Preventing and treating delirium in clinical settings for older adults.

Delirium is a serious consequence of many acute or worsening chronic medical conditions, a side effect of medications, and a precipitant of worsening functional and cognitive status in older adults. It is a syndrome characterized by fluctuations in cognition and impaired attention that develops over a short period of time in response to an underlying medical condition, a substance (prescribed, over the counter, or recreational), or substance withdrawal and can be multi-factorial. We present a narrative review of the literature on nonpharmacologic and pharmacologic approaches to prevention and treatment of delirium with a focus on older adults as a vulnerable population. Older adult patients are most at risk due to decreasing physiologic reserves, with delirium rates of up to 80% in critical care settings. Presentation of delirium can be hyperactive, hypoactive, or mixed, making identification and study challenging as patients with hypoactive delirium are less likely to come to attention in an inpatient or long-term care setting. Studies of delirium focus on prevention and treatment with nonpharmacological or medication interventions, with the preponderance of evidence favoring multi-component nonpharmacological approaches to prevention as the most effective. Though use of antipsychotic medication in delirium is common, existing evidence does not support routine use, showing no clear benefit in clinically significant outcome measures and with evidence of harm in some studies. We therefore suggest that antipsychotics be used to treat agitation, psychosis, and distress associated with delirium at the lowest effective doses and shortest possible duration and not be considered a treatment of delirium itself. Future studies may clarify the use of other agents, such as melatonin and melatonin receptor agonists, alpha-2 receptor agonists, and anti-epileptics.

Treatment with posterior capsular release, botulinum toxin injection, hamstring tenotomy, and peroneal nerve decompression improves flexion contracture after total knee arthroplasty: minimum 2-year follow-up.

PURPOSE: No definite treatment option with reasonable outcome has been presented for old and refractory flexion contracture after total knee arthroplasty (TKA). We describe a surgical technique for 21 refractory cases of knee flexion contracture, including 12 patients with history of failed manipulation under anesthesia (MUA). METHODS: Retrospective review was conducted for procedures performed by a single surgeon between 2005 and 2016. Twenty-one knees (19 patients) with knee flexion contracture after primary TKA were treated with all the following procedures: posterior capsular release, hamstring tenotomy, prophylactic peroneal nerve decompression, and botulinum toxin type A injections. Twelve of the 21 knees had at least 1 prior unsuccessful MUA before this soft-tissue release procedure. Mean age at intervention was 60 years (range 46-78 years). Mean preoperative knee range of motion (ROM) was - 27° extension (range - 20° to - 40°) to 100° flexion (range 90°-115°). All radiographs were evaluated for proper component sizing and signs of loosening. RESULTS: Full extension was achieved immediately after surgery in all patients. Only one knee required repeat botulinum toxin type A injection. All patients had full extension at mean follow-up of 31 months (range 24-49 months). No significant change was observed in knee flexion after the procedure (n.s.). Significant improvement was noted in the postoperative Knee Society Score (KSS) (mean 80, range 70-90) when compared with preoperative KSS (mean 45, range 25-65) (p = 0.008). CONCLUSION: The proposed surgical technique is efficacious in treating patients with refractory knee flexion contracture following TKA to gain and maintain full extension at minimum 2-year follow-up. LEVEL OF EVIDENCE: IV, retrospective case series.

Asymmetric pathology in primary progressive aphasia with progranulin mutations and TDP inclusions.

OBJECTIVE: To investigate quantitative regional distribution and hemispheric asymmetry of TDP-43 (TAR DNA-binding protein 43) inclusions, neurons, and activated microglia in primary progressive aphasia (PPA) with progranulin (GRN) mutations, and to determine concordance between distribution of pathology, clinical phenotype, and known atrophy patterns. METHODS: Antibodies to phospho-TDP-43, NeuN (neuronal nuclei), and HLA-DR were used to visualize inclusions, neurons, and activated microglia in paraffin-embedded tissue sections from 4 participants with PPA: 2 of the agrammatic and 2 of the logopenic subtype. Unbiased stereological counting techniques were used for quantitation of immunoreactive profiles in language- and memory-related cortical areas bilaterally. Patterns of pathology across cortical areas and hemispheres were compared and their relationships with known patterns of atrophy investigated. RESULTS: Numerical densities of TDP-43 inclusions, and less so of activated microglia, were greater in language-related areas compared with memory-related areas. In language areas, neuronal density displayed a pattern opposite to inclusions and activated microglia. Densities of inclusions and microglia were greater (p < 0.05), and densities of neurons were lower (p < 0.005), in the left hemisphere compared with the right. In agrammatic PPA, the highest densities of TDP-43 inclusions were observed in left inferior or middle frontal gyri, and in logopenic participants, the highest density of inclusions was seen in left inferior parietal lobule. This distribution is consistent with subtype-specific peak atrophy sites. CONCLUSIONS: Distribution of TDP-43 inclusions and neurons, and to a smaller extent of activated microglia, show a regional and hemispheric pattern consistent with disease phenotype and known patterns of atrophy in PPA with GRN mutations.

