Innovative health technologies offer much to patients, clinicians, and health systems. Policy makers can, however, be slow to embrace innovation for many reasons, including a less robust body of evidence, perceived high costs, and a fear that once technologies enter the health system, they will be difficult to remove. Health technology funding decisions are usually made after a rigorous health technology assessment (HTA) process, including a cost analysis. However, by focusing on therapeutic value and cost-savings, the traditional HTA framework often fails to capture innovation in the assessment process. How HTA defines, evaluates, and values innovation is currently inconsistent, and it is generally agreed that by explicitly defining innovation would recognize and reward and, in turn, stimulate, encourage, and incentivize future innovation in the system. To foster innovation in health technology, policy needs to be innovative and utilize other HTA tools to inform decision making including horizon scanning, multicriteria decision analysis, and funding mechanisms such as managed agreements and coverage with evidence development. When properly supported and incentivized, and by shifting the focus from cost to investment, innovation in health technology such as genomics, point-of-care testing, and digital health may deliver better patient outcomes. Industry and agency members of the Health Technology Assessment International Asia Policy Forum (APF) met in Taiwan in November 2023 to discuss the potential of HTA to foster innovation, especially in the Asia region. Discussions and presentations during the 2023 APF were informed by a background paper, which forms the basis of this paper.

Background: With the emergence of antibiotic resistant threats and the need for appropriate antibiotic use, laboratory microbiology information is important to guide clinical decision making in nursing homes, where access to such data can be limited. Susceptibility data are necessary to inform antibiotic selection and to monitor changes in resistance patterns over time. To contribute to existing data that describe antibiotic resistance among nursing home residents, we summarized antibiotic susceptibility data from organisms commonly isolated from urine cultures collected as part of the CDC multistate, Emerging Infections Program (EIP) nursing home prevalence survey. Methods: In 2017, urine culture and antibiotic susceptibility data for selected organisms were retrospectively collected from nursing home residents’ medical records by trained EIP staff. Urine culture results reported as negative (no growth) or contaminated were excluded. Susceptibility results were recorded as susceptible, non-susceptible (resistant or intermediate), or not tested. The pooled mean percentage tested and percentage non-susceptible were calculated for selected antibiotic agents and classes using available data. Susceptibility data were analyzed for organisms with ≥20 isolates. The definition for multidrug-resistance (MDR) was based on the CDC and European Centre for Disease Prevention and Control’s interim standard definitions. Data were analyzed using SAS v 9.4 software. Results: Among 161 participating nursing homes and 15,276 residents, 300 residents (2.0%) had documentation of a urine culture at the time of the survey, and 229 (76.3%) were positive. Escherichia coli, Proteus mirabilis, Klebsiella spp, and Enterococcus spp represented 73.0% of all urine isolates (N = 278). There were 215 (77.3%) isolates with reported susceptibility data (Fig. 1). Of these, data were analyzed for 187 (87.0%) (Fig. 2). All isolates tested for carbapenems were susceptible. Fluoroquinolone non-susceptibility was most prevalent among E. coli (42.9%) and P. mirabilis (55.9%). Among Klebsiella spp, the highest percentages of non-susceptibility were observed for extended-spectrum cephalosporins and folate pathway inhibitors (25.0% each). Glycopeptide non-susceptibility was 10.0% for Enterococcus spp. The percentage of isolates classified as MDR ranged from 10.1% for E. coli to 14.7% for P. mirabilis. Conclusions: Substantial levels of non-susceptibility were observed for nursing home residents’ urine isolates, with 10% to 56% reported as non-susceptible to the antibiotics assessed. Non-susceptibility was highest for fluoroquinolones, an antibiotic class commonly used in nursing homes, and ≥ 10% of selected isolates were MDR. Our findings reinforce the importance of nursing homes using susceptibility data from laboratory service providers to guide antibiotic prescribing and to monitor levels of resistance.

