Exploring Antipsychotic Prescribing Behaviors for Nursing Home Residents With Dementia: A Qualitative Study

Objectives

Caution is advised when prescribing antipsychotics to people with dementia. This study explored the determinants of appropriate, evidence-based antipsychotic prescribing behaviors for nursing home residents with dementia, with a view to informing future quality improvement efforts and behavior change interventions.

Accuracy and biological variation of human serum paraoxonase 1 activity and polymorphism (Q192R) by kinetic enzyme assay

BACKGROUND: Paraoxonase 1 (PON1) phenotype is a better predictor of atherosclerosis risk than are PON1 genetic polymorphisms alone. Larger studies are required to determine the role of PON1 and there is a need for standardized PON1 assays between laboratories. METHODS: We have adapted 5 enzyme kinetic assays for high-throughput automated analysis of PON1 activity. Using different substrates and reaction conditions, we measured PON1 activity and used activity ratios to identify the PON1 Q192R genetic polymorphisms and assessed the accuracy of the genotype assignments in 79 adult study participants by comparing them with genotypes determined by AlwI restriction enzyme digestion of a 176-bp PCR amplification product from genomic DNA. Imprecision was determined using pooled serum and purified enzyme preparations. Biological variability was estimated by analysis of serial samples from 17 individuals. Variability parameters were compared with total cholesterol as a point of reference to a recognized biomarker of coronary heart disease risk. RESULTS: Salt stimulation and inhibition ratios were 97.4% and 94.7% correct in assigning Q192R genotype, respectively. Analytical imprecision (CV) was 1.0%-3.0% for phenylacetate and paraoxon substrate assays and 3.0%-8.0% for the para-nitrophenylacetate substrate assays. Combination of the 2 ratios into a double ratio resulted in 100% correct genotype classification. CONCLUSION: The described methods for measurement of PON1 activity and accurate genotype assignment are rapid and have potential to facilitate the efficient investigation of PON1 status in clinical and epidemiological studies.     

Overcoming short gaps in peripheral nerve repair: conduits and human acellular nerve allograft

Nerve conduits and acellular nerve allograft offer efficient and convenient tools for overcoming unexpected gaps during nerve repair. Both techniques offer guidance for migrating Schwann cells and axonal regeneration though utilizing very different scaffolds. The substantially greater amount of animal and clinical data published on nerve conduits is marked by wide discrepancies in results that may be partly explained by a still poorly defined critical repair gap and diameter size. The available information on acellular allografts appears more consistently positive though this tool is also hampered by a longer but also limited critical length. This article reviews the current relative literature and examines pertinent parameters for application of both acellular allograft and nerve conduits in overcoming short nerve gaps.     

Connecting patients,practitioners, and regulators in supporting positive experiences and processes of shared decision making: A progress report

This paper describes a novel approach to explore how regulators, working with patients and practitioners, may contribute to supporting person‐centred care and processes of shared decision making in implementing professional standards and reducing harms. Osteopathic patients report high levels of patient care. However, areas of consultations less likely to be rated as high included “fully understanding your concerns,” “helping you to take control,” and “making a plan of action with you,” suggestive of a paternalistic approach to care and a barrier to the effective implementation of standards. This programme explored how to support patients and practitioners to make more explicit what is important to support consultations with better communication in accordance with standards. A series of workshops took place involving approximately 80 participants, which explored and identified practitioner and patient values; these were themed to develop a common framework and tested using case studies. Aspects of what enables or presents a barrier to a positive consultation were further explored with real patient narratives, and a range of resources were subsequently developed, which may support patients and practitioners to make explicit what is important to them in a consultation. A series of approaches and tools were then developed for piloting including patient curriculum vitae; patient goal planner; patient animation to support preparation for an appointment; infographic: a patient poster or leaflet; practitioner reflective tool; and an audio recording to increase awareness and understanding of values‐based practice. In conclusion, a range of approaches may help to support patients and practitioners to make explicit what is important to them in a consultation. The next phase of our programme will use a range of methods including cluster sampling, pre‐testing and post‐testing with the Consultation and Relational Empathy (CARE) measure tool, and interviews and focus groups with users and practitioners to demonstrate impact.     

