Treatment refusal is a common encounter in clinical practice. The process of deciding to refuse treatment is often complex. It is our responsibility to try and understand this process of decision making and the underlying reasons for treatment refusal. Many of these reasons are often rational in the context where the decision is made. The patients could be making the best decision for themselves even if these decisions are not necessarily the best in our mind. We should at all times discuss our treatment options and assess their ability to make decisions in achieving common goals. These goals should balance our best treatment strategies and the patients’ best interest. This article discusses the reasons underlying treatment refusal and how we can achieve a common goal with our patients.
Patients ; decision ; Treatment Refusal ; therapeutic aspects ; treatment options

Objective: This study explored the stress and coping strategies among retired people in Malaysia. Methods: In-depth interviews were conducted with 36 elderly Malaysian subjects. This protocol was approved by the Ethics Committee of the Management and Science University. The data obtained were sorted into various categories. Results: A total number of 36 retired elderly people participated in this study. The majority of them were in the age group of 55-59 years old, females, Malay and married. The majority defined stress as pressure or tension. Financial difficulties, family and work problems were the main causes of stress in the majority. Also, the majority of respondents mentioned that they coped with stress by sharing problems with others, by resting and relaxing, and/or by doing housework during their free time. A few of them coped with stress by hanging out with friends, going shopping, doing photography, travelling, going fishing, and doing sports. Conclusion: Financial difficulties, family and work problems were the main causes of stress among elderly people. They coped with stress by sharing problems with others, resting and relaxing, and/or doing housework during their free time.

Objective To study whether physiological and psychological stresses during parachuting jumps may result in biochemical changes of plasma in parachutists. Method Differences in the levels of hormones (cortisol, growth hormone, insulin, pancreatic glucagon, endothelin, angiotonin I and II, aldosterone), activities of enzymes (superoxide dismutase, glutathione peroxidase, glutathione S transferase), levels of the free radical damage indicator malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and the main heat stress protein, HSP70,in the plasma and serum were investigated in control (non-parachuting) and parachuting paratroops. Result Significantly higher levels of serum hormones such as growth hormone, insulin, angiotonin I, renin activities, as well as MDA and plasma TNF-α and HSP70 were observed in the parachuting group. Conclusion Whether these changes can potentially serve as useful biomarkers to assess possible abnormal stress in parachutists and to evaluate the health condition and to select parachutists remains to be further studied.

SUMMARY Constitutional full trisomy 21 is a common disorder in which abnormal spermatogenesis has been previously described. However, constitutional mosaic trisomy 21 in an otherwise normal but infertile male has not been explored. We report a case with low level mosaic trisomy 21 in a non-syndrome but azoospermic patient. We also propose that the patient's azoospermia may be related to the constitutional mosaic trisomy 21 and thus resulting in a late onset of testicular failure.

Predictive biomarkers are important to the future of oncology; they can be used to identify patient populations who will benefit from therapy, increase the value of cancer medicines, and decrease the size and cost of clinical trials while increasing their chance of success. But predictive biomarkers do not always work. When unsuccessful, they add cost, complexity, and time to drug development. This perspective describes phases 2 and 3 development methods that efficiently and adaptively check the ability of a biomarker to predict clinical outcomes. In the end, the biomarker is emphasized to the extent that it can actually predict.
Biomarkers, Tumor ; genetics ; metabolism ; Clinical Trials as Topic ; methods ; Decision Support Techniques ; Evidence-Based Medicine ; Humans ; Neoplasms ; diagnosis ; genetics ; metabolism ; Predictive Value of Tests ; Program Development ; methods

