Phase I Dose-Escalation Study of SCB01A,a Microtubule Inhibitor with Vascular Disrupting Activity,in Patients with Advanced Solid Tumors

Lessons Learned

• SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
• This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
• SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.

BackgroundSCB01A, a novel microtubule inhibitor, has vascular disrupting activity.MethodsIn this phase I dose‐escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m² to the maximum tolerated dose (MTD) based on dose‐limiting toxicity (DLT). SCB01A‐induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints.ResultsTreatment‐related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m² cohort; grade 3 gastric hemorrhage in the 6.5 mg/m² cohort; grade 2 thromboembolic event in the 24 mg/m² cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m² cohort. The MTD was 24 mg/m², and average half‐life was ~2.5 hours. The area under the curve‐dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A‐induced neurotoxicity was reversible in vitro.ConclusionThe MTD of SCB01A was 24 mg/m² every 21 days; it is safe and tolerable in patients with solid tumors.     

How physiotherapists perceive,interpret, and respond to the ethical dimensions of practice: A qualitative study

The profile and reach of physiotherapy has expanded in areas of extended scope of practice, and broader engagement with population needs beyond the individual treatment encounter. These changes raise increasingly complex ethical challenges evidenced by growth in physiotherapy-based ethics studies and discussions. This paper examines how a broad cross section of Australian physiotherapists perceive, interpret, and respond to ethical challenges in their work contexts and how professional codes of conduct are used in their practice. Using an interpretive qualitative methodology, purposive sampling of 88 members of national clinical special interest groups were recruited for focus group discussions. Narrative-based and thematic data analysis identified ethical challenges as emerging from specific clinical contexts, and influenced by health organizations, funding policies, workplace relationships, and individually held perspectives. Five themes were developed to represent these findings: (1) the working environment, (2) balancing diverse needs and expectation, (3) defining ethics, (4) striving to act ethically, and (5) talking about ethics. The results portray a diverse and complex ethical landscape where therapists encounter and grapple with ethical questions emerging from the impact of funding models and policies affecting clinical work, expanding boundaries and scope of practice and changing professional roles and relationships. Codes of conduct were described as foundational ethical knowledge but not always helpful for “in the moment” ethical decision-making. Based on this research, we suggest how codes of conduct, educators, and professional associations could cultivate and nurture ethics capability in physiotherapy practitioners for these contemporary challenges.     

Matrine,oxymatrine, and compound Kushen injection from the roots of Sophora flavescens: an overview of their anticancer activities

In the present review, we updated current information on the chemistry, contents, and anticancer properties of matrine (MT), oxymatrine (OMT), and compound Kushen injection (CKI). The anticancer properties were focused on lung, breast, and liver cancer cells because they are most susceptible. Sources of information were from Google, Google Scholar, PubMed, PubMed Central, Science Direct, PubChem, J-Stage, Directory of Open Access Journals (DOAJ), and China National Knowledge Infrastructure (CNKI). Reference was also made on botanical websites, such as Flora of China and World Flora Online. MT and OMT are dominant quinolizidine alkaloids from the roots of Sophora flavescens (Kushen) of the family Fabaceae. Against lung, breast, and liver cancer cells, MT and OMT inhibit cell proliferation; induce cell cycle arrest, apoptosis, and autophagy; restrict angiogenesis; and inhibit cell metastasis, invasion, and migration. The processes involve various molecular targets and signaling pathways. CKI is a traditional Chinese medicine (TCM) composed of root extracts of S. flavescens and Smilax glabra (Baituling) of the family Smilacaceae. With MT and OMT as major components, CKI has been approved for the treatment of cancer in China more than 20 years ago. In recent years, systematic reviews and meta-analysis have been undertaken to evaluate the anticancer effects of CKI. When CKI is used alone and in combination with chemotherapy of western medicine, there is much to be learned concerning their interactions besides their individual and integrated efficacy. Some perspectives of MT, OMT, and CKI are discussed, and their suggestions for future research are provided.     

The Relationship Between Air Pollution and Lung Cancer in Nonsmokers in Taiwan

Introduction

For never-smokers (smoked <100 lifetime cigarettes), lung cancer (LC) has emerged as an important issue. We aimed to investigate the effects of prevalence changes in tobacco smoking and particulate matter (PM) 2.5 (PM_2.5) levels on LC in Taiwan, in relation to contrasting PM_2.5 levels, between Northern Taiwan (NT) and Southern Taiwan (ST).

