Mucosal Gene Expression in Response to SARS-CoV-2 Is Associated with Viral Load.

Little is known about the relationships between symptomatic early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and upper airway mucosal gene expression and immune response. To examine the association of symptomatic SARS-CoV-2 early viral load with upper airway mucosal gene expression, we profiled the host mucosal transcriptome from nasopharyngeal swab samples from 68 adults with symptomatic, mild-to-moderate coronavirus disease 19 (COVID-19). We measured SARS-CoV-2 viral load using reverse transcription-quantitative PCR (RT-qPCR). We then examined the association of SARS-CoV-2 viral load with upper airway mucosal immune response. We detected SARS-CoV-2 in all samples and recovered >80% of the genome from 95% of the samples from symptomatic COVID-19 adults. The respiratory virome was dominated by SARS-CoV-2, with limited codetection of other respiratory viruses, with the human Rhinovirus C being identified in 4 (6%) samples. This limited codetection of other respiratory viral pathogens may be due to the implementation of public health measures, like social distancing and masking practices. We observed a significant positive correlation between SARS-CoV-2 viral load and interferon signaling (OAS2, OAS3, IFIT1, UPS18, ISG15, ISG20, IFITM1, and OASL), chemokine signaling (CXCL10 and CXCL11), and adaptive immune system (IFITM1, CD300E, and SIGLEC1) genes in symptomatic, mild-to-moderate COVID-19 adults, when adjusting for age, sex, and race. Interestingly, the expression levels of most of these genes plateaued at a cycle threshold (CT) value of ~25. Overall, our data show that the early nasal mucosal immune response to SARS-CoV-2 infection is viral load dependent, potentially modifying COVID-19 outcomes. IMPORTANCE Several prior studies have shown that SARS-CoV-2 viral load can predict the likelihood of disease spread and severity. A higher detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity. However, the relationship between SARS-CoV-2 viral load, airway mucosal gene expression, and immune response remains elusive. We profiled the nasal mucosal transcriptome from nasal samples collected from adults infected with SARS-CoV-2 during spring 2020 with mild-to-moderate symptoms using a comprehensive metatranscriptomics method. We observed a positive correlation between SARS-CoV-2 viral load, interferon signaling, chemokine signaling, and adaptive immune system in adults with COVID-19. Our data suggest that early nasal mucosal immune response to SARS-CoV-2 infection was viral load dependent and may modify COVID-19 outcomes.

Trajectories of oral bisphosphonate use after hip fractures: a population-based cohort study.

Bisphosphonates prevent future hip fractures. However, we found that one in six patients with hip fractures had a delay in bisphosphonate initiation and another one-sixth discontinued treatment within 12 months after discharge. Our results highlight the need to address hesitancy in treatment initiation and continuous monitoring. PURPOSE: Suboptimal antiresorptive use is not well understood. This study investigated trajectories of oral bisphosphonate use following first hip fractures and factors associated with different adherence and persistence trajectories. METHODS: We conducted a retrospective study of all patients aged ≥ 50 years dispensed two or more bisphosphonate prescriptions following first hip fracture in Victoria, Australia, from 2012 to 2017. Twelve-month trajectories of bisphosphonate use were categorized using group-based trajectory modeling. Factors associated with different trajectories compared to the persistent adherence trajectory were assessed using multivariate multinomial logistic regression. RESULTS: We identified four patterns of oral bisphosphonate use in 1811 patients: persistent adherence (66%); delayed dispensing (17%); early discontinuation (9%); and late discontinuation (9%). Pre-admission bisphosphonate use was associated with a lower risk of delayed dispensing in both sexes (relative risk [RR] 0.28, 95% confidence interval [CI] 0.21-0.39). Older patients ( ≥ 85 years old versus 50-64 years old, RR 0.38, 95% CI 0.22-0.64) had a lower risk of delayed dispensing. Males with anxiety (RR 9.80, 95% CI 2.24-42.9) and females with previous falls had increased risk of early discontinuation (RR 1.80, 95% CI 1.16-2.78). CONCLUSION: Two-thirds of patients demonstrated good adherence to oral bisphosphonates over 12 months following hip fracture. Efforts to further increase post-discharge antiresorptive use should be sex-specific and address possible persistent uncertainty around delaying treatment initiation.

