The association of disease activity with depression and sleep quality in patients with rheumatoid arthritis in Hong Kong.

Patients with rheumatoid arthritis (RA) often experience depression and poor sleep. Depression and poor sleep may, in turn, worsen RA disease activity. This cross-sectional study aimed to investigate the relationship between RA disease activity as measured using the Disease Activity Score-28 (DAS28-ESR), depression measured using the Beck's Depression Inventory-II (BDI-II), and sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI). Anxiety was measured using the Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A). A total of 164 consecutive patients with RA were recruited from the Rheumatology Specialist Clinic of a regional hospital in Hong Kong. They were asked to complete questionnaires that included demographic information, the Health Assessment Questionnaire (HAQ), BDI-II, HADS-A, and PSQI. The DAS28-ESR was assessed by the attending rheumatologists. Clinical information was retrieved from the electronic medical records. The mean DAS28-ESR score was 3.35 ± 1.24 (SD). The mean BDI-II was 10.97 ± 9.15 (SD). The mean HADS-A score was 5.57 ± 3.77 (SD). The mean PSQI score was 7.55 ± 4.16 (SD). The BDI-II score was statistically correlated with the DAS28-ESR and PSQI scores. Multiple regression analysis revealed that the association of BDI-II with DAS28-ESR and PSQI was confounded by the HAQ. The association of DAS28-ESR with BDI-II but not with PSQI is in accordance with the results of previous studies. The association between the HAQ and BDI-II has also been demonstrated in previous studies. Clinicians should be aware of mood and sleep problems in patients with RA and adopt a multidisciplinary approach to their management. Future studies should provide information on causality in a more representative sample of patients with RA.

Improving fragility hip fracture care through data: a multicentre experience from a country with an emerging economy during the COVID-19 pandemic.

INTRODUCTION: In low-to-middle-income countries (LMIC), the orthogeriatric model of care is still in its early stages of development. This study describes the initial results of the first online fragility hip fracture database to be setup in the Philippines using a modified minimum common dataset to generate outcomes data based on current hospital practices. METHODS: A multicentre prospective cohort study among 12 Philippine hospitals was conducted from June 2020 to February 2021. Thirty-day mortality, morbidity and mobility were measured. Significant factors associated with mortality were determined. RESULTS: 158 elderly patients with fragility hip fractures were included in the study. Nine patients (5.7%) were confirmed or suspected to have COVID-19 infection. Median time of injury to admission was at least 3 days (IQR: 1.0-13.7). Overall, 80% of patients underwent surgical intervention with a median time from admission to surgery of at least 5 days (IQR: 2.5-13.6). Thirty-day mortality and morbidity rates for acute fragility fractures were 3.7%. Factors significantly associated with early mortality were poor prefracture mobility, COVID-19 infection, radiograph of the abnormal chest and conservative treatment. Non-surgical patients had no functional mobility or were wheelchair users and had a significantly higher morbidity rate than surgically treated patients (13.6% vs 1.8%; p=0.031). CONCLUSION: Despite treatment delays unique to an LMIC, short-term outcomes remain favourable for non-COVID-19 fragility hip fracture patients treated with surgery. Prompt admission and multidisciplinary care for elderly hip fracture patients while maintaining protective measures for COVID-19 infection control are recommended. The quality of data collected illustrates how this online database can provide a framework for a sustainable audit or registry as well as provide a platform for the introduction of orthogeriatric concepts at a multiregional scale.

Progression of Stargardt Disease as Determined by Fundus Autofluorescence Over a 24-Month Period (ProgStar Report No. 17).

