Fourth consensus of the International Society for Premenstrual Disorders (ISPMD): auditable standards for diagnosis and management of premenstrual disorder.

Whilst professional bodies such as the Royal College and the American College of Obstetricians and Gynecologists have well-established standards for audit of management for most gynaecology disorders, such standards for premenstrual disorders (PMDs) have yet to be developed. The International Society of Premenstrual Disorders (ISPMD) has already published three consensus papers on PMDs covering areas that include definition, classification/quantification, clinical trial design and management (American College Obstetricians and Gynecologists 2011; Brown et al. in Cochrane Database Syst Rev 2:CD001396, 2009; Dickerson et al. in Am Fam Physician 67(8):1743-1752, 2003). In this fourth consensus of ISPMD, we aim to create a set of auditable standards for the clinical management of PMDs. All members of the original ISPMD consensus group were invited to submit one or more auditable standards to be eligible in the inclusion of the consensus. Ninety-five percent of members (18/19) responded with at least one auditable standard. A total of 66 auditable standards were received, which were returned to all group members who then ranked the standards in order of priority, before the results were collated. Proposed standards related to the diagnosis of PMDs identified the importance of obtaining an accurate history, that a symptom diary should be kept for 2 months prior to diagnosis and that symptom reporting demonstrates symptoms in the premenstrual phase of the menstrual cycle and relieved by menstruation. Regarding treatment, the most important standards were the use of selective serotonin reuptake inhibitors (SSRIs) as a first line treatment, an evidence-based approach to treatment and that SSRI side effects are properly explained to patients. A set of comprehensive standards to be used in the diagnosis and treatment of PMD has been established, for which PMD management can be audited against for standardised and improved care.

What kind of doctor would you like me to be?

BACKGROUND: The modern medical school curriculum highlights the importance of good communication skills, although some clinicians still remain sceptical about the reduction of core science teaching in favour of these so-called softer skills. Previous studies into these topics are few and contradictory, with a heavy dependence on methodology and geographical source. METHODS: A semi-structured interview was conducted using the question 'I am about to qualify as a doctor in less than a year's time. As a patient, what advice would you give me? What kind of doctor would you like me to be if you came to me with an illness?' Responses were recorded anonymously on paper, verbatim. The responses were grouped into four broad classifications: personal qualities; communication skills; knowledge and intelligence; and manual skills. RESULTS: Data were collected from 51 patients. In total 118 attributes were identified and categorised. DISCUSSION: This education evaluation indicates that the patients we talked with in the UK counties of Shropshire and Staffordshire overwhelmingly sought doctors with good personal qualities and communication skills. Of the attributes recorded, 92 per cent were related to such qualities, with only 8 per cent emphasising knowledge and intelligence, and with no comments on manual skills. The results support the current emphasis in UK medical schools on communication skills and professionalism, and the development of personal qualities through the promotion of humanities teaching. The modern medical school curriculum highlights the importance of good communication skills.

Validation and implementation of array comparative genomic hybridisation as a first line test in place of postnatal karyotyping for genome imbalance.

BACKGROUND: Several studies have demonstrated that array comparative genomic hybridisation (CGH) for genome-wide imbalance provides a substantial increase in diagnostic yield for patients traditionally referred for karyotyping by G-banded chromosome analysis. The purpose of this study was to demonstrate the feasibility of and strategies for, the use of array CGH in place of karyotyping for genome imbalance, and to report on the results of the implementation of this approach. RESULTS: Following a validation period, an oligoarray platform was chosen. In order to minimise costs and increase efficiency, a patient/patient hybridisation strategy was used, and analysis criteria were set to optimise detection of pathogenic imbalance. A customised database application with direct links to a number of online resources was developed to allow efficient management and tracking of patient samples and facilitate interpretation of results. Following introduction into our routine diagnostic service for patients with suspected genome imbalance, array CGH as a follow-on test for patients with normal karyotypes (n = 1245) and as a first-line test (n = 1169) gave imbalance detection rates of 26% and 22% respectively (excluding common, benign variants). At least 89% of the abnormalities detected by first line testing would not have been detected by standard karyotype analysis. The average reporting time for first-line tests was 25 days from receipt of sample. CONCLUSIONS: Array CGH can be used in a diagnostic service setting in place of G-banded chromosome analysis, providing a more comprehensive and objective test for patients with suspected genome imbalance. The increase in consumable costs can be minimised by employing appropriate hybridisation strategies; the use of robotics and a customised database application to process multiple samples reduces staffing costs and streamlines analysis, interpretation and reporting of results. Array CGH provides a substantially higher diagnostic yield than G-banded chromosome analysis, thereby alleviating the burden of further clinical investigations.

An update on huperzine A as a treatment for Alzheimer's disease.