Particulate matter exposure is associated with increased inflammatory cytokines and eosinophils in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is thought to result from complex interactions between the host immune system, microbiota, and environmental exposures. Currently, there is limited data regarding the impact of ambient particulate matter ≤2.5 µm in diameter (PM2.5) in the pathogenesis of CRS, despite evidence linking PM2.5 to other respiratory diseases. We hypothesized that PM2.5 may result in differential cytokine patterns that could inform our mechanistic understanding of the effect of environmental factors on CRS. METHODS: We conducted an analysis of data prospectively collected from 308 CRS patients undergoing endoscopic sinus surgery. Cytokines were quantified in intraoperative mucus specimens using a multiplex flow cytometric bead assay. Clinical and demographic data including zip codes were extracted and used to obtain tract-level income and rurality measures. A spatiotemporal machine learning model was used to estimate daily PM2.5 levels for the year prior to each patient's surgery date. Spearman correlations and regression analysis were performed to characterize the relationship between mucus cytokines and PM2.5. RESULTS: Several inflammatory cytokines including IL-2, IL-5/IL-13, IL-12, and 21 were significantly correlated with estimated average 6, 9, and 12-month preoperative PM2.5 levels. These relationships were maintained for most cytokines after adjusting for age, income, body mass index, rurality, polyps, asthma, and allergic rhinitis (AR) (p < .05). There were also higher odds of asthma (OR = 1.5, p = .01) and AR (OR = 1.48, p = .03) with increasing 12-month PM2.5 exposure. Higher tissue eosinophil counts were associated with increasing PM2.5 levels across multiple timeframes (p < .05). CONCLUSIONS: Chronic PM2.5 exposure may be an independent risk factor for development of a mixed, type-2 dominant CRS inflammatory response.

Promoting medication safety for older adults upon hospital discharge: Guiding principles for a medication discharge plan.

Older adults are at risk of adverse drug events during transition of care from hospital to community, thus optimal communication about medications at discharge is essential. Standardization of medication discharge plan (MDP) is lacking. This study aimed to (1) create a standardized MDP for older adults using consensus-based principles, (2) create a short-version MDP and (3) generate a practical guide. Modified Delphi was used to establish consensus on guiding principles for the MDP. Additionally, participants were asked about guiding principles deemed most essential, patient prioritization, the format and mode of transmission of the MDP. Twenty-six guiding principles reached consensus, with 17 prioritized for a short-version MDP. The practical guide includes explanations of the guiding principles, criteria for patient selection and recommendations on the format and mode of transmission. The results of this study will assist implementation of MDPs when older adults are discharged from hospital.

A mixed-methods study on the pharmacological management of pain in Australian and Japanese nursing homes.

BACKGROUND: Understanding how analgesics are used in different countries can inform initiatives to improve the pharmacological management of pain in nursing homes. AIMS: To compare patterns of analgesic use among Australian and Japanese nursing home residents; and explore Australian and Japanese healthcare professionals' perspectives on analgesic use. METHODS: Part one involved a cross-sectional comparison among residents from 12 nursing homes in South Australia (N = 550) in 2019 and four nursing homes in Tokyo (N = 333) in 2020. Part two involved three focus groups with Australian and Japanese healthcare professionals (N = 16) in 2023. Qualitative data were deductively content analysed using the World Health Organization six-step Guide to Good Prescribing. RESULTS: Australian and Japanese residents were similar in age (median: 89 vs 87) and sex (female: 73% vs 73%). Overall, 74% of Australian and 11% of Japanese residents used regular oral acetaminophen, non-steroidal anti-inflammatory drugs or opioids. Australian and Japanese healthcare professionals described individualising pain management and the first-line use of acetaminophen. Australian participants described their therapeutic goal was to alleviate pain and reported analgesics were often prescribed on a regular basis. Japanese participants described their therapeutic goal was to minimise impacts of pain on daily activities and reported analgesics were often prescribed for short-term durations, corresponding to episodes of pain. Japanese participants described regulations that limit opioid use for non-cancer pain in nursing homes. CONCLUSION: Analgesic use is more prevalent in Australian than Japanese nursing homes. Differences in therapeutic goals, culture, analgesic regulations and treatment durations may contribute to this apparent difference.

