Universal logic with encoded spin qubits in silicon.

Quantum computation features known examples of hardware acceleration for certain problems, but is challenging to realize because of its susceptibility to small errors from noise or imperfect control. The principles of fault tolerance may enable computational acceleration with imperfect hardware, but they place strict requirements on the character and correlation of errors1. For many qubit technologies2-21, some challenges to achieving fault tolerance can be traced to correlated errors arising from the need to control qubits by injecting microwave energy matching qubit resonances. Here we demonstrate an alternative approach to quantum computation that uses energy-degenerate encoded qubit states controlled by nearest-neighbour contact interactions that partially swap the spin states of electrons with those of their neighbours. Calibrated sequences of such partial swaps, implemented using only voltage pulses, allow universal quantum control while bypassing microwave-associated correlated error sources1,22-28. We use an array of six 28Si/SiGe quantum dots, built using a platform that is capable of extending in two dimensions following processes used in conventional microelectronics29. We quantify the operational fidelity of universal control of two encoded qubits using interleaved randomized benchmarking30, finding a fidelity of 96.3% ± 0.7% for encoded controlled NOT operations and 99.3% ± 0.5% for encoded SWAP. The quantum coherence offered by enriched silicon5-9,16,18,20,22,27,29,31-37, the all-electrical and low-crosstalk-control of partial swap operations1,22-28 and the configurable insensitivity of our encoding to certain error sources28,33,34,38 all combine to offer a strong pathway towards scalable fault tolerance and computational advantage.

Time-restricted feeding reveals a role for neural respiratory clocks in optimizing daily ventilatory-metabolic coupling in mice.

The master circadian clock, located in the suprachiasmatic nuclei (SCN), organizes the daily rhythm in minute ventilation (VE). However, the extent that the daily rhythm in VE is secondary to SCN-imposed O2 and CO2 cycles (i.e., metabolic rate), or driven by other clock mechanisms, remains unknown. Here, we experimentally shifted metabolic rate using time-restricted feeding (without affecting light-induced synchronization of the SCN) to determine the influence of metabolic rate in orchestrating the daily VE rhythm. Mice eating predominantly at night exhibited robust daily rhythms in O2 consumption (VO2), CO2 production (VCO2), and VE with similar peak times (~ZT18) that were consistent with SCN organization. However, feeding mice exclusively during the day separated the relative timing of metabolic and ventilatory rhythms, resulting in a ~8.5-hr advance in VCO2, and a disruption of the VE rhythm, suggesting opposing circadian and metabolic influences on VE. To determine if the molecular clock of cells involved in the neural control of breathing contribute to the daily VE rhythm, we examined VE in mice lacking BMAL1 in Phox2b-expressing respiratory cells (i.e., BKOP mice). The ventilatory and metabolic rhythms of predominantly night-fed BKOP mice did not differ from wild-type mice. However, in contrast to wild-type mice, exclusive day feeding of BKOP mice led to an unfettered daily VE rhythm with a peak time aligning closely with the daily VCO2 rhythm. Taken together, these results indicate that both daily VCO2 changes and intrinsic circadian time-keeping within Phox2b respiratory cells are predominant orchestrators of the daily rhythm in ventilation.

Potentially Modifiable Risk Factors for Dementia and Mild Cognitive Impairment: An Umbrella Review and Meta-Analysis.

INTRODUCTION: The prevalence of mild and major neurocognitive disorders (NCDs), also referred to as mild cognitive impairment and dementia, is rising globally. The prevention of NCDs is a major global public health interest. We sought to synthesize the literature on potentially modifiable risk factors for NCDs. METHODS: We conducted an umbrella review using a systematic search across multiple databases to identify relevant systematic reviews and meta-analyses. Eligible reviews examined potentially modifiable risk factors for mild or major NCDs. We used a random-effects multi-level meta-analytic approach to synthesize risk ratios for each risk factor while accounting for overlap in the reviews. We further examined risk factors for major NCD due to two common etiologies: Alzheimer's disease and vascular dementia. RESULTS: A total of 45 reviews with 212 meta-analyses were synthesized. We identified fourteen broadly defined modifiable risk factors that were significantly associated with these disorders: alcohol consumption, body weight, depression, diabetes mellitus, diet, hypertension, less education, physical inactivity, sensory loss, sleep disturbance, smoking, social isolation, traumatic brain injury, and vitamin D deficiency. All 14 factors were associated with the risk of major NCD, and five were associated with mild NCD. We found considerably less research for vascular dementia and mild NCD. CONCLUSION: Our review quantifies the risk associated with 14 potentially modifiable risk factors for mild and major NCDs, including several factors infrequently included in dementia action plans. Prevention strategies should consider approaches that reduce the incidence and severity of these risk factors through health promotion, identification, and early management.

