Increasing Enzyme Mannose-6-Phosphate Levels but Not Miglustat Coadministration Enhances the Efficacy of Enzyme Replacement Therapy in Pompe Mice.

Pompe disease is a rare glycogen storage disorder caused by a deficiency in the lysosomal enzyme acid α-glucosidase, which leads to muscle weakness, cardiac and respiratory failure, and early mortality. Alglucosidase alfa, a recombinant human acid α-glucosidase, was the first approved treatment of Pompe disease, but its uptake into skeletal muscle via the cation-independent mannose-6-phosphate (M6P) receptor (CIMPR) is limited. Avalglucosidase alfa has received marketing authorization in several countries for infantile-onset and/or late-onset Pompe disease. This recently approved enzyme replacement therapy (ERT) was glycoengineered to maximize CIMPR binding through high-affinity interactions with ∼7 bis-M6P moieties. Recently, small molecules like the glucosylceramide synthase inhibitor miglustat were reported to increase the stability of recombinant human acid α-glucosidase, and it was suggested that an increased serum half-life would result in better glycogen clearance. Here, the effects of miglustat on alglucosidase alfa and avalglucosidase alfa stability, activity, and efficacy in Pompe mice were evaluated. Although miglustat increased the stability of both enzymes in fluorescent protein thermal shift assays and when incubated in neutral pH buffer over time, it reduced their enzymatic activity by ∼50%. Improvement in tissue glycogen clearance and transcriptional dysregulation in Pompe mice correlated with M6P levels but not with miglustat coadministration. These results further substantiate the crucial role of CIMPR binding in lysosomal targeting of ERTs. SIGNIFICANCE STATEMENT: This work describes important new insights into the treatment of Pompe disease using currently approved enzyme replacement therapies (ERTs) coadministered with miglustat. Although miglustat increased the stability of ERTs in vitro, there was no positive impact to glycogen clearance and transcriptional correction in Pompe mice. However, increasing mannose-6-phosphate levels resulted in increased cell uptake in vitro and increased glycogen clearance and transcriptional correction in Pompe mice, further underscoring the crucial role of cation-independent mannose-6-phosphate receptor-mediated lysosomal targeting for ERTs.

A Cluster Randomized Trial of Primary Care Practice Redesign to Integrate Behavioral Health for Those Who Need It Most: Patients With Multiple Chronic Conditions.

PURPOSE: Patient outcomes can improve when primary care and behavioral health providers use a collaborative system of care, but integrating these services is difficult. We tested the effectiveness of a practice intervention for improving patient outcomes by enhancing integrated behavioral health (IBH) activities. METHODS: We conducted a pragmatic, cluster randomized controlled trial. The intervention combined practice redesign, quality improvement coaching, provider and staff education, and collaborative learning. At baseline and 2 years, staff at 42 primary care practices completed the Practice Integration Profile (PIP) as a measure of IBH. Adult patients with multiple chronic medical and behavioral conditions completed the Patient-Reported Outcomes Measurement Information System (PROMIS-29) survey. Primary outcomes were the change in 8 PROMIS-29 domain scores. Secondary outcomes included change in level of integration. RESULTS: Intervention assignment had no effect on change in outcomes reported by 2,426 patients who completed both baseline and 2-year surveys. Practices assigned to the intervention improved PIP workflow scores but not PIP total scores. Baseline PIP total score was significantly associated with patient-reported function, independent of intervention. Active practices that completed intervention workbooks (n = 13) improved patient-reported outcomes and practice integration (P ≤ .05) compared with other active practices (n = 7). CONCLUSION: Intervention assignment had no effect on change in patient outcomes; however, we did observe improved patient outcomes among practices that entered the study with greater IBH. We also observed more improvement of integration and patient outcomes among active practices that completed the intervention compared to active practices that did not. Additional research is needed to understand how implementation efforts to enhance IBH can best reach patients.

Integrating behavioural health and primary care: qualitative findings on contextual factors that influence integration.

