Although the O-linked N-acetylglucosamine (O-GlcNAc) modification of the RNA polymerase II C-terminal domain was described 20 years ago, the function of this RNA polymerase II (pol II) species is not known. We show here that an O-GlcNAcylated pol II species (pol IIγ) exists on promoters in vitro Inhibition of O-GlcNAc-transferase activity and O-GlcNAcylation prevents pol II entry into the promoter, and O-GlcNAc removal from pol II is an ATP-dependent step during initiation. These data indicate that O-GlcNAc-transferase activity is essential for RNA pol II promoter recruitment and that pol II goes through a cycling of O-GlcNAcylation at the promoter. Mass spectrometry shows that serine residues 2 and 5 of the pol II C-terminal domain are O-GlcNAcylated, suggesting an overlap with the transcription factor IIH (TFIIH)-dependent serine 5 phosphorylation events during initiation and P-TEFb (positive transcriptional elongation factor b) events during elongation. These data provide unexpected and important insights into the role of a previously ill-defined species of RNA polymerase II in regulating transcription.

We proposed the term "dysmobility syndrome" (DS) to identify individuals with impaired musculoskeletal health, a risk factor for falls and fractures. Whether DS is associated with increased risk of incident fracture is unknown. The Osteoporotic Fractures in Men (MrOS) study enrolled 5994 men ages ≥65 years, between March 2000 and April 2002. We used baseline data to determine whether DS increased fracture risk, independent of the Fracture Risk Assessment Tool (FRAX). Men met DS criteria at baseline if they had three or more of the following: appendicular lean mass/height² <7.26 kg/m² , total body fat >30%, spine or hip T-score ≤ -2.5, grip strength <30 kg, gait speed <1.0 m/s, and one or more fall within 12 months. We examined whether baseline DS increased the risk of hip and major osteoporotic fractures (MOFs) over a median of 14 years (IQR, 9 to 15 years). Among 5834 men mean age 74 ± 6 years, 471 (8%) had DS and 635 (11%) experienced an MOF, including 274 (5%) hip fractures. Age (per SD increase) conferred an HR of 1.72 (95% CI, 1.59 to 1.86), DS conferred an HR of 3.45 (95% CI, 2.78 to 4.29) and FRAX calculated with BMD (per %) conferred an HR of 1.10 (95% CI, 1.08 to 1.11) for MOF. Prediction of MOF using the FRAX score provided a concordance value of 0.67 ± 0.012 (concordance values are mean ± SE). Concordance increased to 0.69 ± 0.012 by adding DS and to 0.70 ± 0.012 by adding DS and age to the multivariate model. Kaplan-Meier curves indicated that men with both DS and a FRAX risk above the National Osteoporosis Foundation (NOF) treatment thresholds had higher MOF (HR 6.23; 95% CI, 3.10 to 12.54) and hip (HR 7.73; 95% CI, 5.95 to 10.04) fracture risk than men with neither condition. We suggest further studies to determine the optimal criteria for DS, and to test DS as a predictor of falls and fractures, especially in women. © 2018 American Society for Bone and Mineral Research.

We report the electronic recording of the touch contact and pressure using an active matrix pressure sensor array made of transparent zinc oxide thin-film transistors and tactile feedback display using an array of diaphragm actuators made of an interpenetrating polymer elastomer network. Digital replay, editing and manipulation of the recorded touch events were demonstrated with both spatial and temporal resolutions. Analog reproduction of the force is also shown possible using the polymer actuators, despite of the high driving voltage. The ability to record, store, edit, and replay touch information adds an additional dimension to digital technologies and extends the capabilities of modern information exchange with the potential to revolutionize physical learning, social networking, e-commerce, robotics, gaming, medical and military applications.

Abstract

Background

Nursing home (NH) residents are at high infection and hospital readmission risk. Colonization with multidrug-resistant organisms (MDROs) is common. In ICU and post-hospital discharge settings, decolonization has reduced infection rates. However, the effectiveness of this strategy in NHs is unclear.