Disclosures: None

Funding: None

Background: With an aging population, increasingly complex care, and frequent re-admissions, prevention of healthcare-associated infections (HAIs) in nursing homes (NHs) is a federal priority. However, few contemporary sources of HAI data exist to inform surveillance, prevention, and policy. Prevalence surveys (PSs) are an efficient approach to generating data to measure the burden and describe the types of HAI. In 2017, the Centers for Disease Control and Prevention (CDC) performed its first large-scale HAI PS through the Emerging Infections Program (EIP) to measure the prevalence and describe the epidemiology of HAI in NH residents. Methods: NHs from several states (CA, CO, CT, GA, MD, MN, NM, NY, OR, & TN) were randomly selected and asked to participate in a 1-day HAI PS between April and October 2017; participation was voluntary. EIP staff reviewed available medical records for NH residents present on the survey date to collect demographic and basic clinical information and infection signs and symptoms. HAIs with onset on or after NH day 3 were identified using revised McGeer infection definitions applied to data collected by EIP staff and were reported to the CDC through a web-based system. Data were reviewed by CDC staff for potential errors and to validate HAI classifications prior to analysis. HAI prevalence, number of residents with >1 HAI per number of surveyed residents ×100, and 95% CIs were calculated overall (pooled mean) and for selected resident characteristics. Data were analyzed using SAS v9.4 software. Results: Among 15,296 residents in 161 NHs, 358 residents with 375 HAIs were identified. The most common HAI sites were skin (32%), respiratory tract (29%), and urinary tract (20%). Cellulitis, soft-tissue or wound infection, symptomatic UTI, and cold or pharyngitis were the most common individual HAIs (Fig. 1). Overall HAI prevalence was 2.3 per 100 residents (95% CI, 2.1–2.6); at the NH level, the median HAI prevalence was 1.8 and ranged from 0 to 14.3 (interquartile range, 0–3.1). At the resident level (Fig. 2), HAI prevalence was significantly higher in persons admitted for postacute care with diabetes, with a pressure ulcer, receiving wound care, or with a device. Conclusions: In this large-scale survey, 1 in 43 NH residents had an HAI on a given day. Three HAI types comprised >80% of infections. In addition to identifying characteristics that place residents at higher risk for HAIs, these findings provide important data on HAI epidemiology in NHs that can be used to expand HAI surveillance and inform prevention policies and practices.

Funding: None

Disclosures: None

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a frequent cause of healthcare-associated infections (HAIs). The CDC Emerging Infections Program (EIP) conducted population and laboratory-based surveillance of CRPA in selected areas in 8 states from August 1, 2016, through July 31, 2018. We aimed to describe the molecular epidemiology and mechanisms of resistance of CRPA isolates collected through this surveillance. Methods: We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period; EIP sites submitted a systematic random sample of isolates to CDC for further characterization. Of 1,021 CRPA clinical isolates submitted, 707 have been sequenced to date using an Illumina MiSeq. Sequenced genomes were classified using the 7-gene multilocus sequence typing (MLST) scheme, and a core genome MLST (cgMLST) scheme was used to determine phylogeny. Antimicrobial resistance genes were identified using publicly available databases, and chromosomal mechanisms of carbapenem resistance were determined using previously validated genetic markers. Results: There were 189 sequence types (STs) among the 707 sequenced genomes (Fig. 1). The most frequently occurring were high-risk clones ST235 (8.5%) and ST298 (4.7%), which were found across all EIP sites. Carbapenemase genes were identified in 5 (<1%) isolates. Overall, 95.6% of the isolates had chromosomal mutations associated with carbapenem resistance: 93.2% had porinD-associated mutations that decrease membrane permeability to the drugs; 24.8% had mutations associated with overexpression of the multidrug efflux pump MexAB-OprM; and 22.9% had mutations associated with overexpression of the endogenous β-lactamase ampC. More than 1 such chromosomal resistance mutation type was present in 37.8% of the isolates. Conclusions: The diversity of the sequence types demonstrates that HAIs caused by CRPA can arise from a variety of strains and that high-risk clones are broadly disseminated across the EIP sites but are a minority of CRPA strains overall. Carbapenem resistance in P. aeruginosa was predominantly driven by chromosomal mutations rather than acquired mechanisms (ie, carbapenemases). The diversity of the CRPA isolates and the lack of carbapenemase genes suggest that this ubiquitous pathogen can readily evolve chromosomal resistance mechanisms, but unlike carbapenemases, these cannot be easily spread through horizontal transfer.