BACKGROUND: Integrating behavioural health care into primary care practices may increase patients' access to behavioural health services and improve health outcomes. However, few studies have explored factors that influence integration processes. OBJECTIVE: We sought to better understand contextual factors that support or impede behavioural health integration in primary care practices. METHODS: We conducted 71 semi-structured interviews with providers, staff, and leaders from eight primary care practices in the United States with integrated behavioural health services, which were participating in a randomized control, pragmatic trial: Integrating Behavioural Health and Primary Care. Practices were selected for diversity on geographic location, size, ownership, and experience with integration. We conducted a thematic analysis of the qualitative data derived from the interviews. RESULTS: We identified four categories of contextual factors influencing behavioural health integration: leadership commitment to integration, financial considerations, workflow and communication systems, and providers' perspectives on integration and team-based healthcare. Supportive factors included leaders' commitment to integration, adequate staffing, customized communication and workflow systems, collaborative practice culture, and healthy working relationships amongst providers. Impediments included staffing issues and payment models that do not reimburse for activities required to support integrated care. CONCLUSION: Interviewees described various benefits of integration, including providers feeling better equipped to address patients' needs due to collaboration between medical and behavioural providers and resulting interdisciplinary learning. Given concerns about provider burnout, this finding warrants further study.

This study examines the integration of behavioural health services, such as mental health counselling, into primary care practices. We conducted interviews with representatives from eight primary care practices with integrated behavioural health services. The participating practices are located in diverse geographic locations across the United States, and all were engaged in a large, national project entitled Integrating Behavioural Health and Primary Care. A total of 71 healthcare providers, staff, and practice leaders were interviewed and asked to discuss the factors that influenced efforts to integrate behavioural healthcare in their primary care practice. We analysed the interview transcripts and identified factors that supported or impeded behavioural health integration. Supportive factors included practice leaders' commitment to integration, adequate staffing, customized communication and workflow systems within the practice, a collaborative practice culture, and healthy working relationships amongst the medical and behavioural health providers. Impediments included staffing issues and a lack of reimbursement from insurance companies and government payers for the time and effort that practice staff needs to devote in order to provide integrated care. Interviewees described various benefits of behavioural health integration, including providers feeling better equipped to address patients' needs due to collaboration between medical and behavioural providers.

A Randomized Controlled Trial of an Integrated Alcohol Reduction Intervention in Patients With Hepatitis C Infection.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) and alcohol use are patient risk factors for accelerated fibrosis progression, yet few randomized controlled trials have tested clinic-based alcohol interventions. APPROACH AND RESULTS: A total of 181 patients with HCV and qualifying alcohol screener scores at three liver center settings were randomly assigned to the following: (1) medical provider-delivered Screening, Brief Intervention, and Referral to Treatment (SBIRT), including motivational interviewing counseling and referral out for alcohol treatment (SBIRT-only), or (2) SBIRT plus 6 months of integrated colocated alcohol therapy (SBIRT + Alcohol Treatment). The timeline followback method was used to assess alcohol use at baseline and 3, 6, and 12 months. Coprimary outcomes were alcohol abstinence at 6 months and heavy drinking days between 6 and 12 months. Secondary outcomes included grams of alcohol consumed per week at 6 months. Mean therapy hours across 6 months were 8.8 for SBIRT-only and 10.1 for SBIRT + Alcohol Treatment participants. The proportion of participants exhibiting full alcohol abstinence increased from baseline to 3, 6, and 12 months in both treatment arms, but no significant differences were found between arms (baseline to 6 months, 7.1% to 20.5% for SBIRT-only; 4.2% to 23.3% for SBIRT + Alcohol Treatment; P = 0.70). Proportions of participants with any heavy drinking days decreased in both groups at 6 months but did not significantly differ between the SBIRT-only (87.5% to 26.7%) and SBIRT + Alcohol Treatment (85.7% to 42.1%) arms (P = 0.30). Although both arms reduced average grams of alcohol consumed per week from baseline to 6 and 12 months, between-treatment effects were not significant. CONCLUSIONS: Patients with current or prior HCV infection will engage in alcohol treatment when encouraged by liver medical providers. Liver clinics should consider implementing provider-delivered SBIRT and tailored alcohol treatment referrals as part of the standard of care.

