Screening for cognitive impairment following ICU discharge is recommended but not part of routine care. We sought to understand older adults' perspectives on screening for cognitive impairment ...following an ICU admission to inform the design and delivery of a cognitive screening intervention.
Qualitative study using semi-structured interviews.
Adults 60 years and older within 3 months of discharge from an ICU in an academic health system.
Interviews were conducted via telephone, audio recorded and transcribed verbatim. All transcripts were coded in duplicate. Discrepancies were resolved by consensus. Codes were organized into themes and subthemes inductively.
We completed 22 interviews. The mean age of participants was 71 ± 6 years, 14 (63.6%) were men, 16 (72.7%) were White, and 6 (27.3%) were Black. Thematic analysis was organized around four themes: 1) receptivity to screening, 2) communication preferences, 3) information needs, and 4) provider involvement. Most participants were receptive to cognitive screening; this was influenced by trust in their providers and prior experience with cognitive screening and impairment. Participants preferred simple, direct, compassionate communication. They wanted to understand the screening procedure, the rationale for screening, and expectations for recovery. Participants desired input from their primary care provider to have their cognitive screening results placed in the context of their overall health, because they had a trusted relationship, and for convenience.
Participants demonstrated limited understanding of and exposure to cognitive screening but see it as potentially beneficial following an ICU stay. Providers should use simple, straightforward language and place emphasis on expectations. Resources may be needed to assist primary care providers with capacity to provide cognitive screening and interpret results for ICU survivors. Implementation strategies can include educational materials for clinicians and patients on rationale for screening and recovery expectations.
Airborne measurements of biomass burning organic aerosol (BBOA) from boreal forest fires reveal highly contrasting properties for plumes of different ages. These measurements, performed using an ...Aerodyne Research Inc. compact time-of-flight aerosol mass spectrometer (C-ToF-AMS) during the BORTAS (quantifying the impact of BOReal forest fires on Tropospheric oxidants over the Atlantic using Aircraft and Satellites) experiment in the summer of 2011, have been used to derive normalised excess organic aerosol (OA) mass concentrations ( Delta OA / Delta CO), with higher average ratios observed closer to source (0.190 plus or minus 0.010) than in the far-field (0.097 plus or minus 0.002). The difference in Delta OA / Delta CO between fresh and aged plumes is influenced by a change in dominant combustion conditions throughout the campaign. Measurements at source comprised 3 plume interceptions during a single research flight and sampled largely smouldering fires. Twenty-three interceptions were made across four flights in the far-field, with plumes originating from fires occurring earlier in the campaign when fire activity had been more intense, creating an underlying contrast in emissions prior to any transformations associated with aging. Changing combustion conditions also affect the vertical distribution of biomass burning emissions, as aged plumes from more flaming-dominated fires are injected to higher altitudes of up to 6000 m. Proportional contributions of the mass-to-charge ratio (m/z) 60 and 44 peaks in the AMS mass spectra to the total OA mass (denoted f60 and f44) are used as tracers for primary and oxidised BBOA, respectively. f44 is lower on average in near-field plumes than those sampled in the far-field, in accordance with longer aging times as plumes are transported a greater distance from source. However, high levels of Delta O3 / Delta CO and -log(NOx / NOy) close to source indicate that emissions can be subject to very rapid oxidation over short timescales. Conversely, the lofting of plumes into the upper troposphere can lead to the retention of source profiles after transportation over extensive temporal and spatial scales, with f60 also higher on average in aged plumes. Evolution of OA composition with aging is comparable to observations of BB tracers in previous studies, revealing a consistent progression from f60 to f44. The elevated levels of oxygenation in aged plumes, and their association with lower average Delta OA / Delta CO, are consistent with OA loss through evaporation during aging due to a combination of dilution and chemical processing, while differences in combustion conditions throughout the campaign also have a significant influence on BBOA production and composition.
Objectives Recent advances in airway transplantation have shown the ability of ex vivo or in vivo tracheal regeneration with bioengineered conduits or biological substitutes, respectively. ...Previously, we established a process of in vivo–guided tracheal regeneration using vascular allografts as a biological scaffold. We theorized that tracheal healing was the consequence of a mixed phenomenon associating tracheal contraction and regeneration. The aim of the present study was to determine the role that bone marrow stem cells play in that regenerative process. Methods Three groups of 12 rabbits underwent a gender-mismatched aortic graft transplantation after tracheal resection. The first group received no cells (control group), the second group had previously received autologous green fluorescent protein–labeled mesenchymal stem cell transplantation, and the third group received 3 labeled mesenchymal stem cell injections on postoperative days 0, 10, and 21. Results The clinical results were impaired by stent complications (obstruction or migration), but no anastomotic leakage, dehiscence, or stenosis was observed. The rabbits were killed, and the trachea was excised for analysis at 1 to 18 months after tracheal replacement. In all 3 groups, microscopic examination showed an integrated aortic graft lined by metaplastic epithelium. By 12 months, immature cartilage was detected among disorganized elastic fibers. Positive SRY gene detection served as evidence for engraftment of cells derived from the male recipient. EF-green fluorescent protein detection showed bone marrow–derived mesenchymal stem cell involvement. Conclusions The results of the present study imply a role for bone marrow stem cells in tracheal regeneration after aortic allografting. Studies are necessary to identify the local and systemic factors stimulating that regenerative process.
