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Purpose: The approach and results for identifying and characterizing preventable adverse drug events (pADEs) that are key targets for pharmacist medication therapy management (MTM) are summarized., Methods: This study was part of a larger effort aimed at developing an electronic health record-based prediction model (the complexity score, or C-score) that ranks hospitalized patients according to their risk for pADEs. An environmental scan of published epidemiologic pADE studies and national patient safety priority areas was conducted. The final list of candidate pADEs was then disseminated to ASHP members and a national technical expert panel (TEP) to evaluate the importance, prevalence, severity, preventability, and measurability of these pADEs. Polychoric correlation tests were performed to evaluate and quantify associations between importance and any of the constructs' mean rankings for each individual pADE., Results: The environmental scan yielded a total of 21 candidate pADEs, including drug-induced acute kidney injury, falls, respiratory depression, altered mental status, hemorrhage, hepatic failure, hypoglycemia, seizures, hypotension and bradycardia, ileus, blood dyscrasias, severe electrolyte imbalances, prolonged hyperglycemia, uncontrolled hypertension, uncontrolled arrhythmia, stress ulcers, hospital-acquired infections, uncontrolled hospital-acquired or community-acquired infection, uncontrolled pain, and venous thromboembolism. The survey confirmed all pADEs were important. Ranking of overall importance was mainly driven by perceived pADE severity and, to a lesser extent, by preventability and prevalence ratings., Conclusion: A literature review and survey of ASHP and TEP members were used to compile a list of important hospital-acquired pADEs for incorporation into a model for prioritizing patients for MTM services., (Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Introduction: Intracavernosal injection (ICI) therapy is widely used for the treatment of erectile dysfunction (ED). Its use in practice is largely empirical and has not been validated with evidence-based approaches., Aim: To compare two strategies for ICI, specifically a risk-based approach and an empiric-based approach, and assess the efficacy, patient satisfaction, and complication rates of the two treatment approaches., Methods: After obtaining approval from the institutional review board, a prospective database of patients enrolled in the ICI program at the Johns Hopkins Hospital (Baltimore, MD, USA) from May 2012 through May 2014 was amassed. Demographic information, treatment outcomes, and subjective patient evaluations of sexual function (International Index of Erectile Function erectile function domain [IIEF-EF], Quality of Erection Questionnaire [QEQ], Sexual Quality of Life [SQoL], and Erectile Dysfunction Inventory of Treatment Satisfaction [EDITS]) were obtained at baseline and at 3 and 6 months. Two approaches were compared. Group 1 received empiric ICI treatment initially with prostaglandin E 1 (PGE1) 10 μg irrespective of ED etiology or severity. After initial dosing with PGE1 in the clinic, adjustments were made to titrate or change formulations pending on patient results. Group 2 received a risk-based approach, in which an algorithm that factored in ED etiology and number of ED risk factors was used for a bimix (papaverine 30 mg/mL, phentolamine 1 mg/mL), a low-dose trimix (papaverine 30 mg/mL, phentolamine 1 mg/mL, PGE1 10 μg/mL), or a high-dose trimix (papaverine 30 mg/mL, phentolamine 2 mg/mL, PGE1 40 μg/mL). Dose titration was permitted in the two groups. Statistical analysis was carried out using t-test and χ 2 analysis., Main Outcome Measures: The study design was powered for a non-inferiority comparison of the two approaches, in which the primary end point was a 15-point difference on the EDITS score or a 20% difference in the IIEF-EF score., Results: One hundred seventy-five patients were enrolled (57 in group 1, 118 in group 2) with 3- and 6-month follow-up at 57% and 35%, respectively, and similar between groups. Baseline patient characteristics and sexual function questionnaire responses were similar between groups 1 and 2, although group 1 reported higher-quality erections at baseline (QEQ score = 14.3 vs 7.3, P = .05) and had a smaller proportion of patients with prostatectomy (54.4% vs 74.6%, P = .02). In the two groups, QEQ score (mean = 10.78 vs 56.76, P < .05), SQoL score (mean = 38.41 vs 50.25, P < .05), and IIEF-EF score (mean = 7.51 vs 18.48, P < .05) improved with treatment. However, at 3 and 6 months, there were no statistically significant differences in responses for IIEF, QEQ, SQoL, or EDITS scores and no difference in failure or medication switch rates between groups. There were no significant differences in complication rates, although at 3 months group 2 reported a higher incidence of priapism and pain (23% vs 7.4%, P = .08)., Conclusion: Empiric and risk-based strategies for ICI therapy resulted in significant improvements across multiple domains of sexual function. Complication rates, satisfaction, and efficacy overall were similar between the two approaches. Clinicians can be reassured that no one approach to ICI therapy for ED management appears inferior to another., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pediatric low-grade gliomas (PLGGs), the most frequent pediatric brain tumor, comprise a heterogeneous group of diseases. Recent genomic analyses suggest that these tumors are mostly driven by mitogene-activated protein kinase (MAPK) pathway alterations. However, little is known about the molecular characteristics inherent to their clinical and histological heterogeneity., Methods: We performed gene expression profiling on 151 paraffin-embedded PLGGs from different locations, ages, and histologies. Using unsupervised and supervised analyses, we compared molecular features with age, location, histology, and BRAF genomic status. We compared molecular differences with normal pediatric brain expression profiles to observe whether those patterns were mirrored in normal brain., Results: Unsupervised clustering distinguished 3 molecular groups that correlated with location in the brain and histological subtype. "Not otherwise specified" (NOS) tumors did not constitute a unified class. Supratentorial pilocytic astrocytomas (PAs) were significantly enriched with genes involved in pathways related to inflammatory activity compared with infratentorial tumors. Differences based on tumor location were not mirrored in location-dependent differences in expression within normal brain tissue. We identified significant differences between supratentorial PAs and diffuse astrocytomas as well as between supratentorial PAs and dysembryoplastic neuroepithelial tumors but not between supratentorial PAs and gangliogliomas. Similar expression patterns were observed between childhood and adolescent PAs. We identified differences between BRAF-duplicated and V600E-mutated tumors but not between primary and recurrent PLGGs., Conclusion: Expression profiling of PLGGs reveals significant differences associated with tumor location, histology, and BRAF genomic status. Supratentorial PAs, in particular, are enriched in inflammatory pathways that appear to be tumor-related., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Wells' syndrome is a multifaceted dermatosis with a wide morphological spectrum, ranging from characteristic cellulitis-like erythema and wheals to an unusual presentation of vesicles and bullae. We describe a patient in whom Wells' syndrome presented as an insect-bite-like eruption and was associated with underlying mantle-cell lymphoma. We recommend meticulous investigation of patients diagnosed with Wells' syndrome manifesting as an insect-bite-like eruption.