Preparing emergency physicians for malpractice litigation: a joint emergency medicine residency-law school mock trial competition.

BACKGROUND: Fear of malpractice affects the daily life of many emergency physicians. Educational programs to prepare for litigation are lacking. OBJECTIVES: An educational collaboration between an emergency medicine residency and a law school, whereby a medical malpractice mock trial competition is used to teach residents basic skills for testifying in legal proceedings. METHODS: Ten residents in an academic emergency medicine program volunteered as witnesses in a malpractice mock trial competition at a law school. Residents testified two or three times and, after each appearance, were provided feedback to prepare them for subsequent rounds of testimony. They were also given access to videotaped testimony. Judges rated each resident using a nine-question survey scored on a 10-point Likert scale. Scores were compared as a group between rounds of testimony. RESULTS: Participants demonstrated significant improvement in seven of nine measured categories. p-Values reached significance in: Worked Well on Direct Examination (p < 0.001), Demeanor/Body Language (p < 0.001), Was Not Arrogant/Did Not Lose Poise on Cross-Examination (p = 0.001), Convincing Witness (p = 0.001), Appeared Knowledgeable (p = 0.012), Courtroom Attire (p = 0.012), and Expressed Themselves Clearly (p = 0.017). In addition, residents anonymously reported broad educational benefit. CONCLUSION: This novel educational collaboration taught residents about the process of litigation. It improved their communication skills and expanded their knowledge of documentation pitfalls, problems with staff interaction, and consequences of medical errors. This mutually beneficial partnership between a medical residency and a law school solidified it as a permanent feature of the residency program.

Identification of Selective Imidazopyridine CSF1R Inhibitors.

Colony stimulating factor-1 receptor (CSF1R or c-FMS), a class III receptor tyrosine kinase expressed on members of the mononuclear phagocyte system (MPS), plays a key role in the proper functioning of macrophages, microglia, and related cells. Aberrant signaling through CSF1R has been associated with a variety of disease states, including cancer, inflammation, and neurodegeneration. In this Letter, we detail our efforts to develop novel CSF1R inhibitors. Drawing on previously described compounds, including GW2580 (4), we have discovered a novel series of compounds based on the imidazo[4,5-b]pyridine scaffold. Initial structure-activity relationship studies culminated in the identification of 36, a lead compound with potent CSF1R biochemical and cellular activity, acceptable in vitro ADME properties, and oral exposure in rat.

Tube Thoracostomy Complications in Patients With ARDS Requiring ECMO: Worse in COVID-19 Patients?

INTRODUCTION: The incidence and management outcomes of COVID-19 patients with acute respiratory distress syndrome (ARDS) on veno-venous extracorporeal membrane oxygenation (V-V ECMO) requiring chest tubes are not well-described. This study sought to explore differences in tube thoracostomy rates and subsequent complications between patients with and without COVID-19 ARDS on V-V ECMO. MATERIALS AND METHODS: This study is a single institution, retrospective cohort study of patients with COVID-19 ARDS requiring V-V ECMO. The control cohort consisted of patients who required V-V ECMO for ARDS-related diagnoses from January 2018 to January 2021. The primary outcome was any complication following initial tube thoracostomy placement. Study approval was obtained from the Brooke Army Medical Center Institutional Review Board (C.2017.152d). RESULTS: Twenty-five COVID-19 patients and 38 controls were included. Demographic parameters did not differ between the groups. The incidence of pneumothorax was not significantly different between the two groups (44% COVID-19 vs. 22% control, OR 2.8, 95% CI 0.95-7.9, P = 0.09). Patients with COVID-19 were as likely to receive tube thoracostomy as controls (36% vs. 24%, OR 1.8, 95% CI 0.55-5.7). Complications, however, were more likely to occur in the COVID-19 group (89% vs. 33%, OR 16, 95% CI, 1.6-201, P = 0.0498). CONCLUSIONS: Tube thoracostomy placement in COVID-19 patients with ARDS requiring V-V ECMO is common, as are complications following initial placement. Clinicians should anticipate the need for re-intervention in this patient population. Small-bore (14Fr and smaller) pigtail catheters appeared to be safe and efficacious in this setting, but further study on tube thoracostomy management in ECMO patients is needed.

