871 (0.818 to 0.912)) compared with OCT (pfGCC 0.995 (0.993 to 0.997) and cpRNFL 0.975 (0.964 to 0.984)). Within-subject test-retest SD was 1.17% and 1.22% for pfVD and cpCD, and 0.57 and 1.22 µm for pfGCC and cpRNFL. Older age and lower signal strength index were associated with decreasing long-term variability of vessel densities.

OCTA-measured macula and ONH vascular parameters have good long-term reproducibility, supporting the use of this instrument for longitudinal analysis. OCTA long-term reproducibility is less than OCT-measured thickness reproducibility. This needs to be taken into consideration when serial OCTA images are evaluated for change.

NCT00221897.

NCT00221897.

The choroid is densely innervated by all parts of the autonomic nervous system and further harbours a network of local nerve cells, the intrinsic choroidal neurons (ICN). Their function in ocular control is currently unknown. While morphological data assume a role in intraocular pressure regulation, we here test if increased pressure on isolated choroids may activate ICN.

Donor tissue was transferred into a pressurisable tissue culture chamber, and nasal and temporal choroid halves incubated for 1 or 4 hours, with pressures set to 15 or 50 mm Hg, followed by qRT-PCR expression analysis of the ICN-specific markers VIP, UCN, NOS1, UCH-L1. POL2-normalised data in the different pressure settings, incubation times and localisations were statistically analysed.

The presence of the ICN-specific markers VIP, UCN, NOS1, UCH-L1 was confirmed using immunohistochemistry, and mRNA of all markers was detected in all experimental conditions. Marker analysis revealed no significant changes of mRNA expression levels betel ICN function.

To describe the prevalence and risk factors of primary angle-closure glaucoma (PACG) and to explore nationality difference in Chinese.

The Yunnan Minority Eye Study was conducted in a rural multiethnic area in Yunnan province and included 6546 participants aged over 50 years. PACG was diagnosed based on International Society of Geographical and Epidemiologic Ophthalmology criteria by experienced ophthalmologists. Multivariate regression modelling was conducted to examine risk factors for PACG. Principal component analyis (PCA) was performed to evaluate the effects of ethnicity on PACG.

The overall prevalence of PACG was 0.7% (95% CIs 0.5% to 0.9%). PCA indicated that ethnicity is significantly related to the presence of PACG (p<0.001) after controlling for other risk factors. In addition, higher PACG prevalence was also correlated with older age (60-69 years group (OR 3.47; 95% CI 1.11 to 10.84; p<0.05) and 70-79 years group (OR 4.71; 95% CI 1.40 to 15.86; p<0.05) as compared with 50-59 years group), higher intraocular pressures (OR 1.26; 95% CI 1.17 to 1.36; p<0.001), shorter axial lengths (OR 0.42; 95% CI 0.32 to 0.56; p<0.001) and thinner central corneal thicknesses (OR 0.89; 95% CI 0.81 to 0.99; p<0.05).

This multiethnic study on Chinese adults living in the same geographical location indicated that ethnicity is a significant risk factor for PACG. However, there were still some of the effects of ethnic differences on the prevalence of PACG that could not be explained and further studies should take culture and lifestyle factors into account.

This multiethnic study on Chinese adults living in the same geographical location indicated that ethnicity is a significant risk factor for PACG. However, there were still some of the effects of ethnic differences on the prevalence of PACG that could not be explained and further studies should take culture and lifestyle factors into account.A holocord syringomyelia due to Chiari 1.5 malformation (CM) in a 12-year-old girl was serially imaged with 3 T MRI over 4 years. The serial MRI showed reduction in size of the syrinx, without any surgical intervention or CM improvement, but rather due to spontaneous spinal cord tear. The tear was clearly demonstrated by evidence of flow signal across the tear between syrinx and subarachnoid space at the upper thoracic level. The tear showed spontaneous closure at follow-up. A medullary tear has been described in the adult population as one of the putative causes of spontaneous syringomyelia reduction, but its clear demonstration with modern high-resolution MRI has not been reported in the paediatric population. Moreover, this is the first reported case of syrinx reduction due to spontaneous fissuration in a paediatric patient.

To estimate the association between untreated, community acquired, respiratory tract infections and bleeding in oral anticoagulant users.

Self-controlled case series.

General practices in England contributing data to the Clinical Practice Research Datalink GOLD.