Leptin, lipid and lipid metabolism-related hormones in chronic renal failure in Arabia

SUMMARY: In patients with chronic renal failure (CRF), hyperleptinaemia has been widely reported, but the exact mechanisms leading to elevated leptin levels are unclear. Impaired renal clearance of leptin and the influence of other hormones may be important. In this study, we measured serum leptin levels in 150 patients on haemodialysis, peritoneal dialysis or in the predialysis phase of CRF. Furthermore, we measured plasma levels of insulin, growth hormone (GH) and insulin-like growth factor 1 (IGF-1), as well as plasma levels of triacylglycerols and total low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol. We observed significantly elevated levels of leptin, particularly in female patients, and leptin was shown to correlate significantly with insulin, total and LDL-cholesterol and log triacylglycerols. Leptin was inversely correlated with GH concentrations, but was not correlated with IGF-1 levels. Despite the multiple correlations established between leptin levels and other variables, only hyperinsulinaemia in CRF seems to be important as a determinator of leptin levels.     

Successful balloon pulmonary valvuloplasty for congenital valvular pulmonary stenosis in an octogenarian.

While balloon valvuloplasty has been widely used for the treatment of congenital valvular pulmonary stenosis (PS) in children and adults, its use in elderly patients is less common. An 80-year-old woman with congenital valvular PS received valvuloplasty with double-balloon technique. Right ventricle systolic pressure and pulmonary valve systolic pressure gradient decreased from 95 to 44 mm Hg and from 75 to 35 mm Hg, respectively. Follow-up Doppler echocardiography 2 months later showed further decrease in the transvalvular systolic pressure gradient to 29 mm Hg. The patient had symptomatic relief, and no major complication was noted. Balloon pulmonary valvuloplasty can be an effective treatment for elderly patients with congenital valvular PS.     

Multi-detector CT angiography for lower gastrointestinal bleeding: Can it select patients for endovascular intervention?

This is a retrospective review of the results at our institution of using multi-detector CT angiography (CTA) to localise lower gastrointestinal (GI) bleeding. We hypothesised that in our patient population: (i) CTA was unlikely to demonstrate bleeding in patients who were haemodynamically stable; (ii) in haemodynamically unstable patients in whom CTA was undertaken, the results could be used to select patients who would benefit from catheter angiography; and (iii) in haemodynamically unstable patients in whom CTA was undertaken, a subgroup of patients could be identified who would benefit from primary surgical treatment, avoiding invasive angiography completely. A retrospective review was conducted of the clinical records of all patients undergoing CTA for lower GI haemorrhage at our institution between 1 January 2005 and 30 June 2007. Out of the 20 patients examined, 10 had positive CTAs demonstrating the bleeding site. Nine were haemodynamically unstable at the time of the study. Four patients with positive CT angiograms were able to be treated directly with surgery and avoided invasive angiography. Ten patients had negative CTAs. Four of these were haemodynamically unstable, six haemodynamically stable. Only one required intervention to secure haemostasis, the rest stopped spontaneously. No haemodynamically stable patient who had a negative CTA required intervention. CTA is a useful non-invasive technique for localising the site of lower GI bleeding. In our patient population, in the absence of haemodynamic instability, the diagnostic yield of CTA was low and bleeding was likely to stop spontaneously. In haemodynamically unstable patients, a positive CTA allowed patients to be triaged to surgery or angiography, whereas there was a strong association between a negative CTA and spontaneous cessation of bleeding.     

Development of a risk-adjusted capitation model based on principal inpatient diagnoses in Taiwan.

BACKGROUND AND PURPOSE: Taiwan's National Health Insurance (NHI) program has considered the use of capitation payments to health care providers as a method for control of the rising costs of the system. The establishment of capitation payments usually requires the performance of risk adjustment. The purposes of this study were to develop a diagnosis-based risk adjustment model for the NHI and to evaluate its predictability. METHODS: Using a 2% random sample of 371,620 NHI enrollees, the authors developed a Taiwan version of the Principal Inpatient Diagnosis Cost Groups (TPIPDCGs) from 1996 claim records to predict an individual's expenditure in 1997. Weighted least squares regression models were built in an estimation sample (two-thirds of the study sample), and were cross-validated in a validation sample (the remaining one-third of the study sample). Predictive R2 and predictive ratios were used to evaluate the model's predictability. RESULTS: Only 7.88% of the study sample could be classified into 1 of the 16 TPIPDCGs. Combined with demographic variables, which alone could explain 3.7% of the variation in an individual's future expenditure, the risk adjustment model based on TPIPDCGs could explain 12.2% of expenditure variation. In addition, the finding that the predictive ratios of the TPIPDCG model approximated unity better than those of the demographic model in all subgroups indicates that the capitation payment as predicted by the TPIPDCG model for each subgroup would better correlate to the actual spending. CONCLUSION: Taiwan's risk-adjusted capitation model based on principal inpatient diagnoses has higher predictability on individual's future expenditure than its counterpart in the USA. This finding provides insight into not only the development of Taiwan's diagnosis-based risk adjustment models but also the necessity of modification when applying foreign-developed risk adjustment models to the NHI.