Evaluating methods for risk prediction of Covid-19 mortality in nursing home residents before and after vaccine availability: a retrospective cohort study.

BACKGROUND: SARS-CoV-2 vaccines are effective in reducing hospitalization, COVID-19 symptoms, and COVID-19 mortality for nursing home (NH) residents. We sought to compare the accuracy of various machine learning models, examine changes to model performance, and identify resident characteristics that have the strongest associations with 30-day COVID-19 mortality, before and after vaccine availability. METHODS: We conducted a population-based retrospective cohort study analyzing data from all NH facilities across Ontario, Canada. We included all residents diagnosed with SARS-CoV-2 and living in NHs between March 2020 and July 2021. We employed five machine learning algorithms to predict COVID-19 mortality, including logistic regression, LASSO regression, classification and regression trees (CART), random forests, and gradient boosted trees. The discriminative performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC) for each model using 10-fold cross-validation. Model calibration was determined through evaluation of calibration slopes. Variable importance was calculated by repeatedly and randomly permutating the values of each predictor in the dataset and re-evaluating the model's performance. RESULTS: A total of 14,977 NH residents and 20 resident characteristics were included in the model. The cross-validated AUCs were similar across algorithms and ranged from 0.64 to 0.67. Gradient boosted trees and logistic regression had an AUC of 0.67 pre- and post-vaccine availability. CART had the lowest discrimination ability with an AUC of 0.64 pre-vaccine availability, and 0.65 post-vaccine availability. The most influential resident characteristics, irrespective of vaccine availability, included advanced age (≥ 75 years), health instability, functional and cognitive status, sex (male), and polypharmacy. CONCLUSIONS: The predictive accuracy and discrimination exhibited by all five examined machine learning algorithms were similar. Both logistic regression and gradient boosted trees exhibit comparable performance and display slight superiority over other machine learning algorithms. We observed consistent model performance both before and after vaccine availability. The influence of resident characteristics on COVID-19 mortality remained consistent across time periods, suggesting that changes to pre-vaccination screening practices for high-risk individuals are effective in the post-vaccination era.

Examining the effect of the COVID-19 pandemic on community virus prevalence and healthcare utilisation reveals that peaks in asthma, COPD and respiratory tract infection occur with the re-emergence of rhino/enterovirus.

INTRODUCTION: Airway disease exacerbations are cyclical related to respiratory virus prevalence. The COVID-19 pandemic has been associated with reduced exacerbations possibly related to public health measures and their impact on non-COVID-19 respiratory viruses. We aimed to investigate the prevalence of non-COVID-19 respiratory viruses during the pandemic compared with prior in Ontario, Canada and healthcare utilisation related to asthma, chronic obstructive pulmonary disease (COPD) and respiratory tract infection. METHODS: This is a population-based retrospective analysis of respiratory virus tests, emergency department (ED) visits and hospitalisations between 2015 and 2021 in Ontario. Weekly virus testing data were used to estimate viral prevalence for all non-COVID-19 respiratory viruses. We plotted the %positivity and observed and expected counts of each virus to visualise the impact of the pandemic. We used Poisson and binomial logistic regression models to estimate the change in %positivity, count of positive viral cases and count of healthcare utilisation during the pandemic. RESULTS: The prevalence of all non-COVID-19 respiratory viruses decreased dramatically during the pandemic compared with prior. Comparing periods, the incidence rate ratio (IRR) for positive cases corresponded to a >90% reduction for non-COVID-19 respiratory viruses except adenovirus and rhino/enterovirus. Asthma-related ED visits and hospital admissions fell by 57% (IRR 0.43 (95% CI 0.37 to 0.48)) and 61% (IRR 0.39 (95% CI 0.33 to 0.46)). COPD-related ED visits and admissions fell by 63% (IRR 0.37 (95% CI 0.30 to 0.45)) and 45% (IRR 0.55 (95% CI 0.48 to 0.62)). Respiratory tract infection ED visits and admissions fell by 85% (IRR 0.15 (95% CI 0.10 to 0.22)), and 85% (IRR 0.15 (95% CI 0.09 to 0.24)). Rather than the usual peaks in disease condition, during the pandemic, healthcare utilisation peaked in October when rhino/enterovirus peaked. CONCLUSIONS: The prevalence of nearly all non-COVID-19 respiratory viruses decreased during the pandemic and was associated with marked reductions in ED visits and hospitalisations. The re-emergence of rhino/enterovirus was associated with increased healthcare utilisation.

Single and coupled cavity mode sensing schemes using a diagnostic field.

