Perceived stress in HIV-infected individuals: Phsyiological and psychological correlates

The purpose of this study was to determine the correlation of perceived stress with selected physiological and psychological factors in an HIV-infected, predominantly African American population and to assess the multivariable effects on perceived stress. The variables that correlated significantly with perceived stress were entered into a backward stepwise regression model. Pearson’s r analysis showed significant correlations between perceived stress and state and trait anxiety, depression, HIV-related symptoms, sleep quality, daytime sleepiness and fatigue. State and trait anxiety, depression and fatigue retained significance (p\u3c0.1) in the final regression model. These factors explained approximately 80% of the variance in perceived stress. The significant interactions of multiple physiological and psychological correlates suggest that perceived stress is a complex outcome with a multifactorial etiology. Further, the model suggests that psychological factors may contribute to perceived stress in this population more than physiological factors such as HIV-related symptomatology or stage of disease

HIV/AIDS peer counselors\u27 perspectives on intervention delivery formats

This research sought to elicit HIV/AIDS peer counselors’ perspectives about delivery formats for a counseling intervention. Peer counselors identified personal contact as the major advantage of the face-to-face format. Personal contact afforded counselors better opportunities to understand and assess clients’ physical, emotional, and environmental status and allowed them to connect with peers in more concrete and personal ways. Being physically present was also a very direct and effective way to role model for other HIVpositive women. Peer counselors identified a number of inherent barriers and challenges to telephone interventions but also recognized potential logistic and personal advantages. Despite the overwhelming preference for the faceto- face intervention format, counselors acknowledged the potential for conducting successful peer counseling over the telephone. A significant finding was that the value and meaning of HIV/AIDS peer counselors’ work transcended the limitations of either delivery format

Old dog begging for new tricks: current practices and future directions in the diagnosis of delayed antimicrobial hypersensitivity

Purpose of review: Antimicrobials are a leading cause of severe T cell-mediated adverse drug reactions (ADRs). The purpose of this review is to address the current understanding of antimicrobial cross-reactivity and the ready availability of and evidence for in-vitro, in-vivo, and ex-vivo diagnostics for T cell-mediated ADRs. Recent findings: Recent literature has evaluated the efficacy of traditional antibiotic allergy management, including patch testing, skin prick testing, intradermal testing, and oral challenge. Although patch and intradermal testing are specific for the diagnosis of immune-mediated ADRs, they suffer from drug-specific limitations in sensitivity. The use of ex-vivo diagnostics, especially enzyme-linked immunospot, has been highlighted as a promising new approach to assigning causality. Knowledge of true rates of antimicrobial cross-reactivity aids empirical antibiotic choice in the setting of previous immune-mediated ADRs. Summary: In an era of increasing antimicrobial resistance and use of broad-spectrum antimicrobial therapy, ensuring patients are assigned the correct ‘allergy label’ is essential. Re-exposure to implicated antimicrobials, especially in the setting of severe adverse cutaneous reaction, is associated with significant morbidity and mortality. The process through which an antibiotic label gets assigned, acted on and maintained is still imprecise. Predicting T cell-mediated ADRs via personalized approaches, including human leukocyte antigen-typing, may pave future pathways to safer antimicrobial prescribing guidelines

HLAs: Key regulators of T-cell-mediated drug hypersensitivity

Adverse drug reactions (ADR) can be broadly categorised as either on-target or off-target. On-target ADRs arise as a direct consequence of the pharmacological properties of the drug and are therefore predictable and dose-dependent. On-target ADRs comprise the majority (>80%) of ADRs, relate to the drug's interaction with its known pharmacological target and are a result of a complex interplay of genetic and ecologic factors. In contrast, off-target ADRs, including immune-mediated ADRs (IM-ADRs), are due to unintended pharmacological interactions such as inadvertent ligation of host cell receptors or non-pharmacological interactions mediated through an adaptive immune response. IM-ADRs can be classified according to the primary immune cell involved and include B-cell-mediated (Gell-Coombs type I-III reactions) and T-cell-mediated (Gell-Coombs type IV or delayed hypersensitivity) reactions. IM-ADRs mediated by T cells are associated with phenotypically distinct clinical diagnoses and can vary from a mild delayed rash to a life-threatening cutaneous, systemic or organ disease, such as Stephen Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms and drug-induced liver disease. T-cell-mediated ADRs are strongly linked to the carriage of particular HLA risk alleles which are in the case of abacavir hypersensitivity and HLA-B*57:01 has led to translation into the clinic as a routine screening test. In this review, we will discuss the immunogenetics and pathogenesis of IM-ADRs and how HLA associations inform both pre-drug screening strategies and mechanistic understanding