PURPOSE: To estimate the progression rate of atrophic lesions in Stargardt disease derived from fundus autofluorescence (FAF). DESIGN: International, multicenter, prospective cohort study. METHODS: A total of 259 participants aged ≥6 years with disease-causing variants in the ABCA4 gene were enrolled from 9 centers and followed over a 24-month period. FAF images were obtained every 6 months, and areas of definitely decreased autofluorescence (DDAF) and decreased autofluorescence (DAF) were quantified. Progression rates were estimated from linear mixed models with time as the independent variable. RESULTS: A total of 488 study eyes of 259 participants (88.8% with both eyes) were enrolled and images from 432 eyes were followed for 24 months. The overall estimated progression of DDAF was 0.74 mm2/y (95% CI 0.64-0.85, P < .0001) and that of DAF was 0.64 mm2/y (95% CI 0.57-0.71) over a 24-month period in univariate analysis. Growth rates were strongly dependent on baseline lesion area. After square root transformation, the DDAF growth rate was not dependent on baseline lesion radius (P = .11), whereas the DAF growth rate was dependent (P < .0001). Genotype was not found to significantly impact the growth rate of DDAF or DAF lesions. CONCLUSIONS: FAF may serve as a convenient monitoring tool and suitable end point for interventional clinical trials that aim to slow disease progression. DDAF and DAF lesion sizes at baseline are strong predicting factors for lesion area growth and can be partially accounted for by square root transformation.

Whole-brain radiotherapy associated with structural changes resembling aging as determined by anatomic surface-based deep learning.

BACKGROUND: Brain metastases are the most common intracranial tumors in adults and are associated with significant morbidity and mortality. Whole-brain radiotherapy (WBRT) is used frequently in patients for palliation, but can result in neurocognitive deficits. While dose-dependent injury to individual areas such as the hippocampus has been demonstrated, global structural shape changes after WBRT remain to be studied. METHODS: We studied healthy controls and patients with brain metastases and examined MRI brain anatomic surface data before and after WBRT. We implemented a validated graph convolutional neural network model to estimate patient's "brain age". We further developed a mixed-effects linear model to compare the estimated age of the whole brain and substructures before and after WBRT. RESULTS: 4220 subjects were analyzed (4148 healthy controls and 72 patients). The median radiation dose was 30 Gy (range 25-37.5 Gy). The whole brain and substructures underwent structural change resembling rapid aging in radiated patients compared to healthy controls; the whole brain "aged" 9.32 times faster, the cortex 8.05 times faster, the subcortical structures 12.57 times faster, and the hippocampus 10.14 times faster. In a subset analysis, the hippocampus "aged" 8.88 times faster in patients after conventional WBRT versus after hippocampal avoidance (HA)-WBRT. CONCLUSIONS: Our findings suggest that WBRT causes the brain and its substructures to undergo structural changes at a pace up to 13x of the normal aging pace, where hippocampal avoidance offers focal structural protection. Correlating these structural imaging changes with neurocognitive outcomes following WBRT or HA-WBRT would benefit from future analysis.

Postoperative Pulmonary Complications in the ENIGMA II Trial: A Post Hoc Analysis.

BACKGROUND: Nitrous oxide promotes absorption atelectasis in poorly ventilated lung segments at high inspired concentrations. The Evaluation of Nitrous oxide In the Gas Mixture for Anesthesia (ENIGMA) trial found a higher incidence of postoperative pulmonary complications and wound sepsis with nitrous oxide anesthesia in major surgery compared to a fraction of inspired oxygen of 0.8 without nitrous oxide. The larger ENIGMA II trial randomized patients to nitrous oxide or air at a fraction of inspired oxygen of 0.3 but found no effect on wound infection or sepsis. However, postoperative pulmonary complications were not measured. In the current study, post hoc data were collected to determine whether atelectasis and pneumonia incidences were higher with nitrous oxide in patients who were recruited to the Australian cohort of ENIGMA II. METHODS: Digital health records of patients who participated in the trial at 10 Australian hospitals were examined blinded to trial treatment allocation. The primary endpoint was the incidence of atelectasis, defined as lung atelectasis or collapse reported on chest radiology. Pneumonia, as a secondary endpoint, required a diagnostic chest radiology report with fever, leukocytosis, or positive sputum culture. Comparison of the nitrous oxide and nitrous oxide-free groups was done according to intention to treat using chi-square tests. RESULTS: Data from 2,328 randomized patients were included in the final data set. The two treatment groups were similar in surgical type and duration, risk factors, and perioperative management recorded for ENIGMA II. There was a 19.3% lower incidence of atelectasis with nitrous oxide (171 of 1,169 [14.6%] vs. 210 of 1,159 [18.1%]; odds ratio, 0.77; 95% CI, 0.62 to 0.97; P = 0.023). There was no difference in pneumonia incidence (60 of 1,169 [5.1%] vs. 52 of 1159 [4.5%]; odds ratio, 1.15; 95% CI, 0.77 to 1.72; P = 0.467) or combined pulmonary complications (odds ratio, 0.84; 95% CI, 0.69 to 1.03; P = 0.093). CONCLUSIONS: In contrast to the earlier ENIGMA trial, nitrous oxide anesthesia in the ENIGMA II trial was associated with a lower incidence of lung atelectasis, but not pneumonia, after major surgery.

