Systematic review of drug therapy for chorea in NXK2-1-related disorders: Efficacy and safety evidence from case studies and series.

BACKGROUND: The NKX2-1-related disorders (NKX2-1-RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European Reference Network of Rare Neurological Disorders funded by the European Commission conducted a systematic review to assess drug treatment of chorea in NKX2-1-RD, aiming to provide clinical recommendations for its management. METHODS: A systematic pairwise review using various databases, including MEDLINE, Embase, Cochrane, CINAHL, and PsycInfo, was conducted. The review included patients diagnosed with chorea and NKX2-1-RD genetic diagnosis, drug therapy as intervention, no comparator, and outcomes of chorea improvement and adverse events. The methodological quality of the studies was assessed, and the study protocol was registered in PROSPERO. RESULTS: Of the 1417 studies examined, 28 studies met the selection criteria, consisting of 68 patients. The studies reported 22 different treatments for chorea, including carbidopa/levodopa, tetrabenazine, clonazepam, methylphenidate, carbamazepine, topiramate, trihexyphenidyl, haloperidol, propranolol, risperidone, and valproate. No clinical improvements were observed with carbidopa/levodopa, tetrabenazine, or clonazepam, and various adverse effects were reported. However, most patients treated with methylphenidate experienced improvements in chorea and reported only a few negative effects. The quality of evidence was determined to be low. CONCLUSIONS: The management of chorea in individuals with NKX2-1-RD presents significant heterogeneity and lack of clarity. While the available evidence suggests that methylphenidate may be effective in improving chorea symptoms, the findings should be interpreted with caution due to the limitations of the studies reviewed. Nonetheless, more rigorous and comprehensive studies are necessary to provide sufficient evidence for clinical recommendations.

ImmunoCAP ISAC in food allergy diagnosis: a systematic review of diagnostic test accuracy.

OBJECTIVE: To assess the diagnostic test accuracy of the component-resolved diagnosis device ImmunoCAP ISAC, compared with oral food challenge. DESIGN: Systematic review reported according to the PRISMA-DTA recommendations. DATA SOURCES: Medline, Embase and Cochrane Library databases were searched from inception to May 2019 and updated in March 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included diagnostic test accuracy studies comparing ISAC component results as the index test with oral food challenge as the reference test, in people of any age suspected of IgE mediated food allergy to milk, egg, peanut, shrimp, hake, apple, peach, kiwi, melon, walnut, hazelnut, wheat or pineapple. Risk of bias was evaluated using the QUADAS-2 tool. RESULTS: We screened 799 titles and included 11 studies - seven prospective and two retrospective cohort studies, two case-control studies. Included studies evaluated IgE to Gald1 (three studies, 300 participants, 140 with egg allergy), Bosd5 (three studies, 242 participants, 146 with milk allergy) and Arah1 or 2 (seven studies, 546 participants, 346 with peanut allergy). No studies were identified for other ISAC components. Risk of bias was high or unclear mainly due to inadequate blinding. Applicability was of high or unclear concern due to unclear thresholds, inappropriate exclusions and variable populations. Gald1 sensitivity ranged from 58 to 84%, specificity 87%-97%. Bosd5 sensitivity 24%-40%, specificity 94%-95%. Arah1 sensitivity 45%-91%, specificity 41%-93%. Arah2 sensitivity 70%-94%, specificity 75%-95%. CONCLUSIONS: Diagnostic test accuracy information for ISAC components was only available for milk, egg and peanut. Specificity is generally higher than sensitivity, which contrasts with the performance of skin prick and standard specific IgE tests for diagnosing food allergy. Higher quality information is needed to determine the clinical utility of ISAC for food allergy diagnosis. SYSTEMATIC REVIEW REGISTRATION: Not registered.

Evaluation of the safety, efficacy, effectiveness and cost-effectiveness of implantable Holter for prolonged monitoring in patients with previous stroke: a systematic review.

Background: Atrial fibrillation (AF), which is associated with cryptogenic stroke, is the most common sustained arrhythmia in the general population. Because AF is asymptomatic and intermittent, its detection rate increases with the duration of monitoring. The objective of this study is to review the available evidence on the safety, efficacy, effectiveness and cost-effectiveness of AF diagnosis by prolonged monitoring with an implantable Holter monitor in adult patients with idiopathic or cryptogenic stroke of suspected cardioembolic origin, compared to conventional monitoring. Methods: Two independent reviewers performed a systematic review of the literature, identifying relevant studies through a structured search of Medline (Ovid), EMBASE, Web of Science and Cochrane Library and the databases of national and international health technology assessment agencies. The quality of the included studies was assessed with AGREE-II, AMSTAR-2 and CHEC. GRADE criteria were used to summarise the evidence. Results: Four of the 211 papers identified were included: 1 clinical practice guideline, 2 systematic reviews, and 1 economic evaluation. The quality of the evidence reviewed was low. An implantable Holter monitor might be more effective in detecting AF than conventional monitoring. Serious adverse events were similar in both groups. The economic evaluation suggests that the technology is cost-effective. Conclusions: The available evidence suggests the diagnostic superiority of the implantable Holter monitor over the traditional Holter monitor. Due to the low quality of the evidence, further and higher quality studies on these technologies are needed before solid conclusions can be drawn.