Intellectual disability (ID) is a measurable phenotypic consequence of genetic and environmental factors. In this study, we prospectively assessed the diagnostic yield of genomic tools (molecular karyotyping, multi-gene panel and exome sequencing) in a cohort of 337 ID subjects as a first-tier test and compared it with a standard clinical evaluation performed in parallel. Standard clinical evaluation suggested a diagnosis in 16% of cases (54/337) but only 70% of these (38/54) were subsequently confirmed. On the other hand, the genomic approach revealed a likely diagnosis in 58% (n=196). These included copy number variants in 14% (n=54, 15% are novel), and point mutations revealed by multi-gene panel and exome sequencing in the remaining 43% (1% were found to have Fragile-X). The identified point mutations were mostly recessive (n=117, 81%), consistent with the high consanguinity of the study cohort, but also X-linked (n=8, 6%) and de novo dominant (n=19, 13%). When applied directly on all cases with negative molecular karyotyping, the diagnostic yield of exome sequencing was 60% (77/129). Exome sequencing also identified likely pathogenic variants in three novel candidate genes (DENND5A, NEMF and DNHD1) each of which harbored independent homozygous mutations in patients with overlapping phenotypes. In addition, exome sequencing revealed de novo and recessive variants in 32 genes (MAMDC2, TUBAL3, CPNE6, KLHL24, USP2, PIP5K1A, UBE4A, TP53TG5, ATOH1, C16ORF90, SLC39A14, TRERF1, RGL1, CDH11, SYDE2, HIRA, FEZF2, PROCA1, PIANP, PLK2, QRFPR, AP3B2, NUDT2, UFC1, BTN3A2, TADA1, ARFGEF3, FAM160B1, ZMYM5, SLC45A1, ARHGAP33 and CAPS2), which we highlight as potential candidates on the basis of several lines of evidence, and one of these genes (SLC39A14) was biallelically inactivated in a potentially treatable form of hypermanganesemia and neurodegeneration. Finally, likely causal variants in previously published candidate genes were identified (ASTN1, HELZ, THOC6, WDR45B, ADRA2B and CLIP1), thus supporting their involvement in ID pathogenesis. Our results expand the morbid genome of ID and support the adoption of genomics as a first-tier test for individuals with ID.

BackgroundIn psychiatric inpatients, administration of pro re nata benzodiazepines is a common practice. Benzodiazepine use is associated with potential complications of risk of abuse, cognitive impairment, and falls. An interest in accreditation is growing rapidly among many countries to enhance the quality of health care services. We aimed to investigate whether hospital accreditation drives improvements for administered pro re nata benzodiazepines in psychiatric inpatients.MethodsThe study reviewed medical records of consecutive hospital admissions for pre- and post-accreditation comparisons of PRN benzodiazepine medications in two acute mental health wards at a teaching general hospital. Data obtained from the 12-month-post-accreditation period (July 2011–June 2012) were compared with those from the 12-month-pre-accreditation period (July 2009–June 2010). The adoption of accreditation standards occurred over a 12-month period in the middle of the study (July 2010–June 2011). Compiled information included demographics, diagnosis, assessment, and LOS. All identified charts were reviewed; there were no exclusion criteria. Patients were not contacted.ResultsThere was a statistically significant (P < 0.002) reduction of approximately 22% in the number of administered PRN benzodiazepines. Post-accreditation, the average number of PRN benzodiazepines administrations per patient, was 4.83 ± 2.1 compared to 6.19 ± 3.4 pre-accreditation. There was no significant difference between the two genders. The highest average quantity of PRN benzodiazepines administered was during the time interval of 18–24 h.ConclusionAccreditation may have a positive impact on the process of administering PRN benzodiazepine medications in psychiatric inpatients.

BackgroundAn interest in hospital accreditation is growing rapidly among many countries to enhance the quality of health care services. The literature showed a positive association between accreditation and some processes of health care. One of the main factors that influence bed availability is the length of hospital stay (LOS), which is considered as an important indicator of the quality of inpatient psychiatric hospitalization. We aimed to investigate whether hospital accreditation drives improvements for the length of stay in psychiatric inpatients.MethodsThe study reviewed medical records of consecutive hospital admissions for pre- and post-accreditation comparisons of LOS in two acute mental health wards at a teaching general hospital in Riyadh, Saudi Arabia. Data obtained from the 12-month-post-accreditation period (July 2011 to June 2012) were compared with those from the 12-month-pre-accreditation period (July 2009 to June 2010). The adoption of accreditation program occurred over a 12-month period in the middle of the study (July 2010 to June 2011). Compiled information included demographics, diagnosis, assessment, and LOS. All identified charts were reviewed; there were no exclusion criteria. Patients were not contacted.ResultsPost-accreditation, the mean (SD) length of stay was 35.3 ± 18.5 days and the range was 3–113 days. Whereas in the pre-accreditation period the mean (SD) length of stay was 41.1 ± 29.5 days and the range was 1–167 days. The difference was statistically significant (P = 0.026).ConclusionAccreditation reduces excess LOS and contributes to improving the quality of psychiatric inpatient care and access to psychiatric beds.