A comparative evaluation of propranolol pharmacokinetics in obese versus ideal weight individuals: A blueprint towards a personalised medicine.

The pharmacokinetics of propranolol were investigated in obese and healthy weight groups. Research studies in relation to the presented topic were gathered, evaluated, and compared to distinguish variabilities involved amongst different lipophilic drugs and how they impacted the clinical effectiveness. Propranolol is a lipophilic drug so it was predicted that the pharmacokinetics would differ between obese and ideal-weight individuals. Previous research in other lipophilic drugs shows a trend to increase the volume of distribution and half-life in obese compared to ideal weight individuals. However, the majority of both clinical and preclinical studies gathered in this review, found a decrease in the volume of distribution (VD) and clearance, and minimal significant difference in the half-life, in the obese group when compared with the ideal weight group. Different explanations for this comparison have been theorised including differing tissue blood flow, plasma protein binding, or hepatic clearance in obese compared with ideal weight populations; though the exact reasoning as to why propranolol does not follow the general trend for lipophilic drugs is yet to be determined. These findings regarding propranolol pharmacokinetics can be utilised towards further research and development in personalised medicine for patients with obesity and comorbid cardiovascular disease. The comparative studies highlighted the pharmacokinetic parameters which demonstrated a need for personalised dosage regimes for propranolol and a proposed research direction to understand why the difference exists between these population groups. With the prevalence of obesity continuing to rise, the relative pharmacokinetics of drugs must be evaluated in obese patient groups in order to inform drug dosing regimens and improve current clinical practice.

Multimodal Handheld Probe for Characterizing Otitis Media - Integrating Raman Spectroscopy and Optical Coherence Tomography.

Otitis media (OM) is a common disease of the middle ear, affecting 80% of children before the age of three. The otoscope, a simple illuminated magnifier, is the standard clinical diagnostic tool to observe the middle ear. However, it has limited contrast to detect signs of infection, such as clearly identifying and characterizing middle ear fluid or biofilms that accumulate within the middle ear. Likewise, invasive sampling of every subject is not clinically indicated nor practical. Thus, collecting accurate noninvasive diagnostic factors is vital for clinicians to deliver a precise diagnosis and effective treatment regimen. To address this need, a combined benchtop Raman spectroscopy (RS) and optical coherence tomography (OCT) system was developed. Together, RS-OCT can non-invasively interrogate the structural and biochemical signatures of the middle ear under normal and infected conditions.In this paper, in vivo RS scans from pediatric clinical human subjects presenting with OM were evaluated in parallel with RS-OCT data of physiologically relevant in vitro ear models. Component-level characterization of a healthy tympanic membrane and malleus bone, as well as OM-related middle ear fluid, identified the optimal position within the ear for RS-OCT data collection. To address the design challenges in developing a system specific to clinical use, a prototype non-contact multimodal handheld probe was built and successfully tested in vitro. Design criteria have been developed to successfully address imaging constraints imposed by physiological characteristics of the ear and optical safety limits. Here, we present the pathway for translation of RS-OCT for non-invasive detection of OM.

Stop Codon Usage as a Window into Genome Evolution: Mutation, Selection, Biased Gene Conversion and the TAG Paradox.