Precise optical mode matching is of critical importance in experiments using squeezed-vacuum states. Automatic spatial-mode matching schemes have the potential to reduce losses and improve loss stability. However, in quantum-enhanced coupled-cavity experiments, such as gravitational-wave detectors, one must also ensure that the sub-cavities are also mode matched. We propose what we believe to be a new mode sensing scheme, which works for simple and coupled cavities. The scheme requires no moving parts, nor tuning of Gouy phases. Instead a diagnostic field tuned to the HG20/LG10 mode frequency is used. The error signals are derived to be proportional to the difference in waist position, and difference in Rayleigh ranges, between the sub-cavity eigenmodes. The two error signals are separable by 90 degrees of demodulation phase. We demonstrate reasonable error signals for a simplified Einstein Telescope optical design. This work will facilitate routine use of extremely high levels of squeezing in current and future gravitational-wave detectors.

The Impact of Poorly Differentiated Histology on Immunotherapy in Advanced Gastrointestinal Cancers.

INTRODUCTION: Checkpoint inhibitors (CPI) have significantly improved survival among patients with various cancer types. Prior studies have shown a correlation between immune cell infiltration and poorly differentiated cancers. This study evaluated the impact of poorly differentiated histology on survival in patients with advanced gastrointestinal cancers treated with immunotherapy. METHODS: This study was a retrospective, single-center analysis of patients with gastrointestinal cancers treated with CPIs between 2016 and 2021. Univariate and multivariable analyses were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor and patient characteristics, progression-free survival, and overall survival. RESULTS: A total of 123 patients were eligible and included in the analysis. Median age was 66 years (23-88 years). Majority had stage IV disease (89%), were white (65.5%), and were male (64.5%). Most common diagnoses were hepatocellular carcinoma (30.5%), gastric adenocarcinoma (16.5%), esophageal adenocarcinoma (17%), and colorectal cancer (19.8%). About 32% of the tumors were microsatellite instability-high (MSI-High/dMMR), with BRAF V600E mutation rate of 10%. About 25% of the patients received CPIs as initial treatment, while 35.5% had received two or more prior lines of therapy. Compared with well and moderately differentiated histology, patients with poorly differentiated tumors had a shorter median overall survival (mOS) (not reached [NR] vs. NR vs. 9.3 months, p = 0.0264). There was no statistically significant difference in median progression-free survival (mPFS) between histology types (2.5 vs. 4.2 vs. 2 months, p = 0.1314). On univariate survival analysis, moderately differentiated tumors correlated with a significantly longer mOS (HR: 0.48, CI: 0.24-0.93, p = 0.030) and mPFS (HR: 0.62, 95% CI: 0.38-1.00, p = 0.048) compared to poorly differentiated histology. Female patients (HR: 0.55, 95% CI: 0.34-0.90, p = 0.018) and the Eastern Cooperative Oncology Group (ECOG) of 1 (vs. ≥2) had significantly longer mPFS (HR: 0.58, 95% CI: 0.35-0.97, p = 0.036). ECOG of 1 also correlated with longer mOS (HR: 0.47, 95% CI: 0.23-0.94, p = 0.034). Microsatellite stable (MSS) tumors had significantly shorter mPFS (HR: 5.74, 95% CI: 2.41-13.63, p < 0.001) and mOS (HR: 5.45, 95% CI: 1.64-18.12, p = 0.006). The number of prior systemic therapies was also associated with shorter mPFS (HR: 1.19, 95% CI: 1.03-1.39, p = 0.022) and mOS (HR: 1.23, 95% CI: 1.01-1.50, p = 0.045). On multivariable analyses, ECOG status of 0/1 versus ≥2 and MSI-High/dMMR versus MSS remained significantly associated with longer mPFS and mOS. There was no correlation with histologic differentiation status, race, or mutations such as BRAF V600E or KRAS. CONCLUSION: Results from this study demonstrate that poorly differentiated histology was associated with shorter mOS but was not associated with improved PFS in patients treated with CPI. Treatment-naïve patients, moderately differentiated tumors, female gender, ECOG 1, and MSI-High/dMMR were most likely to benefit from CPI.

The association between frailty, long-term care home characteristics and COVID-19 mortality before and after SARS-CoV-2 vaccination: a retrospective cohort study.

