profile in patients with aHCC in the CheckMate 040 study. Five-year follow-up of the sorafenib-naive and sorafenib-experienced groups of CheckMate 040 is presented here. PATIENTS AND METHODS: Patients received nivolumab monotherapy at dose levels of 0.1-10.0 mg/kg (dose-escalation phase) or 3 mg/kg (dose-expansion phase) every 2 weeks until disease progression or unacceptable toxicity. Primary endpoints were safety and tolerability (dose escalation), and objective response rate (ORR) by blinded independent central review (BICR) and by investigator as per RECIST version 1.1 (dose expansion). RESULTS: Eighty sorafenib-naive and 154 sorafenib-experienced patients were treated. Minimum follow-up in both groups was 60 months. ORR as per BICR was 20% [95% confidence interval (CI) 12% to 30%] and 14% (95% CI 9% to 21%) in the sorafenib-naive and sorafenib-experienced groups, respectively. Responses occurred regardless of HCC etiology or baseline tumor cell programmed death-ligand 1 (PD-L1) expression levels. Median overall survival (OS) was 26.6 months (95% CI 16.6-30.6 months) and 15.1 months (95% CI 13.0-18.2 months) in sorafenib-naive and sorafenib-experienced patients, respectively. The 3-year OS rates were 28% in the sorafenib-naive and 20% in the sorafenib-experienced groups; 5-year OS rates were 14% and 12%, respectively. No new safety signals were identified; grade 3/4 treatment-related adverse events were observed in 33% and 21% of patients in the sorafenib-naive and sorafenib-experienced groups, respectively. Biomarker analyses showed that baseline PD-L1 expression ≥1% was associated with higher ORR and longer OS compared with PD-L1 <1%. In the sorafenib-naive group, patients with OS ≥3 years exhibited higher baseline CD8 T-cell density compared with those with OS <1 year. CONCLUSION: With 5 years of follow-up, nivolumab monotherapy continued to provide durable clinical benefit with manageable safety in sorafenib-naive and sorafenib-experienced patients with aHCC.

Evaluation of contemporary olanzapine- and netupitant/palonosetron-containing antiemetic regimens for chemotherapy-induced nausea and vomiting.

INTRODUCTION: This post-hoc analysis retrospectively assessed data from two recent studies of antiemetic regimens for chemotherapy-induced nausea and vomiting (CINV). The primary objective was to compare olanzapine-based versus netupitant/palonosetron (NEPA)-based regimens in terms of controlling CINV during cycle 1 of doxorubicin/cyclophosphamide (AC) chemotherapy; secondary objectives were to assess quality of life (QOL) and emesis outcomes over four cycles of AC. METHODS: This study included 120 Chinese patients with early-stage breast cancer who were receiving AC; 60 patients received the olanzapine-based antiemetic regimen, whereas 60 patients received the NEPA-based antiemetic regimen. The olanzapine-based regimen comprised aprepitant, ondansetron, dexamethasone, and olanzapine; the NEPA-based regimen comprised NEPA and dexamethasone. Patient outcomes were compared in terms of emesis control and QOL. RESULTS: During cycle 1 of AC, the olanzapine group exhibited a higher rate of 'no use of rescue therapy' in the acute phase (olanzapine vs NEPA: 96.7% vs 85.0%, P=0.0225). No parameters differed between groups in the delayed phase. The olanzapine group had significantly higher rates of 'no use of rescue therapy' (91.7% vs 76.7%, P=0.0244) and 'no significant nausea' (91.7% vs 78.3%, P=0.0408) in the overall phase. There were no differences in QOL between groups. Multiple cycle assessment revealed that the NEPA group had higher rates of total control in the acute phase (cycles 2 and 4) and the overall phase (cycles 3 and 4). CONCLUSION: These results do not conclusively support the superiority of either regimen for patients with breast cancer who are receiving AC.

Preservation of fertility in premenopausal patients with breast cancer.

