Evaluation of a community mental health carepath for early psychosis

PURPOSE: To implement a carepath for early psychosis across all community mental health centres through the Early Psychosis Intervention Programme in the Fraser South Area of British Columbia, Canada. METHODS: Prior to developing the carepath, chart reviews and interviews were performed to assess for adherence to published guidelines for early psychosis intervention. This assessment revealed the inadequacies of narrative recording and that core psychosocial interventions were inconsistently provided. The carepath developed included prompts for interventions and standardized assessments and ultimately replaced the charting system used in the mental health centres for early psychosis clients. RESULTS AND CONCLUSIONS: One-year evaluation revealed some improvements in clinical practice but also identified other areas that require further improvement. This project demonstrated that it is possible to successfully implement a carepath in community mental health and that doing so provides a standardized method for ongoing improvements in care.     

Neutralizing antibodies and persistence of immunity following anthrax vaccination

Anthrax toxin consists of protective antigen (PA) and two toxic components, lethal factor (LF) and edema factor (EF). PA binds to mammalian cellular receptors and delivers the toxic components to the cytoplasm. PA is the primary antigenic component of the current anthrax vaccine. Immunity is due to the generation of antibodies that prevent the PA-mediated internalization of LF and EF. In this study, we characterized sera obtained from vaccinated military personnel. Anthrax vaccine is administered in a series of six injections at 0, 2, and 4 weeks and 6, 12, and 18 months, followed by annual boosters. The vaccination histories of the subjects were highly varied; many subjects had not completed the entire series, and several had not received annual boosters. We developed a simple colorimetric assay using alamarBlue dye to assess the antibody-mediated neutralization of LF-mediated toxicity to the J774A.1 murine macrophage cell line. Recently vaccinated individuals had high antibody levels and neutralizing activity. One individual who had not been boosted for 5 years had low immunoglobulin G antibody levels but a detectable neutralization activity, suggesting that this individual produced low levels of very active antibodies.     

Fabrication of a phospholipid membrane-mimetic film on the luminal surface of an ePTFE vascular graft

A stabilized, membrane-mimetic film was produced on the luminal surface of an ePTFE vascular graft by in situ photopolymerization of an acrylate functonalized phospholipid using a fiber optic diffusing probe. The phospholipid monomer was synthesized, prepared as unilamellar vesicles, and fused onto close-packed octadecyl chains that were components of an amphiphilic terpolymer anchored onto the polyelectrolyte multilayer (PEM) by electrostatic interactions. Scanning electron microscopy (SEM) confirmed that gelatin impregnation of the graft followed by the subsequent biomimetic film coating filled in the fibril and node structure of the luminal surface of the ePTFE graft and was smooth. The lipid film displayed an initial advancing contact angle of 44 degrees , which increased to 55 degrees after being subjected to a wall shear rate of 500s(-1) for 24h at 37 degrees C in phosphate buffered saline (PBS). Fourier transform (FT-IR) spectroscopy was used to characterize the stages of biomimetic film assembly and confirmed the stability of the film under shear flow conditions. In vivo assessment using a baboon femoral arteriovenous shunt model demonstrated minimal platelet and fibrinogen deposition over a 1-h blood-contacting period. The results of this study confirm the versatility of a biomimetic film coating system by successfully transferring the methodology previously developed for planar substrates to the luminal surface of an ePTFE vascular graft.     

The US radiation dosimetry standards for 60Co therapy level beams, and the transfer to the AAPM accredited dosimetry calibration laboratories