Funding: None

Disclosures: None

Background: Antibiotics are among the most commonly prescribed drugs in nursing homes; urinary tract infections (UTIs) are a frequent indication. Although there is no gold standard for the diagnosis of UTIs, various criteria have been developed to inform and standardize nursing home prescribing decisions, with the goal of reducing unnecessary antibiotic prescribing. Using different published criteria designed to guide decisions on initiating treatment of UTIs (ie, symptomatic, catheter-associated, and uncomplicated cystitis), our objective was to assess the appropriateness of antibiotic prescribing among NH residents. Methods: In 2017, the CDC Emerging Infections Program (EIP) performed a prevalence survey of healthcare-associated infections and antibiotic use in 161 nursing homes from 10 states: California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee. EIP staff reviewed resident medical records to collect demographic and clinical information, infection signs, symptoms, and diagnostic testing documented on the day an antibiotic was initiated and 6 days prior. We applied 4 criteria to determine whether initiation of treatment for UTI was supported: (1) the Loeb minimum clinical criteria (Loeb); (2) the Suspected UTI Situation, Background, Assessment, and Recommendation tool (UTI SBAR tool); (3) adaptation of Infectious Diseases Society of America UTI treatment guidelines for nursing home residents (Crnich & Drinka); and (4) diagnostic criteria for uncomplicated cystitis (cystitis consensus) (Fig. 1). We calculated the percentage of residents for whom initiating UTI treatment was appropriate by these criteria. Results: Of 248 residents for whom UTI treatment was initiated in the nursing home, the median age was 79 years [IQR, 19], 63% were female, and 35% were admitted for postacute care. There was substantial variability in the percentage of residents with antibiotic initiation classified as appropriate by each of the criteria, ranging from 8% for the cystitis consensus, to 27% for Loeb, to 33% for the UTI SBAR tool, to 51% for Crnich and Drinka (Fig. 2). Conclusions: Appropriate initiation of UTI treatment among nursing home residents remained low regardless of criteria used. At best only half of antibiotic treatment met published prescribing criteria. Although insufficient documentation of infection signs, symptoms and testing may have contributed to the low percentages observed, adequate documentation in the medical record to support prescribing should be standard practice, as outlined in the CDC Core Elements of Antibiotic Stewardship for nursing homes. Standardized UTI prescribing criteria should be incorporated into nursing home stewardship activities to improve the assessment and documentation of symptomatic UTI and to reduce inappropriate antibiotic use.

Funding: None

Disclosures: None

Background: The transmissibility of vaccine-strain viruses from immunocompromised patients, such as those with severe combined immune deficiency (SCID) is unknown. The infection control management of a patient diagnosed with SCID and infected with vaccine-strain varicella zoster virus (VZV) and measles virus is described below. A previously healthy, full-term boy was vaccinated at 14 months with measles mumps rubella varicella (MMR) vaccine. He had received prior vaccinations, including rotavirus, without adverse effects. During the 6 weeks after vaccination, the patient developed signs and symptoms clinically consistent with chicken pox and measles. An immune work-up revealed SCID. Methods: The Alberta Health Services (AHS) SCID protocol was followed to manage the patient upon admission at 17 months of age. Multiple meetings with various stakeholders were held to ensure appropriate precautions were followed to minimize the risk of pathogen transmission. Results: The patient was placed on airborne and contact precautions in a negative-pressure room. The pressure differential of the room to the corridor was continually monitored and displayed at the entry to the room. Staff known to be immune to VZV or measles were not required to wear an N95 respirator. All intrahospital movement of the patient was coordinated with the respective care teams and departments, including infection prevention and control, facilities maintenance and engineering, respiratory therapy, and diagnostic imaging. A mask was placed on the patient when movement outside the room was required. VZV testing was positive for the Oka/vaccine strain on all samples tested (ie, nasopharyngeal, skin, blood, and cerebrospinal fluid). Nasopharyngeal swabs and blood were PCR positive for measles genotype A/vaccine strain virus. Both viruses were persistently positive in spite of treatment with acyclovir, valganciclovir, varicella zoster immune globulin, and intravenous immune globulin. Conclusions: There is currently no documented transmission of measles vaccine-strain virus, and transmission of VZV vaccine-strain virus is rare. According to the AHS SCID protocol, the use of airborne and contact precautions for a patient identified with measles and/or VZV supersedes the use of a positive-pressure room for patients identified with SCID. Newborn screening for SCID was implemented in Alberta in June 2019. As a result, more SCID patients will be diagnosed earlier in their course, and therefore prior to most routine vaccinations. However, newborn screening will not pick up some types of combined immune deficiencies. Some children may still be at risk of vaccine-associated illnesses due to undiagnosed underlying immune deficiencies.