Development of parallel forms of a brief smell identification test useful for longitudinal testing.

Although there are numerous brief odor identification tests available for quantifying the ability to smell, none are available in multiple parallel forms that can be longitudinally administered without potential confounding from knowledge of prior test items. Moreover, empirical algorithms for establishing optimal test lengths have not been generally applied. In this study, we employed and compared eight machine learning algorithms to develop a set of four brief parallel smell tests employing items from the University of Pennsylvania Smell Identification Test that optimally differentiated 100 COVID-19 patients from 132 healthy controls. Among the algorithms, linear discriminant analysis (LDA) achieved the best overall performance. The minimum number of odorant test items needed to differentiate smell loss accurately was identified as eight. We validated the sensitivity of the four developed tests, whose means and variances did not differ from one another (Bradley-Blackwood test), by sequential testing an independent group of 32 subjects that included persons with smell dysfunction not due to COVID-19. These eight-item tests clearly differentiated the olfactory compromised subjects from normosmics, with areas under the ROC curve ranging from 0.79 to 0.83. Each test was correlated with the overall UPSIT scores from which they were derived. These brief smell tests can be used separately or sequentially over multiple days in a variety of contexts where longitudinal olfactory testing is needed.

Strategies to guide the successful implementation of deprescribing in community practice: Lessons learned from the front line.

Background: Sustainable implementation of new professional services into clinical practice can be difficult. In 2019, a population-wide initiative called SaferMedsNL was implemented across the province of Newfoundland and Labrador (NL), to promote appropriate medication use. Two evidence-based interventions were adapted to the context of NL to promote deprescribing of proton pump inhibitors and sedatives. The objective of this study was to identify and prioritize which actions supported the implementation of deprescribing in community practice for pharmacists, physicians and nurse practitioners across the province. Methods: Community pharmacists, physicians and nurse practitioners were invited to participate in virtual focus groups. Nominal Group Technique was used to elicit responses to the question: "What actions support the implementation of deprescribing into the daily workflow of your practice?" Participants prioritized actions within each group while thematic analysis permitted comparison across groups. Results: Five focus groups were held in fall 2020 involving pharmacists (n = 11), physicians (n = 7) and nurse practitioners (n = 4). Participants worked in rural (n = 10) and urban (n = 12) settings. The different groups agreed on what the top 5 actions were, with the top 5 receiving 68% of the scores: (1) providing patient education, (2) allocating time and resources, (3) building interprofessional collaboration and communication, (4) fostering patient relationships and (5) aligning with public awareness strategies. Conclusion: Pharmacists, physicians and nurse practitioners identified similar actions that supported implementing evidence-based deprescribing into routine clinical practice. Sharing these strategies may help others embed deprescribing into daily practice and assist the uptake of medication appropriateness initiatives by front-line providers. Can Pharm J (Ott) 2024;157:xx-xx.

Central Nervous System-Active Prescriptions in Older Veterans: Trends in Prevalence, Prescribers, and High-risk Populations.