1208 adult users of warfarin or direct oral anticoagulants with a general practice or hospital admission record of a bleeding event between January 2010 and December 2019, and a general practice record of a consultation for a community acquired respiratory tract infection for which immediate antibiotics were not prescribed (that is, untreated).

Relative incidence of major bleeding and clinically relevant non-major bleeding in the 0-14 days after an untreated respiratory tract infection, compared to unexposed time periods.

Of 1208 study participants, 58% (n=701) were male, median age at time of first bleed was 79 years (interquartile range 72-85), with a median observation period of 2.4 years (interquartile range 1.3-3.8). 292 major bleeds al risks and how they might be mitigated.

This study observed a greater than twofold increase in the risk of bleeding during the 0-14 days after an untreated respiratory tract infection. These findings have potential implications for how patients and clinicians manage oral anticoagulant use during an acute intercurrent illness and warrant further investigation into the potential risks and how they might be mitigated.Positron emission tomography (PET) imaging of programmed cell death ligand 1 (PD-L1) may help to non-invasively predict and monitor responses to anti-PD-1/anti-PD-L1 immunotherapies. In this study, we compared the imaging characteristics of three radioligands, derived from the anti-PD-L1 IgG1 C4. In addition to the IgG C4, we produced a fragment antigen-binding (Fab) C4, and a double mutant IgG C4 (H310A/H435Q), with minimal affinity for the murine neonatal Fc receptor (FcRn). Methods The pharmacokinetics (PK), biodistribution, and dosimetry of the three 89Zr-labeled anti-PD-L1 ligands were compared by longitudinal PET/CT imaging in immunocompromised mice bearing human NSCLC xenografts with positive (H1975 model) or negative (A549 model) endogenous PD-L1 expression. Results The 89Zr-labeled C4 ligands substantially accumulated in PD-L1+ tumors, but not in PD-L1- tumors or in blocked PD-L1+ tumors, confirming their PD-L1-specific tumor targeting. 89Zr-Fab C4 and 89Zr-IgG C4 (H310A/H435Q) were rapidly cleared from circulation compared to 89Zr-IgG C4. Consequently, maximal tumor-to-muscle ratios (TMRs) were obtained earlier, at 4 h post-injection (p.i.) for 89Zr-Fab C4 (TMR of ~6) and 24 h p.i. for 89Zr-IgG C4 (H310A/H435Q) (TMR of ~9), versus 48 h p.i. for 89Zr-IgG C4 (TMR of ~8). Background activity in non-tumor tissues was low, except for high kidney retention of 89Zr-Fab C4, and persistent liver accumulation of 89Zr-IgG C4 (H310A/H435Q) compared to 89Zr-IgG C4. Dosimetry estimates suggested that the anti-PD-L1 radioligands would yield organ absorbed doses tolerable for repeated clinical PET imaging studies. Conclusion This study highlights the potential of designing radioligands with shorter PK for PD-L1 immunoPET imaging in a preclinical model, and encourages further clinical translation of such radioligands.Positron emission tomography (PET) radiomics applied to oncology allows the measurement of intra-tumoral heterogeneity. This quantification can be affected by image protocols hence there is an increased interest in understanding how radiomic expression on PET images is affected by different imaging conditions. To address that, this study explores how radiomic features are affected by changes in 18F-FDG uptake time, image reconstruction, lesion delineation, and radiomics binning settings. Methods Ten non-small cell lung cancer (NSCLC) patients underwent 18F-FDG PET scans on two consecutive days. On each day, scans were obtained at 60min and 90min post-injection and reconstructed following EARL version 1 (EARL1) and with point-spread-function resolution modelling (PSF-EARL2). Lesions were delineated using thresholds at SUV=4.0, 40% of SUVmax, and with a contrast-based isocontour. PET image intensity was discretized with both fixed bin width (FBW) and fixed bin number (FBN) before the calculation of the radiomicd, and FBN resulted in lower repeatability than FBW (45% and 6% features were discarded, respectively). Conclusion Repeatability was maximized with PSF-EARL2 reconstruction, lesion delineation at 40% of SUVmax, and FBW intensity discretization. Based on their susceptibility to tracer uptake time, radiomic features were classified into specific NSCLC PET radiomics use-cases.Metastatic castration resistant prostate cancer (mCRPC) is incurable. The expression of the transmembrane protein prostate specific membrane antigen (PSMA) is markedly increased in most mCRPC lesions. PSMA has been recognized as a viable biological target for imaging and radionuclide therapy (theranostics) in mCRPC. The positron emission tomography (PET) agents 68Ga-PSMA-11 and 18F-DCFPyL have recently been approved for imaging evaluation of patients with suspected metastasis who are candidates for initial definitive therapy and patients with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. Radioligand therapy (RLT) with 177Lu-PSMA-617 is anticipated to be approved relatively soon based on the favorable results of the VISION trial. It has been recognized that PET imaging of PSMA expression and glucose metabolism (with 18F-fluorodeoxyglucose) provides a more comprehensive assessment of the tumor burden and heterogeneity. However, there are many unresolved issues that surround whether or not imaging with 18F-fluoroodexyglucose PET is advantageous in the clinical setting of PSMA RLT in mCRPR.Quantitative kinetic modeling requires an input function (IF). A non-invasive image-derived IF (IDIF) can be obtained from dynamic PET images. However, a robust IDIF location, (e.g. aorta), may be far away from a tissue of interest, particularly in total-body PET, introducing a time delay between the IDIF and the tissue. The standard practice of joint estimation (JE) of delay, along with model fitting, is computationally expensive. To improve the efficiency of delay correction for total-body PET parametric imaging, this study investigates the use of pulse timing methods to estimate and correct for delay. Methods Simulation studies were performed with a range of delay values, frame lengths and noise levels, to test the tolerance of two pulse timing methods-leading edge (LE) and constant fraction discrimination (CFD) and their thresholds. The methods were then applied to data from 21 subjects (14 healthy volunteers, 7 cancer patients) that underwent 60-minute dynamic uEXPLORER total-body 18F-FDG PET acquisitions. Region-of-interest (ROI) kinetic analysis and parametric images were generated to compare LE and JE methods of delay correction, as well as no delay correction. Results Simulations demonstrated that a 10% LE threshold resulted in biases and standard deviations at tolerable levels for all noise levels tested, with 2-second frames. Pooled ROI-based results (N = 154) showed strong agreement between LE (10% threshold) and JE methods in estimating delay (Pearson’s r=0.96, P106 voxels in total-body PET datasets.