This work reports the transfer of the primary standard for air kerma from the National Institute of Standards and Technology (NIST) to the secondary laboratories accredited by the American Association of Physics in Medicine (AAPM). This transfer, performed in August of 2003, was motivated by the recent revision of the NIST air-kerma standards for 60Co gamma-ray beams implemented on July 1, 2003. The revision involved a complete recharacterization of the two NIST therapy-level 60Co gamma-ray beam facilities, resulting in new values for the air-kerma rates disseminated by the NIST. Some of the experimental aspects of the determination of the new air-kerma rates are briefly summarized here; the theoretical aspects have been described in detail by Seltzer and Bergstrom ["Changes in the U.S. primary standards for the air-kerma from gamma-ray beams," J. Res. Natl. Inst. Stand. Technol. 108, 359-381 (2003)]. The standard was transferred to reference-class chambers submitted by each of the AAPM Accredited Dosimetry Calibration Laboratories (ADCLs). These secondary-standard instruments were then used to characterize the 60Co gamma-ray beams at the ADCLs. The values of the response (calibration coefficient) of the ADCL secondary-standard ionization chambers are reported and compared to values obtained prior to the change in the NIST air-kerma standards announced on July 1, 2003. The relative change is about 1.1% for all of these chambers, and this value agrees well with the expected change in chambers calibrated at the NIST or at any secondary-standard laboratory traceable to the new NIST standard.     

Clinical evaluation of a type III secretion system real-time PCR assay for diagnosing melioidosis

A Burkholderia pseudomallei type III secretion system real-time PCR assay was evaluated on clinical specimens in a region where melioidosis is endemic. The PCR was positive in 30/33 (91%) patients with culture-confirmed melioidosis. All six patients with melioidosis septic shock were blood PCR positive, suggesting potential for rapid diagnosis and commencement of appropriate therapy.     

Blocking polysynaptic inhibition via opioid receptor activation isolates excitatory synaptic currents without triggering epileptiform activity in organotypic hippocampal slices

The abundance of synaptic connectivity in the cultured hippocampal slice preparation allows measurements of the unitary excitatory connection between pairs of pyramidal neurons using simultaneous presynaptic and postsynaptic intracellular recordings. However, the useful yield of these recordings can be greatly reduced by the presence of polysynaptic inhibition that occludes the measurement of the monosynaptic excitatory postsynaptic current (EPSC). We have found that the traditional method of eliminating contaminating synaptic inhibition with GABA receptor antagonists is of limited usefulness because the recurrent excitatory connections in organotypic slices cause epileptiform bursting in the absence of inhibitory function. This bursting obscures EPSCs to an even greater extent than the normally occurring polysynaptic inhibitory transmission. Here, we report a new method for isolating monosynaptic EPSCs using the mu-opioid agonist peptide DAMGO to reduce polysynaptic inhibition during these recordings. Activation of mu-opioid receptors is known to hyperpolarize inhibitory neurons. We found that DAMGO application reduces the amplitude and frequency of polysynaptic inhibition, allowing isolation of the excitatory connection between the two neurons being recorded. Furthermore, because inhibitory function is not completely eliminated by DAMGO application, epileptiform bursting very rarely develops. Therefore, the use of DAMGO to prevent polysynaptic inhibition without causing epileptiform bursting provides a useful tool to substantially increase the yield of experiments measuring the unitary excitatory connection between pyramidal neurons in the cultured hippocampal slice preparation.     

Relationship of psychiatric history to pain reports in rheumatoid arthritis

OBJECTIVE: The purpose was to examine the relationship of pre-existing psychiatric history to pain reports in a cohort of persons with RA and concomitant major depression who were receiving a trial of antidepressant medication. METHOD: RA patients (n = 41) with a current episode of major depression were divided into two subgroups comprised of those with a previous psychiatric history (PSY+) (n = 20) and those without a previous psychiatric history (PSY-) (n = 21). The groups were compared with regard to their responsiveness to a regimen of antidepressive medication on measures of depression, pain, coping, and life stress over a period of 15 months. RESULTS: Although depression scores for both the PSY+ and the PSY- groups decreased significantly from baseline to 15-month follow-up, the composite pain score was found to be significantly decreased only for the PSY- group. CONCLUSION: Psychiatric history appears to predispose persons with concomitant RA and major depression to report less pain reduction following antidepressive treatment than those persons without a psychiatric history.     