INTRODUCTION: Cancer survivorship is increasingly important with advances in cancer therapeutics. Minimisation of treatment-related morbidity is an area that requires attention. This situation is most pressing in premenopausal patients with breast cancer, in whom advances in hormonal and targeted therapies have improved mortality rates. However, treatment-related infertility is still poorly addressed, and in East Asia, there is limited discussion regarding management of treatment-related infertility. METHODS: A search of the literature was conducted using PubMed, Google Scholar, and Science Direct using the terms "breast cancer", "fertility preservation", "oocyte and embryonic cryopreservation", "GnRH-a co-administration", "ovarian tissue cryopreservation and transplantation", "Japan", "China", "Korea", and 'Singapore". Only studies published in English from 1980-2019 were included. The focus of the review was on identifying the current fertility preservation methods available to premenopausal women with breast cancer and the barriers that impede access. RESULTS: Fertility preservation options include GnRH-a co-administration to minimise treatment-associated infertility, oocyte and embryonic cryopreservation, and emerging treatments such as ovarian tissue cryopreservation and transplantation. In East Asia, the uptake of fertility preservation options has been limited despite it being a major patient concern. A lack of awareness of fertility preservation treatments hinders discussion between patients and clinicians about fertility preservation. CONCLUSION: Despite progress in fertility preservation technologies, their impact for patients will be minimal if there is a lack of awareness/use of the technology. This review aims to raise awareness of such technologies among clinicians, enabling discussion between patients and clinicians about fertility preservation options.

Pre-operative pressure pain thresholds do not meaningfully explain satisfaction or improvement in pain after knee replacement: a cohort study.

OBJECTIVES: Pain sensitization could be a risk factor for poor outcomes after knee replacement surgery (KR) for knee osteoarthritis (KOA). We aimed to evaluate the association between pre-operative central and peripheral pain sensitization measured using a digital pressure algometer and KR outcomes. METHODS: Consecutive patients with severe KOA listed for KR were recruited. Sociodemographic and symptoms data were collected prior to surgery. Pre-operative pressure pain thresholds (PPTs) were measured using a digital pressure algometer at the index knee and forearm. Patient satisfaction at 6 and 12 months after KR was assessed using a 4-point Likert scale, and dichotomized to satisfied and dissatisfied to KR. Western Ontario and McMaster Universities Index (WOMAC) Pain and function was assessed. The associations between pre-operative PPTs with KR outcomes at 6 and 12 months were evaluated. RESULTS: Of the 243 patients recruited, response rate at 6 and 12 months were 95.5% and 96.7%. The dissatisfaction rates were 8.2% and 5.1% at 6 and 12 months. There was no statistically significant association between pre-operative index knee or forearm PPTs and patient satisfaction. PPTs measured at the knee, but not the forearm, were weakly associated with change in the WOMAC pain score at 12 months, after adjustment for confounding factors. CONCLUSION: Pre-operative central sensitization, measured by handheld digital algometry, was not statistically significantly associated with satisfaction or change in pain after KR. Pre-operative peripheral sensitization was associated with change in pain symptoms after KR; however, this association was weak and unlikely to be a meaningful predictor of KR outcome in clinical practice.

Pre-discharge prognostic factors of physical function among older adults with hip fracture surgery: a systematic review.

INTRODUCTION: To identify, organize, and assess the evidence level of pre-discharge prognostic factors of physical function beyond discharge after hip fracture surgery. METHODS: We performed a systematic search of four databases (PubMed, Embase, CINAHL, PsycINFO) for longitudinal studies of prognostic factors of physical function at ≥ 1 month among older adults ≥ 50 years old with surgically treated hip fracture, complemented with hand-searching. Two reviewers independently screened papers for inclusion and assessed the quality of all the included papers using the Quality in Prognosis Studies (QUIPS) tool. We assigned the evidence level for each prognostic factor based on consistency in findings and study quality. RESULTS: From 98 papers that met our inclusion criteria, we identified 107 pre-discharge prognostic factors and organized them into the following seven categories: demographic, physical, cognitive, psychosocial, socioeconomic, injury-related, and process of care. Potentially modifiable factors with strong or moderate evidence of an association included total length of stay, physical function at discharge, and grip strength. Factors with strong or moderate evidence of no association included gender, fracture type, and time to surgery. Factors with limited, conflicting, or inconclusive evidence included body-mass index, psychological resilience, depression, and anxiety. CONCLUSIONS: Our findings highlight potentially modifiable prognostic factors that could be targeted and non-modifiable prognostic factors that could be used to identify patients who may benefit from more intensive intervention or to advise patients on their expectations on recovery. Examining the efficacies of existing interventions targeting these prognostic factors would inform future studies and whether any of such interventions could be incorporated into clinical practice.