To evaluate the appropriateness of ceftazidime-avibactam (C-A), ceftolozane-tazobactam (C-T) and ceftaroline prescriptions according to European Medicines Agency (EMA)/Spanish Agency of Medicines and Medical Devices (AEMPS) approved indications, financed indications in the Spanish health system and hospital Infection Commission (IC) recommendations in a tertiary hospital.

Observational, descriptive and retrospective study of inpatients aged ≥18 years, who were prescribed the above-mentioned antimicrobials during the period January-December 2020. Variables obtained were demographic (sex and age), pharmacological (antibiotic, use – empiric or targeted, indication) and microbiological (sensitivity testing and antibiotic tested) data.

A total of 79 patients were included. C-A (n=40) 67.5% of patients were male, with a mean age of 61 (range 22-87) years. Empiric treatment was applied in 30% of the cases (n=12). De-escalation in 33.33% of individuals. Sensitivity testing was done in 92.86% of patients, includs.

Our results highlight the importance of stewardship programmes in the decision-making process and in the follow-up of patients with infections caused by MDR microorganisms.The prodrug tenofovir alafenamide (TAF) is a first-line antiviral agent for the treatment of chronic hepatitis B infection. TAF activation involves multiple steps, and the first step is an ester hydrolysis reaction catalyzed by hydrolases. This study was to determine the contributions of carboxylesterase 1 (CES1) and cathepsin A (CatA) to TAF hydrolysis in the human liver. Our in vitro incubation studies showed that both CatA and CES1 catalyzed TAF hydrolysis in a pH-dependent manner. At their physiologic pH environment, the activity of CatA (pH 5.2) was approximately 1,000-fold higher than that of CES1 (pH 7.2). Given that the hepatic protein expression of CatA was approximately 200-fold lower than that of CES1, the contribution of CatA to TAF hydrolysis in the human liver was estimated to be much greater than that of CES1, which is contrary to the previous perception that CES1 is the primary hepatic enzyme hydrolyzing TAF. The findings were further supported by a TAF incubation study with the CatA inhibitor telaprevir and the CES1 inhibitor bis-(p-nitrophenyl) phosphate. Moreover, an in vitro study revealed that the CES1 variant G143E (rs71647871) is a loss-of-function variant for CES1-mediated TAF hydrolysis. In summary, our results suggest that CatA may play a more important role in the hepatic activation of TAF than CES1. Additionally, TAF activation in the liver could be affected by CES1 genetic variation, but the magnitude of impact appears to be limited due to the major contribution of CatA to hepatic TAF activation. SIGNIFICANCE STATEMENT Contrary to the general perception that carboxylesterase 1 (CES1) is the major enzyme responsible for tenofovir alafenamide (TAF) hydrolysis in the human liver, the present study demonstrated that cathepsin A may play a more significant role in TAF hepatic hydrolysis. Furthermore, the CES1 variant G143E (rs71647871) was found to be a loss-of-function variant for CES1-mediated TAF hydrolysis.