BACKGROUND: The relative contributions of long-term care (LTC) resident frailty and home-level characteristics on COVID-19 mortality has not been well studied. We examined the association between resident frailty and home-level characteristics with 30-day COVID-19 mortality before and after the availability of SARS-CoV-2 vaccination in LTC. METHODS: We conducted a population-based retrospective cohort study of LTC residents with confirmed SARS-CoV-2 infection in Ontario, Canada. We used multi-level multivariable logistic regression to examine associations between 30-day COVID-19 mortality, the Hubbard Frailty Index (FI), and resident and home-level characteristics. We compared explanatory models before and after vaccine availability. RESULTS: There were 11,179 and 3,655 COVID-19 cases in the pre- and post-vaccine period, respectively. The 30-day COVID-19 mortality was 25.9 and 20.0% during the same periods. The median odds ratios for 30-day COVID-19 mortality between LTC homes were 1.50 (95% credible interval [CrI]: 1.41-1.65) and 1.62 (95% CrI: 1.46-1.96), respectively. In the pre-vaccine period, 30-day COVID-19 mortality was higher for males and those of greater age. For every 0.1 increase in the Hubbard FI, the odds of death were 1.49 (95% CI: 1.42-1.56) times higher. The association between frailty and mortality remained consistent in the post-vaccine period, but sex and age were partly attenuated. Despite the substantial home-level variation, no home-level characteristic examined was significantly associated with 30-day COVID-19 mortality during either period. INTERPRETATION: Frailty is consistently associated with COVID-19 mortality before and after the availability of SARS-CoV-2 vaccination. Home-level characteristics previously attributed to COVID-19 outcomes do not explain significant home-to-home variation in COVID-19 mortality.

Frailty prevalence and efficient screening in primary care-based memory clinics.

BACKGROUND: Little is known about the prevalence of frailty among patients with memory concerns attending a primary care-based memory clinic. OBJECTIVE: This study aims to describe the prevalence of frailty among patients attending a primary care-based memory clinic and to determine if prevalence rates differ based on the screening tool that is used. METHODS: We conducted a retrospective medical record review for all consecutive patients assessed in a primary care-based memory clinic over 8 months. Frailty was measured in 258 patients using the Fried frailty criteria, which relies on physical measures, and the Clinical Frailty Scale (CFS), which relies on functional status. Weighted kappa statistics were calculated to compare the Fried frailty and the CFS. RESULTS: The prevalence of frailty was 16% by Fried criteria and 48% by the CFS. Agreement between Fried frailty and CFS was fair for CFS 5+ (kappa = 0.22; 95% confidence interval: 0.13, 0.32) and moderate for CFS 6+ (kappa = 0.47; 0.34, 0.61). Dual-trait measures of hand grip strength with gait speed were found to be a valid proxy for Fried frailty phenotype. CONCLUSIONS: Among primary care patients with memory concerns, frailty prevalence rates differed based on the measure used. Screening for frailty in this population using measures relying on physical performance may be a more efficient approach for persons already at risk of further health instability from cognitive impairment. Our findings demonstrate how measure selection should be based on the objectives and context in which frailty screening occurs.

There is some evidence that frailty and dementia are inter-related. This study aimed to describe the prevalence of frailty among patients attending a primary care-based memory clinic using 2 commonly used frailty measures: the Fried frailty phenotype criteria and the Clinical Frailty Scale (CFS). Frailty prevalence in patients with memory concerns is at least double that of regular primary care practice; prevalence is 16% when the Fried frailty phenotype is used, which incorporates physical frailty measures, as compared with prevalence of 48% when the more function-based measure of CFS is used. Screening tools should be selected considering the objectives and context in which they are used. Within primary care-based memory clinics, physical frailty measures may be most optimal. Using hand grip and gait speed screening as a valid proxy for Fried frailty phenotype offers a feasible and practical way of identifying frailty relating more to physical underlying conditions. Based on our study findings, frailty screening within primary care-based memory clinics is justified for patients 65 years+; early identification and intervention may prevent further decline and adverse outcomes. Further research in this area will increase our understanding of frailty and dementia in this context and how to best plan care.

Recent functional decline and outpatient follow-up after hospital discharge: a cohort study.