International Biological Engagement Programs Facilitate Newcastle Disease Epidemiological Studies.

Infections of poultry species with virulent strains of Newcastle disease virus (NDV) cause Newcastle disease (ND), one of the most economically significant and devastating diseases for poultry producers worldwide. Biological engagement programs between the Southeast Poultry Research Laboratory (SEPRL) of the United States Department of Agriculture and laboratories from Russia, Pakistan, Ukraine, Kazakhstan, and Indonesia collectively have produced a better understanding of the genetic diversity and evolution of the viruses responsible for ND, which is crucial for the control of the disease. The data from Kazakhstan, Russia, and Ukraine identified possible migratory routes for birds that may carry both virulent NDV (vNDV) and NDV of low virulence into Europe. In addition, related NDV strains were isolated from wild birds in Ukraine and Nigeria, and from birds in continental USA, Alaska, Russia, and Japan, identifying wild birds as a possible mechanism of intercontinental spread of NDV of low virulence. More recently, the detection of new sub-genotypes of vNDV suggests that a new, fifth, panzootic of ND has already originated in Southeast Asia, extended to the Middle East, and is now entering into Eastern Europe. Despite expected challenges when multiple independent laboratories interact, many scientists from the collaborating countries have successfully been trained by SEPRL on molecular diagnostics, best laboratory practices, and critical biosecurity protocols, providing our partners the capacity to further train other employes and to identify locally the viruses that cause this OIE listed disease. These and other collaborations with partners in Mexico, Bulgaria, Israel, and Tanzania have allowed SEPRL scientists to engage in field studies, to elucidate more aspects of ND epidemiology in endemic countries, and to understand the challenges that the scientists and field veterinarians in these countries face on a daily basis. Finally, new viral characterization tools have been developed and are now available to the scientific community.

Loss of calbindin-D28K is associated with the full range of tangle pathology within basal forebrain cholinergic neurons in Alzheimer's disease.

Basal forebrain cholinergic neurons (BFCN) are selectively vulnerable in Alzheimer's disease (AD). We have shown that most of the BFCN in the human brain contain the calcium-binding protein calbindin-D28K (CB), a large proportion lose their CB in the course of normal aging, and the BFCN which degenerate in AD lack CB. Here, we investigated the relationship between CB in the BFCN and the process of tangle formation in AD using antibodies to tau epitopes that appear early, intermediate or late in the process of tangle formation. Very small percentages (0%-3.7%) of CB-positive BFCN contained pretangles and/or tangles, and very small percentages (0%-5%) of the total BFCN pretangles and/or tangles were in CB-immunoreactive neurons. The number of CB-positive BFCN which contained tau immunoreactivity was highest for the early epitope and lower for intermediate epitopes. A late appearing epitope was absent from CB-positive BFCN. Age-related loss of CB appears to coincide with tangle formation in the BFCN and is associated with the full range of tau pathology, including late appearing epitopes.

Morphometric and histologic substrates of cingulate integrity in elders with exceptional memory capacity.

This human study is based on an established cohort of "SuperAgers," 80+-year-old individuals with episodic memory function at a level equal to, or better than, individuals 20-30 years younger. A preliminary investigation using structural brain imaging revealed a region of anterior cingulate cortex that was thicker in SuperAgers compared with healthy 50- to 65-year-olds. Here, we investigated the in vivo structural features of cingulate cortex in a larger sample of SuperAgers and conducted a histologic analysis of this region in postmortem specimens. A region-of-interest MRI structural analysis found cingulate cortex to be thinner in cognitively average 80+ year olds (n = 21) than in the healthy middle-aged group (n = 18). A region of the anterior cingulate cortex in the right hemisphere displayed greater thickness in SuperAgers (n = 31) compared with cognitively average 80+ year olds and also to the much younger healthy 50-60 year olds (p < 0.01). Postmortem investigations were conducted in the cingulate cortex in five SuperAgers, five cognitively average elderly individuals, and five individuals with amnestic mild cognitive impairment. Compared with other subject groups, SuperAgers showed a lower frequency of Alzheimer-type neurofibrillary tangles (p < 0.05). There were no differences in total neuronal size or count between subject groups. Interestingly, relative to total neuronal packing density, there was a higher density of von Economo neurons (p < 0.05), particularly in anterior cingulate regions of SuperAgers. These findings suggest that reduced vulnerability to the age-related emergence of Alzheimer pathology and higher von Economo neuron density in anterior cingulate cortex may represent biological correlates of high memory capacity in advanced old age.

Repeated Δ9-tetrahydrocannabinol exposure in adolescent monkeys: persistent effects selective for spatial working memory.

