Pulmonary biomarkers based on alterations in protein expression after exposure to arsenic

OBJECTIVE: Environmental exposure to arsenic results in multiple adverse effects in the lung. Our objective was to identify potential pulmonary protein biomarkers in the lung-lining fluid of mice chronically exposed to low-dose As and to validate these protein changes in human populations exposed to As. METHODS: Mice were administered 10 or 50 ppb As (sodium arsenite) in their drinking water for 4 weeks. Proteins in the lung-lining fluid were identified using two-dimensional gel electrophoresis (n = 3) or multidimensional protein identification technology (MUDPIT) (n = 2) coupled with mass spectrometry. Lung-induced sputum samples were collected from 57 individuals (tap water As ranged from ~ 5 to 20 ppb). Protein levels in sputum were determined by ELISA, and As species were analyzed in first morning void urine. RESULTS: Proteins in mouse lung-lining fluid whose expression was consistently altered by As included glutathione-S-transferase (GST)-omega-1, contraspin, apolipoprotein A-I and A-IV, enolase-1, peroxiredoxin-6, and receptor for advanced glycation end products (RAGE). Validation of the putative biomarkers was carried out by evaluating As-induced alterations in RAGE in humans. Regression analysis demonstrated a significant negative correlation (p = 0.016) between sputum levels of RAGE and total urinary inorganic As, similar to results seen in our animal model. CONCLUSION: Combinations of proteomic analyses of animal models followed by specific analysis of human samples provide an unbiased determination of important, previously unidentified putative biomarkers that may be related to human disease.     

Differences in perceived risks and benefits of herbal, over-the-counter conventional, and prescribed conventional, medicines, and the implications of this for the safe and effective use of herbal products

OBJECTIVES: To investigate people's views about the efficacy and specific risks of herbal, over-the-counter (OTC) conventional, and prescribed conventional medicines, and their likelihood of taking a second (herbal or OTC conventional) product in addition to a prescribed medicine. METHODS: Experiment 1 (1 factor within-participant design); Experiment 2 (1 factor between-participant design). Convenience samples of general population were given a hypothetical scenario and required to make a number of judgements. RESULTS: People believed herbal remedies to be less effective, but less risky than OTC and prescribed conventional medicines. Herbal medicines were not seen as being safer simply because of their easier availability. Participants indicated that they would be more likely to take a herbal medicine than a conventional OTC medicine in addition to a prescribed medicine, and less likely to consult their doctor in advance. CONCLUSION: People believe that herbal medicines are natural and relatively safe and can be used with less caution. People need to be given clear information about the risks and benefits of herbal medicines if they are to use such products safely and effectively.     

The risk of breast cancer in BRCA1 and BRCA2 mutation carriers without a first‐degree relative with breast cancer

The objective of this study was to estimate the lifetime risk of breast cancer in women with a BRCA1 or BRCA2 mutation with and without at least 1 first‐degree relative with breast cancer. A total of 2835 women with a BRCA1 or BRCA2 mutation were followed. Age‐ and gene‐specific breast cancer rates were calculated. The relative risks of breast cancer for subjects with a family history of breast cancer, compared to no family history were calculated. The mean age at baseline was 41.1 years, and they were followed for a mean of 6.0 years. The estimated penetrance of breast cancer to age 80 years was 60.8% for BRCA1 and 63.1% for BRCA2. For all BRCA carriers, the penetrance of breast cancer to age 80 for those with no first‐degree relative with breast cancer was 60.4% and 63.3% for those with at least 1 first‐degree relative with breast cancer. The risk of breast cancer for BRCA carriers with no first‐degree relative with breast cancer is substantial, and as a result, clinical management for these women should be the same as those for women with an affected relative.     

Long-term effectiveness and safety of once-daily,single-entity,extended-release hydrocodone in patients of ≥75 years of age with moderate to severe nonmalignant and nonneuropathic pain

In elderly (≥75 years) individuals, age-associated physiologic changes and a higher prevalence of comorbidities, polypharmacy, and increased susceptibility to medication-induced side effects complicate pain management. Hysingla^® ER (HYD) is a once-daily, single-entity, extended-release hydrocodone formulation approved for the treatment of chronic pain that is insufficiently controlled by alternative treatments. In this post-hoc analysis of a previously reported study, the effectiveness and safety of HYD for the treatment of moderate-to-severe chronic pain among the elderly (≥75 years) for a 52-week duration was investigated. HYD dose administered during the maintenance period-remained relatively stable and provided clinically meaningful decreases in mean “pain over the last 24 h” and pain interference scores. Patients achieved pain control without additional non-study opioid use at the end of the study. Adverse events were typical of opioids. In summary, HYD provided clinically meaningful reduction of pain scores in elderly patients that were maintained over a 52-week period.     