Objective
To evaluate the oncologic and functional outcomes of transoral laser microsurgery (TLM) for glottic cancers in patients ≥80 years.
Study Design
Prospectively collected case series.
Setting
...QEII Health Sciences Centre, Halifax, Canada.
Methods
This case series used a prospectively collected glottic cancer database to examine consecutive elderly patients (≥80 years old) undergoing TLM. Kaplan-Meier analysis was used to evaluate rates of disease-free, disease-specific, and overall survival as the primary end points of oncologic control. Secondary functional outcomes included voice function, length of hospital stay, and time to readmission.
Results
From 2005 to 2017, 17 octogenarian patients underwent TLM for glottic cancer. Median follow-up was 4.19 years (interquartile range, 0.71-6.95). Kaplan-Meier estimates of 5-year survival were 78.4% (disease free), 92.9% (disease specific), and 81.9% (overall). The median length of hospital stay was 1 day (range, 0-8). There was only 1 readmission within 30 days of surgery. No patients in this study developed significant surgical or postoperative complications requiring unplanned readmissions. Patient-perceived voice function improved to normal after treatment in 62.5% of patients.
Conclusion
The results of this study suggest that TLM is a safe and effective treatment modality for glottic cancer in patients aged ≥80 years, providing good oncologic control and satisfactory functional outcomes.
Abstract Objectives The aim of this paper was to identify sex differences in survival of patients awaiting orthotopic heart transplantation (OHT). Background Women have a higher mortality rate while ...awaiting OHT than men, and the reason has not been fully determined. Methods We included all adult patients in the Scientific Registry of Transplant Recipients (SRTR) placed on the OHT waiting list from 2000 to 2010. The primary endpoint was all-cause mortality before receiving OHT, analyzed using time-to-event analysis. Multivariate Cox proportional hazards models were used to evaluate sex differences in survival, with data stratified by United Network for Organ Sharing (UNOS) status at time of listing. Results There were 28,852 patients (24% women) awaiting OHT. This cohort included 6,163 UNOS status 1A (25% women), 9,168 UNOS status 1B (25% women), and 13,521 UNOS status 2 (24% women) patients. During a median follow-up of 3.7 years, 1,290 women and 4,286 men died. Female sex was associated with a significant risk of death among UNOS status 1A (adjusted hazard ratio HR: 1.20; 95% confidence interval CI: 1.05 to 1.37, p = 0.01) after adjusting for more than 30 baseline variables. In contrast, female sex was significantly protective for time to death among UNOS status 2 patients (adjusted HR: 0.75; 95% CI: 0.67 to 0.84, p < 0.001). No sex differences were noted among UNOS status 1B patients. Conclusions There are sex differences in survival between women and men awaiting heart transplantation, and the current UNOS transplant criteria do not account for this disparity.
Women with coronary heart disease (CHD) have higher mortality compared with men. Atherosclerotic imaging risk markers are associated with higher mortality and relative risk of CHD events in women ...compared with men. However, data on the predictive accuracy of coronary artery calcium (CAC) in women are scarce. We performed a systematic review of the published literature from 2003 to 2006 on the prognostic value of CAC in women and men. Two investigators reviewed Medline for prospective registries on annual rates of CHD death or myocardial infarction (MI) by CAC results. Three studies in 6,481 women and 13,697 men reported results by gender. We also analyzed 2 observational registries for annual all-cause death rates by CAC scores in women (n = 17,779) and men (n = 17,850). Summary relative risk ratios and 95% confidence intervals were calculated using a random effects model. For all-cause mortality, rates were 0.1% to 1.6% per year for women and 0.1% to 2.6% for men with CAC scores from 0 to 10 to ≥1,000, respectively (p <0.0001). For CHD death or MI, annual rates were 0.2% to 1.3% in women and 0.3% to 2.4% for men with low- to high-risk CAC scores. For women with a CAC score of 0, annual CHD death or MI rates were 0.16%, similar to that of men (p = 0.55). Summary relative risk ratios increased 4.9-fold (p = 0.006), 5.5-fold (p = 0.002), and 8.7-fold (p <0.0001) for mild-, moderate-, and high-risk CAC scores, respectively. A comparative analysis of gender differences showed no significant differences between women and men for mild- to high-risk CAC scores (p = 0.66), suggesting an equivalent ability to risk stratify by gender. In conclusion, this meta- and pooled analysis revealed that CAC screening is equally accurate in stratifying risk in women and men.