Hippocampal hyperactivation associated with cortical thinning in Alzheimer's disease signature regions in non-demented elderly adults.

Alzheimer's disease (AD) is associated with functional and structural alterations in a distributed network of brain regions supporting memory and other cognitive domains. Functional abnormalities are present in mild cognitive impairment (MCI) with evidence of early hyperactivity in medial temporal lobe regions, followed by failure of hippocampal activation as dementia develops. Atrophy in a consistent set of cortical regions, the "cortical signature of AD," has been reported at the stage of dementia, MCI, and even in clinically normal (CN) older individuals predicted to develop AD. Despite multiple lines of evidence for each of these findings, the relationship between this structural marker of AD-related neurodegeneration and this functional marker of the integrity of the episodic memory system has not yet been elucidated. We investigated this relationship in 34 nondemented older humans (CN, N = 18; MCI, N = 16). Consistent with previous studies, we found evidence of hippocampal hyperactivation in MCI compared with CN. Additionally, within this MCI group, increased hippocampal activation correlated with cortical thinning in AD-signature regions. Even within the CN group, increased hippocampal activity was negatively correlated with cortical thinning in a subset of regions, including the superior parietal lobule (r = -0.66; p < 0.01). These findings, across a continuum of nondemented and mildly impaired older adults, support the hypothesis that paradoxically increased hippocampal activity may be an early indicator of AD-related neurodegeneration in a distributed network.

Inhibiting TGF-ß activity improves respiratory function in mdx mice.

Respiratory function is the main cause of mortality in patients with Duchenne muscular dystrophy (DMD). Elevated levels of TGF-ß play a key role in the pathophysiology of DMD. To determine whether therapeutic attenuation of TGF-ß signaling improves respiratory function, mdx mice were treated from 2 weeks of age to 2 months or 9 months of age with either 1D11 (a neutralizing antibody to all three isoforms of TGF-ß), losartan (an angiotensin receptor antagonist), or a combination of the two agents. Respiratory function was measured in nonanesthetized mice by plethysmography. The 9-month-old mdx mice had elevated Penh values and decreased breathing frequency, due primarily to decreased inspiratory flow rate. All treatments normalized Penh values and increased peak inspiratory flow, leading to decreased inspiration times and breathing frequency. Additionally, forelimb grip strength was improved after 1D11 treatment at both 2 and 9 months of age, whereas, losartan improved grip strength only at 2 months. Decreased serum creatine kinase levels (significant improvement for all groups), increased diaphragm muscle fiber density, and decreased hydroxyproline levels (significant improvement for 1D11 only) also suggested improved muscle function after treatment. For all endpoints, 1D11 was equivalent or superior to losartan; coadministration of the two agents was not superior to 1D11 alone. In conclusion, TGF-ß antagonism may be a useful therapeutic approach for treating DMD patients.

Percutaneous Pulmonary Artery Cannulation to Treat Acute Secondary Right Heart Failure While on Veno-venous Extracorporeal Membrane Oxygenation.

Right heart failure (RHF) is a common, yet difficult to manage, complication of severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation (ECMO) that is associated with increased mortality. Reports of the use of percutaneous mechanical circulatory support devices for concurrent right heart and respiratory failure are limited. This series describes the percutaneous cannulation of the pulmonary artery for conversion from veno-venous to veno-pulmonary artery return ECMO in 21 patients who developed secondary RHF. All patients cannulated between May 2019 and September 2021 were included. Either a 19 or 21 French venous cannula was placed percutaneously into the pulmonary artery via the internal jugular or subclavian vein, providing a total of 821 days of support (median 23 [4-71] days per patient) with flows up to 6 L/min. Five patients underwent cannulation at the bedside, with the remainder performed in the cardiac catheterization laboratory. Pulmonary artery cannulation occurred after 12 [8.5-23.5] days of ECMO support. Vasoactive infusion requirements decreased significantly within 24 hours of pulmonary artery cannula placement (p = 0.0004). Nonetheless, 75% of these patients expired after a median of 12 [4-63] days of support, with three patients found to have had significant pericardial effusions peri-arrest. This cannulation technique may be an effective alternative to veno-arterial ECMO cannulation or the placement of a dual-lumen cannula for the treatment of RHF.

