Analysis of ASPM in an ethnically diverse cohort of 400 patient samples: perspectives of the molecular diagnostic laboratory

Primary Autosomal Recessive Microcephaly (MCPH) is characterized by congenital microcephaly usually without additional clinical findings. The most common gene implicated in MCPH is ASPM and a large percentage of mutations described have been homozygous and in consanguineous families primarily of East Asian and Middle Eastern origin. ASPM sequencing was performed on 400 patients between the years 2009 and 2012. Seventy of the patient samples were also analyzed for copy number changes in the ASPM gene. Forty protein truncating mutations, including 29 novel mutations, were identified in 39 patients with MCPH. Approximately one third of patients were compound heterozygotes, indicative of non‐consanguinity in these patients. In addition, 46 non‐synonymous variants were identified and interpreted as variants of uncertain significance. No deletion/duplication in ASPM was identified in the patients analyzed. A wide ethnic distribution was observed, including the first reported patients with ASPM‐related MCPH of Hispanic descent. Clinical information was collected for 26 of the ASPM‐positive patients and 41 of the ASPM‐negative patients. As more individuals are identified with MCPH, we anticipate that we will continue to identify ASPM mutation‐positive patients from all ethnic origins supporting the occurrence of this genetic condition beyond that of consanguineous families of certain ethnic populations.     

Active tuberculosis in inflammatory bowel disease patients under treatment from an endemic area in Latin America

BACKGROUNDThere has been an increase in cases of inflammatory bowel disease (IBD) in recent years. There is also greater access and availability of immunosuppressive and biological agents, which increase the risk of opportunistic infection despite improving the quality of life and promoting mucosal healing. Tuberculosis (TB) remains a public health problem, and it has a high incidence in several countries. Therefore, knowledge of the risk of developing TB in patients with IBD is important.AIMTo evaluate the risk of active TB in patients with IBD under treatment from an endemic area in Latin America.METHODSA standard questionnaire included demographic variables, clinical aspects of IBD disease, history of active TB during treatment, active TB characteristics and evolution, initial screening and results and time from the start of anti-tumor necrosis factor alpha (TNFα) to TB development.RESULTSAzathioprine, anti-TNFα and the combination of these two drugs were associated with a higher risk of active TB incidence. The TNFα blockers increased the relative risk of developing active TB compared to other treatments. All four multivariable models showed that the use of TNFα blockers alone or in combination with azathioprine was an important risk factor for the incidence of active TB. After adjustment for sex, age, type of IBD and latent TB, anti-TNFα with azathioprine increased the relative risk to 17.8 times more than conventional treatment. Late TB, which was diagnosed 3 mo after the start of anti-TNFα, was the most frequent.CONCLUSIONTreatment with anti-TNFα increased the risk of active TB in IBD patients from an endemic area in Latin America. This risk was increased when anti-TNFα was combined with azathioprine. The time from the beginning of the treatment to the active TB diagnosis suggests a new TB infection.     

Impact of Vendor Computerized Physician Order Entry in Community Hospitals

BACKGROUND

It is uncertain if computerized physician order entry (CPOE) systems are effective at reducing adverse drug event (ADE) rates in community hospitals, where mainly vendor-developed applications are used.

OBJECTIVE

To evaluate the impact of vendor CPOE systems on the frequency of ADEs.

DESIGN AND PATIENTS

Prospective before-and-after study conducted from January 2005 to September 2010 at five Massachusetts community hospitals. Participants were adults admitted during the study period. A total of 2,000 charts were reviewed for orders, medication lists, laboratory reports, admission histories, notes, discharge summaries, and flow sheets.

MAIN MEASURES

The primary outcome measure was the rate of preventable ADEs. Rates of potential ADEs and overall ADEs were secondary outcomes.

KEY RESULTS

The rate of preventable ADEs decreased following implementation (10.6/100 vs. 7.0/100 admissions; p?=?0.007) with a similar effect observed at each site. However, the associated decrease in preventable ADEs was balanced against an increase in potential ADEs (44.4/100 vs. 57.5/100 admissions; p?p?=?0.03), which was driven by non-preventable events (4.0/100 vs. 11.7/100 admissions; p?CONCLUSIONS Adoption of vendor CPOE systems was associated with a decrease in the preventable ADE rate by a third, although the rates of potential ADEs and overall ADEs increased. Our findings support the use of vendor CPOE systems as a means to reduce drug-related injury and harm. The potential ADE rate could be reduced by making refinements to the vendor applications and their associated decision support.