Protein coding genes terminate with one of three stop codons (TAA, TGA, or TAG) that, like synonymous codons, are not employed equally. With TGA and TAG having identical nucleotide content, analysis of their differential usage provides an unusual window into the forces operating on what are ostensibly functionally identical residues. Across genomes and between isochores within the human genome, TGA usage increases with G + C content but, with a common G + C → A + T mutation bias, this cannot be explained by mutation bias-drift equilibrium. Increased usage of TGA in G + C-rich genomes or genomic regions is also unlikely to reflect selection for the optimal stop codon, as TAA appears to be universally optimal, probably because it has the lowest read-through rate. Despite TAA being favored by selection and mutation bias, as with codon usage bias G + C pressure is the prime determinant of between-species TGA usage trends. In species with strong G + C-biased gene conversion (gBGC), such as mammals and birds, the high usage and conservation of TGA is best explained by an A + T → G + C repair bias. How to explain TGA enrichment in other G + C-rich genomes is less clear. Enigmatically, across bacterial and archaeal species and between human isochores TAG usage is mostly unresponsive to G + C pressure. This unresponsiveness we dub the TAG paradox as currently no mutational, selective, or gBGC model provides a well-supported explanation. That TAG does increase with G + C usage across eukaryotes makes the usage elsewhere yet more enigmatic. We suggest resolution of the TAG paradox may provide insights into either an unknown but common selective preference (probably at the DNA/RNA level) or an unrecognized complexity to the action of gBGC.

Mean Brain Dose Remains Uninfluenced by the Lesion Number for Gamma Knife Stereotactic Radiosurgery for 10+ Metastases.

OBJECTIVE: Gamma Knife (GK) stereotactic radiosurgery (SRS) is increasingly used as an initial treatment for patients with 10 or more brain metastases. However, the clinical and dosimetric consequences of this practice are not well established. METHODS: We performed a single-institution, retrospective analysis of 30 patients who received Gamma Knife SRS for 10 or more brain metastases in 1 session. We utilized MIM Software to contour the whole brain and accumulated the doses from all treated lesions to determine the mean dose delivered to the whole brain. Patient outcomes were determined from chart review. RESULTS: Our cohort had a median number of 13 treated lesions (range 10-26 lesions) for a total of 427 treated lesions. The mean dose to the whole brain was determined to be 1.8 ± 0.91 Gy (range 0.70-3.8 Gy). The mean dose to the whole brain did not correlate with the number of treated lesions (Pearson r = 0.23, P = 0.21), but was closely associated with tumor volume (Pearson r = 0.95, P < 0.0001). There were no significant correlations between overall survival and number of lesions or aggregate tumor volume. Fourteen patients (47%) underwent additional SRS sessions and 6 patients (20%) underwent whole-brain radiotherapy with a median of 6.6 months (range 3.0-50 months) after SRS. Two patients (6.6%) developed grade 2 radionecrosis following SRS beyond earlier whole-brain radiotherapy. CONCLUSION: The mean dose to the whole brain in patients treated with Gamma Knife SRS for 10 or more brain metastases remained low with an acceptable rate of radionecrosis. This strategy allowed the majority of patients to avoid subsequent whole-brain radiotherapy.

Tumor-associated alterations in white matter connectivity have prognostic significance in MGMT-unmethylated glioblastoma.

PURPOSE: We investigated the prognostic significance of tumor-associated white matter (TA-WM) tracts in glioblastoma (GBM) using magnetic resonance-diffusion tensor imaging (MR-DTI). We hypothesized that (1) TA-WM tracts harbor microscopic disease not targeted through surgery or radiotherapy (RT), and (2) the greater the extent of TA-WM involvement, the worse the survival outcomes. METHODS: We studied a retrospective cohort of 76 GBM patients. TA-WM tracts were identified by MR-DTI fractional anisotropy (FA) maps. For each patient, 22 TA-WM tracts were analyzed and each tract was graded 1-3 based on FA. A TA-WM score (TA-WMS) was computed based on number of involved tracts and corresponding FA grade of involvement. Kaplan-Meier statistics were utilized to determine survival outcomes, log-rank test was used to compare survival between groups, and Cox regression was utilized to determine prognostic variables. RESULTS: For the MGMT-unmethylated cohort, there was a decrease in OS for increasing TA-WMS (median OS 16.5 months for TA-WMS 0-4; 13.6 months for TA-WMS 5-8; 7.3 months for TA-WMS > 9; p = 0.0002). This trend was not observed in the MGMT-methylated cohort. For MGMT-unmethylated patients with TA-WMS > 6 and involvement of tracts passing through brainstem or contralateral hemisphere, median OS was 8.3 months versus median OS 14.1 months with TA-WMS > 6 but not involving aforementioned critical tracts (p = 0.003 log-rank test). For MGMT-unmethylated patients, TA-WMS was predictive of overall survival in multivariate analysis (HR = 1.14, 95% CI 1.03-1.27, p = 0.012) while age, gender, and largest tumor dimension were non-significant. CONCLUSION: Increased TA-WMS and involvement of critical tracts are associated with decreased overall survival in MGMT-unmethylated GBM.