A literature review was conducted to identify the drug classes, types of errors, and types of adverse outcomes related to preventable adverse drug events (pADEs). Studies were identified by keyword search of MEDLINE and International Pharmaceutical Abstracts and by a manual search. The search was limited to peer-reviewed literature reporting pADEs in hospitalized patients and the frequencies of at least one pADE characteristic. The frequencies of pADEs and their characteristics were summarized using median and range. Ten studies published between 1994 and 2001 were included in the review. The reported median frequency of pADEs was 1.8% (range, 1.3-7.8%), and the median preventability rate of ADEs in the hospitals was 35.2% (range, 18.7-73.2%). Cardiovascular drugs were implicated for 17.9% of pADEs (range, 4.3-28.1%). Most pADEs occurred in the prescribing stage of the medication-use process and were dose related. Inappropriate prescribing decisions and patient monitoring were the most frequently identified causes of pADEs. The most common adverse outcomes were allergic reactions, hepatic or renal problems, cardiovascular problems, hematologic problems and bleeding, and central nervous system problems. Frequently reported examples of pADEs included antihypertensive overdose associated with bradycardia or hypotension, antiinfectives prescribed despite a history of allergy, warfarin overdose and inappropriate monitoring resulting in hemorrhage, and opioid overdose or underdose associated with respiratory depression or poor pain control, respectively. Despite the heterogeneity of pADEs, the results of this literature review suggest that a few types of drugs, errors, and adverse outcomes constitute a substantial proportion of pADEs. Targeting these high-priority areas could significantly reduce the overall frequency of pADEs.