People with diabetes mellitus commonly experience hypoglycemia, but they may not necessarily present to hospital after severe hypoglycemia requiring paramedic assistance. We sought to describe the incidence and characteristics of calls for hypoglycemia requiring paramedic assistance among adults in southwestern Ontario, Canada, and to determine predictors of hospital transport.

This population-based retrospective cohort study used data extracted from ambulance call reports (ACRs) of 8 paramedic services of the Southwest Ontario Regional Base Hospital Program from January 2008 to June 2014. We described calls in which treatment for hypoglycemia was administered, summarized the incidence of hypoglycemia calls and performed logistic regression to determine predictors of hospital transport.

Out of 470 467 ACRs during the study period, 9185 paramedic calls occurred in which hypoglycemia treatment was administered to an adult (mean age 60.2 yr, 56.8% male, 81.1% with documented diabetes). Refusal of hospital edic assistance in southwestern Ontario is common, and close to 25% of calls do not result in hospital transport. Physicians managing diabetes care may be unaware of patients’ hypoglycemia requiring paramedic care, suggesting a potential gap in follow-up care; we suggest that paramedics play an important role in identifying those at high recurrence risk and communicating with their care providers.

During the COVID-19 pandemic, universities transitioned to primarily online delivery, and it is important to understand what implications the transition back to in-person activities may have on spread of SARS-CoV-2 in the student population. The specific aim of our study was to provide insights into the effect of timetabling decisions on the spread of SARS-CoV-2 in a population of undergraduate engineering students.

We developed an agent-based modelling simulation that used a Canadian first-year undergraduate engineering program with an enrolment of 180 students in 5 courses of 12.7 weeks in length. Each course involved 150 minutes of lectures and 110 minutes of tutorials or laboratories per week. We considered several online and in-person timetabling scenarios with different scheduling frequencies and section sizes, in combination with surveillance and testing interventions. The study was conducted from May 1 to Aug. 31, 2021.

When timetabling interventions were applied, we found a reduction in the measolations) reduced. However, given the emergence of SARS-CoV-2 variants, transitions from online to in-person classes should proceed cautiously from small biweekly classes, for example, to manage risk.

Our modelling showed that by taking advantage of timetabling opportunities and applying appropriate interventions (contact tracing, randomized testing and vaccination), SARS-CoV-2 infections may be averted and disruptions (case isolations) reduced. However, given the emergence of SARS-CoV-2 variants, transitions from online to in-person classes should proceed cautiously from small biweekly classes, for example, to manage risk.

Patient-level surveillance of antimicrobial use (AMU) in Canadian hospitals empowers the reduction of inappropriate AMU and was piloted in 2017 among 14 hospitals in Canada. We aimed to describe AMU on the basis of patient-level data in Canadian hospitals in 2018 in terms of antimicrobial prescribing prevalence and proportions, antimicrobial indications, and agent selection in medical, surgical and intensive care wards.

Canadian adult, pediatric and neonatal hospitals were invited to participate in the standardized web-based cross-sectional Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (Global-PPS) conducted in 2018. An identified site administrator assigned all wards admitting inpatients to specific surveyors. A physician, pharmacist or nurse with infectious disease training performed the survey. The primary outcomes were point prevalence rates for AMU over the study period regarding prescriptions, indications and agent selection in medical, surgical and intensive care wards.MU was for therapeutic use across participating hospitals. Canadian hospitals should be further incentivized to create and adapt local guidelines on the basis of recent antimicrobial resistance data.

Overall, three-quarters of AMU was for therapeutic use across participating hospitals. Canadian hospitals should be further incentivized to create and adapt local guidelines on the basis of recent antimicrobial resistance data.

Limited space and resources are potential obstacles to infection prevention and control (IPAC) measures in in-centre hemodialysis units. We aimed to assess IPAC measures implemented in Quebec’s hemodialysis units during the spring of 2020, describe the characteristics of these units and document the cumulative infection rates during the first year of the COVID-19 pandemic.