The language and communication attributes of graphic symbol communication aids – a systematic review and narrative synthesis

Background: Symbol communication aids are used by children with little or no intelligible speech as an Augmentative and Alternative Communication strategy. Graphic symbols are used to help support understanding of language and used in symbol communication aids to support expressive communication. The decision making related to the selection of a symbol communication aid for a child is poorly understood and little is known about what language and communication attributes are considered in this selection.

Aim: To identify from the literature the language or communication attributes of graphic symbol communication aids that currently influence AAC practice.

Method and Procedure: A search strategy was developed and searches were performed on a range of electronic databases for papers published since 1970. Quality appraisal was carried out using the CCAT tool and papers rated as weak were not included in the review.

Results: Eleven studies were included in the review reporting data from 66 participants. Weaknesses were identified in most studies that would limit the validity of the results for application to practice. Included studies investigated aspects of vocabulary organization and design, the process of vocabulary selection, and the choice of the symbol system and encoding method. Two studies also evaluated innovative communication aid attributes.

Conclusions: Information from studies reported in the research literature provides a sparse source of information about symbol communication aids from which clinicians, children or family members may make informed decisions.

• Implications for Rehabilitation

• This review is the first to systematically appraise the literature to answer the question what evidence exists to inform clinical decision making in relation to the language or communication attributes of graphic symbol based communication aids? The review establishes that there is a paucity of evidence from studies and that these decisions must thus be based on other information and factors.

• The review does establish a small number of language or communication attributes of symbol communication aids, but no synthesis of the results of these studies was possible. This review thus suggests that vocabulary design and organization, symbol system and encoding method, and the choice of vocabulary selection method are attributes that clinicians may carefully review in order to inform decisions.

• Clinicians encountering symbol vocabulary packages claiming to be ‘evidence based’ should query the nature of this evidence.

• The rehabilitation research community should debate and develop appropriate research designs that will facilitate future robust studies investigating the effect of specific language or communication attributes of communication aids.

     

Retention of CPR skills learned in a traditional AHA Heartsaver course versus 30-min video self-training: a controlled randomized study

BACKGROUND: Bystander CPR improves outcomes after out of hospital cardiac arrest. The length of current 4-h classes in cardiopulmonary resuscitation (CPR) is a barrier to more widespread dissemination of CPR training and older adults in particular are underrepresented in traditional classes. Training with a brief video self-instruction (VSI) program has shown that this type of training can produce short-term skill performance at least as good as that seen with traditional American Heart Association (AHA) Heartsaver training, although it is unclear whether there is comparable skill retention. METHODS AND RESULTS: Two hundred and eight-five adults between the ages of 40 and 70 who had no CPR training within the past 5 years were assigned at random to a no-training control group, Heartsaver (HS) training, or one of three versions of brief VSI (i.e., self-trained-ST subjects). Post-training performance of CPR skills was assessed in a scenario format by human examiners and by sensored manikin at Time 1 (immediately post-training) and again at Time 2 (2 months post-training). Performance by controls was assessed only once. Significant (P<.001) decline was observed in the three measures recorded by examiners; assess responsiveness (from 72% to 60% for HS subjects and from 90% to 77% for ST subjects), call 911 (from 82% to 74% for HS subjects and from 71% to 53% for ST subjects), and overall performance (from 42% to 30% for HS subjects and from 60% to 44% for ST subjects). Significant (P<.001) decline was observed in two of three skills measured by a sensored manikin: ventilation volume (from 40% to 36% for HS subjects and from 61% to 41% for ST subjects, with a significant [P=.028] interaction) and correct hand placement (from 68% to 59% for HS subjects and from 80% to 64% for ST subjects). Heartsaver and self-trained subjects generally showed similar rates of decline. At Time 2, examiners rated trained subjects better than untrained controls in all skills except calling 911, where self-trained subjects did not differ from controls; manikin data revealed that trained subjects' performance was better than that of controls for ventilation volume, but had declined to the level of controls for both hand placement and compression depth. CONCLUSIONS: Adults between 40 and 70 years of age who participated in a CPR VSI program experienced performance decline in their CPR skills after a post-training interval of 2 months. However, this decline was no greater than that seen in subjects who took Heartsaver training. The VSI program produced retention performance at least as good as that seen with traditional training. Additional effort is needed to improve both initial performance and retention of CPR skills. CONDENSED ABSTRACT: Retention of CPR skills was compared 2 months post-training for adults between 40 and 70 years old who had taken either a traditional Heartsaver CPR course or a 22-min video self-directed training course. Although performance declines occurred in the 2-month interval, self-trained subjects generally demonstrated CPR skill retention equivalent to that of Heartsaver-trained subjects, although for both groups skill decline on some measures reached the level of untrained controls.