Variable region gene family 3 (V(H)3) is the predominant immunoglobulin (Ig) gene family used in human antibodies to pneumococcal capsular polysaccharide (PPS). This study examined whether highly active antiretroviral therapy (HAART) restores the ability of human immunodeficiency virus (HIV)-infected individuals to generate a V(H)3-positive response to PPS. The IgM, IgG, and V(H)3 (represented by antibodies expressing the determinant recognized by the monoclonal antibody D12) responses to PPS were determined for first-time recipients of a 23-valent PPS vaccine, both receiving and not receiving HAART, and second-time vaccine recipients receiving HAART. The results showed that only the individuals receiving HAART manifested a V(H)3-(D12)-positive response to PPS, despite a similar IgG response in each group. There was also a negative correlation between HIV load and PPS response for the groups receiving HAART. These findings suggest that HAART may influence qualitative aspects of the PPS response by restoring expression of certain V(H)3 genes used in the normal PPS response.

Two peptides, based on the sequences of the complementarity-determining regions (CDR) 1 and 3 of a pathogenic murine monoclonal anti-DNA autoatibody that bears the 16/6 idiotype (Id), were shown to either prevent or treat an already established systemic lupus erythematosus (SLE) in two murine models of lupus. Two additional peptides based on the human monoclonal anti-DNA, 16/6 Id were synthesized. This study was undertaken in order to investigate the ability of the CDR-based peptides to immunomodulate SLE-associated responses of peripheral blood lymphocytes (PBL) of SLE patients. PBL of 24 of the 62 SLE patients tested proliferated in vitro following stimulation with the human 16/6 Id. Peptides based on the CDRs of both the human and murine anti-DNA autoantibodies inhibited efficiently and specifically the 16/6 Id-induced proliferation and IL-2 production. The latter inhibitions correlated with an up-regulated production (by 2.5-3.5-fold) of the immunosuppressive cytokine, TGF-beta. Overall, the results of our study demonstrate that the CDR-based peptides are capable of down-regulating in vitro autoreactive T cell responses of PBL of SLE patients. Thus, these peptides are potential candidates for a novel specific treatment of SLE patients.

The ability of a hospital's adverse drug reaction (ADR) database to identify common and repeated patterns of preventable adverse drug events (ADEs) was analyzed. ADR reports collected from 1994 through 2000 were extracted from a teaching hospital's ADR database. Reports were assessed concurrently in accordance with seven previously published explicit criteria for preventability. Only cases considered clinically significant were included in this analysis. Events that occurred in the ambulatory care setting were excluded. Preventable ADEs were categorized by drug or drug class, type of medication error, and the subsequent adverse outcome. Novel in this analysis was the linking of these three descriptors. Of the 2571 ADR reports assessed, 415 ADEs were deemed preventable. Of the preventable ADEs, 98 were not analyzed because they occurred in the ambulatory care setting, leaving 317 preventable ADEs in 275 inpatients (mean age +/- S.D., 48.5 +/- 23.9 years) for analysis. Although 93 drugs were associated with these ADEs, only 10 drugs accounted for more than 60% of the events. Analysis and categorization by type of error and outcome suggested that three high-priority preventable ADEs accounted for 50% of all reports: (1) overdoses of anticoagulants or insufficient monitoring and adjustments (according to laboratory test values) were associated with hemorrhagic events, (2) overdosing or failure to adjust for drug-drug interactions of opiate agonists was associated with somnolence and respiratory depression, and (3) inappropriate dosing or insufficient monitoring of insulins was associated with hypoglycemia. Analysis of a hospital ADR database identified prevalent and preventable clinically significant ADEs.