OBJECTIVE: Epidemiological findings suggest that, relative to adults, adolescents are more vulnerable to the adverse persistent effects of cannabis on working memory. However, the potential confounds inherent in human studies preclude direct determination of a cause-and-effect relationship between adolescent cannabis use and heightened susceptibility to persistent working memory impairments. Consequently, the authors examined the effects of repeated exposure to Δ9-tetrahydrocannabinol (THC) on performance of spatial and object working memory tasks in adolescent monkeys. METHOD: Seven pairs of male adolescent rhesus monkeys, matched for baseline cognitive performance, received vehicle or THC intravenously 5 days/week for 6 months. Performance on spatial and object memory tasks was assessed 23 or 71 hours after drug administration throughout the study. In addition, acute effects on working memory were also assessed at the beginning and end of the 6-month period. RESULTS: Relative to the vehicle-exposed control animals, those with repeated THC exposure had a blunted trajectory of accuracy improvements on the spatial working memory task in a delay-dependent manner. Accuracy improvements on the object working memory task did not differ between groups. Relative to the acute effects of THC on working memory at the beginning of the study, neither sensitivity nor tolerance was evident after 6 months of THC exposure. CONCLUSIONS: Because maturation of performance is later for spatial than for object working memory, these findings suggest that persistent effects of THC on cognitive abilities are more evident when exposure coincides with the developmental stage during which the underlying neural circuits are actively maturing.

Prevalence of adjunctive antipsychotic treatment for non -psychotic predominantly Latino depressed adults: a retrospective study / Prevalencia del tratamiento adjunto con antipsicóticos en pacientes adultos predominantemente Latinos con depresión no psicótica: Un estudio retrospectivo

The use of atypical antipsychotics as an adjunctive therapy to antidepressants for treating non-psychotic major depressive disorder (MDD) has been a common practice long before large-scale randomized double-blind placebo-controlled clinical trials demonstrated their efficacy. In this study, we aimed to study the frequency with whichpatients with non-psychotic major depression were prescribed antipsychotics (AP) and to examine the effect of age, race, and ethnicity on the type and dose of individual antipsychotics prescribed, in a cohort of patients before the recent Food and Drug Administration (FDA) approval of adjunctive aripiprazole. The charts of 1537 patients with unipolar depression were analyzed. 1376 had non-psychotic depression; among them 466 (33.9%) patients were prescribed antipsychotics with a significant predilection towards males (males vs. females: 41.7% vs. 27.8%. z=2.4, p<.02; odds ratio=1.97 with a standard error of 0.57) of Hispanic origin (X 2 = 35.8, df = 1, p < 0.0001).Quetiapine was the most commonly prescribed antipsychotic (n=209, 44.8%) with a mean (±SEM) 195.1±13.1 mg. Our results confirm previous reports of the common clinical practice of the use of atypical antipsychotics, specifically quetiapine, as adjunctive treatment for non-psychotic patients with unipolar depression. Further research is required to study the long term effect of this class of medications in patients without a primary psychotic disorder.

El uso de antipsicóticos atípicos como terapia adjunta a antidepresivos en el tratamiento del trastorno depresivomayor (TDM) no psicótico fue práctica común por un largo periodo antes de que los ensayos clínicos a doble-ciego,controlados (con placebo) y al azar, llevados a cabo a gran escala, demostraran su eficacia. El presente estudio se propuso evaluar la frecuencia con la cual pacientes diagnosticados con TDM recibieron tratamiento con agentes antipsicóticos (AP) y examinar los efectos de edad, raza y etnicidad sobre el tipo y dosis de los anti-psicóticos prescritos a una cohorte de pacientes antes de la reciente aprobación de aripiprazole por la Administración de Alimentos y Drogas (FDA), como medicación adjunta para el manejo de esta entidad clínica. Se analizaron lashistorias clínicas de 1537 pacientes portadores del diagnóstico de depresión unipolar. 1376 presentaron depresiónno psicótica y de ellos, 466 (33,9%) recibieron antipsicóticos con predominio de pacientes varones (hombres vs. mujeres: 41,7% vs. 27,8%. z=2,4, p<0,02; odds ratio (OR)=1,97, con error estándar (SE) de 0,57) de origen Hispánico (X2= 35,8, df = 1, p < 0,0001). Quetiapina fue el antipsicótico más comúnmente prescrito (n=209,44,8%) con una dosis promedio (±SEM) de 195,1±13,1 mg. Nuestros resultados confirman reportes previos del uso de antipsicóticos (específicamente quetiapina) en la práctica clínica habitual, como tratamiento adjunto en pacientesno psicóticos con diagnóstico de depresión unipolar. Se requiere investigación adicional que indague los efectos a largo plazo de este tipo de medicación en pacientes sin un diagnóstico de trastorno psicótico primario.