Funding: None

Disclosures: None

Acute change in mental status (ACMS), defined by the Confusion Assessment Method, is used to identify infections in nursing home residents. A medical record review revealed that none of 15,276 residents had an ACMS documented. Using the revised McGeer criteria with a possible ACMS definition, we identified 296 residents and 21 additional infections. The use of a possible ACMS definition should be considered for retrospective nursing home infection surveillance.

Trichodinids are parasites generally found on gills and skin of a broad number of aquatic animals. Only a small number of endozoic species has been reported from the urinary tract, intestine and urogenital system in some fish, amphibians and molluscs. This is the first report on the presence of endozoic trichodinids in the spleen, kidney and liver of shorthorn sculpin (Myoxocephalus scorpius). In the present study, trichodinids displayed some of the typical morphological characteristics of endozoic trichodinids with narrow blades and straight rays of adhesive disc denticles. The parasites were observed at a relatively high prevalence (23.9%). There was a positive correlation between intensity of endozoic trichodinids in the internal organs and ectozoic trichodinids on the gills (R = 0.5, n = 46, P < 0.001) whereas there was no correlation between intensity of endozoic trichodinids and the host's body length, body weight or liver weight. Infection levels of endozoic trichodinids were not dependent upon sculpin sex and there was no effect of sampling locations on prevalence and intensity of endozoic trichodinids.

This study aims to assess the validity of maternal recall for several perinatal variables 8–10 years after pregnancy in a twin sample. Retrospective information was collected 8–10 years after the delivery event in a cohort of mothers from the University of Southern California Twin Study (N = 611) and compared with medical records for validity analysis. Recall of most variables showed substantial to perfect agreement (κ = 0.60–1.00), with notable exceptions for specific medical problems during pregnancy (κ ≤ 0.40) and substance use when mothers provided continuous data (e.g., number of cigarettes per day; r ≤ 0.24). With the exception of delivery method, neonatal intensive care unit admission, birth weight, neonatal information, and post-delivery complications were also recalled with low accuracy. For mothers of twins, maternal recall is generally a valid measure for perinatal variables 10 years after pregnancy. However, caution should be taken regarding variables such as substance use, medical problems, birth length, and post-delivery complications.

The addition of high refractive index (RI) inorganic nanoparticles (NPs) to LED encapsulation materials can lead to higher light extraction efficiency. In addition, the NPs can be carriers for additional functionality such as color conversion. Using a simple “grafting-to” approach, bimodal polydimethylsiloxane (PDMS) brushes were grafted onto high-RI ZrO2 NPs. Subsequently, an organic phosphor, 6-[fluorescein-5(6)-carboxamido]hexanoic acid (FCHA), was attached onto the PDMS-grafted ZrO2 NPs via a facile ligand exchange process. The bimodal polymer brush design enables homogenous dispersion of the surface functionalized NPs within the silicone matrix. The functionalized NPs with ∼53 wt% ZrO2 core have a ∼0.08 higher RI than neat silicone, and the NP-filled silicone nanocomposites exhibit a transparency of ∼ 90% in the 550-800 nm wavelength range. In addition, the nanocomposites could be excited at a wavelength around 455 nm by a blue LED and undergo secondary yellow emission at around 571 nm. It is expected that the prepared nanocomposites can be used as high-efficiency, non-scattering, color-tuned materials for advanced LED encapsulation.