Objectives Ultrasound-mediated gene delivery can be amplified by acoustic disruption of microbubble carriers that undergo cavitation. We hypothesized that endothelial targeting of microbubbles ...bearing cDNA is feasible and, through optimizing proximity to the vessel wall, increases the efficacy of gene transfection. Background Contrast ultrasound-mediated gene delivery is a promising approach for site-specific gene therapy, although there are concerns with the reproducibility of this technique and the safety when using high-power ultrasound. Methods Cationic lipid-shelled decafluorobutane microbubbles bearing a targeting moiety were prepared and compared with nontargeted microbubbles. Microbubble targeting efficiency to endothelial adhesion molecules (P-selectin or intercellular adhesion molecule ICAM-1) was tested using in vitro flow chamber studies, intravital microscopy of tumor necrosis factor-alpha (TNF-α)–stimulated murine cremaster muscle, and targeted contrast ultrasound imaging of P-selectin in a model of murine limb ischemia. Ultrasound-mediated transfection of luciferase reporter plasmid charge coupled to microbubbles in the post-ischemic hindlimb muscle was assessed by in vivo optical imaging. Results Charge coupling of cDNA to the microbubble surface was not influenced by the presence of targeting ligand, and did not alter the cavitation properties of cationic microbubbles. In flow chamber studies, surface conjugation of cDNA did not affect attachment of targeted microbubbles at microvascular shear stresses (0.6 and 1.5 dyne/cm2 ). Attachment in vivo was also not affected by cDNA according to intravital microscopy observations of venular adhesion of ICAM-1–targeted microbubbles and by ultrasound molecular imaging of P-selectin–targeted microbubbles in the post-ischemic hindlimb in mice. Transfection at the site of high acoustic pressures (1.0 and 1.8 MPa) was similar for control and P-selectin–targeted microbubbles but was associated with vascular rupture and hemorrhage. At 0.6 MPa, there were no adverse bioeffects, and transfection was 5-fold greater with P-selectin–targeted microbubbles. Conclusions We conclude that ultrasound-mediated transfection at safe acoustic pressures can be markedly augmented by endothelial juxtaposition.
Syndromes of Thrombotic Microangiopathy Shatzel, Joseph J; Taylor, Jason A
The Medical clinics of North America,
03/2017, Letnik:
101, Številka:
2
Journal Article
Recenzirano
Thrombotic thrombocytopenia purpura (TTP) and the hemolytic uremic syndrome (HUS) are rare thrombotic microangiopathies that can be rapidly fatal. Although the acquired versions of TTP and HUS are ...generally highest on this broad differential, multiple rarer entities can produce a clinical picture similar to TTP/HUS, including microangiopathic hemolysis, renal failure, and neurologic compromise. More recent analysis has discovered a host of genetic factors that can produce microangiopathic hemolytic syndromes. This article discusses the current understanding of thrombotic microangiopathy and outlines the pathophysiology and causative agents associated with each distinct syndrome as well as the most accepted treatments.
Radiation therapy remains the standard of care for many cancers, including the malignant pediatric brain tumor medulloblastoma. Radiation leads to long-term side effects, whereas radioresistance ...contributes to tumor recurrence. Radio-resistant medulloblastoma cells occupy the perivascular niche. They express Yes-associated protein (YAP), a Sonic hedgehog (Shh) target markedly elevated in Shh-driven medulloblastomas. Here we report that YAP accelerates tumor growth and confers radioresistance, promoting ongoing proliferation after radiation. YAP activity enables cells to enter mitosis with un-repaired DNA through driving insulin-like growth factor 2 (IGF2) expression and Akt activation, resulting in ATM/Chk2 inactivation and abrogation of cell cycle checkpoints. Our results establish a central role for YAP in counteracting radiation-based therapies and driving genomic instability, and indicate the YAP/IGF2/Akt axis as a therapeutic target in medulloblastoma.
Objective: Inadequate response to clozapine treatment is frequently encountered in practice and augmentation strategies have been developed in an attempt to improve response. Aims of the study were ...to evaluate the therapeutic effect of adding an antipsychotic drug to clozapine treatment.
Method: Meta‐analysis of randomized, placebo‐controlled studies of antipsychotic augmentation of clozapine treatment.
Results: Ten studies (including 522 subjects) met inclusion criteria. Antipsychotic augmentation showed significant benefit over the addition of placebo on only one outcome measure examined mean effect size for rating scale score (BPRS/PANSS) −0.180, 95% CI −0.356 to −0.004. Antipsychotic augmentation showed no advantage on withdrawals from trials (risk ratio 1.261, 95% CI 0.679–2.345) or on CGI scores (effect size −0.661, 95% CI −1.475 to 0.151). Duration of study was not associated with outcome (P = 0.95). There was no evidence of publication bias.
Conclusion: In studies lasting up to 16 weeks, the addition of an antipsychotic to clozapine treatment has marginal therapeutic benefit. Longer and larger trials are necessary to demonstrate the precise therapeutic utility of antipsychotic co‐therapy with clozapine.
PDF