Evolution of dental school clinics as patient care delivery centers.

Dental school clinics, originally envisioned as closely similar to private practice, evolved instead as teaching clinics. In the former, graduate and licensed dentists perform the treatment while undergraduate dental students are assigned treatment within their capabilities. In the latter, dental students provide the treatment under faculty supervision. It is generally recognized that the care provided by the teaching clinics is inefficient. However, in the last quarter of the twentieth century, dental school clinics began to pay much more attention to how treatment is rendered. The comprehensive care movement and quality assurance systems are leading towards more efficient patient-centered care. Case studies at the University of Maryland, Columbia University, and University of Louisville describe activities to make their clinic programs more efficient and patient-friendly. This article explores whether the potential exists for faculty to take a direct patient care delivery role in dental clinics in order for those clinics to become efficient patient care delivery systems as originally envisioned in the early part of the twentieth century.

Academic tenure and higher education in the United States: implications for the dental education workforce in the twenty-first century.

This article reviews the literature related to the evolution and implementation of academic tenure (AT) in U.S. higher education. It is intended to highlight AT implications for the recruitment, retention, and development of the dental education workforce in the twenty-first century and the need for this workforce to implement change in dental education. The dental education workforce is shrinking, and a further decrease is projected, yet the demand for dental education is increasing. AT is becoming increasingly controversial, and the proportion of tenured to nontenured (i.e., contingent) faculty is declining within an already shrinking faculty pool. Confusion regarding the definition of scholarship and its relationship to research and publishing further confounds discussions about AT. Whether the principles of academic freedom and due process require tenure for their preservation in a democratic society is open to question. In view of competing time demands and increasing pressure to publish and apply for grants, factors including the seven-year probationary period for tenure, the decreased availability of tenured positions, and the often perceived inequities between tenured and contingent (i.e., nontenured track) faculty may pose an obstacle to faculty recruitment and retention. These factors may severely limit the diversity and skill mix of the dental education workforce, resulting in a decrease in staffing flexibility that appears to be needed in the twenty-first century. Politics, increasing dependence on grant funding by some institutions, resistance to change, and insufficient mentoring are all stimulating discussions about the future of tenure and its implications for U.S. dental education.

Evolution of dental school clinics as patient care delivery centers.

Dental school clinics, originally envisioned as closely similar to private practice, evolved instead as teaching clinics. In the former, graduate and licensed dentists perform the treatment while undergraduate dental students are assigned treatment within their capabilities. In the latter, dental students provide the treatment under faculty supervision. It is generally recognized that the care provided by the teaching clinics is inefficient. However, in the last quarter of the twentieth century, dental school clinics began to pay much more attention to how treatment is rendered. The comprehensive care movement and quality assurance systems are leading towards more efficient patient-centered care. Case studies at the University of Maryland, Columbia University, and University of Louisville describe activities to make their clinic programs more efficient and patient-friendly. This article explores whether the potential exists for faculty to take a direct patient care delivery role in dental clinics in order for those clinics to become efficient patient care delivery systems as originally envisioned in the early part of the twentieth century.

Recruiting research participants at community education sites.

BACKGROUND: Minority groups are underrepresented in research, making it difficult to apply medical advances with confidence. In this study, we explored whether community-based cancer education sites and educators serving the African American community could be used to recruit minority participants to research. METHODS: We invited Individuals at community education sites to provide buccal scrapings, saliva samples, psychometric data, and personal information anonymously. RESULTS: Culturally aligned community sites (100%) collaborated in the research recruitment, as did 83% of the individuals at those sites. CONCLUSION: Community-based education sites offer exceptional promise for teaching about research benefits and recruiting members of minority groups to research studies.

Perspectives on affirmative action in academic dental institutions: the U.S. Supreme Court rulings in the University of Michigan cases.

In June 2003 the U.S. Supreme Court upheld the constitutionality of using race as a factor in higher education admissions decisions. This article considers the impact of the Supreme Court decisions on admissions procedures at selected academic dental institutions (ADI) and their parent institutions. We interviewed fifty-eight leaders considered to be individual stakeholders at seven ADI and their related parent institutions, state dental associations, and state legislatures using a common set of questions about the Supreme Court decisions. Educators from the ADI and their parent institutions were consistent in their responses that the rulings upheld affirmative action as necessary to achieve diversity. State organized dentistry officials did not appear to be as aware as others of the rulings, whereas legislators were mixed in their responses. Except for the University of Michigan undergraduate admissions procedures, it remains to be seen what the impact will be for other higher education institutions and for academic dental institutions. Although the rulings have provided guidelines for achieving diversity using race/ ethnicity as one of several factors, the rulings will possibly be challenged, thus requiring vigilance on the part of parent institutions and their ADI to ensure compliance with the spirit of the rulings and to avoid attack from opponents of affirmative action.