Methods

We performed a cluster randomized trial of 1:1 universal decolonization (decol) vs standard of care bathing (control) in 28 California NHs. After an 18 month baseline evaluation of hospitalization rates due to infection and MDRO prevalence, NHs were randomized to decol or control. Decol consisted of 1) chlorhexidine bathing; 2) nasal povidone iodine bid on admission x 5d and then M-F biweekly x 18 mo. Primary outcome was the probability that a transfer to a hospital was due to infection. Secondary outcome was the probability that a NH discharge was to a hospital.

Results

Four of 28 NHs dropped from the trial (3 decol, 1 control). Mean facility baseline of hospital transfers due to infection was 58% and 57% in the control and decol groups. In the intervention period, proportions were 57% and 48% in the control and decol groups. When accounting for clustering within NHs, hospital transfers due to infection had an OR of 0.91 (95% CI: 0.82-1.02) in the control group and an OR of 0.73 (95% CI: 0.56-0.95) in the decol group when comparing intervention to baseline period. For the primary outcome, decol had a 18% greater impact v. control (P=0.005, Fig. A). Baseline proportion of NH discharges due to hospitalization was 37% and 39% in the control and decol groups. In the intervention period, proportions were 36% and 33%. When accounting for clustering within NHs, the proportion of discharges due to hospitalization had an OR of 1.14 (95% CI: 1.06-1.22) in the control group and 0.91 (CI: 0.77-1.07) in the decol group when comparing the intervention period to the baseline period. For the secondary outcome, decol had a 23% greater impact v. control (P< 0.0001, Fig. B). In this figure, each nursing home is represented by a circle. The size of the circle represents the amount of contributed patient days to the trial. The groups represent “as randomized” categories. Panel A) compares the probability that a transfer to a hospital was due to infection; panel B) compares the probability that a nursing home discharge was to a hospital. The y-axis represents the odds ratio of these probabilities comparing the baseline to the intervention period. The p values represent the significance of the difference between groups (the trial effect).

Conclusion

Universal NH decolonization with chlorhexidine and nasal iodophor significantly reduced the proportion of transfers to hospitals due to infection and discharges due to hospitalization. Our findings suggest that NH decolonization reduces serious infections and can decrease morbidity in this vulnerable population.

Disclosures

Loren G. Miller, MD, MPH, Medline (Grant/Research Support, Other Financial or Material Support, Contributed product) Stryker (Other Financial or Material Support, Contributed product) Xttrium (Other Financial or Material Support, Contributed product) James A. McKinnell, MD, Medline (Grant/Research Support) Raveena Singh, MA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Gabrielle Gussin, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Ken Kleinman, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Raheeb Saavedra, AS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Lauren Heim, MPH, Medline (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Stryker (Sage) (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product) Xttrium (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product) Shruti K. Gohil, MD, MPH, Medline (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Molnycke (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Stryker (Sage) (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Susan S. Huang, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)

Abstract

Background

Patient movement between hospitals, nursing homes (NH), and long-term acute care facilities (LTACs) contributes to MDRO spread. SHIELD OC is a regional decolonization collaborative among adult facilities with high patient sharing designed to reduce countywide MDRO prevalence. We report pre- and post-intervention MDRO colonization prevalence.

Methods

Decolonization included chlorhexidine bath (CHG) (4% liquid or 2% cloth) and twice-daily nasal swab 10% povidone–iodine (PI). LTAC and NH used CHG for all baths and PI 5 days on admission and Monday–Friday every other week. Patients in contact precautions (CP) at hospitals had daily CHG and 5-days PI on admission. Point-prevalence screening for MRSA, VRE, ESBL, and CRE using nares, axilla/groin, and peri-rectal swabs was conducted pre-intervention (September 2016–March 2017) and post-intervention (August 2018–April 2019); 50 random LTAC and 50 CP hospitalized patients were sampled; for NH up to 50 were sampled at baseline and all residents post-intervention. Raw impact of the intervention was assessed by the average change in colonization prevalence, with each facility carrying equal weight. Generalized linear mixed models (GLM) stratified by facility type were used to assess the impact on MDRO colonization when clustering by facility.