For this cross-sectional survey, we invited leaders from 54 hemodialysis units in Quebec to report information on the physical characteristics of the unit and their perceptions of crowdedness, which IPAC measures were implemented from Mar. 1 to June 30, 2020, and adherence to and feasibility of appropriate IPAC measures. Participating units were contacted again in March 2021 to collect information on the number of COVID-19 cases in order to derive the cumulative infection rate of each unit.

Data were obtained from 38 of the 54 units contacted (70% response rate), which provided care to 4485 patients at the time of survey completion. Fg. Future hemodialysis units should be designed to minimize airborne and droplet transmission of infection.

Rates of COVID-19 infection among hemodialysis recipients in Quebec were elevated compared to the general population during the first year of the pandemic, and although hemodialysis units throughout the province implemented appropriate IPAC measures rapidly in the spring of 2020, many units were crowded and could not maintain physical distancing. Future hemodialysis units should be designed to minimize airborne and droplet transmission of infection.

The COVID-19 pandemic has led to an increased demand for health care resources and, in some cases, shortage of medical equipment and staff. Our objective was to develop and validate a multivariable model to predict risk of hospitalization for patients infected with SARS-CoV-2.

We used routinely collected health records in a patient cohort to develop and validate our prediction model. This cohort included adult patients (age ≥ 18 yr) from Ontario, Canada, who tested positive for SARS-CoV-2 ribonucleic acid by polymerase chain reaction between Feb. 2 and Oct. 5, 2020, and were followed up through Nov. 5, 2020. Patients living in long-term care facilities were excluded, as they were all assumed to be at high risk of hospitalization for COVID-19. Risk of hospitalization within 30 days of diagnosis of SARS-CoV-2 infection was estimated via gradient-boosting decision trees, and variable importance examined via Shapley values. We built a gradient-boosting model using the Extreme Gradient Boosting (XGBoost) algord health administrative data. We envision that modelling such risk stratification based on routinely collected health data could support management of COVID-19 on a population health level.

We developed and validated an accurate risk stratification model using routinely collected health administrative data. We envision that modelling such risk stratification based on routinely collected health data could support management of COVID-19 on a population health level.

Previous Canadian studies have identified problems regarding health care access for transgender (trans) and nonbinary people, but all-ages national data have been lacking. This study describes access to care among trans and nonbinary people in Canada, and compares health care access across provinces or regions.

We conducted a bilingual, multimode cross-sectional survey (Trans PULSE Canada) from July 26 to Oct. 1, 2019. We recruited trans and nonbinary people aged 14 years and older using convenience sampling. We assessed 5 outcomes having a primary care provider, having a primary care provider with whom the respondent was comfortable discussing trans health issues, past-year unmet health care need, medical gender affirmation status, and being on a wait-list to access gender-affirming medical care. Average marginal predictions were estimated from multivariable logistic regression models with multiply imputed data.

The survey included 2873 participants, and 2217 surveys were analyzed after exclusions. Of trans issues, varied significantly by province or region (

< 0.05).

Participants reported considerable unmet needs or delays in primary, general and gender-affirming care, with significant regional variation. Our results indicate that, despite efforts toward equity in access to care for trans and nonbinary people in Canada, inequities persist.

Participants reported considerable unmet needs or delays in primary, general and gender-affirming care, with significant regional variation. Our results indicate that, despite efforts toward equity in access to care for trans and nonbinary people in Canada, inequities persist.

Breast cancer screening in Ontario, Canada, was deferred during the first wave of the COVID-19 pandemic, and a prioritization framework to resume services according to breast cancer risk was developed. The purpose of this study was to assess the impact of the pandemic within the Ontario Breast Screening Program (OBSP) by comparing total volumes of screening mammographic examinations and volumes of screening mammographic examinations with abnormal results before and during the pandemic, and to assess backlogs on the basis of adherence to the prioritization framework.

A descriptive study was conducted among women aged 50 to 74 years at average risk and women aged 30 to 69 years at high risk, who participated in the OBSP. Percentage change was calculated by comparing observed monthly volumes of mammographic examinations from March 2020 to March 2021 with 2019 volumes and proportions by risk group. We plotted estimates of backlog volumes of mammographic examinations by risk group, comparing pandemic with prep-term harms caused by the pandemic. This further supports the clinical utility of risk-stratified cancer screening.

Prioritizing screening for those at higher risk for breast cancer may increase diagnostic yield and redirect resources to minimize potential long-term harms caused by the pandemic. This further supports the clinical utility of risk-stratified cancer screening.