Surgical management of pulsatile tinnitus secondary to jugular bulb or sigmoid sinus diverticulum with review of literature.

INTRODUCTION: Jugular bulb and sigmoid sinus anomalies are well-known causes of vascular pulsatile tinnitus. Common anomalies reported in the literature include high-riding and/or dehiscent jugular bulb, and sigmoid sinus dehiscence. However, cases of pulsatile tinnitus due to diverticulosis of the jugular bulb or sigmoid sinus are less commonly encountered, with the best management option yet to be established. In particular, reports on surgical management of pulsatile tinnitus caused by jugular bulb diverticulum have been lacking in the literature. OBJECTIVES: To report two cases of pulsatile tinnitus with jugular bulb and/or sigmoid sinus diverticulum, and their management strategies and outcomes. In this series, we describe the first reported successful case of pulsatile tinnitus due to jugular bulb diverticulum that was surgically-treated. SUBJECTS AND METHODS: Two patients diagnosed with either jugular bulb and/or sigmoid sinus diverticulum, who had presented to the Otolaryngology clinic with pulsatile tinnitus between 2016 and 2017, were studied. Demographic and clinical data were obtained, including their management details and clinical outcomes. RESULTS: Two cases (one with jugular bulb diverticulum and one with both sigmoid sinus and jugular bulb diverticula) underwent surgical intervention, and both had immediate resolution of pulsatile tinnitus post-operatively. This was sustained at subsequent follow-up visits at the outpatient clinic, and there were no major complications encountered for both cases intra- and post-operatively. CONCLUSION: Transmastoid reconstruction/resurfacing of jugular bulb and sigmoid sinus diverticulum with/without obliteration of the diverticulum is a safe and effective approach in the management of bothersome pulsatile tinnitus arising from these causes.

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

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

Comparing the meanings of living with advanced breast cancer between women resilient to distress and women with persistent distress: a qualitative study.

BACKGROUND: Most women with advanced breast cancer (ABC) show little distress, but about one in ten show persistent distress over time. It remains unclear if meanings ascribed by patients to ABC differentiate these distress trajectories. STUDY AIMS: This qualitative study (a) compared illness meanings of ABC between women with persistent psychological distress and those with low/transient distress, and (b) examined how illness meanings might influence coping strategies. METHODS: The sample was drawn from a prior quantitative study exploring psychological distress trajectories following ABC diagnosis. Overall, 42 Cantonese- or Mandarin-speaking Chinese women diagnosed with locally advanced or metastatic ABC were recruited based on their distress trajectory status (low-stable, transient, or persistent distress). Interviews were recorded, transcribed, and analyzed following grounded theory approach using simultaneous analysis. RESULTS: Women with persistent distress viewed their diagnosis as another blow in life, the illness was global, permeating every aspect of their life. Maladaptive rumination and thought suppression were common responses to illness demands. These women had poor social support. A sense of demoralization stood out in their narratives. In contrast, women with transient/low-stable distress encapsulated the illness, with minimum impacts of their life. They did not evidence dysfunctional repetitive thoughts. Living in a supportive environment, they were able to accept and/or live in the present-moment. CONCLUSIONS: Rumination, thought suppression, social constraints, and pre-existing exposure to life stress may be potential risks for chronic distress in response to advanced breast cancer. Persistent and transient distress responses to cancer may have different underpinnings. Copyright © 2016 John Wiley & Sons, Ltd.

