Preimplantation genetic testing for Marfan syndrome

Marfan syndrome (MFS) is an autosomal dominant disease thataffects the skeletal, ocular and cardiovascular systems. Defectsin the gene that codes for fibrillin (FBN-1) are responsiblefor MFS. Here we report the world‘s first use of preimplantationgenetic testing (PGT) to achieve a clinical pregnancy and livebirth of a baby free of a Marfan mutation. One or two blastomeresfrom each embryo were tested for a CA repeat within the FBN-1gene. The prospective mother is homozygous for the CA repeat(2/2) and has two normal copies of the FBN-1 gene, while theprospective father is heterozygous for the CA repeat (1/2),and is affected with the Marfan syndrome. In the father’sfamily, allele 2 segregates with the mutated FBN-1 gene. ForPGT, any embryo diagnosed as heterozygous for the CA repeat(1/2) would be presumed to have inherited normal FBN-1 genesfrom the father and the mother and be unaffected. One in-vitrofertilization (IVF) cycle yielded 12 embryos for preimplantationtesting; six of the embryos were heterozygous for the CA repeat(1/2) and presumed to be free of the Marfan mutation. Five ofthe six embryos were subsequently transferred into the uterus.The fetus was tested by chorionic villus sampling and foundto be free of the Marfan mutation by the same linkage analysis,had a normal fetal echocardiogram, and was normal at birth. fibrillin-1/linkage analysis/Marfan syndrome/polymerase chain reaction (PCR)/preimplantation genetic testing (PGT)     

MHC2 Medical and Economic Outcomes of Noncompliance with Dilantin in Adult Medicaid Epileptics

Major depressive disorder (MDD) is one of the most prevalent mental disorders in the US with social costs up-wards of $43 billion. The Agency for Health Care Policy and Research has disseminated diagnosis and management guidelines for MDD in primary care.
OBJECTIVE: Our aim was to develop a simulation model to evaluate clinical and economic consequences of following AHCPR treatment recommendations. A secondary objective was to create a tool that could be used by health plan decision-makers to assess the value of alternative treatments for MDD.
METHODS: A discrete state simulation model was developed to evaluate primary care management of adults with MDD following the AHCPR guidelines. The perspective of the model was that of the health plan; the time horizon was 1 year from the initiation of pharmacotherapy. Uncertainty was evaluated using Monte Carlo simulation techniques. Endpoints included clinical remission, hospitalization for MDD, or psychiatric referral for treatment failure. Efficacy and safety data were drawn from published randomized, nonrandomized, and synthesized studies, and cost data were derived from modal reimbursement rates from a large managed care organization in Washington state.
RESULTS: The results of the base case simulation demonstrated that initial treatment of MDD with serotonin reuptake inhibitors provided better clinical outcomes at similar costs when compared to tricyclic antidepressants.
CONCLUSION: Simulation models of treatment guidelines are an important and useful extension of outcomes research because they can simultaneously account for costs and effectiveness not otherwise available from a single published study. Further, models such as this can prove useful to health plan decision-makers interested in the ex ante evaluations of individual antidepresant agents for formulary decisions.     

垂体催乳素瘤的诊断和治疗指南

2.药物选择:多巴胺激动剂(dopaminergic agonist,DA),如溴隐亭(bromociptine,BRC)和卡麦角林(cabergoline,CAB),为高催乳素血症和PRL腺瘤患者的首选治疗.药物能使绝大多数病人PRL水平正常和肿瘤体积显著缩小,大量的经验证实药物适用于各种大小的肿瘤.     

Radioiodine therapy and Graves' ophthalmopathy

Appearances of and increases in Graves' ophthalmopathy (GO) have been reported after treatment of patients with hyperthyroidism with radioiodine. We sought to determine the rates of appearance or increase in manifestations of GO in American patients treated with radioiodine for hyperthyroidism. METHODS: The study population, which consisted of 76 patients (range, 10.6-72 y), included 61 women and individuals of diverse ethnicity. The patients were followed for 1 y after radioiodine treatment. The clinical activity score (CAS) included 10 items of ophthalmic change that were evaluated at 2 and 6 mo and at 1 y; appearance of a new item scored 1 point. We evaluated interactions of 6 covariates-prolonged hyperthyroidism, prolonged hypothyroidism, smoking, treatment with an antithyroid drug (ATD), and serum levels of thyroid-stimulating immunoglobulin (TSI) and of high free T3 (FT3)--with the numbers of patients with 2 or more CAS points and with exophthalmometer readings increased by at least 2 mm. In addition, patients completed a scored quality-of-life (QOL) questionnaire at baseline and at 1 y to assess eye symptoms. RESULTS: The mean CAS points for all patients at 2 mo was 0.63 and was not significantly different at 1 y. In 9 of 10 CAS items, there were few patients affected at 1 y and for the most part there were fewer patients affected than at baseline. However, exophthalmometer readings increased in 39% of patients by a mean of 2.6 mm. Individual patients frequently exhibited increases and decreases in item manifestations. Exophthalmometer readings decreased by 2 mm or less in 13%. Of the covariates, only hyperthyroidism prolonged by at least 2.5 mo was significantly associated with 2 or more CAS points at 1 y; no covariate was significantly associated with the development of increased exophthalmometer readings. Eye symptoms recorded in the QOL were insignificantly improved over the year; symptoms did not correlate with CAS points or with exophthalmometer readings. CONCLUSION: After radioiodine treatment, no substantial change was seen in manifestations of CAS items except for a modest increase in exophthalmometer readings in 39% of patients. Manifestations of CAS items frequently appeared and disappeared. Prolonged hyperthyroidism is best avoided. Ocular symptoms were insignificantly fewer at 1 y after radioiodine therapy. The observed changes do not warrant prophylactic treatment of patients with steroids.     