Despite their popularity, the efficacy of interventions targeting gut microbiota to improve depressive symptoms is unknown. Our objective is to summarize the effect of microbiome-targeting interventions on depressive symptoms.

We conducted a systematic review and meta-analysis. We searched MEDLINE, Embase, PsycINFO, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews and the Cochrane Controlled Register of Trials from inception to Mar. 5, 2021. We included studies that evaluated probiotic, prebiotic, synbiotic, paraprobiotic or fecal microbiota transplant interventions in an adult population (age ≥ 18 yr) with an inactive or placebo comparator (defined by the absence of active intervention). Studies must have measured depressive symptoms with a validated scale, and used a randomized controlled trial study design. We conducted a random effects meta-analysis of change scores, using standardized mean difference as the measure of effect.

Sixty-two studies formed the final data set, with 50 included in the meta-analysis. Probiotic, prebiotic, and synbiotic interventions on depressive symptoms showed statistically significant benefits. In the single studies evaluating each of fecal microbiota transplant and paraprobiotic interventions, neither showed a statistically significant benefit.

Despite promising findings of benefit of probiotic, prebiotic and synbiotic interventions for depressive symptoms in study populations, there is not yet strong enough evidence to favour inclusion of these interventions in treatment guidelines for depression. Critical questions about species administered, dosage and timing relative to other antidepressant medications remain to be answered.

PROSPERO no. 143178.

PROSPERO no. 143178.

Access to care is essential for patients with diabetes to maintain health and prevent complications, and is important for health equity. New York State’s Health Homes (HHs) provide care management services to Medicaid-insured patients with chronic conditions, including diabetes, and aim to improve quality of care and outcomes. There is inconsistent evidence on the impact of HHs, and care management programs more broadly, on access to care.

Using a cohort of patients with diabetes derived from electronic health records from the INSIGHT Clinical Research Network, we analyzed Medicaid data for HH enrollees and a matched comparison group of HH non-enrollees. We estimated HH impacts on several access measures using natural experiment methods.

We identified and matched 11 646 HH enrollees; patients were largely non-Hispanic Black (29.9%) and Hispanic (48.7%), and had high rates of dual eligibility (33.0%), Supplemental Security Income disability enrollment (49.1%), and multiple comorbidities. In the 12 monthss have implications for New York State Medicaid as well as other providers and care management programs.

Hypoglycemia is the most common serious adverse effect of diabetes treatment and a major cause of medication-related hospitalization. This study aimed to identify trends and predictors of hospital utilization for hypoglycemia among patients with type 2 diabetes using electronic health record data pooled from six academic health systems.

This retrospective open cohort study included 549 041 adults with type 2 diabetes receiving regular care from the included health systems between 2009 and 2019. The primary outcome was the yearly event rate for hypoglycemia hospital utilization emergency department visits, observation visits, or inpatient admissions for hypoglycemia identified using a validated International Classification of Diseases Ninth Revision (ICD-9) algorithm from 2009 to 2014. After the transition to ICD-10 in 2015, we used two ICD-10 code sets (limited and expanded) for hypoglycemia hospital utilization from prior studies. We identified independent predictors of hypoglycemia hospital utilization CD-9.

Rates of hypoglycemia hospital utilization decreased from 2009 to 2014 and varied considerably by clinical risk factors such that younger adults, insulin users, and those with chronic kidney disease were at especially high risk. There is a need to validate hypoglycemia ascertainment using ICD-10 codes, which detect a substantially higher number of events compared with ICD-9.

The prevalence of diabetes self-management education and support (DSME/S) use among patients with newly diagnosed type 2 diabetes mellitus (T2DM) and patients with insulin prescription has not been evaluated. It is also unclear what demographic, behavioral, and clinical factors associated with use of DSME/S.

This retrospective analysis was based on electronic health records from the Research Action for Health Network (2013-2019). Patients with newly diagnosed T2DM were identified as 35-94 year-olds diagnosed with T2DM≥1 year after the first recorded office visit. Patients with insulin were identified by the first insulin prescription records. DSME/S (Healthcare Common Procedure Coding System G0108 and G0109) codes that occurred from 2 months before the 'new diagnosis date’ or first insulin prescription date through 1 year after were defined as use of DSME/S. Age-matched controls (non-users) were identified from the Electronic Health Records (EHR). The date of first DSME/S record was selected as the index Our findings demonstrated heterogeneity in factors influencing DSME/S use between patients with newly diagnosed T2D and patients with insulin.