Adjuvant S-1 chemotherapy after curative resection of gastric cancer in Chinese patients: assessment of treatment tolerability and associated risk factors.

INTRODUCTION: The use of adjuvant chemotherapy with S-1 (tegafur, gimeracil, and oteracil potassium) has been shown to improve the outcome of patients with gastric cancer. There are limited data on the tolerability of S-1 in Chinese patients. In this multicentre retrospective study, we assessed the toxicity profile in local patients. METHODS: Patients with stage II-IIIC gastric adenocarcinoma who had undergone curative resection and who had received S-1 adjuvant chemotherapy were included in the study. Patient demographics, tumour characteristics, chemotherapy records, as well as biochemical, haematological, and other toxicity profiles were extracted from medical charts. Potential factors associated with grade 2-4 toxicities were identified. RESULTS: Adjuvant S-1 was administered to 30 patients. Overall, 19 (63%) patients completed eight cycles. The most common grade 3-4 adverse events included neutropaenia (10%), anaemia (6.7%), septic episode (16.7%), diarrhoea (6.7%), hyperbilirubinaemia (6.7%), and syncope (6.7%). Dose reductions were made in 22 (73.3%) patients and 12 (40.0%) patients had dose delays. Univariate analyses showed that patients who underwent total gastrectomy were more likely to experience adverse haematological events (P=0.034). Patients with nodal involvement were more likely to report adverse non-haematological events (P=0.031). Patients with a history of regular alcohol intake were more likely to have earlier treatment withdrawal (P=0.044). Lower body weight (P=0.007) and lower body surface area (P=0.017) were associated with dose interruptions. CONCLUSIONS: The tolerability of adjuvant S-1 in our patient population was similar to that in other Asian patient populations. The awareness of S-1-related toxicities and increasing knowledge of potential associated factors may enable optimisation of S-1 therapy.

Use of romiplostim in patients with chronic idiopathic thrombocytopenic purpura during perioperative period.

INTRODUCTION: In patients with chronic idiopathic thrombocytopenic purpura (cITP), the platelet count tends to be quite variable and, in the majority of cases, specific therapy is not warranted on a regular basis. However, patients with low platelet count (<30 nL) or with bleeding complications would require therapy, such as prednisolone, intravenous immunoglobulin infusions, splenectomy and/or immunosuppression. Romiplostim, a thrombopoietin agonist, has also proven to be useful in improving platelet counts. cITP can be associated with bleeding complications perioperatively. As such, a higher platelet count is warranted (approximately 80 nL), particularly for invasive surgeries, such as orthopaedic surgery, cardio-thoracic surgery, head and neck surgery and abdominal surgery, where risk of bleeding is quite high already. AIM: The aim of this study is to evaluate the safety and efficacy of short-term use of romiplostim, perioperatively. METHODS: Patients with chronic ITP requiring major surgical interventions were enrolled in the study. Patients with malignancies or myelodysplastic syndromes, major bleeding disorders, under 18 years of age or pregnancy were excluded. CONCLUSION: This study has shown that the use of romiplostim is safe and effective in improving platelet counts preoperatively and that this could achieve excellent haemostasis, with no associated bleeding complications or rebound thrombocytopenia. A larger study involving multiple centres is required to verify these findings.

Using structural neuroanatomy to identify trauma survivors with and without post-traumatic stress disorder at the individual level.

