Drug usage guidelines, Part 2: Analysis of program outcome

The effect of integrating a Drug Usage Guidelines (DUG) program with a hospital formulary system was analyzed. Significant changes were observed in both the number of requests submitted to the P & T Committee and the number of drugs added to the formulary after implementation of the DUG program. Failure to follow the DUG submission protocol, particularly with respect to the requirement for supportive clinical data from the primary literature, led to delayed consideration and eventual withdrawal of several highly promoted drug products. The initial involvement of physicians in the planning and implementation of the DUG program has been an important factor in the continued success of the program.     

Strengthening the formulary system by implementing a drug usage guidelines program

The development and implementation of a Drug Usage Guidelines (DUG) program in a 1,200-bed, federal teaching hospital are described. The program was designed to promote effective formulary control through established procedures for the review and evaluation of drugs submitted to the Pharmacy and Therapeutics (P & T) Committee for addition to the formulary. The procedures required the submission of the DUG and an oral presentation to the Committee prior to any final vote on the request. Anticipated potential benefits of the DUG program are to: (1) stimulate rational drug therapy, (2) provide reliable drug information to the professional staff in a usable format, (3) promote a thorough evaluation of therapeutic agents before approving for formulary inclusion, and (4) provide physician-generated guidelines for use as criteria in drug utilization review audits.     

Using Intraindividual Variability to Detect Malingering in Cognitive Performance

The utility of measures for detecting malingering was evaluated using a simulation design in which half the participants were encouraged to do their best and half were asked to feign head injury. Particular attention was focused on the utility of repeated assessment (intraindividual variability) in discriminating the groups. Participants were tested on three occasions on measures commonly used to detect malingering including a specific symptom validity test (SVT). The results indicated that multiple measures of malingering obtained in single assessment (occasion one) discriminated the groups effectively. In addition, however, intraindividual variability in performance, particularly of indicators from the SVT, provided unique information beyond level of performance. The results suggest that response inconsistency across testing sessions may be a clinically useful measure for the detection of malingering.     

Survey of US Correctional Institutions for Routine HCV Testing

To ascertain HCV testing practices among US prisons and jails, we conducted a survey study in 2012, consisting of medical directors of all US state prisons and 40 of the largest US jails, that demonstrated a minority of US prisons and jails conduct routine HCV testing. Routine voluntary HCV testing in correctional facilities is urgently needed to increase diagnosis, enable risk-reduction counseling and preventive health care, and facilitate evaluation for antiviral treatment.There are an estimated 4 to 7 million persons in the United States infected with HCV.1,2 Morbidity and mortality from HCV are increasing and in 2007, death from HCV exceeded that from HIV infection for the first time.3,4 Persons who inject drugs are at increased risk for HCV infection and for being incarcerated. Multiple studies have demonstrated high HCV prevalence rates among persons behind bars.5–7 In 2010, the Institute of Medicine (IOM) called for the development of comprehensive viral hepatitis services for incarcerated populations including offering testing, hepatitis B virus vaccination, education, and medical management in partnership with community providers.8Despite the Centers for Disease Control and Prevention (CDC) releasing HCV testing recommendations in 1998 and subsequent recommendations for prevention and control of viral hepatitis within correctional facilities in 2003,9-10 recent studies estimate that 50% of persons infected with HCV are unaware of their infection,11–14 thus reducing opportunities for risk-reduction counseling and treatment. In response to this, the CDC updated HCV testing recommendations for the US general population in 2012, which added at least 1-time testing among persons born between 1945 and 1965, now commonly referred to as the “birth cohort” screening recommendations.15 However, the 2012 recommendations did not provide a specific testing recommendation for incarcerated individuals. Given the increased prevalence of HCV among criminal justice populations, we conducted a survey among US prisons and jails to gain a better understanding of current HCV testing practices within correctional facilities.     

Mutations in SYNGAP1 Cause Intellectual Disability,Autism, and a Specific Form of Epilepsy by Inducing Haploinsufficiency

De novo mutations in SYNGAP1, which codes for a RAS/RAP GTP‐activating protein, cause nonsyndromic intellectual disability (NSID). All disease‐causing point mutations identified until now in SYNGAP1 are truncating, raising the possibility of an association between this type of mutations and NSID. Here, we report the identification of the first pathogenic missense mutations (c.1084T>C [p.W362R], c.1685C>T [p.P562L]) and three novel truncating mutations (c.283dupC [p.H95PfsX5], c.2212_2213del [p.S738X], and (c.2184del [p.N729TfsX31]) in SYNGAP1 in patients with NSID. A subset of these patients also showed ataxia, autism, and a specific form of generalized epilepsy that can be refractory to treatment. All of these mutations occurred de novo, except c.283dupC, which was inherited from a father who is a mosaic. Biolistic transfection of wild‐type SYNGAP1 in pyramidal cells from cortical organotypic cultures significantly reduced activity‐dependent phosphorylated extracellular signal‐regulated kinase (pERK) levels. In contrast, constructs expressing p.W362R, p.P562L, or the previously described p.R579X had no significant effect on pERK levels. These experiments suggest that the de novo missense mutations, p.R579X, and possibly all the other truncating mutations in SYNGAP1 result in a loss of its function. Moreover, our study confirms the involvement of SYNGAP1 in autism while providing novel insight into the epileptic manifestations associated with its disruption.     

Diagnosis and management of nocardiosis after bone marrow stem cell transplantation in adults: Lack of lymphocyte recovery as a major contributing factor

Hematopoietic cell transplantation (HCT) is a curative treatment for hematological malignancies. This therapeutic approach is associated with a profound immune deficiency and an increased rate of opportunistic infections. Nocardiosis is a rare bacterial infection occurring mainly in patients with deficient cell-mediated immunity, such as AIDS patients or transplant recipients. Diagnosis of nocardiosis can be challenging, as signs and symptoms are non-specific. Routine prophylaxis with trimethoprin/sulfamethoxazole (TMP/SMZ) does not prevent the risk of infection. Between May 2001 and December 2009, five cases of nocardiosis were diagnosed from the 366 allogeneic HCT recipients in our centre. Four patients developed a disseminated nocardiosis within the first year after HCT. The fifth patient presented a localized cutaneous nocardiosis. In disseminated cases, median total CD4+ T-cells were below 100 cells/μL. Naive CD4+ CD45RA+/RO− T-cells were almost undetectable. CD8⁺ T-cells and NK cells were below the normal range and CD19+ B-cell reconstitution was completely deficient. In a localized case, we observed a lack of naive thymic emigrants CD4+ CD45RA+/RO− T-cells.