Reliability of functional magnetic resonance imaging associative encoding memory paradigms in non-demented elderly adults.

Functional magnetic resonance imaging (fMRI) holds significant potential to aid in the development of early interventions to improve memory function, and to assess longitudinal change in memory systems in aging and early Alzheimer's disease (AD). However, the test-retest reliability of hippocampal activation and of "beneficial" deactivation in the precuneus has yet to be fully established during memory encoding tasks in older subjects. Using a mixed block and event-related face-name associative encoding paradigm, we assessed the reliability of hippocampal activation and default network deactivation over a 4- to 6-week interscan interval in 27 older individuals who were cognitively normal [Clinical Dementia Rating (CDR) Scale = 0; n = 18] or mildly impaired (CDR = 0.5; n = 9). Reliability was assessed in whole brain maps and regions of interest using both a full-task paradigm of six functional runs as well as an abbreviated paradigm of the first two functional runs, which would be advantageous for use in clinical trials. We found reliable hippocampal signal response across both block- and event-related designs in the right hippocampus. Comparable reliability in hippocampal activation was found in the full and the abbreviated paradigm. Similar reliability in hippocampal activation was observed across both CDR groups overall, but the CDR 0.5 group was more variable in left hippocampal activity. Task-related deactivation in the precuneus demonstrated much greater variability than hippocampal activation in all analyses. Overall, these results are encouraging for the utility of fMRI in "Proof of Concept" clinical trials investigating the efficacy of potentially therapeutic agents for treatment of age-related memory changes, cognitive impairment, and early AD.

Argatroban for Anticoagulation in Patients Requiring Venovenous Extracorporeal Membrane Oxygenation in Coronavirus Disease 2019.

A significant proportion of patients with coronavirus disease 2019 requiring venovenous extracorporeal membrane oxygenation at our institution demonstrated heparin resistance, which in combination with a heparin shortage resulted in the transition to argatroban with or without aspirin as an alternative anticoagulation strategy. The optimal anticoagulation strategy for coronavirus disease 2019 patients requiring venovenous extracorporeal membrane oxygenation is unknown, and therefore, we sought to evaluate the efficacy and safety of argatroban with or without aspirin as an alternative anticoagulation strategy in this patient population. DESIGN: Retrospective cohort. SETTING: Single-center tertiary-care facility in Fort Sam Houston, TX, from 2020 to 2021. PATIENTS: Twenty-four patients who were cannulated for venovenous extracorporeal membrane oxygenation due to respiratory failure secondary to coronavirus disease 2019. INTERVENTIONS: Argatroban, with or without aspirin, was substituted for heparin in coronavirus disease 2019 patients requiring venovenous extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Eighty percent of our coronavirus disease 2019 patients requiring venovenous extracorporeal membrane oxygenation demonstrated heparin resistance, and patients who were initially started on heparin were significantly more likely to require a change to argatroban than vice versa due to difficulty achieving or maintaining therapeutic anticoagulation goals (93.4% vs 11.1%; p < 0.0001). The time to reach the therapeutic anticoagulation goal was significantly longer for patients who were initially started on heparin in comparison with argatroban (24 vs 6 hr; p = 0.0173). Bleeding and thrombotic complications were not significantly different between the two cohorts. CONCLUSIONS: Argatroban, with or without aspirin, is an effective anticoagulation strategy for patients who require venovenous extracorporeal membrane oxygenation support secondary to coronavirus disease 2019. In comparison with heparin, this anticoagulation strategy was not associated with a significant difference in bleeding or thrombotic complications, and was associated with a significantly decreased time to therapeutic anticoagulation goal, likely as a result of high rates of heparin resistance observed in this patient population.