Unusual mammalian usage of TGA stop codons reveals that sequence conservation need not imply purifying selection.

The assumption that conservation of sequence implies the action of purifying selection is central to diverse methodologies to infer functional importance. GC-biased gene conversion (gBGC), a meiotic mismatch repair bias strongly favouring GC over AT, can in principle mimic the action of selection, this being thought to be especially important in mammals. As mutation is GC→AT biased, to demonstrate that gBGC does indeed cause false signals requires evidence that an AT-rich residue is selectively optimal compared to its more GC-rich allele, while showing also that the GC-rich alternative is conserved. We propose that mammalian stop codon evolution provides a robust test case. Although in most taxa TAA is the optimal stop codon, TGA is both abundant and conserved in mammalian genomes. We show that this mammalian exceptionalism is well explained by gBGC mimicking purifying selection and that TAA is the selectively optimal codon. Supportive of gBGC, we observe (i) TGA usage trends are consistent at the focal stop codon and elsewhere (in UTR sequences); (ii) that higher TGA usage and higher TAA→TGA substitution rates are predicted by a high recombination rate; and (iii) across species the difference in TAA <-> TGA substitution rates between GC-rich and GC-poor genes is largest in genomes that possess higher between-gene GC variation. TAA optimality is supported both by enrichment in highly expressed genes and trends associated with effective population size. High TGA usage and high TAA→TGA rates in mammals are thus consistent with gBGC's predicted ability to "drive" deleterious mutations and supports the hypothesis that sequence conservation need not be indicative of purifying selection. A general trend for GC-rich trinucleotides to reside at frequencies far above their mutational equilibrium in high recombining domains supports the generality of these results.

Longitudinal Changes in Scotopic and Mesopic Macular Function as Assessed with Microperimetry in Patients With Stargardt Disease: SMART Study Report No. 2.

PURPOSE: To estimate and compare cross-sectional scotopic versus mesopic macular sensitivity losses measured by microperimetry, and to report and compare the longitudinal rates of scotopic and mesopic macular sensitivity losses in ABCA4 gene-associated Stargardt disease (STGD1). DESIGN: This was a multicenter prospective cohort study. METHODS: Participants comprised 127 molecularly confirmed STGD1 patients enrolled from 6 centers in the United States and Europe and followed up every 6 months for up to 2 years. The Nidek MP-1S device was used to measure macular sensitivities of the central 20° under mesopic and scotopic conditions. The mean deviations (MD) from normal for mesopic macular sensitivity for the fovea (within 2° eccentricity) and extrafovea (4°-10° eccentricity), and the MD for scotopic sensitivity for the extrafovea, were calculated. Linear mixed effects models were used to estimate mesopic and scotopic changes. Main outcome measures were baseline mesopic mean deviation (mMD) and scotopic MD (sMD) and rates of longitudinal changes in the mMDs and sMD. RESULTS: At baseline, all eyes had larger sMD, and the difference between extrafoveal sMD and mMD was 10.7 dB (P < .001). Longitudinally, all eyes showed a statistically significant worsening trend: the rates of foveal mMD and extrafoveal mMD and sMD changes were 0.72 (95% CI = 0.37-1.07), 0.86 (95% CI = 0.58-1.14), and 1.12 (95% CI = 0.66-1.57) dB per year, respectively. CONCLUSIONS: In STGD1, in extrafovea, loss of scotopic macular function preceded and was faster than the loss of mesopic macular function. Scotopic and mesopic macular sensitivities using microperimetry provide alternative visual function outcomes for STGD1 treatment trials.