Results

Across 35 facilities (16 hospitals, 16 NHs, 3 LTACs), the overall MDRO prevalence was reduced 22% in NHs (OR 0.58, P < 0.001), 34% LTACs (OR = 0.27, P < 0.001), and 11% CP patients (OR = 0.67, P < 0.001, Table 1). For MRSA, raw reductions were 31% NHs (OR = 0.58, P < 0.001), 39% LTACs (OR = 0.51, P = 0.01), and 3% CP patients (OR = 0.88, P = NS). For VRE, raw reductions were 40% NHs (OR = 0.62, P = 0.001), 55% LTACs (OR = 0.26, P < 0.001), and 15% CP patients (OR = 0.67, P = 0.004). For ESBLs, raw reductions were 24% NHs (OR = 0.65, P < 0.001), 34% LTACs (OR = 0.53, P = 0.01), and 26% CP patients (OR = 0.64, P < 0.001). For CRE, raw reductions were 24% NHs (OR = 0.70, P = NS), and 23% LTACs (OR = 0.75, P = NS). CRE increased by 26% in CP averaged across hospitals, although patient -level CRE declined 2.4% to 1.8% (OR = 0.74, P = NS).

Conclusion

MDRO carriage was common in highly inter-connected NHs, LTACs and hospitals. A regional collaborative of universal decolonization in long-term care and targeted decolonization of CP patients in hospitals led to sizeable reductions in MDRO carriage.

Disclosures

All Authors: No reported Disclosures.

Background

Nursing home residents are at high risk for infection, hospitalization, and colonization with multidrug-resistant organisms.

Methods

We performed a cluster-randomized trial of universal decolonization as compared with routine-care bathing in nursing homes. The trial included an 18-month baseline period and an 18-month intervention period. Decolonization entailed the use of chlorhexidine for all routine bathing and showering and administration of nasal povidone-iodine twice daily for the first 5 days after admission and then twice daily for 5 days every other week. The primary outcome was transfer to a hospital due to infection. The secondary outcome was transfer to a hospital for any reason. An intention-to-treat (as-assigned) difference-in-differences analysis was performed for each outcome with the use of generalized linear mixed models to compare the intervention period with the baseline period across trial groups.

Results

Data were obtained from 28 nursing homes with a total of 28,956 residents. Among the transfers to a hospital in the routine-care group, 62.2% (the mean across facilities) were due to infection during the baseline period and 62.6% were due to infection during the intervention period (risk ratio, 1.00; 95% confidence interval [CI], 0.96 to 1.04). The corresponding values in the decolonization group were 62.9% and 52.2% (risk ratio, 0.83; 95% CI, 0.79 to 0.88), for a difference in risk ratio, as compared with routine care, of 16.6% (95% CI, 11.0 to 21.8; P<0.001). Among the discharges from the nursing home in the routine-care group, transfer to a hospital for any reason accounted for 36.6% during the baseline period and for 39.2% during the intervention period (risk ratio, 1.08; 95% CI, 1.04 to 1.12). The corresponding values in the decolonization group were 35.5% and 32.4% (risk ratio, 0.92; 95% CI, 0.88 to 0.96), for a difference in risk ratio, as compared with routine care, of 14.6% (95% CI, 9.7 to 19.2). The number needed to treat was 9.7 to prevent one infection-related hospitalization and 8.9 to prevent one hospitalization for any reason.

Conclusions

In nursing homes, universal decolonization with chlorhexidine and nasal iodophor led to a significantly lower risk of transfer to a hospital due to infection than routine care. (Funded by the Agency for Healthcare Research and Quality; Protect ClinicalTrials.gov number, NCT03118232.).