Integrating Behavioral Health and Primary Care (IBH-PC) to improve patient-centered outcomes in adults with multiple chronic medical and behavioral health conditions: study protocol for a pragmatic cluster-randomized control trial.

BACKGROUND: Chronic diseases that drive morbidity, mortality, and health care costs are largely influenced by human behavior. Behavioral health conditions such as anxiety, depression, and substance use disorders can often be effectively managed. The majority of patients in need of behavioral health care are seen in primary care, which often has difficulty responding. Some primary care practices are providing integrated behavioral health care (IBH), where primary care and behavioral health providers work together, in one location, using a team-based approach. Research suggests there may be an association between IBH and improved patient outcomes. However, it is often difficult for practices to achieve high levels of integration. The Integrating Behavioral Health and Primary Care study responds to this need by testing the effectiveness of a comprehensive practice-level intervention designed to improve outcomes in patients with multiple chronic medical and behavioral health conditions by increasing the practice's degree of behavioral health integration. METHODS: Forty-five primary care practices, with existing onsite behavioral health care, will be recruited for this study. Forty-three practices will be randomized to the intervention or usual care arm, while 2 practices will be considered "Vanguard" (pilot) practices for developing the intervention. The intervention is a 24-month supported practice change process including an online curriculum, a practice redesign and implementation workbook, remote quality improvement coaching services, and an online learning community. Each practice's degree of behavioral health integration will be measured using the Practice Integration Profile. Approximately 75 patients with both chronic medical and behavioral health conditions from each practice will be asked to complete a series of surveys to measure patient-centered outcomes. Change in practice degree of behavioral health integration and patient-centered outcomes will be compared between the two groups. Practice-level case studies will be conducted to better understand the contextual factors influencing integration. DISCUSSION: As primary care practices are encouraged to provide IBH services, evidence-based interventions to increase practice integration will be needed. This study will demonstrate the effectiveness of one such intervention in a pragmatic, real-world setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT02868983 . Registered on August 16, 2016.

Intrinsic connectivity between the hippocampus and posteromedial cortex predicts memory performance in cognitively intact older individuals.

Coherent fluctuations of spontaneous brain activity are present in distinct functional-anatomic brain systems during undirected wakefulness. However, the behavioral significance of this spontaneous activity has only begun to be investigated. Our previous studies have demonstrated that successful memory formation requires coordinated neural activity in a distributed memory network including the hippocampus and posteromedial cortices, specifically the precuneus and posterior cingulate (PPC), thought to be integral nodes of the default network. In this study, we examined whether intrinsic connectivity during the resting state between the hippocampus and PPC can predict individual differences in the performance of an associative memory task among cognitively intact older individuals. The intrinsic connectivity, between regions within the hippocampus and PPC that were maximally engaged during a subsequent memory fMRI task, was measured during a period of rest prior to the performance of the memory paradigm. Stronger connectivity between the hippocampal and posteromedial regions during rest predicted better performance on the memory task. Furthermore, hippocampal-PPC intrinsic connectivity was also significantly correlated with episodic memory measures on neuropsychological tests, but not with performance in non-memory domains. Whole-brain exploratory analyses further confirmed the spatial specificity of the relationship between hippocampal-default network posteromedial cortical connectivity and memory performance in older subjects. Our findings provide support for the hypothesis that one of the functions of this large-scale brain network is to subserve episodic memory processes. Research is ongoing to determine if impaired connectivity between these regions may serve as a predictor of memory decline related to early Alzheimer's disease.

Evidence of altered posteromedial cortical FMRI activity in subjects at risk for Alzheimer disease.