BACKGROUND: Little is known about the prevalence or chronicity of prescriptions of central nervous system-active (CNS-active) medications in older Veterans. OBJECTIVE: We sought to describe (1) the prevalence and trends in prescription of CNS-active medications in older Veterans over time; (2) variation in prescriptions across high-risk groups; and (3) where the prescription originated (VA or Medicare Part D). DESIGN: Retrospective cohort study from 2015 to 2019. PARTICIPANTS: Veterans age ≥ 65 enrolled in the Medicare and the VA residing in Veterans Integrated Service Network 4 (incorporating Pennsylvania and parts of surrounding states). MAIN MEASURES: Drug classes included antipsychotics, gabapentinoids, muscle relaxants, opioids, sedative-hypnotics, and anticholinergics. We described prescribing patterns overall and in three subgroups: Veterans with a diagnosis of dementia, Veterans with high predicted utilization, and frail Veterans. We calculated both prevalence (any fill) and percent of days covered (chronicity) for each drug class, and CNS-active polypharmacy (≥ 2 CNS-active medications) rates in each year in these groups. KEY RESULTS: The sample included 460,142 Veterans and 1,862,544 person-years. While opioid and sedative-hypnotic prevalence decreased, gabapentinoids exhibited the largest increase in both prevalence and percent of days covered. Each subgroup exhibited different patterns of prescribing, but all had double the rates of CNS-active polypharmacy compared to the overall study population. Opioid and sedative-hypnotic prevalence was higher in Medicare Part D prescriptions, but the percent of days covered of nearly all drug classes was higher in VA prescriptions. CONCLUSIONS: The concurrent increase of gabapentinoid prescribing paralleling a decrease in opioid and sedative-hypnotics is a new phenomenon that merits further evaluation of patient safety outcomes. In addition, we found substantial potential opportunities for deprescribing CNS-active medications in high-risk groups. Finally, the increased chronicity of VA prescriptions versus Medicare Part D is novel and should be further evaluated in terms of its mechanism and impact on Medicare-VA dual users.

Current insight into treatment of chronic rhinosinusitis: Phenotypes, endotypes, and implications for targeted therapeutics.

Chronic rhinosinusitis is characterized by persistent locoregional mucosal inflammation of the paranasal sinuses and upper airway that has substantial associated health care costs. Personalized approaches to care that incorporate use of molecular biomarkers, phenotypes, and inflammatory endotypes is a major focus of research at this time, and the concurrent rise of targeted therapeutics and biologic therapies has the potential to rapidly advance care and improve outcomes. Recent findings suggest that improved understanding of chronic rhinosinusitis phenotypic and endotypic heterogeneity, and incorporation of these characteristics into clinical care pathways, may facilitate more effective selection of surgical and/or therapeutic interventions. Ultimately, these personalized approaches have the potential to target specific inflammatory pathways, increase efficacy, reduce costs, and limit side effects. This review summarizes recent advances in the identification and characterization of chronic rhinosinusitis phenotypes, endotypes, and biomarkers and reviews potential implications for targeted therapeutics.

Addressing Barriers to Reducing Prescribing and Implementing Deprescribing of Sedative-Hypnotics in Primary Care.

OBJECTIVE: To describe interventions that target patient, provider, and system barriers to sedative-hypnotic (SH) deprescribing in the community and suggest strategies for healthcare teams. DATA SOURCES: Ovid MEDLINE ALL and EMBASE Classic + EMBASE (March 10, 2021). STUDY SELECTION AND DATA EXTRACTION: English-language studies in primary care settings. DATA SYNTHESIS: 20 studies were themed as patient-related and prescriber inertia, physician skills and awareness, and health system constraints. Patient education strategies reduced SH dose for 10% to 62% of participants, leading to discontinuation in 13% to 80% of participants. Policy interventions reduced targeted medication use by 10% to 50%. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Patient engagement and empowerment successfully convince patients to deprescribe chronic SHs. Quality improvement strategies should also consider interventions directed at prescribers, including education and training, drug utilization reviews, or computer alerts indicating a potentially inappropriate prescription by medication, age, dose, or disease. Educational interventions were effective when they facilitated patient engagement and provided information on the harms and limited evidence supporting chronic use as well as the effectiveness of alternatives. Decision support tools were less effective than prescriber education with patient engagement, although they can be readily incorporated in the workflow through prescribing software. CONCLUSIONS: Several strategies with demonstrated efficacy in reducing SH use in community practice were identified. Education regarding SH risks, how to taper, and potential alternatives are essential details to provide to clinicians, patients, and families. The strategies presented can guide community healthcare teams toward reducing the community burden of SH use.

