"It's Really Like Any Other Study": Rural Radiology Facilities Performing Low-Dose Computed Tomography for Lung Cancer Screening.

Rationale: The majority of eligible people have not been screened for lung cancer. There is emerging evidence that there are location-based disparities applicable to lung cancer screening (LCS). Objectives: To describe LCS radiologic services in rural Oregon and understand the barriers and facilitators to implementation of LCS using low-dose computed tomography (LDCT). Methods: This was a mixed-method descriptive study using surveys and semistructured interviews of key informants. We approached representatives from all 37 small and rural hospitals in Oregon. We purposively interviewed key informants from a subset based on LDCT implementation outcomes. Results: We surveyed representatives from 29 radiology facilities and qualitatively interviewed 18 key informants from 19 facilities (representing 12 healthcare systems). Among the surveyed radiology facilities, 59% were performing LDCT for LCS. Key informants reported that facilities that performed this service were often motivated by community needs and were less motivated by financial gain or evidence strength, and all described the importance of having a champion. Key informants described that LCS programmatic components that were within their normal scope of practice (e.g., specifying the LDCT parameters) were burdensome to establish but that barriers were surmountable. Most informants reported they did not perform other components of high-quality programs (e.g., ensuring adherence to recommended follow-up testing) and suggested that these steps were important but were the responsibility of primary care providers. Conclusions: Many rural hospital facilities in Oregon offer LDCT for LCS but do not perform all the recommended components of a screening program. Disparities in LCS use and adherence are unlikely to be solved by an exclusive focus at the radiology facility level and may require additional interventions at the primary care level.

Pre-discharge home visits: A qualitative exploration of the experience of occupational therapists and multidisciplinary stakeholders.

INTRODUCTION: The evidence base surrounding occupational therapy pre-discharge home visits discusses current practices, potential beneficial outcomes and limitations. However, research is limited, regarding how clinical teams determine which patients receive this service. This study aims to explore perceptions of occupational therapists and multidisciplinary stakeholders concerning pre-discharge home visits through their experiences and current practice in the Australian context. METHOD: A qualitative descriptive approach, using thematic analysis, was employed. Four focus groups were included, comprising 27 health professionals: novice occupational therapists (n = 6), experienced occupational therapists (n = 8), occupational therapy managers (n = 5), and multidisciplinary team members (n = 8). RESULTS: Three key themes relating to pre-discharge home visits in clinical practice emerged. The first theme of 'Recognition of Clinical Factors' reflected that aspects of the person's occupational performance, environmental and care needs, were prime indicators considered for a pre-discharge home visit. Secondly, 'Contextual and Pragmatic Influences', described clinical setting realities as being significant considerations and strongly mediating practice. A third theme of 'Perceptions of Value' showed awareness of the utility of pre-discharge home visits, while also recognising need to enhance ongoing practice. CONCLUSION: This qualitative study provides information on factors influencing decision-making regarding pre-discharge home visits from the hospital setting. Clinical factors were presented as key considerations, but clinicians' experiences and perceptions of contextual influences suggest an explanatory factor for practice variation. While multidisciplinary stakeholders' broadly demonstrated similar rationales for pre-discharge home visits as those of occupational therapists, therapists' decision-making processes for pre-discharge home visits were shaped by their experience level. Clinicians' experience finds pre-discharge home visits to have value and in the absence of clear evidence-based criteria for whom this element of practice should be provided, participants supported the development of a decision-making support tool to assist in decision-making.

Implementation of an opioid management initiative by a state Medicaid program.

BACKGROUND: The utilization of prescription opioids has increased over the last 2 decades. Associated with this is the misuse of prescription opioids for nonmedical purposes. Medicaid programs have struggled with developing strategies that balance best practice models, appropriate utilization, and reduction in costs associated with the opioid medication class. OBJECTIVE: To examine the impact of a 2-year stepwise initiative to reduce utilization and therapy costs of long-acting opioid analgesics (LAOA) by addressing issues of high dose, daily dose, and preferred therapeutic alternatives. METHODS: Utilization data from the Massachusetts Medicaid pharmacy program for LAOAs were reviewed and compared for 2 time periods. The calendar year prior to the initiative, 2002, was used as a base year and represents a time period when there were no restrictions in place for members to obtain long-acting opioids. The calendar year 2005 was the comparison year representing a time period after the multiple steps of the initiative had been implemented. A retrospective claims-based analysis was performed to determine the impact of restrictions on LAOAs, defined as brand and generic versions of oxycodone ER, morphine ER, methadone, and fentanyl transdermal system. The primary measure was the percentage of change of unique utilizers, paid claims, and average daily dose for each LAOA following the implementation of the opioid management initiative. Secondary measures included a cost analysis. RESULTS: Compared with 2002, the overall number of LAOA unique utilizers declined 17.8% (P < 0.0001), and the overall number of claims declined by 4.1% (P < 0.0001), while Medicaid pharmacy benefit member enrollment remained relatively stable. Average daily dose declined in methadone and morphine ER and increased in oxycodone ER and fentanyl transdermal system. The 2005 overall cost of LAOAs decreased 8.0% compared with the overall cost in 2002. The per-member-per-month (PMPM) cost for opioid users in 2002 was $110.57 ($120.04 when adjusted to 2005 dollars) compared with $123.75 in 2005. In comparison, the overall PMPM for all members in 2002 was $3.52 ($3.82 when adjusted to 2005 dollars) compared with $3.59 in 2005. CONCLUSIONS: Our study successfully demonstrated that a state Medicaid program initiative can result in a significant overall decrease in opioid class utilization specifically for the targeted, more costly agents. This was achieved via the implementation of a Therapeutic Class Management multidisciplinary workgroup that established a prior authorization process implementing limits on dose, as well as identified preferred less costly agents. It further facilitated the direct opportunity for pharmacy-prescriber collaboration for LAOA medication management.