BACKGROUND: At present there are no objective, biological markers that can be used to reliably identify individuals with post-traumatic stress disorder (PTSD). This study assessed the diagnostic potential of structural magnetic resonance imaging (sMRI) for identifying trauma-exposed individuals with and without PTSD. METHOD: sMRI scans were acquired from 50 survivors of the Sichuan earthquake of 2008 who had developed PTSD, 50 survivors who had not developed PTSD and 40 healthy controls who had not been exposed to the earthquake. Support vector machine (SVM), a multivariate pattern recognition technique, was used to develop an algorithm that distinguished between the three groups at an individual level. The accuracy of the algorithm and its statistical significance were estimated using leave-one-out cross-validation and permutation testing. RESULTS: When survivors with PTSD were compared against healthy controls, both grey and white matter allowed discrimination with an accuracy of 91% (p < 0.001). When survivors without PTSD were compared against healthy controls, the two groups could be discriminated with accuracies of 76% (p < 0.001) and 85% (p < 0.001) based on grey and white matter, respectively. Finally, when survivors with and without PTSD were compared directly, grey matter allowed discrimination with an accuracy of 67% (p < 0.001); in contrast the two groups could not be distinguished based on white matter. CONCLUSIONS: These results reveal patterns of neuroanatomical alterations that could be used to inform the identification of trauma survivors with and without PTSD at the individual level, and provide preliminary support to the development of SVM as a clinically useful diagnostic aid.

Is routine chest X-ray after surgical and percutaneous tracheostomy necessary in adults: a systemic review of the current literature.

BACKGROUND: For many years, routine post-tracheostomy chest X-ray has been the standard of care for patients in many countries. However, recent evidence suggests that this is unnecessary and cost-ineffective. OBJECTIVE: To review the current literature and examine the role of routine post-tracheostomy chest X-ray in adult patients. TYPE OF REVIEW: Systemic review. SEARCH STRATEGY: Electronic databases (PubMed, EMBASE, Cochrane) were searched using the keywords 'chest X-ray/radiography/radiograph' and 'tracheostomy/tracheotomy' in various permutations. Search period ranged from 1960 to 2012. Inclusion criteria included systematic reviews, meta-analyses, randomised control trials, prospective and retrospective case series. Paediatric and non-English articles were excluded. Abstracts and subsequently full text articles were screened by two of the authors independently. References from obtained articles were also examined. EVALUATION METHOD: Specific outcome measures were collated to evaluate the usefulness of post-tracheostomy chest X-ray: Chest X-ray detected (tracheostomy-related) complication rates Proportion of cases requiring significant intervention Potential predictors of complications RESULTS: Routine post-tracheostomy chest X-ray is of a low yield, and its findings had limited impact on patient management. Complication detection rates for surgical and percutaneous tracheostomy are 2.2% and 3.2%, respectively. Only 0.7% and 1.8% of chest X-rays performed in surgical and percutaneous tracheostomy cases, respectively, required intervention. Certain groups of patients, however, are at higher risks of complications, and may benefit from post-tracheostomy chest X-ray. For surgical tracheostomy, these groups include those with post-operative signs and symptoms of complications or had emergent or 'difficult' tracheostomies. For percutaneous tracheostomy, high-risk patients include trauma cases (unspecified), patients with post-procedural signs and symptoms of complications, patients who have high ventilatory requirements, difficult tracheostomy cases or tracheostomy cases performed without bronchoscopic guidance. CONCLUSION: The practice of routine post-tracheostomy chest X-ray is debatable owing to its low yield and minimal impact on clinical management. However, certain groups of patients appear to be at higher risks of post-tracheostomy complications; currently, there is insufficient evidence to conclude the absolute need for routine chest X-ray in these groups of patients, although it may be prudent to do so based on available evidence in the literature and logical clinical reasoning.

Using genetic, cognitive and multi-modal neuroimaging data to identify ultra-high-risk and first-episode psychosis at the individual level.