Variation in Release Factor Abundance Is Not Needed to Explain Trends in Bacterial Stop Codon Usage.

In bacteria stop codons are recognized by one of two class I release factors (RF1) recognizing TAG, RF2 recognizing TGA, and TAA being recognized by both. Variation across bacteria in the relative abundance of RF1 and RF2 is thus hypothesized to select for different TGA/TAG usage. This has been supported by correlations between TAG:TGA ratios and RF1:RF2 ratios across multiple bacterial species, potentially also explaining why TAG usage is approximately constant despite extensive variation in GC content. It is, however, possible that stop codon trends are determined by other forces and that RF ratios adapt to stop codon usage, rather than vice versa. Here, we determine which direction of the causal arrow is the more parsimonious. Our results support the notion that RF1/RF2 ratios become adapted to stop codon usage as the same trends, notably the anomalous TAG behavior, are seen in contexts where RF1:RF2 ratios cannot be, or are unlikely to be, causative, that is, at 3'untranslated sites never used for translation termination, in intragenomic analyses, and across archaeal species (that possess only one RF1). We conclude that specifics of RF biology are unlikely to fully explain TGA/TAG relative usage. We discuss why the causal relationships for the evolution of synonymous stop codon usage might be different from those affecting synonymous sense codon usage, noting that transitions between TGA and TAG require two-point mutations one of which is likely to be deleterious.

Visualizing and Quantifying Pharmaceutical Compounds within Skin using Coherent Raman Scattering Imaging.

Cutaneous pharmacokinetics (cPK) after topical formulation application has been a research area of particular interest for regulatory and drug development scientists to mechanistically understand topical bioavailability (BA). Semi-invasive techniques, such as tape-stripping, dermal microdialysis, or dermal open-flow microperfusion, all quantify macroscale cPK. While these techniques have provided vast cPK knowledge, the community lacks a mechanistic understanding of active pharmaceutical ingredient (API) penetration and permeation at the cellular level. One noninvasive approach to address microscale cPK is coherent Raman scattering imaging (CRI), which selectively targets intrinsic molecular vibrations without the need for extrinsic labels or chemical modification. CRI has two main methods-coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS)-that enable sensitive and selective quantification of APIs or inactive ingredients. CARS is typically utilized to derive structural skin information or visualize chemical contrast. In contrast, the SRS signal, which is linear with molecular concentration, is used to quantify APIs or inactive ingredients within skin stratifications. Although mouse tissue has commonly been utilized for cPK with CRI, topical BA and bioequivalence (BE) must ultimately be assessed in human tissue before regulatory approval. This paper presents a methodology to prepare and image ex vivo skin to be used in quantitative pharmacokinetic CRI studies in the evaluation of topical BA and BE. This methodology enables reliable and reproducible API quantification within human and mouse skin over time. The concentrations within lipid-rich and lipid-poor compartments, as well as total API concentration over time are quantified; these are utilized for estimates of micro- and macroscale BA and, potentially, BE.

Causes and Consequences of Purifying Selection on SARS-CoV-2.

Owing to a lag between a deleterious mutation's appearance and its selective removal, gold-standard methods for mutation rate estimation assume no meaningful loss of mutations between parents and offspring. Indeed, from analysis of closely related lineages, in SARS-CoV-2, the Ka/Ks ratio was previously estimated as 1.008, suggesting no within-host selection. By contrast, we find a higher number of observed SNPs at 4-fold degenerate sites than elsewhere and, allowing for the virus's complex mutational and compositional biases, estimate that the mutation rate is at least 49-67% higher than would be estimated based on the rate of appearance of variants in sampled genomes. Given the high Ka/Ks one might assume that the majority of such intrahost selection is the purging of nonsense mutations. However, we estimate that selection against nonsense mutations accounts for only ∼10% of all the "missing" mutations. Instead, classical protein-level selective filters (against chemically disparate amino acids and those predicted to disrupt protein functionality) account for many missing mutations. It is less obvious why for an intracellular parasite, amino acid cost parameters, notably amino acid decay rate, is also significant. Perhaps most surprisingly, we also find evidence for real-time selection against synonymous mutations that move codon usage away from that of humans. We conclude that there is common intrahost selection on SARS-CoV-2 that acts on nonsense, missense, and possibly synonymous mutations. This has implications for methods of mutation rate estimation, for determining times to common ancestry and the potential for intrahost evolution including vaccine escape.