SARS-CoV-2 infection and viral load are associated with the upper respiratory tract microbiome.

BACKGROUND: Little is known about the relationships between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the respiratory virus responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic, and the upper respiratory tract (URT) microbiome. OBJECTIVE: We sought to compare the URT microbiome between SARS-CoV-2-infected and -uninfected adults and to examine the association of SARS-CoV-2 viral load with the URT microbiome during COVID-19. METHODS: We characterized the URT microbiome using 16S ribosomal RNA sequencing in 59 adults (38 with confirmed, symptomatic, mild to moderate COVID-19 and 21 asymptomatic, uninfected controls). In those with COVID-19, we measured SARS-CoV-2 viral load using quantitative reverse transcription PCR. We then examined the association of SARS-CoV-2 infection status and its viral load with the ⍺-diversity, ß-diversity, and abundance of bacterial taxa of the URT microbiome. Our main models were all adjusted for age and sex. RESULTS: The observed species index was significantly higher in SARS-CoV-2-infected than in -uninfected adults (ß linear regression coefficient = 7.53; 95% CI, 0.17-14.89; P = .045). In differential abundance testing, 9 amplicon sequence variants were significantly different in both of our comparisons, with Peptoniphilus lacrimalis, Campylobacter hominis, Prevotella 9 copri, and an Anaerococcus unclassified amplicon sequence variant being more abundant in those with SARS-CoV-2 infection and in those with high viral load during COVID-19, whereas Corynebacterium unclassified, Staphylococcus haemolyticus, Prevotella disiens, and 2 Corynebacterium_1 unclassified amplicon sequence variants were more abundant in those without SARS-CoV-2 infection and in those with low viral load during COVID-19. CONCLUSIONS: Our findings suggest complex associations between SARS-CoV-2 and the URT microbiome in adults. Future studies are needed to examine how these viral-bacterial interactions can impact the clinical progression, severity, and recovery of COVID-19.

Inflammatory heterogeneity in aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a mechanistically distinct subtype of chronic rhinosinusitis with nasal polyps (CRSwNP). Although frequently associated with type 2 inflammation, literature characterizing the milieu of inflammatory cytokines and lipid mediators in AERD has been conflicting. OBJECTIVE: We sought to identify differences in the upper airway inflammatory signature between CRSwNP and AERD and determine whether endotypic subtypes of AERD may exist. METHODS: Levels of 7 cytokines representative of type 1, type 2, and type 3 inflammation, and 21 lipid mediators were measured in nasal mucus from 109 patients with CRSwNP, 30 patients with AERD, and 64 non-CRS controls. Differences in inflammatory mediators were identified between groups, and patterns of inflammation among patients with AERD were determined by hierarchical cluster analysis. RESULTS: AERD could be distinguished from CRSwNP by profound elevations in IL-5, IL-6, IL-13, and IFN-γ; however, significant heterogeneity existed between patients. Hierarchical cluster analysis identified 3 inflammatory subendotypes of AERD characterized by (1) low inflammatory burden, (2) high type 2 cytokines, and (3) comparatively low type 2 cytokines and high levels of type 1 and type 3 cytokines. Several lipid mediators were associated with asthma and sinonasal disease severity; however, lipid mediators showed less variability than cytokines. CONCLUSIONS: AERD is associated with elevations in type 2 cytokines (IL-5 and IL-13) and the type 1 cytokine, IFN-γ. Among patients with AERD, the inflammatory signature is heterogeneous, supporting subendotypes of the disease. Variability in AERD immune signatures should be further clarified because this may predict clinical response to biologic medications that target type 2 inflammation.

"Bayis Ilh Tus - a strong breath" a community-based research project to estimate the prevalence of chronic obstructive pulmonary disease in remote and rural first nations communities in Canada: research protocol.