BACKGROUND: Group-level results suggest that relative to healthy controls (HCs), ultra-high-risk (UHR) and first-episode psychosis (FEP) subjects show alterations in neuroanatomy, neurofunction and cognition that may be mediated genetically. It is unclear, however, whether these groups can be differentiated at single-subject level, for instance using the machine learning analysis support vector machine (SVM). Here, we used a multimodal approach to examine the ability of structural magnetic resonance imaging (sMRI), functional MRI (fMRI), diffusion tensor neuroimaging (DTI), genetic and cognitive data to differentiate between UHR, FEP and HC subjects at the single-subject level using SVM. METHOD: Three age- and gender-matched SVM paired comparison groups were created comprising 19, 19 and 15 subject pairs for FEP versus HC, UHR versus HC and FEP versus UHR, respectively. Genetic, sMRI, DTI, fMRI and cognitive data were obtained for each participant and the ability of each to discriminate subjects at the individual level in conjunction with SVM was tested. RESULTS: Successful classification accuracies (p < 0.05) comprised FEP versus HC (genotype, 67.86%; DTI, 65.79%; fMRI, 65.79% and 68.42%; cognitive data, 73.69%), UHR versus HC (sMRI, 68.42%; DTI, 65.79%), and FEP versus UHR (sMRI, 76.67%; fMRI, 73.33%; cognitive data, 66.67%). CONCLUSIONS: The results suggest that FEP subjects are identifiable at the individual level using a range of biological and cognitive measures. Comparatively, only sMRI and DTI allowed discrimination of UHR from HC subjects. For the first time FEP and UHR subjects have been shown to be directly differentiable at the single-subject level using cognitive, sMRI and fMRI data. Preliminarily, the results support clinical development of SVM to help inform identification of FEP and UHR subjects, though future work is needed to provide enhanced levels of accuracy.

The evolution of psychological distress trajectories in women diagnosed with advanced breast cancer: a longitudinal study.

BACKGROUND: Anxiety and depression (distress) over the first year following the initial adjuvant therapy for advanced breast cancer (ABC) remain poorly documented in non-Caucasian populations. This study describes trajectories of distress and their determinants in Chinese women with ABC. METHODS: Of the 228 Chinese women newly diagnosed with ABC recruited from six oncology units, 192 completed an interview before their first course of chemotherapy (baseline) and follow-up interviews at 1.5, 3, 6, and 12 months thereafter. At baseline, participants were assessed for supportive care needs, psychological distress, physical symptom distress, optimism, and cancer-related rumination. At follow-up, participants completed the measure of psychological distress. Latent growth mixture modeling was used to identify trajectory patterns of distress. Multinominal logistic regression was used to identify predictors of trajectory patterns adjusted for demographic and medical characteristics. RESULTS: Four distinct trajectories of anxiety and depression were identified. Most women showed low-stable levels of anxiety (68%) and depression (68%), but one in 11 women were chronically anxious (9%) and depressed (9%). Optimism, negative cancer-related rumination, and physical symptom distress predicted both anxiety and depression trajectories. Psychological needs predicted anxiety trajectories. Women in the low-stable distress group reported high optimism, low psychological supportive care needs, low physical symptom distress, and low negative cancer-related rumination. CONCLUSION: Most women with ABC did not experience psychological distress over 12 months following diagnosis of ABC. Preventive interventions should focus on women at risk of high persistent distress and reducing rumination, providing emotional support, and managing physical symptoms.

Rapid extraction and preservation of genomic DNA from human samples.

Simple and rapid extraction of human genomic DNA remains a bottleneck for genome analysis and disease diagnosis. Current methods using microfilters require cumbersome, multiple handling steps in part because salt conditions must be controlled for attraction and elution of DNA in porous silica. We report a novel extraction method of human genomic DNA from buccal swab and saliva samples. DNA is attracted onto a gold-coated microchip by an electric field and capillary action while the captured DNA is eluted by thermal heating at 70 °C. A prototype device was designed to handle four microchips, and a compatible protocol was developed. The extracted DNA using microchips was characterized by qPCR for different sample volumes, using different lengths of PCR amplicon, and nuclear and mitochondrial genes. In comparison with a commercial kit, an equivalent yield of DNA extraction was achieved with fewer steps. Room-temperature preservation for 1 month was demonstrated for captured DNA, facilitating straightforward collection, delivery, and handling of genomic DNA in an environment-friendly protocol.

How can we improve junior doctor prescribing?

The large number of medications available has complicated the learning of drug therapy for medical students at a time when pharmacology training has been substantially reduced. Attempts to remedy this include: improving the pharmaco-therapeutics curriculum; interactive web-based learning and students developing a personal formulary. The approach adopted by the University of Wollongong Medical School is to integrate clinical pharmacology throughout the course, with the Student Preferred-drugs Formulary linking pharmacology and common diseases. Evidence from other countries suggests this should enhance prescribing by medical graduates.