BACKGROUND: Functional decline is common following acute hospitalization and is associated with hospital readmission, institutionalization, and mortality. People with functional decline may have difficulty accessing post-discharge medical care, even though early physician follow-up has the potential to prevent poor outcomes and is integral to high-quality transitional care. We sought to determine whether recent functional decline was associated with lower rates of post-discharge physician follow-up, and whether this association changed during the COVID-19 pandemic, given that both functional decline and COVID-19 may affect access to post-discharge care. METHOD: We conducted a retrospective cohort study using health administrative data from Ontario, Canada. We included patients over 65 who were discharged from an acute care facility during March 1st, 2019 - January 31st, 2020 (pre-COVID-19 period), and March 1st, 2020 - January 31st, 2021 (COVID-19 period), and who were assessed for home care while in hospital. Patients with and without functional decline were compared. Our primary outcome was any physician follow-up visit within 7 days of discharge. We used propensity score weighting to compare outcomes between those with and without functional decline. RESULTS: Our study included 21,771 (pre-COVID) and 17,248 (COVID) hospitalized patients, of whom 15,637 (71.8%) and 12,965 (75.2%) had recent functional decline. Pre-COVID, there was no difference in physician follow-up within 7 days of discharge (Functional decline 45.0% vs. No functional decline 44.0%; RR = 1.02, 95% CI 0.98-1.06). These results did not change in the COVID-19 period (Functional decline 51.1% vs. No functional decline 49.4%; RR = 1.03, 95% CI 0.99-1.08, Z-test for interaction p = 0.72). In the COVID-19 cohort, functional decline was associated with having a 7-day physician virtual visit (RR 1.15; 95% CI 1.08-1.24) and a 7-day physician home visit (RR 1.64; 95% CI 1.10-2.43). CONCLUSIONS: Functional decline was not associated with reduced 7-day post-discharge physician follow-up in either the pre-COVID-19 or COVID-19 periods. In the COVID-19 period, functional decline was positively associated with 7-day virtual and home-visit follow-up.

Medical treatments for idiopathic pulmonary fibrosis: a systematic review and network meta-analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder with a poor prognosis. Our objective is to assess the comparative effectiveness of 22 approved or studied IPF drug treatments. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov from inception to 2 April 2021. We included randomised controlled trials (RCTs) for adult patients with IPF receiving one or more of 22 drug treatments. Pairs of reviewers independently identified randomised trials that compared one or more of the target medical treatments in patients with IPF. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for network meta-analysis. We calculated pooled relative risk (RR) ratios and presented direct or network estimates with 95% credibility intervals (95% CI), within the GRADE framework. RESULTS: We identified 48 (10 326 patients) eligible studies for analysis. Nintedanib [RR 0.69 (0.44 to 1.1), pirfenidone [RR 0.63 (0.37 to 1.09); direct estimate), and sildenafil [RR (0.44 (0.16 to 1.09)] probably reduce mortality (all moderate certainty). Nintedanib (2.92% (1.51 to 4.14)), nintedanib+sildenafil (157 mL (-88.35 to 411.12)), pirfenidone (2.47% (-0.1 to 5)), pamrevlumab (4.3% (0.5 to 8.1)) and pentraxin (2.74% (1 to 4.83)) probably reduce decline of overall forced vital capacity (all moderate certainty). Only sildenafil probably reduces acute exacerbation and hospitalisations (moderate certainty). Corticosteroids+azathioprine+N-acetylcysteine increased risk of serious adverse events versus placebo (high certainty). CONCLUSION AND RELEVANCE: Future guidelines should consider sildenafil for IPF and further research needs to be done on promising IPF treatments such as pamrevlumab and pentraxin as phase 3 trials are completed.

Observing the optical modes of parametric instability.

Parametric instability (PI) is a phenomenon that results from resonant interactions between optical and acoustic modes of a laser cavity. This is problematic in gravitational wave interferometers where the high intracavity power and low mechanical loss mirror suspension systems create an environment where three-mode PI will occur without intervention. We demonstrate a technique for real-time imaging of the amplitude and phase of the optical modes of PI yielding, to the best of the authors' knowledge, the first ever images of this phenomenon which could form part of active control strategies for future detectors.

Comparing Somatostatin Analogs in the Treatment of Advanced Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND: The 2 approved somatostatin analogs (SSAs) in the first-line treatment of advanced, well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are octreotide long-acting release (Sandostatin LAR) and somatuline depot (Lanreotide). The study's objective was to compare progression-free survival (PFS) and overall survival (OS) of patients (pts) with GEP-NETs treated with somatuline or octreotide LAR. Pts and Methods: Pts with advanced well-differentiated GEP-NET who received either SSA at Emory University between 1995 and 2019 were included after institutional review board approval. The primary end point was PFS, defined as time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.1, or clinical progression) or death. The secondary end point was OS. Kaplan-Meier curves were generated, and log-rank tests were conducted to compare the survival outcomes. RESULTS: A total of 105 pts were identified. The mean age was 62.1 years (SD ± 11.8). The male-to-female ratio was 51:54. The majority (N = 69, 65.7%) were white. Most pts had grade 2 (G2) disease (N = 44, 41.9%). Primary location was small bowel in 58 (55.2%), pancreas in 27 (25.7%), and other in 20 (19.0%). Functional tumors were defined in 32 pts distributed equally between the 2 groups. Distribution of treatment was similar in the 2 groups, with 54 receiving octreotide LAR and 51 receiving somatuline depot. The median PFS for the octreotide LAR and somatuline depot groups was 12 months (95% CI, 6-18 months) and 10.8 months (95% CI, 6-15.6 months), respectively, and the difference was not statistically significant (p = 0.2665). For pts with G1 disease, the median PFS for the octreotide LAR and somatuline depot was 8.4 versus 32.4 months, respectively, and the difference was not statistically significant (p = 0.159). For G2 disease, the difference in median PFS between octreotide LAR and somutaline depot groups was statistically significant (12 vs. 7.2 months, respectively; p = 0.0372). The mean follow-up time for octreotide LAR was 21.6 months versus 11.3 months for somatuline depot. CONCLUSIONS: Overall, there was no difference in PFS between octreotide LAR and somatuline depot for pts with well-differentiated, metastatic GEP-NETs. A prospective study is worth designing selecting for G.

