Diverse point mutations result in glucose-6-phosphate dehydrogenase (G6PD) polymorphism in Taiwan.

Glucose-6-PHOSPHATE dehydrogenase (G6PD; EC 1.1.1.49) deficiency is the most common human enzymopathy, affecting more than 200 million people worldwide. Although greater than 400 variants have been described based on clinical and biochemical criteria, little is known about the molecular basis of these G6PD deficiencies. Recently, the gene that encodes human G6PD has been cloned and sequenced, which enables us to examine directly the heterogeneity of G6PD at the DNA level. During the past 10 years, we examined the G6PD activity in 21,271 newborn Chinese infants (11,400 males and 9,871 females) and identified 314 (2.8%) males and 246 (2.5%) females having low G6PD activity. The G6PD gene from 10 randomly selected affected individuals and their relatives was polymerase chain reaction (PCR) amplified, subcloned, and sequenced. Our results indicate that at least four types of mutation are responsible for the G6PD polymorphism in Taiwan. The first type of mutation (487 G----A) was found in an affected Chinese with a G to A change at nucleotide 487, which results in a (163)Gly to Ser substitution. The second type of mutation (493 A----G) is a novel mutation that has not been reported in any other ethnic group and was identified in two affected Chinese. This mutation causes an A to G change at nucleotide position 493, producing an (165)Asn to Asp substitution. Interestingly, the 487 G----A and 493 A----G mutations create Alu I and Ava II recognition sites, respectively, which enabled us to rapidly detect these two mutations by PCR/restriction enzyme (RE) digestion method. The third mutation (1376 G----T) was found in four affected Chinese. This mutation causes a G to T change at nucleotide position 1376 that results in an (459)Arg to Leu substitution. The 1376 G----T mutation seems to be the dominant allele that causes G6PD deficiency in Taiwan. Finally, two affected Chinese were identified as having the fourth mutation (1388 G----A). This mutation causes a G to A change at nucleotide 1388 that produces an (463)Arg to His substitution. Our studies provide the direct proof of the genetic heterogeneity of G6PD deficiency in the Chinese populations of Taiwan and the PCR/RE digestion method is suitable for simultaneous detection of the 487 G----A and 493 A----G mutations.     

WHO Group 5 Drugs and Difficult Multidrug-Resistant Tuberculosis: a Systematic Review with Cohort Analysis and Meta-Analysis

It is often necessary to include WHO group 5 drugs in the treatment of extensively drug-resistant tuberculosis (XDR-TB) and fluoroquinolone-resistant multidrug-resistant tuberculosis (MDR-TB). As clinical evidence about the use of group 5 drugs is scarce, we conducted a systematic review using published individual patient data. We searched PubMed and OvidSP through 7 April 2013 for publications in English to assemble a cohort with fluoroquinolone-resistant MDR-TB treated with group 5 drugs. Favorable outcome was defined as sputum culture conversion, cure, or treatment completion in the absence of death, default, treatment failure, or relapse. A cohort of 194 patients was assembled from 20 articles involving 12 geographical regions. In descending order of frequency, linezolid was used in treatment of 162 (84%) patients, macrolides in 84 (43%), clofazimine in 65 (34%), amoxicillin with clavulanate in 56 (29%), thioridazine in 18 (9%), carbapenem in 16 (8%), and high-dose isoniazid in 16 (8%). Cohort analysis with robust Poisson regression models and random-effects meta-analysis similarly suggested that linezolid use significantly increased the probability (95% confidence interval) of favorable outcome by 57% (10% to 124%) and 55% (10% to 121%), respectively. Defining significant associations by risk ratios ≥ 1.2 or ≤ 0.9, neither cohort analysis nor meta-analysis demonstrated any significant add-on benefit from the use of other group 5 drugs with respect to outcome for patients treated with linezolid, although selection bias might have led to underestimation of their effects. Our findings substantiated the use of linezolid in the treatment of XDR-TB or fluoroquinolone-resistant MDR-TB and call for further studies to evaluate the roles of other group 5 drugs.     

Can Intermittent Dosing Optimize Prolonged Linezolid Treatment of Difficult Multidrug-Resistant Tuberculosis?

We evaluated treatment with linezolid, dosed at 800 mg once daily for 1 to 4 months as guided by sputum culture status and tolerance and then at 1,200 mg thrice weekly until ≥1 year after culture conversion, in addition to individually optimized regimens among 10 consecutive patients with extensively drug-resistant tuberculosis or fluoroquinolone-resistant multidrug-resistant tuberculosis. All achieved stable cure, with anemia corrected and neuropathy stabilized, ameliorated, or avoided after switching to intermittent dosing. Serum linezolid profiles appeared better optimized.     