The posteromedial cortices and other regions of the "default network" are particularly vulnerable to the pathology of Alzheimer disease (AD). In this study, we performed functional magnetic resonance imaging (fMRI) to investigate whether the presence of apolipoprotein E (APOE) epsilon allele and degree of memory impairment were associated with the dysfunction of these brain regions. Seventy-five elderly subjects ranging from cognitively normal to mild AD, divided into epsilon carriers and noncarriers, underwent fMRI during a memory-encoding task. Across all subjects, posteromedial and ventral anterior cingulate cortices (key components of the default network) as well as right middle and inferior prefrontal regions demonstrated reduced task-induced deactivation in the epsilon carriers relative to noncarriers. Even among cognitively normal subjects, epsilon carriers demonstrated reduced posteromedial deactivation compared with the noncarriers in the same regions which demonstrated failure of deactivation in AD patients. Greater failure of posteromedial deactivation was related to worse memory performance (delayed recall) across all subjects and within the range of cognitively normal subjects. In summary, the posteromedial cortical fMRI response pattern is modulated both by the presence of APOE epsilon and episodic memory capability. Altered fMRI activity of the posteromedial areas of the brain default network may be an early indicator of risk for AD.

A comprehensive protocol to diagnose and treat pain of muscular origin may successfully and reliably decrease or eliminate pain in a chronic pain population.

OBJECTIVE: A comprehensive protocol is presented to identify muscular causes of regional pain syndromes utilizing an electrical stimulus in lieu of palpation, and combining elements of Prolotherapy with trigger point injections. METHODS: One hundred seventy-six consecutive patients were evaluated for the presence of muscle pain by utilizing an electrical stimulus produced by the Muscle Pain Detection Device. The diagnosis of "Muscle Pain Amenable to Injection" (MPAI), rather than trigger points, was made if pain was produced for the duration of the stimulation. If MPAI was found, muscle tendon injections (MTI) were offered to patients along with post-MTI physical therapy, providing neuromuscular electrical stimulation followed by a validated exercise program [1]. A control group, evaluated 1 month prior to their actual consultation/evaluation when muscle pain was identified but not yet treated, was used for comparison. RESULTS: Forty-five patients who met criteria completed treatment. Patients' scores on the Brief Pain Inventory decreased an average of 62%; median 70% (P < 0.001) for pain severity and 68%; median 85% (P < 0.001) for pain interference one month following treatment. These changes were significantly greater (P < 0.001) than those observed in the untreated controls. CONCLUSION: A protocol incorporating an easily reproducible electrical stimulus to diagnose a muscle causing pain in a region of the body followed by an injection technique that involves the entirety of the muscle, and post injection restoration of muscle function, can successfully eliminate or significantly reduce regional pain present for years.

An evidence-based approach to abnormal vision in the emergency department

Patients present to the ED with visual disturbances that may be painful or painless and may include loss of visual acuity, field cuts, diplopia, and headache. A detailed history and complete ocular examination are essential to obtaining the correct diagnosis and offering expedited treatment and referral. This review discusses the differential diagnosis for patients experiencing abnormal vision from a nontraumatic or minimally traumatic etiology, and reviews diagnostic and treatment strategies from an evidence-based perspective, including point-of-care ocular ultrasound. Management of the needs of special populations, such as patients with sickle cell disease, HIV, and those with a ventriculo-peritoneal shunt, is reviewed.

Application of the cloze procedure to evaluate comprehension and demonstrate rewriting of pharmacy educational materials.