BACKGROUND: Respiratory health conditions appear to be more common among First Nations people versus non-First Nations people in Canada. However, the prevalence of chronic obstructive pulmonary disease (COPD) and its associated risk factors in First Nations communities are unknown. This project aims to estimate the prevalence of COPD in several First Nations communities in British Columbia, Canada and to characterize respiratory symptoms, COPD risk factors, and healthcare utilization. METHODS: This project is approved by both the University of British Columbia and Carrier Sekani Family Services Research Ethics Boards. We will randomly sample 220 adults, 30 years and older, from 11 participating First Nations. Each participant will complete pre- and post-bronchodilator spirometry tests and the adapted American Thoracic Society Epidemiological Questionnaire with items about smoking history, respiratory symptoms, co-morbidities, and exposures, in order to identify the presence of COPD and its associated individual, occupational, and community risk factors. Homes will be assessed for air quality measures including particulate matter, carbon monoxide and carbon dioxide, and humidity. Health care utilization will be abstracted from the electronic medical record. DISCUSSION: This is the first project in Canada to estimate the prevalence of COPD in First Nations communities using a random-sampling approach to recruitment. Additionally, although this study will collect detailed information on smoking history, we will also characterize past and current risk factors beyond cigarette smoking. Finally, our methodology ensures that the benefits to the communities are realized during the study period. Individual results will be shared with individuals and health providers to facilitate care. Air quality results will be sent to each Nation's governing council to facilitate remediation where necessary. TRIAL REGISTRATION: The study has been retrospectively registered at clinicaltrials.gov ( NCT04105088 ).

Cultural determinants of food attitudes in anosmic patients.

The decrease in food enjoyment is a major factor why patients suffer from depression when having anosmia, or total loss of smell. While we have some knowledge about how food preferences and attitudes change with dysosmia, these findings are limited because other factors such as culture are not factored in. It is likely that the culture in which an anosmic patient identifies with will influence how their smell loss impacts their relationship with food. This study examined the current attitudes within the United States and Germany towards foods, focusing on the comparison between anosmic patients (N = 53) and those with a healthy sense of smell (N = 121). A survey was used to collect free responses for liking on a variety of foods (N = 15) that were also rated for their overall liking. Additionally, individuals rated and ranked their liking for sensory attributes in relation to their enjoyment of food. Free responses were classified into categories and subcategories, the frequency of those responses were then compared across groups. The patient population of each culture gave lower importance to aroma and flavor; however, the U.S.A. patient population showed a larger decrease from their healthy counterparts. Furthermore, anosmic patients from the U.S.A. showed less overall liking towards the food stimuli compared to their healthy counterparts, while no such effect observed among the German population. Reasons to enjoy a food were largely explained by the culture, and patients within a culture took on different compensation strategies which we use to explain their effectiveness.

Chronic rhinosinusitis in elderly patients is associated with an exaggerated neutrophilic proinflammatory response to pathogenic bacteria.

BACKGROUND: Potential effects of aging on chronic rhinosinusitis (CRS) pathophysiology have not been well defined but might have important ramifications given a rapidly aging US and world population. OBJECTIVE: The goal of the current study was to determine whether advanced age is associated with specific inflammatory CRS endotypes or immune signatures. METHODS: Levels of 17 mucus cytokines and inflammatory mediators were measured in 147 patients with CRS. Hierarchical cluster analysis was used to identify and characterize inflammatory CRS endotypes, as well as to determine whether age was associated with specific immune signatures. RESULTS: A CRS endotype with a proinflammatory neutrophilic immune signature was enriched in older patients. In the overall cohort patients 60 years and older had increased mucus levels of IL-1ß, IL-6, IL-8, and TNF-α when compared with their younger counterparts. Increases in levels of proinflammatory cytokines were associated with both tissue neutrophilia and symptomatic bacterial infection/colonization in aged patients. CONCLUSIONS: Aged patients with CRS have a unique inflammatory signature that corresponds to a neutrophilic proinflammatory response. Neutrophil-driven inflammation in aged patients with CRS might be less likely to respond to corticosteroids and might be closely linked to chronic microbial infection or colonization.

