Validation of MCADD newborn screening

Medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid β‐oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut‐off policies, false‐positive and negative rates. In a retrospective case‐control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false‐positives, and 34 patients. c.985A>G was more frequently identified in the study group and false‐positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false‐positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false‐negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C₈) and three secondary markers in the initial and follow‐up sample. The new approach allowed a reduction of false‐positives (by defining high cut‐offs: 1.4 μmol/l for C₈; 7 for C₈/C₁₂) and false‐negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42→88%) and to target NBS to MCADD‐subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS‐based NBS.     

Comparative study of immunochromatographic sets for rapid diagnosis of syphilis

The paper presents the results of the comparative study of 9 commercial kits made in foreign countries for the rapid diagnosis of syphilis, performed at the Central Research Institute of Dermatovenereological Infections, Russian Agency for Health Care, within the framework of the International Sexual Transmitted Diseases Diagnostic Initiative Program under the aegis of the World Health Organization during 2002-2005. The above diagnostic kits were assessed in the context of the availability of and statement simplicity in the instruction for use; the technological complexity in performing a study procedure and the simplicity in interpreting the findings; the necessity of employing additional laboratory equipment. The parameters of the clinical efficiency (sensitivity and specificity) were studied; a passive sensitized red blood cell agglutination test was used as a reference method. The comprehensive study showed that the "Determine Syphilis TP test system ("Abbot Lab", USA) yielded the best results with a total of 10 scores at 100% sensitivity and 100% sensitivity) while the "Bioline Syphilis anti-TP Test Card" ("Pacific Biotech Co.", Thailand) provided a total of 9 scores at 96% sensitivity and 98% specificity.     

The Influence of Two Different Invitation Letters on Chlamydia Testing Participation: Randomized Controlled Trial

Background

In the Netherlands, screening for chlamydia (the most prevalent sexually transmitted infection worldwide) is a relatively simple and free procedure. Via an invitation letter sent by the public health services (PHS), people are asked to visit a website to request a test kit. They can then do a chlamydia test at home, send it anonymously to a laboratory, and, within two weeks, they can review their test results online and be treated by their general practitioner or the PHS. Unfortunately, the participation rates are low and the process is believed to be not (cost-) effective.

Objective

The objective of this study was to assess whether the low participation rate of screening for chlamydia at home, via an invitation letter asking to visit a website and request a test kit, could be improved by optimizing the invitation letter through systematically applied behavior change theories and evidence.

Methods

The original letter and a revised letter were randomly sent out to 13,551 citizens, 16 to 29 years old, in a Dutch municipality. Using behavior change theories, the revised letter sought to increase motivation to conduct chlamydia screening tests. The revised letter was tailored to beliefs that were found in earlier studies: risk perception, advantages and disadvantages (attitude), moral norm, social influence, and response- and self-efficacy. Revisions to the new letter also sought to avoid possible unwanted resistance caused when people feel pressured, and included prompts to trigger the desired behavior.

Results

No significant differences in test package requests were found between the two letters. There were also no differences between the original and revised letters in the rates of returned tests (11.80%, 581/4922 vs 11.07%, 549/4961) or positive test results (4.8%, 23/484 vs 4.1%, 19/460). It is evident that the new letter did not improve participation compared to the original letter.

Conclusions

It is clear that the approach of inviting the target population through a letter does not lead to higher participation rates for chlamydia screening. Other approaches have to be developed and pilot tested.     

高脂血症性急性胰腺炎的特点与临床治疗研究

目的探讨高脂血症性急性胰腺炎(HAP)和非高脂血症性急性胰腺炎的特点及临床救治效果。方法回顾分析我院在2013年1月至2013年12月收治的99例急性胰腺炎的临床资料,根据患者有无高脂血症将其分为HAP组(高脂血症患者)和对照组(无高脂血症的AP患者);患者均接受标准化临床治疗,比较2组患者病情、血浆生化指标、治疗转归、住院时间与费用、复发等情况。结果 HAP组重度胰腺炎比例(13.6%)明显高于对照组(7.8%),HAP组血糖和尿酸均显著高于对照组,其中HAP组血糖平均值达到对照组的171%,而HAP组的血淀粉酶却仅为对照组的44.5%;HAP组1年内的复发率(13.6%)显著高对于照组(2.6%),P0.01差异有统计学意义。结论高血脂对急性胰腺炎的病情、表现和治疗结果均有明显影响,应引起高度重视。     

儿童癌症幸存者成年后的慢性疾病

由于治疗方法的进步,近80%的儿童和青少年癌症患者能够长期生存。在美国,约有270000例儿童癌症的幸存者,即每640名20至39岁成年人中就有一名幸存者。大量的幸存者有利于儿童癌症治疗后长期健康结果的研究。现在可以明确的是,化疗和放疗所致的儿童各器官系统损害在临床上可能潜伏多年。为了全面了解治疗儿童癌症而继发的健康问题,重要的是衡量三项长期结果:健康状况、死亡率和患病率。这三项中,关于前两项已有相当好的研究报道。在一项对20227例癌症5年生存者的回顾性分析中,Mertens等发现以下原因导致的超额死亡率具有统计学意义:继发癌症(…