BACKGROUND: Written materials are commonly used to communicate pharmacy-relevant information to patients. However, they are often composed at a level that limits comprehension, mitigating a well-intended effect. OBJECTIVE: To (1) use the cloze procedure (a test designed to assess reading comprehension) to evaluate an individual's understanding of a pharmacy-relevant educational pamphlet; (2) compare results of the cloze procedure with the reading comprehension component of the Short Test of Functional Health Literacy in Adults (S-TOFHLA); and (3) use results to demonstrate rewriting of the educational pamphlet. METHODS: The cloze procedure was applied to a pharmacy-relevant educational pamphlet describing safe medication practices. A total of 162 subjects were recruited from university faculty, staff, and students; a local adult literacy center; and community senior centers. Subjects completed a background interview, the S-TOFHLA, and cloze procedure for the pharmacy-relevant educational pamphlet. S-TOFHLA and cloze procedure scores were described and compared. Cloze procedure responses were used to demonstrate revision of the pamphlet. RESULTS: Of the 154 subjects analyzed, mean +/- SD age was 56.5 +/- 20.4 years. Subjects were predominantly white (93.5%), female (71.4%), and college graduates (42.2%). Mean score on the S-TOFHLA was 92.1%. A majority (95.5%, 147/154) of subjects demonstrated adequate functional health literacy. In contrast, mean score on the cloze procedure was 53.3%. Internal consistencies of the S-TOFHLA and the cloze procedure were 0.92 and 0.90, respectively. Scores on the cloze procedure and the S-TOFHLA were highly correlated (r = 0.71, p < 0.001). Performance on the cloze procedure indicated that 55.2% of subjects required supplemental teaching. CONCLUSIONS: In this highly educated, health-literate sample, a majority did not understand the pharmacy-relevant educational pamphlet despite adequate performance on a standard measure of health literacy. The cloze procedure can be used to assess comprehension of educational materials, solicit feedback from intended users, and guide the revision of educational materials.

Brief report: do individuals with autism spectrum disorder think they know their own minds?

How much do individuals with autism spectrum disorder (ASD) think they know about their inner states? To find out, we asked 24 participants with ASD and 24 non-clinical participants to rate how well they knew about six topics of self knowledge; they also rated how well a comparison individual knew these things about them. Participants with ASD differed from the non-clinical participants in assigning about the same amount of knowledge to the comparison individual as to themselves. Non-clinical participants, in contrast, assigned relatively more knowledge to themselves. The findings are consistent with the possibility that individuals with ASD do not appreciate the value of having first-person privileged access to their own inner states.

Promoting health communication between the community-dwelling well-elderly and pharmacists: the Ask Me 3 program.

OBJECTIVE: To describe readiness to use clear health communication principles with a pharmacist before and after participating in the Ask Me 3 (What is my main problem?, What do I need to do?, Why is it important for me to do this?) program. DESIGN: Modified, separate-sample, pretest-posttest study. SETTING: Senior centers in Polk County, IA, between March 2006 and February 2007. PARTICIPANTS: 106 community-dwelling well-elderly. INTERVENTION: Information on demographic characteristics, regularity of health care and medication use, health literacy level, and a measurement of multidimensional health locus of control were collected from participants, who were then were randomly allocated to one of three assessment subgroups: (1) pretest-posttest, (2) pretest only, and (3) posttest only during each of 12 Ask Me 3 program educational sessions. MAIN OUTCOME MEASURE: Readiness to use the seven principles of clear health communication described in the Ask Me 3 program. RESULTS: Participants were predominantly women and white, had a high school education or higher, had a yearly income of $25,000 or less, and had a mean age of 75.1 years. A majority reported good to excellent health status and visited their physician two or more times per year. All took medications regularly for a medical problem. A minority had inadequate to marginal health literacy. Before the Ask Me 3 program, a majority reported planning to or actively asking their pharmacist (1) for help with questions about their medications (88.2%), (2) to explain how to take their medication (82.6%), (3) to describe the main problem for which their medication is being prescribed (78.6%), and (4) to describe what can happen if they don't take their medication (74.3%). Approximately one-half of participants (55.2%) made a list of health or medication concerns to tell their pharmacist. A minority brought a list of current medications (47.8%) or brought a friend or family member to help when visiting their pharmacist (27.9%). A significantly higher proportion of participants reported planning to or actively bringing a list of current medications when visiting the pharmacist (P < or = 0.025) after participating in the Ask Me 3 program. Increases were not statistically significant for the remaining principles. CONCLUSION: The Ask Me 3 program is a practical tool that creates awareness and reinforces principles of clear health communication. The Ask Me 3 program should be evaluated in diverse pharmacy and health care settings with patients at high risk for poor health communication.