groEL and dnaK are the most highly conserved protein-coding genes known. Most groEL operons and several dnaK and dnaJ operons contain a highly conserved inverted repeat (IR) sequence in their regulatory region. So far, this IR has been found only as part of the groE, dnaK and dnaJ operons and genes. In most cases, the IR is part of the operon transcript, and is involved in the regulation of expression at both the DNA and mRNA levels. A detailed analysis of groE and dnaK operons indicates that the organization of the groE operons is highly conserved. They contain only the groES and groEL genes and always in the same order. In contrast, the organization of the dnaK operons has changed during evolution: genes have been added and deleted from it, and the gene order within the operon is variable.

The development and validation of a behavioral pharmaceutical care scale (BPCS) is described. The BPCS items were constructed by conducting an extensive review of the literature on pharmaceutical care and a focus group meeting. To validate the instrument, data were collected from 617 community pharmacists in Florida. Reliability coefficients for the BPCS domains were > 0.70, and the content validity index value for the whole instrument was 0.79. Evidence supporting trait validity of the BPCS was provided by using confirmatory factor analysis to confirm the instrument's dimensionality. Nomologic validity was established by confirming the hypothesis that pharmacists who in a prior survey reported they intend to provide pharmaceutical care would have a significantly higher BPCS score than those who reported they do not intend to provide pharmaceutical care. The behavioral pharmaceutical care scale, developed as a tool for measuring pharmacists' efforts to provide pharmaceutical care, was found to be reliable, sensitive, and valid.

The objective of this study was to determine the effects of Methotrexate (MTX) on the development and the course of experimental murine SLE, as well as on the cytokine profile involved in the disease. SLE was induced in naive BALB/c female mice by injection of the human anti-DNA MoAb bearing a common idiotype (16/6 Id). Six weeks following immunization, when high levels of autoantibodies were demonstrated, the mice were treated with MTX (2 mg/kg once a week) for a period of 10 months. MTX treatment had no effect on 16/6 Id-induced autoantibody production. However, MTX treatment had beneficial effects on the clinical manifestations of the experimental disease (i.e. leucocyte counts, levels of protein in the urine and immune complex deposits in the kidneys). Thus, only 20% of 16/6 Id-immunized BALB/c mice that were treated with MTX had immune complex deposits in their kidneys compared with 100% of SLE-afflicted BALB/c mice that were not treated. We have observed a significant elevation in IL-1, tumour necrosis factor (TNF) and IL-10 secretion in BALB/c mice afflicted with experimental SLE. IL-2, IL-4, IL-6 and interferon-gamma (INF-gamma) levels were decreased in these mice compared with the levels detected in healthy controls. Treatment with MTX reversed the levels of all the above cytokines to normal levels observed in control mice. These studies demonstrate therapeutic effects of MTX on murine experimental SLE. The normal cytokine profile observed following treatment with MTX is suggested to play a role in the amelioration of the clinical manifestations of experimental SLE.

A 68-year-old liver transplant recipient who was being treated with FK 506 and immunosuppressive steroid therapy was admitted to our medical center because of a tonic-clonic seizure. Computed tomography of the head revealed multiple discrete cerebral abscesses, and culture of fluid drained intraoperatively yielded a dematiaceous fungus. The isolate was susceptible to amphotericin B and itraconazole but was resistant to flucytosine and fluconazole. The patient was successfully treated with a prolonged course of amphotericin B colloidal dispersion and itraconazole, as evidenced by both clinical and radiographic resolution of disease over a 2-year follow-up.