Huperzine A is a natural cholinesterase inhibitor derived from the Chinese herb Huperzia serrata. There is evidence that huperzine A may compare favorably in symptomatic efficacy to cholinesterase inhibitors in use. In addition, huperzine A has antioxidant and neuroprotective properties that suggest that it may be useful as a disease-modifying treatment for Alzheimer's disease (AD). The drug is available as a nutriceutical in the US. However, there have been no published controlled clinical trials outside China assessing its toxicity and efficacy. This paper reviews the development of huperzine A as a treatment for AD, including the Phase II trial now under way in the US.

ADCS Prevention Instrument Project: the Mail-In Cognitive Function Screening Instrument (MCFSI).

In future research on the prevention of Alzheimer Disease (AD), a large simple prevention trial might test a safe intervention (eg, vitamins) in a very large population (eg, 10,000 subjects), powered to detect a modest treatment effect size. In a large, simple design, regular assessments must be very low cost, for example, handled by mail. The Mail-In Cognitive Function Screening Instrument (MCFSI) was developed for the Alzheimer's Disease Cooperative Study Prevention Instrument Project to evaluate whether a brief mail-in screening tool can be used as a specific and sensitive trigger for a diagnostic evaluation in the course of a prevention trial. The MCFSI consists of 2 similar sets of 14 questions mailed separately to the subject and the study partner, who are asked to complete them independently. The questions are derived from a standard clinical assessment of dementia; they ask about decline in function over the last year. We are currently evaluating the utility of the instrument in 640 subjects over the course of the "simulated" AD prevention trial. Analysis of baseline data showed significant differences in mean MCFSI scores between sex and ethnic groups (for subjects), age groups (for partners), and Clinical Dementia Rating global score groups (both subject and partner). In this nondemented population, both subject's and partner's MCFSI responses were related to cognitive performance. There was no significant association between MCFSI score for either subjects or partners and apolipoprotein E genotype. The MCFSI captures information related to cognitive and functional status in nondemented elderly individuals; the Alzheimer's Disease Cooperative Study Prevention Instrument Project will determine whether this brief, mail-in questionnaire is useful as a trigger for diagnostic evaluation in an AD primary prevention trial.

Complete discrepancy between abnormal fetal karyotypes predicted by QF-PCR rapid testing and karyotyped cultured cells in a first-trimester CVS.

A chorion villus sample (CVS) biopsied at 11 weeks' gestation for raised nuchal translucency, revealed monosomy X (presumptive 45,X karyotype) by QF-PCR for rapid aneuploidy testing for chromosomes 13, 18, 21, X and Y. Long-term culture gave the karyotype: 47,XY,+ 21[66]/49,XYY,+ 21,+ 21 [22]. This discrepancy prompted redigestion of the combined residual villus fragments from the original QF-PCR assay. The repeat QF-PCR assay identified the presence of trisomy 21 and a Y chromosome consistent with a 47,XY,+ 21 karyotype. A double non-disjunction event early in embryogenesis in a 47,XY,+ 21 conceptus with subsequent cell lineage compartmentalisation of the three observed cell lines (45,X; 47,XY,+ 21 and 49,XYY,+ 21,+ 21) would account for these results. This is the first reported case to describe complete discrepancy at diagnosis between abnormal karyotypes detected by QF-PCR rapid aneuploidy testing and a cultured karyotype in the same CVS.

VNS and depression: current status and future directions.

Vagus nerve stimulation (VNS) is an established anticonvulsant therapy in treatment-resistant patients with epilepsy. The known anatomical projections of the vagus nerve to many brain regions that have been implicated in mood disorders suggest that VNS may also have useful antidepressant effects. There has been growing interest in the potential application of VNS in the nonpharmacological management of treatment-resistant depression. Results from an open-label study, in which 59 subjects with treatment-resistant depression were treated for 10 weeks with VNS therapy, reported a 31% response rate. In a recent controlled double-blind trial of VNS and depression, short-term treatment for 10 weeks failed to demonstrate statistical improvement over sham treatment. Results from the long-term phase of this trial may be more significant, however published data are awaited.

Inflammatory processes and Alzheimer's disease.

The inflammatory hypothesis of Alzheimer's disease, which states that anti-inflammatory drugs could have beneficial effects on the pathophysiology of Alzheimer's disease, has been extensively investigated in clinical, epidemiological and basic research studies over the last 20 years. However, despite much hope, the hypothesis remains unproven. Although the results from the first small clinical trial with an anti-inflammatory agent in Alzheimer's disease appeared promising, subsequent trials with a variety of anti-inflammatory agents have failed to show beneficial effects. There are many potential reasons for this including drug selection, drug dose, timing and duration of treatment. This article reviews evidence in support of the inflammatory hypothesis in Alzheimer's disease, as well as the progress of clinical trials using specific anti-inflammatory treatment regimens. It is concluded that such treatments should not be recommended, although additional investigation is warranted.