The effects of a computer skill training programme adopting social comparison and self-efficacy enhancement strategies on self-concept and skill outcome in trainees with physical disabilities

Purpose : The aim of this controlled, quasi-experimental study was to evaluate the effects of both self-efficacy enhancement and social comparison training strategy on computer skills learning and self-concept outcome of trainees with physical disabilities. Method : The self-efficacy enhancement group comprised 16 trainees, the tutorial training group comprised 15 trainees, and there were 25 subjects in the control group. Both the self-efficacy enhancement group and the tutorial training group received a 15 week computer skills training course, including generic Chinese computer operation, Chinese word processing and Chinese desktop publishing skills. The self-efficacy enhancement group received training with tutorial instructions that incorporated self-efficacy enhancement strategies and experienced self-enhancing social comparisons. The tutorial training group received behavioural learning-based tutorials only, and the control group did not receive any training. The following measurements were employed to evaluate the outcomes: the Self-Concept Questionnaire for the Physically Disabled Hong Kong Chinese (SCQPD), the computer selfefficacy rating scale and the computer performance rating scale. Results : The self-efficacy enhancement group showed significantly better computer skills learning outcome, total selfconcept, and social self-concept than the tutorial training group. The self-efficacy enhancement group did not show significant changes in their computer self-efficacy; however, the tutorial training group showed a significant lowering of their computer self-efficacy. Conclusions : The training strategy that incorporated selfefficacy enhancement and positive social comparison experiences maintained the computer self-efficacy of trainees with physical disabilities. This strategy was more effective in improving the learning outcome ( p = 0.01) and self-concept ( p = 0.05) of the trainees than the conventional tutorial-based training strategy.     

Diagnostic and psychodynamic aspects of sexual addiction appearing as a non‐paraphiliac form of compulsive sexual behaviour

Background: In recent decades, the diagnosis of sexual or love addiction has increasingly become part of the spectrum of addiction medicine. Although it does not figure under this name in either the BNO‐10 or DSM‐IV, the present scientific position is that it can be regarded as a compulsive sexual behaviour disorder that does not show the criteria of paraphilia.

Method: A case report.

Results: In the case of the 61‐year‐old patient we observed, the problems of an extramarital relationship play a central part in the syndrome with a serious conflict situation and prolonged personal and family crisis. This sexual addiction can be interpreted as identification with the father and also as the means of masculine identity. The sexual behaviour meets the criteria of addiction. Follow‐up will decide the stability of the diagnosis. In connection with this case, the authors attempt a psychodynamic analysis of triangular relationships destabilizing couple relationships.     

Recent trends in the prevalence of Helicobacter Pylori in symptomatic children: A 12-year retrospective study in a tertiary centre

Objective

Helicobacter pylori infection is common among Asians. However, evidence in the recent years has demonstrated a decrease in the prevalence of H. pylori infection among children and adults worldwide. Our aim was to update its prevalence in symptomatic children in our locality in the recent 12?years and compared to the results of our previous review published in 2005.

A nested case-control study on treatment-related risk factors for early relapse of tuberculosis

This nested case-control study aimed at evaluating treatment-related risk factors of relapse of tuberculosis under a service program of directly observed treatment. Out of 12,183 patients with pulmonary tuberculosis who completed treatment within 1 year, 113 relapsed within 30 months after commencement of therapy. The overall 30-month relapse rate was 0.9% (95% confidence interval [CI] 0.8-1.1%). On matching 113 cases with 226 control subjects in a conditional logistic model, thrice-weekly treatment increased the risk of relapse in comparison with daily treatment (odds ratio 3.92, 95% CI 1.78-8.63), whereas prolonging both intensive phase and overall treatment by 50% or more protected against relapse (odds ratio 0.24, 95% CI 0.08-0.70). When pretreatment culture was positive and cavitation was absent, the 30-month relapse rate for standard thrice-weekly regimen was 1.1% (95% CI 0.6-2.0%). The corresponding rates in the presence of cavitation were 7.8% (95% CI 4.0-14.6%) for standard thrice-weekly regimen; 3.3% (95% CI 1.9-5.5%) for standard daily regimen; 0.5% (95% CI 0.1-2.6%) for extended thrice-weekly regimen; and 0.4% (95% CI 0.1-0.9%) for extended daily regimen. Further studies are required to reduce the risk of relapse under program settings.