A model in which experimental SLE is induced in normal mice by the injection of a human anti-DNA MoAb expressing a common idiotype 16/6 Id has been established in our laboratory. In the present study we have attempted the induction of experimental SLE in mice with SCID by the transfer of lymphocytes obtained from mice with experimental SLE. Disease could not be induced by direct immunization of SCID mice with the 16/6 Id nor by transfusion of normal splenocytes and immunization with the 16/6 Id thereafter. In contrast, disease was induced in SCID mice which were transplanted with splenic lymphocytes obtained from SLE afflicted BALB/c mice. The disease was expressed by the presence of high titres of antibodies and glomerular immune complex deposits were present in the kidney sections of these mice. Mice that received spleen cells from donors with experimental SLE together with the 16/6 Id developed higher titres of autoantibodies and had, in addition to the immune complex deposits, glomerular histological pathology. The model of experimental SLE induction in SCID mice should help in the elucidation of the role of different cell types in the pathogenesis of SLE.

We examined the proliferative responses of T cells of patients with systemic lupus erythematosus (SLE), their first-degree relatives, and healthy donors, to a human monoclonal antibody that bears a common anti-DNA idiotype, 16/6 Id, and to a murine, 16/6 Id-specific, monoclonal antibody. Both 16/6 Id+ and 16/6 Id-specific antibodies were previously shown to be involved in the induction of experimental SLE in mice. Here we show that T cells of fewer SLE patients, as compared with healthy donors, could proliferate to both antibodies. The difference between T cell responses of patients and controls to the 16/6 was found to be significant. The proliferative responses of T cells of first degree relatives of SLE patients to the anti-16/6 Id were found to be significantly lower compared with the responses detected in healthy donors and in SLE patients. The responses of T cells of SLE relatives to the 16/6 Id were found to be lower than those of healthy donors, but this difference was not significant. The present study suggests a possible involvement of T cells, and specifically of idiotype and anti-idiotype specific T cells, in SLE.

Pityriasis rotunda (PR) has been known to affect, almost exclusively, Japanese and South African Bantu, often in association with various systemic diseases. However, the occurrence of PR in Caucasian patients is extremely rare, and has been previously described in only three reports. We hereby report a case of an apparently healthy Caucasian woman from Israel having clinical and histological features characteristic of PR. Pityriasis rotunda (PR) is a rare disorder of keratinization characterized by strikingly well demarcated, perfectly round scaly brownish patches of variable number and diameter located mainly on the trunk and extremities. The exact place of this disorder within the nosology of the cutaneous dermatoses is not yet fully established. However, most authors regard it as a special circumscribed form of acquired ichthyosis with a histological resemblance to ichthyosis vulgaris. For more than half a century following the first description of this disorder in 1906 cases reported were almost exclusively from the Far East, particularly from Japan, or in South African Negroids, with a few cases of West Indian Negroids, usually in association with various debilitating diseases. The first report of a Caucasian patient appeared in the literature in 1966 and since then there have been only two additional reports of PR in Caucasian patients.

Methotrexate (MTX) levels were studied following intravenous MTX in both serum and synovial fluid (SF) of rheumatoid arthritis patients. Two hours after injection serum MTX levels were higher than those of SF. At 24 hours SF levels of MTX exceeded those of the serum, while at 72 hours both blood and SF concentrations were undetectable. The localization of parenteral MTX in the SF may have importance in the understanding of its mechanism and site of action in rheumatoid arthritis.

Fourteen families with first degree relatives of patients with systemic lupus erythematosus (SLE) were studied for the ability of their members to respond to the synthetic polypeptide antigen (T,G)-A-L. The family members were also tested for their HLA determinants. All SLE patients tested responded to (T,G)-A-L as measured by the production of (T,G)-A-L specific T cell helper factors by their antigen activated T cells, confirming our previous findings that 100% of SLE donors responded to (T,G)-A-L in contrast to 50% responders in a control population of healthy donors. The general defect in the regulation of immune responses in SLE patients was further indicated by the demonstration that an SLE patient who is a daughter of non-responder parents to (T,G)-A-L, responded to this genetically regulated antigen. In contrast to our observations with SLE patients, the genetic regulation of the ability to respond to (T,G)-A-L was shown not to be impaired in healthy first degree family members of SLE patients and the segregation of the immune response potential in these families was as expected from an inherited dominant trait.