垂体催乳素瘤的诊断和治疗指南

2005年6月,在San Diego举行了第九届国际垂体研究大会.大会邀请在催乳素瘤治疗领域被认可的国际知名专家,包括内分泌专家和神经外科专家,特定召开专业委员会,对催乳素瘤的诊断和治疗进行探讨,并形成该指南.指南发表在2006年8月的临床内分泌学杂志上(Clinical Endocrinology, 2006, 65: 265-273).     

Volumetric self-sampling of cervicovaginal fluid to determine potential fertility: a multicentre pre-effectiveness study of the Rovumeter

The aim of this study was to assess how effectively the Rovumeter, designed for the volumetric self-sampling of cervicovaginal fluid (CVF), can be used to locate the minimum period of potential fertility (PPF) during ovulatory cycles. A multicentre, prospective study was undertaken of volunteers (attending natural family planning clinics) over three consecutive, apparently normal, menstrual cycles. All women collected daily samples of early morning urine and CVF and recorded the volumes (to the nearest 1.0 and 0.1 ml respectively). The concentrations of oestrone glucuronide (EG), luteinizing hormone (LH) and pregnanediol glucuronide (PG) were measured in all samples of early morning urine by immunoassay. A preliminary data set was used to optimize an algorithm to detect the start and end of potential fertility from the volumes of CVF. The end-points used were the normality of each menstrual cycle from its length, the length of luteal phase, and concentrations of EG, LH and PG, the start and end days of potential fertility from CVF volumes, and the minimum PPF, which was defined as the day of the LH peak minus 3 to day plus 2 inclusive. Overall, 72 women (median age 30 years, range 24-38) were recruited from three centres (23 from Birmingham, 24 from Milan, 25 from Santiago) and contributed data from 235 menstrual cycles (median length 28 days, range 23-44). The urinary LH peak was identified in 228 cycles (97%; median time, day 15 from day 1 of last menses, with range day 10 to day 35). The use of the Rovumeter gave start and end signals of potential fertility during 138 cycles (59%). The median length of the derived PPF was 8 days (range 4-18). The signals covered the defined, minimum PPF in 113 cycles [i.e. 50% of those with an LH peak; range 28% (Milan) to 62% (Birmingham)]. Overall 16/72 women (22%) had successful tests over three consecutive menstrual cycles [range 2/24 (8%; Milan) to 8/23 (35%; Birmingham)]. We conclude that signals from daily changes in the volume of CVF as determined by the use of the Rovumeter consistently locate the minimum period of potential fertility in only a small proportion of women.      

Using the theory of planned behaviour to develop an assessment of attitudes and beliefs towards prosthetic use in amputees

Purpose: To develop a questionnaire based on the theory of planned behaviour (TPB) to predict prosthetic use.

Method: In part one, 31 amputees over 50 years of age with peripheral arterial disease completed attitude items containing 27 bipolar adjectives and open-ended questions on behavioural, normative and control beliefs relating to using the prosthesis. Academic, clinical and patient experts (n = 12) identified bipolar adjectives with best face validity. In part two, 15 amputees completed three behavioural format questions relating to prosthetic use and were asked to indicate the easiest to answer.

Results: Following the completion of the attitude items by the amputees and the expert panel review, 5 items remained (Cronbach's alpha = 0.87) with corrected item-total correlations ranging from 0.43 to 0.83. Modal behavioural beliefs concerned mobility (46.5%), independence (25.6%) and participation restrictions (16.3%), normative beliefs concerned family (33.3%), NHS staff (31.7%), friends (19.1%) and other patients (15.9%) and control beliefs concerned stairs (21.1%), slippery/rough surfaces (28.9%), disabled facilities (54.8%) and people helping (22.6%). In relation to part 2, an exact numerical report of hours and days of prosthetic use was found easiest to answer (73%).

Conclusions: Based on this qualitative and quantitative development work, the questionnaire contains five attitude items, six behavioural, eight normative, eight control belief items and two self-report questions of the behaviour.