We showed a low rate of DSME/S use in Louisiana, especially in patients with newly diagnosed T2DM. Our findings demonstrated heterogeneity in factors influencing DSME/S use between patients with newly diagnosed T2D and patients with insulin.

Most patients with diabetes mellitus are prescribed medications to control their blood glucose. The implementation of the Affordable Care Act (ACA) led to improved access to healthcare for patients with diabetes. However, impact of the ACA on prescribing trends by diabetes drug category is less clear. This study aims to assess if long-acting insulin and novel agents were prescribed more frequently following the ACA in states that expanded Medicaid compared with non-expansion states.

In this analysis of a natural experiment, prescriptions reimbursed by Medicaid (US public insurance) for long-acting insulins, metformin, and novel agent medications (DPP4 inhibitors, sodium/glucose cotransporter 2 inhibitor antagonists, and glucagon-like peptide-1 receptor agonists) from 2012 to 2017 were obtained from public records. For each medication category, we performed difference-in-differences (DID) analysis modeling change in rate level from pre-ACA to post-ACA in Medicaid expansion states relative to Medicaid non-ents in expansion states relative to non-expansion states after accounting for number of enrollees. Reducing administrative barriers and improving the ability of providers to prescribe such newer therapies will be critical for caring for patients with diabetes-particularly in Medicaid non-expansion states.

Corticosteroids remain the mainstay of treatment for rheumatic diseases but can cause hepatitis B virus (HBV) reactivation in patients with resolved HBV infection. Risk assessment and stratification are needed to guide the management of these patients before corticosteroid therapy.

We prospectively enrolled patients with negative hepatitis B surface antigen positive Anti-hepatitis B core status with or without corticosteroid use and determined corticosteroid exposure by calculating cumulative dose and time-weighted average daily dose of prednisone. The primary outcome was the time to a composite of HBV reactivation, hepatitis flare or severe hepatitis.

Among 1303 participants, the median of cumulative dose and time-weighted average dose of prednisone used in this cohort was 3000 mg (IQR 300-6750 mg) and 15 mg/day (IQR 10-20 mg/day), respectively. In multivariable analyses, cumulative dose showed inverted V-shaped relationship with primary events, which peaked at a cumulative dose of 1506 mg (HR 3.72; 95% CI, 1.96 to 7.08). Quartiles of time-weighted average dose were independently associated with a monotonic increase in event risk (HR per quartile increase 2.15; 95% CI, 1.56 to 2.98), reaching an HR of 49.48 (95% CI, 6.24 to 392.48) in the top quartile. The incidence of primary outcome was 16.67 per 100 person-years in the top quartile of time-weighted average dose (Q4>20 mg/day). Other quartiles all had an incidence of primary outcome less than 10 per 100 person-years.

Patients with time-weighted average prednisone dose greater than 20 mg/day would be classified as the high risk for HBV reactivation or hepatitis flare. Prophylactic Anti-HBV therapy may be needed for these high-risk patients.

ChiCTR1900023955.

ChiCTR1900023955.

To evaluate pathological complete response as a surrogate endpoint for disease-free survival and overall survival in regulatory neoadjuvant trials of early stage breast cancer.

Systematic review and meta-analysis.

Medline, Embase, and Scopus to 1 December 2020.

Randomised clinical trials that tested neoadjuvant chemotherapy given alone or combined with other treatments, including anti-human epidermal growth factor 2 (anti-HER2) drugs, targeted treatments, antivascular agents, bisphosphonates, and immune checkpoint inhibitors.

Trial level associations between the surrogate endpoint pathological complete response and disease-free survival and overall survival.

A weighted regression analysis was performed on log transformed treatment effect estimates (hazard ratio for disease-free survival and overall survival and relative risk for pathological complete response), and the coefficient of determination (R

) was used to quantify the association. The secondary objective was to explore heterogeneity of r not be used as primary endpoint in regulatory neoadjuvant trials of early stage breast cancer.

The COVID-19 pandemic significantly impacted on the provision of oesophageal physiology investigations. During the recovery phase, triaging tools were empirically recommended by national bodies for prioritisation of referrals amidst rising waiting lists and reduced capacity. We evaluated the performance of an enhanced triage process (ETP) consisting of telephone triage combined with the hierarchical 'traffic light system’ recommended in the UK for prioritising oesophageal physiology referrals.

