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91.
Implementing a screening and diagnosis program for dementia in primary care 总被引:1,自引:0,他引:1 下载免费PDF全文
Boustani M Callahan CM Unverzagt FW Austrom MG Perkins AJ Fultz BA Hui SL Hendrie HC 《Journal of general internal medicine》2005,20(7):572-577
BACKGROUND: Primary care physicians are positioned to provide early recognition and treatment of dementia. We evaluated the feasibility
and utility of a comprehensive screening and diagnosis program for dementia in primary care.
METHODS: We screened individuals aged 65 and older attending 7 urban and racially diverse primary care practices in Indianapolis.
Dementia was diagnosed according to International Classification of Diseases (ICD)-10 criteria by an expert panel using the
results of neuropsychologic testing and information collected from patients, caregivers, and medical records.
RESULTS: Among 3,340 patients screened, 434 scored positive but only 227 would agree to a formal diagnostic assessment. Among those
who completed the diagnostic assessment, 47% were diagnosed with dementia, 33% had cognitive impairment—no dementia (CIND),
and 20% were considered to have no cognitive deficit. The overall estimated prevalence of dementia was 6.0% (95% confidence
interval (CI) 5.5% to 6.6%) and the overall estimate of the program cost was $128 per patient screened for dementia and $3,983
per patient diagnosed with dementia. Only 19% of patients with confirmed dementia diagnosis had documentation of dementia
in their medical record.
CONCLUSIONS: Dementia is common and undiagnosed in primary care. Screening instruments alone have insufficient specificity to establish
a valid diagnosis of dementia when used in a comprehensive screening program; these results may not be generalized to older
adults presenting with cognitive complaints. Multiple health system and patient-level factors present barriers to this formal
assessment and thus render the current standard of care for dementia diagnosis impractical in primary care settings.
Supported by grant R01 HS10884-01 from the Agency for Healthcare Research and Quality. 相似文献
92.
Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans 总被引:3,自引:0,他引:3
Granowitz EV; Porat R; Mier JW; Orencole SF; Callahan MV; Cannon JG; Lynch EA; Ye K; Poutsiaka DD; Vannier E 《Blood》1993,82(10):2985-2990
Endotoxin is a component of gram-negative bacteria that causes hematologic and immunologic changes through its induction of cytokines. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1 that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We investigated the ability of human recombinant IL-1Ra to block the effects of low-dose endotoxin. Fourteen healthy male volunteers between 18 and 30 years old were injected intravenously with 3 ng/kg Escherichia coli endotoxin. Concurrent with the injections, nine volunteers received a 3-hour continuous intravenous infusion of IL-1Ra. The other five subjects were given a 3-hour infusion of saline. Volunteers injected with endotoxin experienced a threefold increase in circulating neutrophils over baseline. This neutrophilia was significantly reduced by 48% in subjects administered endotoxin plus IL-1Ra (P = .0253). Ex vivo mitogen-induced peripheral blood mononuclear cell proliferation decreased by greater than 60% at 3 and 6 hours after endotoxin injection (P = .0053). This endotoxin-induced reduction in mitogen response was reversed in subjects coinjected with IL-1Ra (P = .0253). Endotoxin-induced symptoms, fever, and tachycardia were unaffected by IL-1Ra. IL-1 appears to be an important mediator in endotoxemia because some of its hematologic and immunomodulatory effects can be blocked by IL-1Ra. 相似文献
93.
