Deploying a national clinical text processing infrastructure.

OBJECTIVES: Clinical text processing offers a promising avenue for improving multiple aspects of healthcare, though operational deployment remains a substantial challenge. This case report details the implementation of a national clinical text processing infrastructure within the Department of Veterans Affairs (VA). METHODS: Two foundational use cases, cancer case management and suicide and overdose prevention, illustrate how text processing can be practically implemented at scale for diverse clinical applications using shared services. RESULTS: Insights from these use cases underline both commonalities and differences, providing a replicable model for future text processing applications. CONCLUSIONS: This project enables more efficient initiation, testing, and future deployment of text processing models, streamlining the integration of these use cases into healthcare operations. This project implementation is in a large integrated health delivery system in the United States, but we expect the lessons learned to be relevant to any health system, including smaller local and regional health systems in the United States.

Project STEP: Implementing the Veterans Health Administration's Stepped Care Model of Pain Management.

Objective: The "stepped care model of pain management" (SCM-PM) prioritizes the role of primary care providers in optimizing pharmacological management and timely and equitable access to patient-centered, evidence-based nonpharmacological approaches, when indicated. Over the past several years, the Veterans Health Administration (VHA) has supported implementation of SCM-PM, but few data exist regarding changes in pain care resulting from implementation. We examined trends in prescribing and referral practices of primary care providers with hypotheses of decreased opioid prescribing, increased nonopioid prescribing, and increased referrals to specialty care for nonpharmacological services. Design: An initiative was designed to foster implementation and systematic evaluation of the SCM-PM over a five-year period at the VA Connecticut Healthcare System (VACHS) while fostering collaborative, partnered initiatives to promote organizational improvements in the delivery of pain care. Subjects: Participants were veterans receiving care at VACHS with at least one pain intensity rating ≥4/10 over the course of the study period (7/2008-6/2013). Methods: We used electronic health record data to examine changes in indicators of pain care including pharmacy and health care utilization data. Results: We observed hypothesized changes in long-term opioid and nonopioid analgesic prescribing and increased utilization of nonpharmacological treatments such as physical therapy, occupational therapy, and clinical health psychology. Conclusions: Through a multifaceted comprehensive implementation approach, primary care providers demonstrated increases in guideline-concordant pain care practices. Findings suggest that engagement of interdisciplinary teams and partnerships to promote organizational improvements is a useful strategy to increase the use of integrated, multimodal pain care for veterans, consistent with VHA's SCM-PM.

Dementia knowledge transfer project in a rural area.

INTRODUCTION: Rural Scotland has an ageing population. There has been an increase in the number of people with dementia and as the proportion of people aged over 75 years continues to rise, this will increase still further. The Scottish Government has produced a dementia strategy and implementing this will be a challenge for rural Scotland. METHODS: Transferring academic knowledge into practice is challenging. A Knowledge Transfer Partnership was formed between NHS Highland and the University of Stirling. A literature review was undertaken of the rural dementia literature; local services were surveyed and described; and interviews were undertaken with people with dementia and carers. Work was conducted on training, diagnostic service provision and local policy. Throughout the project, a collaborative approach was used, which aimed at the joint production of knowledge. RESULTS: Involving University staff in local service development had a substantial impact. Reviewing existing research knowledge and setting it in the context of local services, and of experience of service use, allowed the relevant priorities to be identified. As well as identifying training needs and providing training, the work influenced local decisions on diagnostic service design and standards, and on policy. CONCLUSION: This embedded engagement model appeared to produce more rapid change than traditional models of use of academic knowledge.

Synthesis and pharmacological evaluation of phenylethynyl[1,2,4]methyltriazines as analogues of 3-methyl-6-(phenylethynyl)pyridine.

Procedures were developed for the synthesis of 3-methyl-5-phenylethynyl[1,2,4]triazine (4), 6-methyl-3-phenylethynyl[1,2,4]triazine (5), and 5-methyl-3-phenylethynyl[1,2,4]triazine (6a) as analogues of 2-methyl-6-(phenylethynyl)pyridine (2). The compounds were evaluated for antagonism of glutamate-mediated mobilization of internal calcium in an mGluR5 in vitro efficacy assay. The most potent of the three analogues was 6a. Twenty additional analogues of 6a were synthesized and evaluated for mGluR5 antagonist efficacy. The most potent compounds were 3-(3-methylphenylethynyl)-5-methyl[1,2,4]triazine (6b), 5-(3-chlorophenylethynyl)-5-methyl[1,2,4]triazine (6c), and 3-(3-bromophenylethynyl)-5-methyl[1,2,4]triazine (6d).

Enhancement of bupivacaine local anesthesia with the potassium channel blocker ibutilide.