Increasing patient participation in hand hygiene practices in adult surgical wards in a tertiary institution: a best practice implementation project.

INTRODUCTION: The WHO states that hospital-acquired infections may be transmitted through contaminated hands. Practicing hand hygiene using alcohol-based handrub or soap and water reduces harmful organisms. The Joanna Briggs Institute (JBI) best practice recommends empowering patients with hand hygiene knowledge and engaging their involvement to strengthen hand hygiene practices. AIMS: The aim of this project was to improve hand hygiene among surgical inpatients. METHODS: This evidence-based quality improvement project was conducted in three phases: the baseline audit, implementing best practice, and the postimplementation audit. Participants were patients hospitalized in three surgical wards of a 1200-bed acute care tertiary hospital. This project utilized the online JBI Practical Application of Clinical Evidence System and The Getting Research into Practice program to identify barriers and strategies. Nurses provided patients with an education pamphlet and regularly reminded them to improve their hand hygiene practices. RESULTS: Ninety-four patients were audited between April and June 2018. Patients' hand hygiene practices improved from 19.1% at baseline audit to 61.7% (P < 0.01) at first follow-up audit. Patients' hand hygiene improved from 48.9 to 72.3% (P = 0.03) before meals, and from 92.6 to 98.9% (P = 0.65) after toileting. The proportion of patients who received a hand hygiene information leaflet in an appropriate language increased from 64.9 to 89.4% (P < 0.01). CONCLUSION: Patients' involvement in the hand hygiene program has significantly improved their hand hygiene practices. Patient education and patient information leaflet continue to be an effective strategy to improve knowledge and practices.

Visualizing and quantifying antimicrobial drug distribution in tissue.

The biodistribution and pharmacokinetics of drugs are vital to the mechanistic understanding of their efficacy. Measuring antimicrobial drug efficacy has been challenging as plasma drug concentration is used as a surrogate for tissue drug concentration, yet typically does not reflect that at the intended site(s) of action. Utilizing an image-guided approach, it is feasible to accurately quantify the biodistribution and pharmacokinetics within the desired site(s) of action. We outline imaging modalities used in visualizing drug distribution with examples ranging from in vitro cellular drug uptake to clinical treatment of microbial infections. The imaging modalities of interest are: radio-labeling, magnetic resonance, mass spectrometry imaging, computed tomography, fluorescence, and Raman spectroscopy. We outline the progress, limitations, and future outlook for each methodology. Further advances in these optical approaches would benefit patients and researchers alike, as non-invasive imaging could yield more profound insights with a lower clinical burden than invasive measurement approaches used today.

Recent progress in plasmonic nanoparticle-based biomarker detection and cytometry for the study of central nervous system disorders.

Neurological disorders affect hundreds of millions of people around the world, are often life-threatening, untreatable, and can result in debilitating symptoms. The high prevalence of these disorders, which feature biochemical or structural abnormalities in neuronal systems, has spurned innovations in both rapid and early detection to assist in the selection of appropriate treatment strategies to improve the patients' quality of life. Plasmonic nanoparticles (PNPs), a versatile and promising class of nanomaterials, are widely utilized in numerous imaging techniques, drug delivery systems, and biomarker detection methods. Recently, PNP-based nanoprobes have attracted considerable attention for the early diagnosis of neurological disorders. Gold nanoparticles (AuNPs), with high local surface plasmon resonance (LSPR) signals, have been particularly well exploited as probes for dynamic biomarker detection, with quantification sensitivity demonstrated down to the single-molecule level. In this review, we will discuss the possibilities of PNPs in the methodological development for rapid neurological disease identification. In addition, we will also describe a new digital cytometry method that combines dark-field imaging and machine learning for precise biomarker enumeration on single cells. The aim of this review is to attract researchers working on the future development of new plasmonic nanoprobe-based strategies for the diagnosis of neurological disorders.