An Integrated Course in Pain Management and Palliative Care Bridging the Basic Sciences and Pharmacy Practice

Objective. To describe the development of an integrated pain and palliative care course and to investigate the long-term effectiveness of the course during doctor of pharmacy (PharmD) students’ advanced pharmacy practice experiences (APPEs) and in their practice after graduation.Design. Roseman University College of Pharmacy faculty developed a 3-week elective course in pain and palliative care by integrating relevant clinical and pharmaceutical sciences. Instructional strategies included lectures, team and individual activities, case studies, and student presentations.Assessment. Students who participated in the course in 2010 and 2011 were surveyed anonymously to gain their perception about the class as well as the utility of the course during their APPEs and in their everyday practice. Traditional and nontraditional assessment of students confirmed that the learning outcomes objectives were achieved.Conclusions. Students taking the integrated course on pain management and palliative care achieved mastery of the learning outcome objectives. Surveys of students and practicing pharmacists who completed the course showed that the learning experience as well as retention was improved with the integrated mode of teaching. Integrating basic and clinical sciences in therapeutic courses is an effective learning strategy.     

Care of the dying in long-term care settings

A team of caregivers provides health care in nursing homes. This team is led by a nurse and includes a physician, nursing assistants, and other nursing home staff. Given the future demand for palliative care in this setting, the roles of all caregivers need to be supported with meaningful training, improved working conditions, and respect for each caregiver's contribution.     

Effect of Losartan on Prevention and Progression of Early Diabetic Nephropathy in American Indians With Type 2 Diabetes

Angiotensin receptor blockers are renoprotective in hypertensive azotemic patients with type 2 diabetes, but their efficacy in early diabetic kidney disease is uncertain. We performed a 6-year randomized clinical trial in 169 American Indians with type 2 diabetes and normoalbuminuria (albumin/creatinine ratio [ACR] <30 mg/g; n = 91) or microalbuminuria (ACR 30–299 mg/g; n = 78) at baseline. The primary outcome was decline in glomerular filtration rate (GFR) to ≤60 mL/min or to half the baseline value in subjects who entered with GFR <120 mL/min. Another outcome was differences in glomerular structure at end of treatment. Subjects received 100 mg losartan or placebo daily. GFR was measured annually; 111 subjects underwent kidney biopsies. Only nine subjects reached the GFR outcome, and the unadjusted hazard ratio (losartan vs. placebo) was 0.50 (95% CI, 0.12–1.99). Differences in mesangial fractional volume were not estimated in the combined albuminuria groups because of an interaction with treatment assignment. In separate analyses, mesangial fractional volume was lower in subjects treated with losartan in the microalbuminuria group (18.8 vs. 25.6%; P = 0.02), but not in the normoalbuminuria group (19.6 vs. 17.8%; P = 0.86). Treatment with losartan may preserve some features of kidney structure in American Indians with type 2 diabetes and microalbuminuria.Angiotensin receptor blockers (ARBs) reduce the rate of diabetic kidney disease progression in hypertensive azotemic patients with type 2 diabetes (1,2). Their efficacy in slowing progression of early kidney disease, however, is less certain, and surrogate end points, such as albuminuria progression, complicate interpretation of most studies (3). In the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA 2) study (4), frequency of progression to macroalbuminuria was reduced by the study drug, but decline in glomerular filtration rate (GFR), as estimated by creatinine clearance, was not. Similarly, in the Steno-2 study (5), intensive multifactorial intervention in patients with type 2 diabetes and microalbuminuria significantly reduced progression to proteinuria but did not alter the rate of GFR decline.Efficacy of ARBs in the primary prevention of diabetic kidney disease is less certain. The Renin Angiotensin System Study (RASS) (6), a clinical trial of losartan or enalapril versus placebo in patients with type 1 diabetes and normoalbuminuria, found no benefit of treatment over 5 years in either change in GFR or change in mesangial fractional volume of serial kidney biopsies. Moreover, the 5-year cumulative incidence of microalbuminuria was higher in those receiving losartan than in either of the other groups, suggesting the potential for harm.We performed a randomized, placebo-controlled, clinical trial to test whether the ARB losartan offered renoprotection to persons with type 2 diabetes who had either normal urinary albumin excretion or microalbuminuria at baseline. Clinical outcomes included changes in GFR from baseline and differences in glomerular structure on kidney biopsies performed at the end of the study period. We also examined the effect of losartan on urinary albumin excretion.