Use of multicriteria decision analysis for assessing the benefit and risk of over-the-counter analgesics

Objectives To test the ability of a multicriteria decision analysis (MCDA) model to incorporate disparate data sources of varying quality along with clinical judgement in a benefit–risk assessment of six well-known pain-relief drugs. Methods Six over-the-counter (OTC) analgesics were evaluated against three favourable effects and eight unfavourable effects by seven experts who specialise in the relief of pain, two in a 2-day facilitated workshop whose input data and judgements were later peer-reviewed by five additional experts. Key findings Ibuprofen salts and solubilised emerged with the best benefit–risk profile, followed by naproxen, ibuprofen acid, diclofenac, paracetamol and aspirin. Conclusions Multicriteria decision analysis enabled participants to evaluate the OTC analgesics against a range of favourable and unfavourable effects in a group setting that enabled all issues to be openly aired and debated. The model was easily communicated and understood by the peer reviewers, so the model should be comprehensible to physicians, pharmacists and other health professionals

Review of Dental Impression Materials

Major advances in impression materials and their application have occurred during the last decade, with greater emphasis being placed on rubber impression materials than on dental compound, zinc oxide-eugenol, and agar and alginate. Of particular interest has been the effect of disinfection solutions on the qualities of impressions and the biocompatibility of impression materials. The principal advance in hydrocolloids has been the introduction of the agar/alginate impression technique, which has simplified the procedure and improved the quality of gypsum dies compared with those prepared in alginate impressions. The tear strength of some alginates has been improved, and some have been formulated so that the powder is dustless, thus reducing the health hazard as a result of patient inhalation of dust during the dispensing process. Polyether and silicone impression materials have been modified so that the working time, viscosity, and flexibility of the polyethers have been improved and, with the introduction of addition silicones, their accuracy has become exceptional. Although the early addition silicones liberated hydrogen after setting, thus delaying the pouring of models and dies, most addition silicones have been improved so that no hydrogen is released and dies can be poured immediately. The introduction of automatic mixing systems for addition silicones has simplified their manipulation, has reduced the number of voids in impressions, and has reduced the amount of material wasted. The incorporation of surfactants into addition silicones has made them hydrophilic, with wetting properties similar to those of polyethers, and has made pouring bubble-free gypsum dies easier. This review is confined to published and unpublished information of the past decade. It will also suggest trends that should be anticipated in the near future based on this information. The review will not present information developed before 1975, which is available in several textbooks on dental materials by Craig (1985a), Phillips (1982), and Williams and Cunningham (1979).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66604/2/10.1177_08959374880020012001.pd

HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms

Background Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS) which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy which impacts future treatment choices. Variations in human leukocyte antigen (HLA) class I in particular have been associated with serious T-cell mediated adverse drug reactions which has led to preventive screening strategies for some drugs. Objective To determine if variation in the HLA region is associated with vancomycin-induced DRESS. Methods Probable vancomycin DRESS cases were matched 1:2 with tolerant controls based on sex, race, and age using BioVU, Vanderbilt’s deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by conditional logistic regression. An extended sample set from BioVU was utilized to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele. Results Twenty-three individuals met inclusion criteria for vancomycin-associated DRESS. 19/23 (82.6%) cases carried HLA-A*32:01 compared to 0/46 (0%) of the matched vancomycin tolerant controls (p=1x10-8) and 6.3% of the BioVU population (n=54,249) (p=2x10-16). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01 positive group indicated that 19.2% developed DRESS and did so within four weeks. Conclusions HLA-A*32:01 is strongly associated with vancomycin DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug and preserve future treatment options with co-administered antibiotics

Use of multicriteria decision analysis for assessing the benefit and risk of over-the-counter analgesics

Objectives : To test the ability of a multi-criteria decision analysis (MCDA) model to incorporate disparate data sources of varying quality along with clinical judgement in a benefit-risk assessment of six well-known pain-relief drugs. Methods: Six OTC analgesics were evaluated against three favourable effects and eight unfavourable effects by seven experts who specialise in the relief of pain, two in a two-day facilitated workshop whose input data and judgements were later peer-reviewed by five additional experts. Key findings: Ibuprofen salts & solubilised emerged with the best benefit-risk profile, followed by naproxen, ibuprofen acid, diclofenac, paracetamol, and aspirin. Conclusions: MCDA enabled participants to evaluate the OTC analgesics against a range of favourable and unfavourable effects in a group setting that enabled all issues to be openly aired and debated. The model was easily communicated and understood by the peer reviewers, so the model should be comprehensible to physicians, pharmacists, and other health professional

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results