Sildenafil for idiopathic pulmonary fibrosis: A systematic review and meta-analysis.

BACKGROUND: Patients with idiopathic pulmonary fibrosis have a poor overall prognosis and there are few evidence-based drug therapies that reduce mortality. OBJECTIVE: We aimed to perform a systematic review and meta-analysis to assess whether sildenafil reduces mortality, disease progression and adverse side effects. METHODS: We reviewed randomized controlled studies (RCTs) from MEDLINE, Cochrane registry of clinical trials, and EMBASE. Our outcomes of interest included mortality, change in FVC, acute exacerbations and hospitalizations and adverse drug effects leading to discontinuation. We used an inverse variance fixed effects meta-analysis method to calculate pooled relative risk (RR) and mean difference (MD). RESULTS: A total of 4 studies were included in the systematic review. Sildenafil probably reduces mortality when compared to placebo or to standard care, [RR 0.73 (95% CI 0.51 to 1.04); moderate certainty]. Pooled estimates showed sildenafil may not alter the rate of change of FVC [MD 0.61% (95% CI -0.29 to 1.52)], or DLCO [MD 0.97% (95% CI 0.04 to 1.90)] (both low certainty). Pooled estimated showed sildenafil may not reduce the number of hospitalizations or acute exacerbations, [RR 1.10 (95% CI 0.61 to 1.98); low certainty]. There is probably no difference in drug discontinuation due to adverse effects when comparing sildenafil to the control group, [RR 0.79 (95% CI 0.56, 1.10); moderate certainty]. CONCLUSION: Sildenafil probably reduces all-cause mortality in IPF patients. More studies need to be done to confirm the magnitude and reliability of the point estimate.

"No-regrets" pathways for navigating climate change: planning for connectivity with land use, topography, and climate.

As both plant and animal species shift their ranges in response to a changing climate, maintaining connectivity between present habitat and suitable habitat in the future will become increasingly important to ensure lasting protection for biodiversity. Because the temporal period commensurate with planning for mid-century change is multi-generational for most species, connectivity designed to facilitate climate adaptation requires pathways with 'stepping-stones' between current and future habitat. These areas should have habitats suitable not only for dispersal, but for all aspects of species lifecycles. We integrated present-day land use, topographic diversity, and projections of shifting climate regimes into a single connectivity modeling approach to identify pathways for mid-century shifts in species ranges. Using Omniscape we identified climate linkages, or areas important for climate change-driven movement, as the areas with more current flow than would be expected in the absence of climate considerations. This approach identified connectivity potential between natural lands in the present climate and natural lands with future analogous climate following topo-climatically diverse routes. We then translated the model output into a strategic framework to improve interpretation and to facilitate a more direct connection with conservation action. Across modified landscapes, pathways important to climate-driven movement were highly coincident with the last remaining present-day linkages, reinforcing their importance. Across unfragmented lands, the presence of climate-adapted pathways helped inform the prioritization of conservation actions in areas where multiple connectivity options still exist. Many climate linkages follow major watercourses along elevational gradients, highlighting the importance of protecting or managing for these natural linear pathways that provide movement routes for climate adaptation. By integrating enduring landscape features with climate projections and present-day land uses, our approach reveals "no-regrets" pathways to plan for a connected landscape in an uncertain future.

Rates of health services use among residents of retirement homes in Ontario: a population-based cohort study.