Phosphodiesterase 2 (PDE2) is an enzyme responsible for hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) to restrict intracellular signalling of these second messenger molecules. This study investigated how PDE2 inhibitor Bay 60-7550 affects the dysregulated glucocorticoid signalling in neuronal cells and regulates depressive behaviours after chronic stress in mice. We found that exposure of hippocampal neurons to corticosterone resulted in time- and concentration-dependent increases in PDE2 expression. These intriguing findings were confirmed in the hippocampal cell line HT-22. After corticosterone exposure for 24 h, HT-22 cells showed a concentration-dependent increase in mRNA levels for PDE2 subtypes, PDE2A1 and 2A3, as well as for the total PDE2A protein expression. Bay 60-7550 was found to reverse the cell lesion induced by corticosterone (50 μm). This neuroprotective effect was blocked by pretreatment with protein kinase G inhibitor KT5823, but not protein kinase A inhibitor H89, suggesting the involvement of cGMP-dependent signalling. Although Bay 60-7550 treatment for 24 h did not change the levels of phosphorylated mitogen-activated protein kinases ERK1/2 (pERK) and phosphorylated cAMP response element-binding protein (pCREB), it down-regulated pERK at 2 h and up-regulated a CREB co-activator, CREB-binding protein, at 24 h. Both of these effects were blocked by KT 5823. Furthermore, Bay 60-7550 reversed corticosterone-induced down-regulation of brain-derived neurotrophic factor protein levels 24 h after corticosterone exposure. In behavioural testing, Bay 60-7550 produced antidepressant-like effects and reduced corticosterone levels in stressed mice, further supporting the involvement of a PDE2-dependent pathway in mediating Bay 60-7550's effect during stress hormone insults.

Polymer nanocomposites (PNC) are complex material systems in which the dominant length scales converge. Our approach to understanding nanocomposite tradespace uses Materials Quantitative Structure-Property Relationships (MQSPRs) to relate molecular structures to the polar and dispersive components of corresponding surface tensions. If the polar and dispersive components of surface tensions in the nanofiller and polymer could be determined a priori, then the propensity to aggregate and the change in polymer mobility near the particle could be predicted. Derived energetic parameters such as work of adhesion, work of spreading and the equilibrium wetting angle may then used as input to continuum mechanics approaches that have been shown able to predict the thermomechanical response of nanocomposites and that have been validated by experiment. The informatics approach developed in this work thus enables future in silico nanocomposite design by enabling virtual experiments to be performed on proposed nanocomposite compositions prior to fabrication and testing.

This study examined whether participation in a variety of lifestyle activities was comparable to frequent participation in cognitively challenging activities in mitigating impairments in cognitive abilities susceptible to aging in healthy, community-dwelling older women. Frequencies of participation in various lifestyle activities on the Lifestyle Activities Questionnaire (LAQ) were divided according to high (e.g., reading), moderate (e.g., discussing politics), and low (e.g., watching television) cognitive demand. We also considered the utility of participation in a variety of lifestyle activities regardless of cognitive challenge. Immediate and delayed verbal recall, psychomotor speed, and executive function were each measured at baseline and at five successive exams, spanning a 9.5-year interval. Greater variety of participation in activities, regardless of cognitive challenge, was associated with an 8 to 11% reduction in the risk of impairment in verbal memory and global cognitive outcomes. Participation in a variety of lifestyle activities was more predictive than frequency or level of cognitive challenge for significant reductions in risk of incident impairment on measures sensitive to cognitive aging and risk for dementia. Our findings offer new perspectives in promoting a diverse repertoire of activities to mitigate age-related cognitive declines. (JINS, 2012, 18, 286–294)