Polypharmacy cut-points in older people with cancer: how many medications are too many?

PURPOSE: Polypharmacy is often defined as use of 'five-or-more-medications'. However, the optimal polypharmacy cut-point for predicting clinically important adverse events in older people with cancer is unclear. The aim was to determine the sensitivities and specificities of a range of polypharmacy cut-points in relation to a variety of adverse events in older people with cancer. METHODS: Data on medication use, falls and frailty criteria were collected from 385 patients aged ≥70 years presenting to a medical oncology outpatient clinic. Receiver operating characteristic (ROC) curves were produced to examine sensitivities and specificities for varying definitions of polypharmacy in relation to exhaustion, falls, physical function, Karnofsky Performance Scale (KPS) and frailty. Sub-analyses were performed when stratifying by age, sex, comorbidity status and analgesic use. RESULTS: Patients had a mean age of 76.7 years. Using Youden's index, the optimal polypharmacy cut-point was 6.5 medications for predicting frailty (specificity 67.0 %, sensitivity 70.0 %), physical function (80.2 %, 49.3 %) and KPS (69.8 %, 52.1 %), 5.5 for falls (59.2 %, 73.0 %) and 3.5 for exhaustion (43.4 %, 74.5 %). For polypharmacy defined as five-or-more-medications, the specificities and sensitivities were frailty (44.9 %, 77.5 %), physical function (58.0 %, 69.7 %), KPS (47.7 %, 69.4 %), falls (44.5 %, 75.7 %) and exhaustion (52.6 %, 64.1 %). The optimal polypharmacy cut-points were similar when the sample was stratified by age, sex, comorbidity status and analgesic use. CONCLUSIONS: Our results suggest that no single polypharmacy cut-point is optimal for predicting multiple adverse events in older people with cancer. In this population, the common definition of five-or-more-medications is reasonable for identifying 'at-risk' patients for medication review.

Differential effect of omalizumab on pulmonary function in patients with allergic asthma with and without chronic rhinosinusitis.

BACKGROUND: Omalizumab, an anti-immunoglobulin E monoclonal antibody, is approved by the U.S. Food and Drug Administration for the management of patients with allergic asthma and with refractory disease, and has also proven beneficial in the management of selected patients with chronic rhinosinusitis (CRS). The common airway model indicates that patients with both allergic asthma and CRS may be more challenging to manage clinically. This is the first study to evaluate the response of omalizumab in patients with asthma and CRS versus those with asthma alone. OBJECTIVE: To compare pulmonary function test (PFT) responses in omalizumab-treated patients with asthma with CRS with omalizumab-treated patients with asthma without CRS. METHODS: This was a retrospective case-control study at a tertiary university clinic. Between 2007 and 2014, a total of 259 patients with allergic asthma had been prescribed omalizumab for asthma. Outcome measures were absolute, and the percentage changes in PFT results were compared with the baseline. RESULTS: Overall, 81 patients had serial PFT results available for evaluation, among whom 59 (73%) had CRS. Average treatment duration was 27.2, 27.7, and 25.8 months for the entire sample, for patients with asthma and CRS, and for patients with asthma and without CRS, respectively. Overall, PFT metrics improved across all parameters (forced expiratory volume in 1 second, forced vital capacity, forced expiratory volume in 1 second to forced vital capacity ratio, and forced expiratory flow 25-75%). Significant improvement (p < 0.05, paired t-test) was observed for three of four metrics in patients with comorbid CRS but in none of these parameters in patients without CRS. CONCLUSION: Patients with allergic asthma who were treated with omalizumab manifested some improvement in PFT scores. CRS may add to the overall symptom burden experienced by patients with asthma, especially in those with increasing severity, but comorbid CRS did not adversely impact the therapeutic potential of omalizumab. In fact, the benefit of omalizumab was more likely to be observed in patients with asthma and with CRS than in patients with asthma and without CRS.