BACKGROUND: Because there are no standardized reporting systems specific to residents of retirement homes in North America, little is known about the health of this distinct population of older adults. We evaluated rates of health services use by residents of retirement homes relative to those of residents of long-term care homes and other populations of older adults. METHODS: We conducted a retrospective cohort study using population health administrative data from 2018 on adults 65 years or older in Ontario. We matched the postal codes of individuals to those of licensed retirement homes to identify residents of retirement homes. Outcomes included rates of hospital-based care and physician visits. RESULTS: We identified 54 733 residents of 757 retirement homes (mean age 86.7 years, 69.0% female) and 2 354 385 residents of other settings. Compared to residents of long-term care homes, residents of retirement homes had significantly higher rates per 1000 person months of emergency department visits (10.62 v. 4.48, adjusted relative rate [RR] 2.61, 95% confidence interval [CI] 2.55 to 2.67), hospital admissions (5.42 v. 2.08, adjusted RR 2.77, 95% CI 2.71 to 2.82), alternate level of care (ALC) days (6.01 v. 2.96, adjusted RR 1.51, 95% CI 1.48 to 1.54), and specialist physician visits (6.27 v. 3.21, adjusted RR 1.64, 95% CI 1.61 to 1.68), but a significantly lower rate of primary care visits (16.71 v. 108.47, adjusted RR 0.13, 95% CI 0.13 to 0.14). INTERPRETATION: Residents of retirement homes are a distinct population with higher rates of hospital-based care. Our findings can help to inform policy debates about the need for more coordinated primary and supportive health care in privately operated congregate care homes.

Frailty screening in older adults: is annual screening necessary in primary care?

BACKGROUND: The Case-finding for Complex Chronic Conditions in Adults 75+ (C5-75) involves annual frailty screening in primary care using dual-trait screening measures of handgrip strength and gait speed, with additional screening for co-existing conditions in those deemed frail. OBJECTIVE: To identify low-risk individuals who could be screened for frailty every 2 years, rather than annually. METHODS: This study examined a prospective cohort of patients who completed at least two annual C5-75 screenings between April 2014 and December 2018. Handgrip strength and gait speed on initial assessment were categorized based on proximity to frailty thresholds and were used to predict frailty risk on the second assessment. We used Fisher's exact test to assess differences in risk. Logistic regression models tested associations between independent variables of age, patient activity level, falls history, grip strength and gait speed on first assessment and dependent variable of frailty on subsequent assessment. RESULTS: Analyses included 571 patients with two annual assessments. Frailty risk on the second assessment was significantly higher for patients who had gait speed or grip strength within 20% of the frailty threshold (5.7%), compared with the other categories (0.7%, 0.9%, 0%; P = 0.002); 60% of patients fell within these lower risk categories. Controlling for grip strength and gait speed, no other measures had significant associations with frailty risk. CONCLUSIONS: Our results demonstrate that 60% patients are at low risk (<1%) of transitioning to frailty by the next annual assessment. Reducing screening frequency from annually to every 2 years may be appropriate for these patients.

Frail older adults are at greater risk for illness, functional decline, increased health service use and institutionalization. Adults 75 years of age and older should be screened regularly for frailty to provide early treatment for co-occurring conditions that may impact frailty but that may also be affected by frailty. Walking (gait) speed and handgrip strength are feasible measures of frailty to use on an annual basis in primary care. This study assesses the transition to frailty over a 1-year time period for the purpose of streamlining frailty screening in primary care for those patients who do not require annual screening. We found that when patients' grip strength and gait speed scores were 20% higher than the point at which people are identified as frail, they are at low risk for becoming frail by their next annual assessment. Frailty screening every 2 years may be appropriate for these patients. This streamlined screening process may make it more feasible for busy family practices to implement this type of frailty screening.

The predictive utility of functional status at discharge: a population-level cohort analysis.

BACKGROUND: Functional status is a patient-important, patient-centered measurement. The utility of functional status measures to inform post-discharge patient needs is unknown. We sought to examine the utility of routinely collected functional status measures gathered from older hospitalized patients to predict a panel of post-discharge outcomes. METHODS: In this population-based retrospective cohort study, Adults 65+ discharged from an acute hospitalization between 4 November 2008 and 18 March 2016 in Ontario, Canada and received an assessment of functional status at discharge using the Health Outcomes for Better Information and Care tool were included. Multivariable regression analysis was used to determine the relationship between functional status and emergency department (ED) re-presentation, hospital readmission, long term care facility (LTCF) admission or wait listing ('LTCF readiness'), and death at 180 days from discharge. RESULTS: A total of 80 020 discharges were included. 38 928 (48.6%) re-presented to the ED, 24 222 (30.3%) were re-admitted, 5 037 (6.3%) were LTCF ready, and 9 047 (11.3%) died at 180 days. Beyond age, diminished functional status at discharge was the factor most associated with LTCF readiness (adjusted Odds Ratio [OR] 4.11 for those who are completely dependent for activities of daily living compared to those who are independent; 95% Confidence Interval [CI]: 3.70-4.57) and death (OR 3.99; 95% CI: 3.67-4.35). Functional status also had a graded relationship with each outcome and improved the discriminability of the models predicting death and LTCF readiness (p<0.01) but not ED re-presentation or hospital re-admission. CONCLUSION: Routinely collected functional status at discharge meaningfully improves the prediction of long term care home readiness and death. The routine assessment of functional status can inform post-discharge care and planning for older adults.