In some clinical settings it is necessary to inject large volumes of local anesthetic--and consequently very high doses--in order to provide an adequate level of block. Subsequent absorption of these high doses, or inadvertent intravenous administration of even small doses, has led to systemic toxicity. Thus, it is desirable to develop adjuvants that are inert alone, but would enhance the potency and/or efficacy of local anesthetics to improve their safety. Adelta/C fibers possess K(+) channels identified as sustained delayed rectifier type K(DR) currents and transient A-type K(A) currents. In the heart, the class III antiarrhythmic drug ibutilide blocks the cardiac component of the rapid delayed rectifying K(+) current (IKr). Experiments were conducted to determine whether co-administration of the K(+) channel blocker ibutilide would enhance the local anesthetic bupivacaine in mice. After injecting bupivacaine mixed with vehicle or ibutilide in the popliteal region of mice, paw withdrawal latencies were determined by applying the plantar aspect of a single hind-paw to the surface a 55 degrees C hot-plate device. 0.5% Bupivacaine+ibutilide (7.8x10(-5) M) elicited significantly longer hot-plate latencies than 0.5% bupivacaine+vehicle. In addition, bupivacaine was 2.6-fold more potent when co-administered with ibutilide rather than vehicle. Epinephrine extends the tissue concentrations of local anesthetics by inducing localized vasoconstriction. Epinephrine augmented the enhancement by ibutilide of bupivacaine's potency by 6.8-fold. In summary, ibutilide may enhance the effects of bupivacaine by blocking K(+) channels on sensory nociceptive nerves.

Influence of intracellular Ca2+ release modulating drugs on bupivacaine infiltration anesthesia in mice.

The endoplasmic reticulum inside neurons can provide enormous amounts of releasable Ca2+ to increase cytosolic Ca2+ levels through the activation of endoplasmic membrane ion channels. Ryanodine (RyR) channels release Ca2+ into the cytosol when activated by Ca2+ influx through voltage-gated channels, or by cyclicADP ribose. Inositol tris-phosphate (IP3) channels are stimulated by phospolipid metabolism and the release of IP3. The hypothesis was tested that drugs that bind RyR or IP3 channels would affect the anesthetic potency of bupivacaine. The radiant heat tail-flick test was used to assess for anesthesia following subcutaneous infiltration of bupivacaine and Ca2+ modulating drugs in the tails of mice. No musculature is contained in the tail that could result in motor block. The RyR channel agonists 4-chloro-m-cresol and poly-L-lysine significantly reduced the anesthetic potency of bupivacaine. The plant alkaloid ryanodine elicited a bi-phasic effect, with low concentrations blocking bupivacaine anesthesia, and a high concentration enhancing anesthesia. Alternatively, the RyR channel antagonist dantrolene sodium dose-dependently increased bupivacaine's potency. However, the IP3 channel drugs were inactive. The IP3 agonist adenophostin A failed to affect bupivacaine anesthesia. Furthermore, bupivacaine was unaffected by the IP3 channel antagonists xestospongin C or low molecular weight heparin. Our results indicate that only the RyR channel drugs modulated the anesthetic effects of bupivacaine. Electrophysiological and molecular studies of sensory dorsal root ganglia neurons, the source of Adelta and C-fiber nociceptors, have demonstrated the presence of RyR3 Ca2+ release channels. This provides the first evidence that RyR channels might affect bupivacaine anesthesia in some fashion.

Factors involved in long- and short-term mandibular plate exposure.

OBJECTIVES: To evaluate and to compare rates and timing of exposure of alloplastic mandibular plates by plate type and tissue reconstruction technique. DESIGN: A retrospective review series of 92 consecutive patients for 4 years (mean follow-up, 30 months). SETTING: National Cancer Institute-designated comprehensive cancer center in a freestanding cancer hospital. PATIENTS: Seventy-nine patients received alloplastic mandibular plates for segmental defects, and 13 patients received compression plates for mandibular osteotomies following ablative cancer surgery, including 21 titanium hollow osseointegrating reconstruction, 41 Storz, 16 Synthes, and 5 AO/ASIF (Arbeitsgemein schott fur Ostcosynthese fragen/Association for the Study of Internal Fixation) plates. Primary flap repair was provided by 71 pedicled soft tissue and 19 osseocutaneous free flaps, with primary closure in the remaining 2. INTERVENTION: Most of the reconstructions of the mandibular defect was with an alloplastic plate with musculocutaneous flap or revascularized bone graft. OUTCOME MEASURES: Clinically apparent intraoral or extraoral plate exposure. RESULTS: Plate exposure occurred in 25 cases. Nine plates were exposed extraorally, at a mean postoperative interval of 40 weeks. The remaining 16 plates were exposed intraorally at a mean postoperative interval of 16 weeks. There was no significant difference in the exposure rates of different plate types or methods of reconstruction. The titanium hollow osseointegrating reconstruction plate had a similar exposure rate compared with the other plates. Size and site of the defect were the only significant predictors of plate exposure Radiotherapy and postoperative complications did not affect the rate of exposure. CONCLUSIONS: Extraoral plate exposure occurs less commonly and later in the postoperative period than intraoral exposure, suggesting different causes. Plate type and type of flap reconstruction do not affect the rate of exposure. This may reflect long follow-up.