Vamsee V. A. Mallajosyula Michael Citron Francesca Ferrara Xianghan Lu Cheryl Callahan Gwendolyn J. Heidecker Siddhartha P. Sarma Jessica A. Flynn Nigel J. Temperton Xiaoping Liang Raghavan Varadarajan 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(25):E2514-E2523
Influenza hemagglutinin (HA) is the primary target of the humoral response during infection/vaccination. Current influenza vaccines typically fail to elicit/boost broadly neutralizing antibodies (bnAbs), thereby limiting their efficacy. Although several bnAbs bind to the conserved stem domain of HA, focusing the immune response to this conserved stem in the presence of the immunodominant, variable head domain of HA is challenging. We report the design of a thermotolerant, disulfide-free, and trimeric HA stem-fragment immunogen which mimics the native, prefusion conformation of HA and binds conformation specific bnAbs with high affinity. The immunogen elicited bnAbs that neutralized highly divergent group 1 (H1 and H5 subtypes) and 2 (H3 subtype) influenza virus strains in vitro. Stem immunogens designed from unmatched, highly drifted influenza strains conferred robust protection against a lethal heterologous A/Puerto Rico/8/34 virus challenge in vivo. Soluble, bacterial expression of such designed immunogens allows for rapid scale-up during pandemic outbreaks.Seasonal influenza outbreaks across the globe cause an estimated 250,000–500,000 deaths annually (1). Current influenza vaccines need to be updated every few years because of antigenic drift (2). Despite intensive monitoring, strain mismatch between vaccine formulation and influenza viruses circulating within the population has occurred in the past (2). Public health is further compromised when an unpredictable mixing event among influenza virus genomes leads to antigenic shift facilitating a potential pandemic outbreak. These concerns have expedited efforts toward developing a universal influenza vaccine.Neutralizing antibodies (nAbs) against hemagglutinin (HA) are the primary correlate for protection in humans and hence HA is an attractive target for vaccine development (3). The precursor polypeptide, HA0, is assembled into a trimer along the secretory pathway and transported to the cell surface. Cleavage of HA0 generates the disulfide-linked HA1 and HA2 subunits. Mature HA has a globular head domain which mediates receptor binding and is primarily composed of the HA1 subunit, whereas the stem domain predominantly comprises the HA2 subunit. The HA stem is trapped in a metastable state and undergoes an extensive low-pH-induced conformational rearrangement in the host-cell endosomes to adopt the virus–host membrane fusion-competent state (4, 5).The antigenic sites on the globular head of HA are subjected to heightened immune pressure resulting in escape variants, thereby limiting the breadth of head-directed nAbs (6). However, extensive efforts have resulted in the isolation of monoclonal antibodies (mAbs) that bind within the globular head and inhibit receptor attachment, which neutralize drifted variants of an HA subtype or heterosubtypic HA (7–16). The HA stem is targeted by several broadly neutralizing antibodies (bnAbs) with neutralizing activity against diverse influenza A virus subtypes (17). The epitopes of these bnAbs in the HA stem are more conserved across different influenza HA subtypes compared with the antigenic sites in the HA globular head (18).During a primary infection, the immunodominant globular head domain suppresses the response toward the conserved stem. Several efforts have been made to circumvent this problem. Repeated immunizations with full-length, chimeric HAs (cHAs) in a protracted vaccination regimen have been shown to boost stem-directed responses in mice (19). Alternatively, full-length HA presented on nanoparticles (np) has been shown to elicit stem-directed nAbs (20). Attempts have also been made to steer the immune response toward the conserved HA stem by hyperglycosylating the head domain (21). Although the aforementioned strategies need to be further evaluated and provide novel alternatives, detrimental interference from the highly variable immunodominant head domain in eliciting a broad functional response cannot be completely evaded. A “headless” stem domain immunogen offers an attractive solution. However, early attempts at expressing the HA2 subunit independently in a native, prefusion conformation were unsuccessful. In the absence of the head domain, the HA2 subunit expressed in Escherichia coli spontaneously adopted the low-pH conformation (22) in which the functional epitopes of stem-directed bnAbs are disrupted. More recently, the entire HA stem region has been expressed in a prefusion, native-like conformation in both prokaryotic and eukaryotic systems adopting multiple strategies (23–26).Design of independently folding HA stem fragments which adopt the prefusion HA conformation presents another approach to elicit bnAbs against influenza (27, 28). The A helix of the HA2 subunit contributes substantial contact surface to the epitope of stem-directed bnAbs such as CR6261, F10, and others. Although multivalent display of A helix on the flock house virus as a virus-like particle platform elicited cross-reactive antibodies, it conferred only minimal protection (20%) against virus challenge in mice (29).We report the design and characterization of engineered headless HA stem immunogens based on the influenza A/Puerto Rico/8/34 (H1N1) subtype. H1HA10-Foldon, a trimeric derivative of our parent construct (H1HA10), bound conformation-sensitive, stem-directed bnAbs such as CR6261 (30), F10 (31), and FI6v3 (32) with a high-affinity [equilibrium dissociation constant (KD) of 10–50 nM]. The designed immunogens elicited broadly cross-reactive antiviral antibodies which neutralized highly drifted influenza virus strains belonging to both group 1 (H1 and H5 subtypes) and 2 (H3 subtype) in vitro. Significantly, stem immunogens designed from unmatched, highly drifted influenza strains conferred protection against a lethal (2LD90) heterologous A/Puerto Rico/8/34 virus challenge in mice. Our immunogens confer robust subtype-specific and modest heterosubtypic protection in vivo. In contrast to previous stem domain immunogens (23–25), the designed immunogens were purified from the soluble fraction in E. coli. The HA stem-fragment immunogens do not aggregate even at high concentrations and are cysteine-free, which eliminates the complications arising from incorrect disulfide-linked, misfolded conformations. The aforementioned properties of the HA stem-fragment immunogens make it amenable for scalability at short notice which is vital during pandemic outbreaks. 相似文献
94.