Hospital initiatives in promoting smoking cessation: a survey of Internet and hospital-based programs targeted at consumers

STUDY OBJECTIVES: This study assesses how often local US hospitals provide smoking cessation information in the following two ways: via hospital Web sites; and via routing incoming phone calls to their hospital switchboards to an in-house smoking cessation clinic. DESIGN: Random survey of US hospitals. SETTING: US hospital Web pages and telephone switchboards. Patients or participants: One hundred two randomly selected US hospitals. INTERVENTIONS: One hundred two hospital Web sites were randomly selected across the United States. The site was searched for the topic of smoking cessation. In the second phase of the survey, the main switchboard number of the same 102 hospitals was anonymously called and the "stop smoking clinic" was asked for. MEASUREMENTS AND RESULTS: The overall results indicate that among the hospital Web sites surveyed, only 30% contained information relating to smoking cessation programs. The phone survey of hospital switchboards showed that 47% had a smoking cessation program available via phone inquiry, while 53% did not. CONCLUSIONS: Of the US hospital Web sites visited, only 30% contained information on smoking cessation. The yield of finding the desired information was increased by the presence of an intrasite search option, which is a low-cost enhancement to any complex Web site. The relatively low cost of promoting healthy behaviors such as smoking cessation on a hospital Web site should be used more widely. Surprisingly, the phone survey of hospitals showed that the lower technology route of providing smoking cessation information to patients via a patient-initiated phone call is only available in 47% of hospitals. Both the Internet and phone-based switchboard referrals could be more widely and effectively used. Joint Commission on Accreditation of Healthcare Organizations guidelines would be one avenue of increasing the availability of smoking cessation information at hospital switchboards and Web sites.     

Erythrophagocytosis by dysplastic neutrophils in chronic myelomonocytic leukemia and subsequent transformation to acute myeloid leukemia

Erythrophagocytosis by neutrophils is a rare phenomenon in myeloid malignancies, and its clinicopathologic significance is not fully understood. We report a unique case of erythrophagocytosis by dysplastic neutrophils in chronic myelomonocytic leukemia (CMML) and subsequent transformation to acute myeloid leukemia (AML). Review of multiple marrow samples, both pretreatment and post-treatment, demonstrated a correlation between percentage of dysplastic neutrophils and degree of erythrophagocytosis. Erythrophagocytosis was observed only in dysplastic forms of neutrophils. Post-transplant marrows with engraftment of donor cells showed no neutrophilic dysplasia or erythrophagocytosis. Possible mechanisms of neutrophilic erythrophagocytosis in myeloid malignancies are discussed.     

ROMK1 channel activity is regulated by monoubiquitination

The ubiquitination of proteins can signal their degradation, modify their activity or target them to specific membranes or cellular organelles. Here, we show that monoubiquitination regulates the plasma membrane abundance and function of the potassium channel, ROMK. Immunoprecipitation of proteins obtained from renal cortex and outer medulla with ROMK antibody revealed that this channel was monoubiquitinated. To determine the ubiquitin binding site on ROMK1, all intracellular lysine (Lys) residues of ROMK1 were individually mutated to arginine (Arg), and a two-electrode voltage clamp was used to measure the ROMK1 channel activity in Xenopus oocytes. ROMK1 channel activity increased from 8.1 to 27.2 microA only when Lys-22 was mutated to Arg. Furthermore, Western blotting failed to detect the ubiquitinated ROMK1 in oocytes injected with R1K22R. Patch-clamp experiments showed that biophysical properties of R1K22R were identical to those of wild-type ROMK1. Although total protein expression levels of GFP-ROMK1 and GFP-R1K22R in oocytes were similar, confocal microscopy showed that the surface fluorescence intensity in oocytes injected with GFP-R1K22R was higher than that of GFP-ROMK1. In addition, biotin labeling of ROMK1 and R1K22R proteins expressed in HEK293 cells showed increased surface expression of the Lys-22 mutant channel. Finally, expression of R1K22R in COS7 cells significantly stimulated the surface expression of ROMK1. We conclude that ROMK1 can be monoubiquitinated and that Lys-22 is an ubiquitin-binding site. Thus, monoubiquitination of ROMK1 regulates channel activity by reducing the surface expression of channel protein. This finding implicates the linking of a single ubiquitin molecule to channels as an important posttranslational regulatory signal.