Electrophysiological studies can provide objective and quantifiable assessments of movement disorders. They are useful in the diagnosis of hyperkinetic movement disorders, particularly tremors and myoclonus. The most commonly used measures are surface electromyography (sEMG), electroencephalography (EEG) and accelerometry. Frequency and coherence analyses of sEMG signals may reveal the nature of tremors and the source of the tremors. The effects of voluntary tapping, ballistic movements and weighting of the limbs can help to distinguish between organic and functional tremors. The presence of Bereitschafts-potentials and beta-band desynchronization recorded by EEG before movement onset provide strong evidence for functional movement disorders. EMG burst durations, distributions and muscle recruitment orders may identify and classify myoclonus to cortical, subcortical or spinal origins and help in the diagnosis of functional myoclonus. Organic and functional cervical dystonia can potentially be distinguished by EMG power spectral analysis. Several reflex circuits, such as the long latency reflex, blink reflex and startle reflex, can be elicited with different types of external stimuli and are useful in the assessment of myoclonus, excessive startle and stiff person syndrome. However, limitations of the tests should be recognized, and the results should be interpreted together with clinical observations.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease. A cardinal histopathologic feature of HD is the progressive loss of striatal medium spiny neurons. As there is no effective treatment for this fatal disease so far, we explore the therapeutic potential of nortriptyline to identify drugs that might be effective treatments for HD. N548mu [ 1955-128] huntingtin stable ST14A cell line was cultured and incubated in the presence or absence of serial concentrations of nortriptyline. Then R6/2 transgenic HD mice were treated with nortriptyline from five to twenty-one weeks of age. Nortriptyline protected striatal cells expressing mutant huntingtin when shifted to a nonpermissive temperature. Nortriptyline delay the disease onset to 127 d in R6/2 mice as compared with 102 d in saline-treated controls, but nortriptyline did not significantly delay mortality. As a gross marker of lack of systemic toxicity, there was no significant difference in the weight of the treated and control R6/2 mice. The results demonstrate that clinically reasonable doses of one of the identified drugs, nortriptyline, delays disease onset in a mouse model of the disease more than any previously identified compound. The most desirable features of a drug for HD are minimal toxicity and the ability to extend symptom-free living. Nortriptyline appears to be one such good candidate.

BACKGROUNDSYBR Green I is a non-probe real-time PCR method. It is quite convenient and its specificity is good. The aim of this study is to establish a quantitative SYBR Green I real-time PCR method for detection of PEDF gene in non-small cell lung cancer (NSCLC), and to investigate the relationship between PEDF mRNA expression and the clinicopathological characteristics.

METHODSThe target segments of PEDF and GAPDH proliferated by RT-PCR were diluted and used as the standard templates. PEDF mRNA was detected in 21 NSCLC tissues and matched paracancerous pulmonary tissues by relative quantitative method.

RESULTSAll the lung cancer tissues and the matched paracancerous pulmonary tissues had expression of PEDF mRNA. The relative level of PEDF mRNA expression was 0.5505±0.3590 (0.11-1.11) in the lung cancer tissues and 0.7219±0.2582 (0.29-1.31) in the matched paracancerous pulmonary tissues respectively (P=0.024). PEDF expression was significantly related to TNM stages (I-II vs III-IV, P=0.010) and the tumor size (T1 vs T2-4, P=0.007).

CONCLUSIONSThe established SYBR Green I quantitative real-time PCR method can successfully detect the expression of PEDF mRNA. The primary results show that PEDF may be a protective factor in oncogenesis and development of NSCLC.

Objective: To evaluate the cost-effectiveness of olaparib as a maintenance treatment versus routine surveillance (RS) in patients with BRCA mutated (BRCAm) advanced ovarian cancer (OC) following response to first-line platinum-based chemotherapy in Singapore. Methods: A 4-health state partitioned survival model was developed to simulate the lifetime (50 years) incremental cost-effectiveness ratio (ICER) of olaparib versus RS from a healthcare payer perspective. Progression-free survival, time to second disease progression, and overall survival were estimated using SOLO-1 data and extrapolated beyond the trial period using parametric survival models. Any patient who remained progression-free at year 7 was assumed to be no longer at risk of progression. Mortality rates were based on all-cause mortality, adjusted based on BRCA1/2 mutation. Health state utilities and adverse event frequencies were from SOLO-1. Drug costs were from local public healthcare institutions. Healthcare resource usage and costs were from local clinician input and publications. A 3% discount rate was applied to costs and outcomes. Deterministic and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of results. Results: The base-case analysis of olaparib maintenance therapy versus RS resulted in an ICER of Singapore dollar (SGD) 19,822 per quality-adjusted life-year (QALY) gained. The ICER was most sensitive to variations in the discount rate. PSA demonstrated that olaparib had an 87% probability of being cost-effective versus RS at a willingness-to-pay of SGD 60,000 per QALY gained. Conclusion Olaparib has a high potential of being a cost-effective maintenance treatment versus RS for patients with BRCA1/2m advanced OC after response to first-line chemotherapy in Singapore.