Phase I and pharmacodynamic study of an orally administered novel inhibitor of histone deacetylases, SB939, in patients with refractory solid malignancies.

BACKGROUND: The objective of this study was to assess the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary efficacy of SB939, a novel histone deacetylase (HDAC) inhibitor, in patients with advanced solid malignancies. PATIENTS AND METHODS: Dose-escalating cohorts of three to six patients received SB939 orally thrice weekly for 3 weeks in a 4-week cycle. Acetylated histone H3 (acH3) was measured in peripheral blood mononuclear cells (PBMCs). RESULTS: Thirty patients treated at one of five doses (10-80 mg/day) received 79 cycles of SB939 (range, 1-12 cycles). Dose-limiting toxic effects were fatigue, hypokalemia, troponin T elevation, and QTc prolongation. Peak plasma concentration (C(max)) and area under the concentration-time curve extrapolated to infinity increased dose proportionally. The MTD of SB939 was 80 mg/day. The mean elimination half-life and oral clearance of SB939 were 7.2 ± 0.6 h and 53.0 ± 8.5 l/h, respectively, with no substantial accumulation on day 15. An increase in acH3 was observed at hour 3 and correlated with dose and C(max). Stable disease was seen in several tumor types treated at ≥40 mg. HDAC inhibition was consistently observed at 60 mg, the recommended dose. CONCLUSIONS: SB939 can be safely administered at the recommended dose and reaches plasma levels that strongly inhibit HDAC in PBMCs. These data support further efficacy studies of SB939.

Validation of the Chinese version of the short-form Supportive Care Needs Survey Questionnaire (SCNS-SF34-C).

BACKGROUND: There is no instrument available in Chinese for assessing psychosocial needs. This study aimed to assess the validity and reliability of the Chinese version of the Supportive Care Needs Survey short form (SCNS-SF34-C) in Chinese women with breast cancer (BC). METHODS: The Chinese version of the 34-item SCNS-SF34-C, a self-report measure for assessing psychosocial unmet needs, was administered to 348 Chinese women with BC at the outpatient oncology unit. Exploratory factor analysis (EFA) tested the factor structure. The internal consistency, convergent, divergent, and discriminant validity of the identified factor structure were assessed. RESULTS: In contrast to the five-factor structure identified in the original 34-item SCNS-SF34, our EFA produced a 33-item solution accounting for 54% of score variance comprising four-factors: (1) Health system, information, and patient support, (2) Psychological needs, (3) Physical and daily living, and (4) Sexuality needs. Separate dimensions for Health system and information, and the Patient care and support domains were not supported. Cronbach alphas ranged from 0.75 to 0.92. Correlations of psychological and physical symptom distress measures indicated acceptable convergent validity. No correlation with optimism and positive affect measures indicated divergent validity. Discriminant validity was demonstrated by effective differentiation between clinically distinct patient groups (no active treatment versus active treatment; advanced BC versus localized BC). DISCUSSION: The Chinese version of the Supportive Care Needs Survey has suitable factor structure and psychometric properties for use in assessing psychosocial needs among Chinese women with BC. Further validation is needed for other cancer types.

Induced pluripotent stem cells: history, properties and potential applications.

The development of induced pluripotent stem cells (iPSCs) has been met with much enthusiasm and hailed as a breakthrough discovery by the scientific and research communities amidst the divisive and ongoing debates surrounding human embryonic stem cells (hESC) research. The discovery reveals the fact that embryonic pluripotency can be generated from adult somatic cells by the induction of appropriate transcriptional factor genes essential for maintaining the pluripotency. They provide an alternative source for pluripotent stem cells, thus representing a powerful new research tool besides their potential application in the field of regenerative medicine. In this review, the historical background of iPSCs generation will be discussed together with their properties and characteristics as well as their potential therapeutic applications.