Posing the research question: not so simple.

PURPOSE: The success of any research process relies, in part, on how well investigators are able to translate a clinical problem into a research question-a task that is not so simple for novice investigators. The PICOT approach requires that the framing of the research question specify the target Population, the Intervention of interest, the Comparator intervention, key Outcomes, and the Time frame over which the outcomes are assessed. This paper describes the use of the PICOT structure in framing research questions and examines PICOT criteria as applied to the anesthesia literature. We also provide a roadmap for applying the PICOT format in identifying and framing clear research questions. METHODS: In addition to searching MEDLINE for the literature on framing research questions, we performed a systematic review of articles published in four key anesthesia journals in 2006, including Anesthesiology, Anesthesia & Analgesia, the British Journal of Anaesthesia, and the Canadian Journal of Anesthesia. RESULTS: Three hundred thirteen articles (n = 313) were included in this review, with the following distribution by study design: 139 (44%) randomized controlled trials, 129 (41%) cohort studies, and 45 (15%) case-controlled, cross-sectional studies or systematic reviews. Overall, 96% (95% confidence interval: 91,100) of articles did not apply the PICOT approach in reporting the research question. CONCLUSIONS: The PICOT approach may be helpful in defining and clearly stating the research question. It remains to be determined whether or not compliance with the PICOT style, or any other format for framing research questions, is associated with a higher quality of research reporting.

Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease.

Increased levels of a 40-42 amino-acid peptide called the amyloid beta protein (A beta) and evidence of oxidative damage are early neuropathological markers of Alzheimer's disease (AD). Previous investigations have demonstrated that melatonin is decreased during the aging process and that patients with AD have more profound reductions of this hormone. It has also been recently shown that melatonin protects neuronal cells from A beta-mediated oxidative damage and inhibits the formation of amyloid fibrils in vitro. However, a direct relationship between melatonin and the biochemical pathology of AD had not been demonstrated. We used a transgenic mouse model of Alzheimer's amyloidosis and monitored over time the effects of administering melatonin on brain levels of A beta, abnormal protein nitration, and survival of the mice. We report here that administration of melatonin partially inhibited the expected time-dependent elevation of beta-amyloid, reduced abnormal nitration of proteins, and increased survival in the treated transgenic mice. These findings may bear relevance to the pathogenesis and therapy of AD.

Cholesterol, oxidative stress, and Alzheimer's disease: expanding the horizons of pathogenesis.

Recent epidemiological, clinical, and experimental data suggest that cholesterol may play a role in Alzheimer's disease (AD). We have recently shown that cholesterolemia has a profound effect in the development and modulation of amyloid pathology in a transgenic model of AD. This review summarizes recent advancements in our understanding of the potential role of cholesterol and the amyloid beta protein in initiating the generation of free radicals and points out their role in a chain of events that causes damage of essential macromolecules in the central nervous system and culminates in neuronal dysfunction and loss. Experimental data links cholesterol and oxidative stress with some neurodegenerative aspects of AD.

The neuroprotective activities of melatonin against the Alzheimer beta-protein are not mediated by melatonin membrane receptors.

Exposure of neuronal cells to the Alzheimer's amyloid beta protein (Abeta) results in extensive oxidative damage of bio-molecules that are profoundly harmful to neuronal homeostasis. It has been demonstrated that melatonin protects neurons against Abeta-mediated neurotoxicity, including cell death and a spectrum of oxidative lesions. We undertook the current study to determine whether melatonin membrane receptors are involved in the mechanism of neuroprotection against Abeta neurotoxicity. For this purpose, we characterized the free-radical scavenging potency of several compounds exhibiting various affinities for melatonin membrane receptors (MLT 1a and 1b). Abeta-mediated neurotoxicity was assessed in human neuroblastoma cells and in primary hippocampal neurons. In sharp contrast with melatonin, no neuroprotection against Abeta toxicity was observed when we used melatonin membrane receptor agonists that were devoid of antioxidant activity. In contrast, the cells were fully protected in parallel control experiments when either melatonin, or the structurally unrelated free-radical scavenger phenyl-N-t-butyl nitrone (PBN), were added to Abeta-containing culture media. This study demonstrates that the neuroprotective properties of melatonin against Abeta-mediated toxicity does not require binding of melatonin to a membrane receptor and is likely the result of the antioxidant and antiamyloidogenic features of the agent.

Deficiency of chaperonin 60 in Down's syndrome.

Patients with Down syndrome (DS) and Alzheimer's disease (AD) share a number of characteristic neuropathologic lesions. Several lines of evidence suggest that mitochondria and the oxidative stress response are involved in the pathogenesis of both conditions. In the process of investigating the stress response in DS, we discovered a defective basal expression of a major mitochondrial heat shock protein, chaperonin 60 (Cpn60) in non-transformed dermal fibroblast cell lines from DS individuals. Such a defect was not present in control cells that had been cultured under identical physiological growth conditions. A quantitative analysis by Western blots showed a marked reduction of Cpn60 per equal amount of total protein in DS cells to an average of 35% of normal. Northern blot studies confirmed the defect and also showed a marked reduction of the mRNA signal for Cpn60 in all the DS cell lines. To gain further information, experiments were conducted to study the rate of de-novo synthesis of Cpn60 at normal and supraoptimal temperatures in DS and controls. Results showed no significant differences between the two study groups. HSP60 is important in mitochondrial function and defects in these organelles have been reported in DS and AD. Thus, the findings may have potential implications in the neuropathology of DS.