ABSTRACT
BACKGROUND: Autistic spectrum disorders (ASD) are severe neurodevelopmental alterations characterised by deficits in social communication and repetitive and restricted behaviours. About a third of patients receive pharmacological treatment for comorbid symptoms. However, 30-50% do not respond adequately and/or present severe and long-lasting side effects. METHODS: Genetic variants in CYP1A2, CYP2C19, CYP2D6 and SLC6A4 were investigated in N = 42 ASD sufferers resistant to pharmacological treatment. Clinical recommendations based on their pharmacogenetic profiles were provided within 24-48 h of receiving a biological sample. RESULTS: A total of 39 participants (93%) improved after the pharmacogenetic intervention according to their CGI scores (difference in basal-final scores: 2.26, SD 1.55) and 37 participants (88%) according to their CGAS scores (average improvement of 20.29, SD 11.85). Twenty-three of them (55%) achieved symptom stability (CGI ≤ 3 and CGAS improvement ≥ 20 points), requiring less frequent visits to their clinicians and hospital stays. Furthermore, the clinical improvement was higher than that observed in a control group (N = 62) with no pharmacogenetic interventions, in which 66% responded to treatment (difference in CGI scores: -0.87, SD 9.4, p = 1 × 10-5; difference in CGAS scores: 6.59, SD 7.76, p = 5 × 10-8). CONCLUSIONS: The implementation of pharmacogenetic interventions has the potential to significantly improve the clinical outcomes in severe comorbid ASD populations with drug treatment resistance and poor prognosis.
ABSTRACT
PURPOSE: To determine whether Repetitive Extragenic Palindromic PCR (rep-PCR) genotyping can improve the diagnosis of coagulase-negative staphylococcal (CoNS) orthopaedic infections in comparison to phenotyping. METHODS: Prospective study comparing the results of phenotypic/genotypic (rep-PCR) testing in patients with suspected CoNS infection. Each strain was analysed using both methods. Strains identified as identical in ≥2 samples were considered as pathogenic. RESULTS: 255 CoNS strains from 52 surgical episodes were included. Infection was diagnosed by phenotyping in 38(73%) cases and by genotyping in 40(77%). The Kappa index was 0.59. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for phenotyping (vs. rep-PCR) were: 88%, 75%, 92%, and 64%. 5/14(36%) of cases not considered as true infections by phenotyping were diagnosed as infections with genotyping. In a subgroup of 203 strains from 41 surgical procedures with orthopaedic implants, the kappa index was 0.68. Sensitivity, Specificity, PPV, and NPV for phenotyping were: 93%, 73%, 90% and 80%. Again, 2/10 episodes in which CoNS were considered non-infective by phenotyping were diagnosed as infected by genotyping. CONCLUSIONS: Rep-PCR genotyping can identify identical CoNS strains that differ in their phenotype and should be used as a complementary technique. One-third of infected cases may be misdiagnosed without genotypic analysis.