Clinical factors associated with recent medical care visits in nursing homes: a multi-site cross-sectional study.

OBJECTIVES: We examined which resident-level clinical factors influence the provision of a recent medical care visit in nursing homes (NHs). DESIGN: Multi-site cross-sectional. SETTING AND PARTICIPANTS: We extracted data on 3,556 NH residents from 18 NH facilities in Ontario, Canada, who received at minimum, an admission and first-quarterly assessment with the Resident Assessment Instrument Minimum Data Set (MDS) 2.0 between November 1, 2009, and October 31, 2017. METHODS: We conducted a secondary analysis of routinely collected MDS 2.0 data. The provision of a recent medical care visit by a physician (or authorized clinician) was assessed in the 14-day period preceding a resident's first-quarterly MDS 2.0 assessment. We utilized best-subset multivariable logistic regression to model the adjusted associations between resident-level clinical factors and a recent medical care visit. RESULTS: Two thousand eight hundred fifty nine (80.4%) NH residents had one or more medical care visits prior to their first-quarterly MDS 2.0 assessment. Six clinically relevant factors were identified to be associated with recent medical care visits in the final model: exhibiting wandering behaviours (OR = 1.34, 95% CI 1.09 - 1.63), presence of a pressure ulcer (OR = 1.37, 95% CI 1.05 - 1.78), a urinary tract infection (UTI) (OR = 1.52, 95% CI 1.06 - 2.18), end-stage disease (OR = 9.70, 95% CI 1.32 - 71.02), new medication use (OR = 1.31, 95% CI 1.09 - 1.57), and analgesic use (OR = 1.24, 95% CI 1.03 - 1.49). CONCLUSIONS AND IMPLICATIONS: Our findings suggest that resident-level clinical factors drive the provision of medical care visits following NH admission. Clinical factors associated with medical care visits align with the minimum competencies expected of physicians in NH practice, including managing safety risks, infections, medications, and death. Ensuring that NH physicians have opportunities to acquire and strengthen these competencies may be transformative to meet the ongoing needs of NH residents.

Symptoms of depression and anxiety, and unmet healthcare needs in adults during the COVID-19 pandemic: a cross-sectional study from the Canadian Longitudinal Study on Aging.

BACKGROUND: The COVID-19 pandemic disrupted access to healthcare services in Canada. Research prior to the pandemic has found that depression and anxiety symptoms were associated with increased unmet healthcare needs. The primary objective of this study was to examine if mental health was associated with perceived access to healthcare during the pandemic METHODS: A cross-sectional study was conducted using data from 23,972 participants (aged 50-96) in the Canadian Longitudinal Study on Aging COVID-19 Exit Survey (Sept-Dec 2020). We used logistic regression to estimate how the presence of depression and anxiety symptoms, defined using scores of ≥10 on the Center for Epidemiologic Studies Depression Scale and ≥10 on the Generalized Anxiety Disorder Scale, were associated with the odds of reporting: 1) challenges accessing healthcare, 2) not going to a hospital or seeing a doctor when needed, 3) experiencing barriers to COVID-19 testing. Models were adjusted for sex, age, region, urban/rural residence, racial background, immigrant status, income, marital status, work status, chronic conditions, and pre-pandemic unmet needs. RESULTS: The presence of depressive (aOR=1.96; 95% CI=1.82, 2.11) and anxiety symptoms (aOR=2.33; 95% CI=2.04, 2.66) compared to the absence of these symptoms were independently associated with higher odds of challenges accessing healthcare. A statistically significant interaction with sex suggested stronger associations in females with anxiety. Symptoms of depression (aOR=2.88; 95% CI=2.58, 3.21) and anxiety (aOR=3.05; 95% CI=2.58, 3.60) were also associated with increased odds of not going to a hospital or seeing a doctor when needed. Lastly, depressive (aOR=1.99; 95% CI=1.71, 2.31) and anxiety symptoms (aOR=2.01; 95% CI=1.58, 2.56) were associated with higher odds of reporting barriers to COVID-19 testing. There was no significantly significant interaction with sex for the latter two outcomes. CONCLUSION: The presence of depression and anxiety symptoms were strongly associated with perceived unmet healthcare needs during the COVID-19 pandemic. Interventions to improve healthcare access for adults with depression and anxiety during the pandemic may be necessary.