95.
[目的]调查产后抑郁症患者的现状及需求,探讨预防措施。[方法]定性与定量研究相结合,定性采用专题小组讨论和半结构性访谈,12人参加专题讨论、9人半结构性访谈;定量研究随机抽取本市各社区产后42d的产妇776例行问卷调查。[结果]产妇月子期间常发生头疼、恶心、焦虑、恐惧、失眠以及照顾新生儿困难;半结构性访谈中有1产妇处于产后抑郁症的临界,EPDS量表测定为12分;776例产妇月子里有身心健康问题者692例,求助者91.0%,其中需要社区护理人员帮助的71.7%,实际寻求帮助仅12.7%。[结论]预防产后抑郁症应实行社区医护人员培训与产后访视人员的准入制度,采取社区医护干预的三级预防,同时拓展社区产后保健服务的内涵。 相似文献
96.
97.
Leigh F. Callahan Wendy J. Smith Theodore Pincus 《Arthritis \u0026amp; Rheumatology》1989,2(4):122-131
Self-report questionnaire scales to assess various constructs of health status were compared in 602 patients with five rheumatic diseases, including 134 rheumatoid arthritis (RA), 216 osteoarthritis (OA), 84 fibromyalgia, 124 systemic lupus erythematosus (SLE), and 43 scleroderma patients. RA patients showed significantly higher degrees of difficulty, dissatisfaction, and pain in performing eight activities of daily living (ADL) compared to patients with the other four diseases (P < 0.01), while SLE patients reported the least difficulty, dissatisfaction and pain. Fibromyalgia patients showed significantly higher scores on a visual analog pain scale than patients with the other four diseases (P < 0.05), followed by OA patients. Fibromyalgia patients reported significantly higher levels of learned helplessness, assessed according to a rheumatology attitudes index (RAI), than patients with all other diseases, and scleroderma patients showed significantly lower RAI scores (P < 0.05). Patients with all five diseases who had not completed high school showed poorer clinical status than patients who had completed high school on all six scales. Significant differences in questionnaire scores were seen for 24 of 30 comparisons (five diseases and six scales) according to formal education level, versus only two according to age, and none according to duration of disease. 相似文献
98.
Sebastian P. Mondaca MD Dazhi Liu PharmD BCOP Jessica R. Flynn Sandy Badson Stefan Hamaway BS Mrinal M. Gounder MD Danny N. Khalil MD PhD Alexander E. Drilon MD Bob T. Li MD MPH Komal L. Jhaveri MD Alison M. Schram MD Katherine E. Kargus RN Mary Kate Kasler DNP MSN Natalie M. Blauvelt Neil H. Segal MD PhD Marinela Capanu PhD Margaret K. Callahan MD PhD David M. Hyman MD Maya Gambarin-Gelwan MD James J. Harding MD 《Cancer》2020,126(22):4967-4974
99.
Scott D. Nash Tigist Astale Andrew W. Nute Danaya Bethea Ambahun Chernet Eshetu Sata Mulat Zerihun Demelash Gessese Gedefaw Ayenew Zebene Ayele Berhanu Melak Mahteme Haile Taye Zeru Zerihun Tadesse Benjamin F. Arnold Elizabeth Kelly Callahan Diana L. Martin 《The American journal of tropical medicine and hygiene》2021,104(1):207
100.
Daniel Callahan 《The Hastings Center report》2018,48(2):18-21
Steven Pinker, a cognitive psychologist and linguist at Harvard and a savant of big ideas, is one of the latest to take on the idea of progress. He does it under the aegis of “enlightenment,” which comes down to a kind of holy trinity of reason, science, and humanism. His new book, Enlightenment Now: The Case for Reason, Science, Humanism, and Progress, is ambitious and cantankerous and heady with hope. On the whole, Pinker makes a good case for the benefits of progress, but with an overdose of feel‐good prose. His greatest failure comes in exaggerating the threats to science and in avoiding some problems altogether. He ignores its complexity, its shadows, its creation of new problems raised by its solutions to old ones. Pinker has a particular animus against bioethics, and he misses what has been, I would argue, at the heart of bioethics from its beginning fifty or so years ago. Bioethics was prompted by a new class of medical dilemmas that require a difficult balancing of harms and benefits. Most of them are still with us, and most of them are the result of the progress of postwar medical research and fast‐changing clinical practices. 相似文献