, Melissa Yssel, MB ChB, FC Path(SA) Chem 139, and Wendy M. Zakowicz, BS 79 Purpose: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. Methods: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25-30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration.

This study suggests that there is considerable delay before appropriate therapy in RLS. A large number have EDS and insomnia among others, is the commonest presenting feature. Phenotypic heterogeneity may cause diagnostic difficulty.

BackgroundNarcolepsy is a chronic primary sleep disorder, characterized by excessive daytime sleepiness and sleep dysfunction with or without cataplexy. Narcolepsy is uncommon, with a low prevalence rate which makes it difficult to diagnose definitively without a complex series of tests and a detailed history. The aim of this study was to review patients referred to a tertiary sleep centre who had been labelled with a diagnosis of narcolepsy prior to referral in order to assess if the diagnosis was accurate, and if not, to determine the cause of diagnostic misattribution.MethodsAll patients seen at a sleep centre from 2007–2013 (n = 551) who underwent detailed objective testing including an MSLT PSG, as well as wearing an actigraphy watch and completing a sleep diary for 2 weeks, were assessed for a pre-referral and final diagnosis of narcolepsy.ResultsOf the 41 directly referred patients with a diagnostic label of narcolepsy, 19 (46 %) were subsequently confirmed to have narcolepsy on objective testing and assessment by a sleep physician using ICSD-2 criteria.ConclusionsThe diagnosis of narcolepsy was incorrectly attributed to almost 50 % of patients labelled with a diagnosis of narcolepsy who were referred for further opinion by a variety of specialists and generalists. Accurate diagnosis of narcolepsy is critical for many reasons, such as the impact it has on quality of life, driving, employment, insurance and pregnancy in women as well as medication management.

IntroductionJuvenile-onset systemic lupus erythematous (JSLE) is a rare multisystem autoimmune disorder. In 2012, the Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) initiative developed recommendations for the diagnosis/management of JSLE, lupus nephritis (LN) and childhood-onset anti-phospholipid syndrome (APS). These recommendations were based upon available evidence informing international expert consensus meetings.ObjectiveTo review new evidence published since 2012 relating to the management of JSLE, LN and APS in children, since the original literature searches informing the SHARE recommendations were performed.MethodMEDLINE, EMBASE and CINAHL were systematically searched for relevant literature (2012-2021) using the following criteria: (1) English language studies; (2) original research studies regarding management of JSLE, LN, APS in children; (3) adult studies with 3 or more patients <18-years old, or where the lower limit of age range ≤16-years and the mean/median age is ≤30-years; (4) randomized controlled trials (RCTs), cohort studies, case control studies, observational studies, case-series with >3 patients. Three reviewers independently screened all titles/abstracts against predefined inclusion/exclusion criteria. All relevant manuscripts were reviewed independently by at least two reviewers. Data extraction, assessment of the level of evidence/methodological quality of the manuscripts was undertaken in-line with the original SHARE processes. Specific PUBMED literature searches were also performed to identify new evidence relating to each existing SHARE treatment recommendation.ResultsSix publications met the inclusion/exclusion criteria for JSLE: three RCTs, one feasibility trial, one case series. For LN, 16 publications met the inclusion/exclusion criteria: eight randomized trials, three open label prospective clinical trials, five observational/cohort studies. For APS, no publications met the inclusion criteria. The study with the highest evidence was an RCT comparing belimumab vs. placebo, including 93 JSLE patients. Whilst the primary-endpoint was not met, a significantly higher proportion of belimumab-treated patients met the PRINTO/ACR cSLE response to therapy criteria. New evidence specifically addressing each SHARE recommendation remains limited.ConclusionSince the original SHARE literature searches, undertaken >10-years ago, the main advance in JSLE treatment evidence relates to belimumab. Additional studies are urgently needed to test new/existing agents, and assess their long-term safety profile in JSLE, to facilitate evidence-based practice.

BACKGROUNDMultifetal gestation is responsible for a disproportionate amount of overall perinatal mortality and morbidity. Multifetal pregnancies have increased due to fertility treatment for assisted reproductive techniques.

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Narcolepsy with cataplexy is a chronic sleep disorder characterised by excessive daytime sleepiness, and is associated with sleep paralysis, hypnagogic hallucinations, disrupted nocturnal sleep, and sleep attacks. It is a relatively uncommon condition, with a prevalence of 0.01-0.05%, and can be difficult to diagnose with significant long term impact on an individual's health. Current guidelines suggest that narcolepsy with cataplexy can be diagnosed on history alone, without the need for further investigations. Objectives To determine the rate of misdiagnosis of narcolepsy with cataplexy in a general neurology clinic. Methods Case notes were reviewed for patients referred to a new sub-specialty neurology sleep clinic with a potential diagnosis of narcolepsy with cataplexy over a 2 year period. Results Of 10 patients referred who had been diagnosed with narcolepsy and prescribed pharmacological treatment, other diagnoses were established in 5 patients following specialist sleep assessment and where appropriate, objective testing. These diagnoses include obstructive sleep apnoea, COPD, Circadian phase reversal, delayed sleep phase syndrome and behavioural sleep problems. Conclusion The use of history alone to establish a diagnosis of narcolepsy with cataplexy is insufficient in a general neurology clinic. We argue that objective testing, including actigraphy, polysomnography and multiple sleep latency testing in conjunction with a detailed history is the most effective method of establishing a correct diagnosis.

BACKGROUNDCervical cancer is the most common cancer in Indian females. Globally, it stands second in female malignancies. Study of cervical cytology by Papanicolaou smear is a modality making earlier diagnosis of pathological cell changes, making it possible to reduce morbidity and mortality associated with cervical cancer.