In a cross-sectional study of patients referred for oesophageal physiology studies at a tertiary centre, data were compared between patients who underwent oesophageal physiology studies 6 months prior to the COVID-19 pandemic and those who were investigated within 6 months after service resumption with implementation of the ETP.

Adjusted time from referral to investigation; non-attendance rates; the detection of Chicago Classification (CC) oesophageal motility disorders on oesophageal manometry and severity of acid reflux on 24 hours pH/impedance monitoring.

Following service resumption, the ETP reduced non-attendance rates from 9.1% to 2.8% (p=0.021). Use of the 'traffic light system’ identified a higher proportion of patients with CC oesophageal motility disorders in the 'amber’ and 'red’ triage categories, compared with the 'green’ category (p=0.011). ETP also reduced the time to test for those who were subsequently found to have a major CC oesophageal motility diagnosis compared with those with minor CC disorders and normal motility (p=0.004). The ETP did not affect the yield or timing of acid reflux studies.

ETPs can effectively prioritise patients with oesophageal motility disorders and may therefore have a role beyond the current pandemic.

ETPs can effectively prioritise patients with oesophageal motility disorders and may therefore have a role beyond the current pandemic.

To explore factors influencing surgical provider productivity and identify barriers against and opportunities to increase individual surgical productivity in Sierra Leone, in order to explain the observed increase in unmet surgical need from 92.2% to 92.7% and the decrease in surgical productivity to 1.7 surgical procedures per provider per week between 2012 and 2017.

This explanatory qualitative study consisted of in-depth interviews about factors influencing surgical productivity in Sierra Leone. Interviews were analysed with a thematic network analysis and used to develop a conceptual framework.

21 surgical providers and hospital managers working in 12 public and private non-profit hospitals in all regions in Sierra Leone.

Surgical providers in Sierra Leone experience a broad range of factors within and outside the health system that influence their productivity. The main barriers involve both patient and facility financial constraints, lack of equipment and supplies, weak regulation of providers aroductivity and meet surgical needs in Sierra Leone. Development of a national strategy for surgery, obstetrics and anaesthesia, including methods to reduce financial barriers for patients, improve supply-mechanisms and expand training opportunities for new and established surgical providers can increase surgical capacity. Establishment of legal frameworks and appropriate remuneration are crucial for sustainability and retention of surgical health workers.

We aimed to identify populations at a high risk for SARS-CoV-2 infection but who are less likely to present for testing, by determining which sociodemographic and household factors are associated with a lower propensity to be tested and, if tested, with a higher risk of a positive test result.

Internet-based participatory surveillance data from the general population of the Netherlands.

Weekly survey data collected over a 5-month period (17 November 2020 to 18 April 2021) from a total of 12 026 participants who had contributed at least 2 weekly surveys was analysed.

Multivariable analyses using generalised estimating equations for binomial outcomes were conducted to estimate the adjusted ORs of testing and of test positivity associated with participant and household characteristics.

Male sex (adjusted OR for testing (OR

) 0.92; adjusted OR for positivity (OR

) 1.30, age groups<20 (OR

0.89; OR

1.27), 50-64 years (OR

0.94; OR

1.06) and 65+ years (OR

0.78; OR

1.24), diabetics (OR

0.97; OR

1.06) and sales/administrative employees (OR

0.93; OR

1.90) were distinguished as lower test propensity/higher test positivity factors.

The factors identified using this approach can help identify potential target groups for improving communication and encouraging testing among those with symptoms, and thus increase the effectiveness of testing, which is essential for the response to the COVID-19 pandemic and for public health strategies in the longer term.

The factors identified using this approach can help identify potential target groups for improving communication and encouraging testing among those with symptoms, and thus increase the effectiveness of testing, which is essential for the response to the COVID-19 pandemic and for public health strategies in the longer term.

Neonatal heart rate variability (HRV) is widely used as a research tool. However, HRV calculation methods are highly variable making it difficult for comparisons between studies.

To describe the different types of investigations where neonatal HRV was used, study characteristics, and types of analyses performed.

Human neonates ≤1 month of corrected age.

A protocol and search strategy of the literature was developed in collaboration with the McGill University Health Center’s librarians and articles were obtained from searches in the Biosis, Cochrane, Embase, Medline and Web of Science databases published between 1 January 2000 and 1 July 2020.

A single reviewer screened for eligibility and data were extracted from the included articles. Information collected included the study characteristics and population, type of HRV analysis used (time domain, frequency domain, non-linear, heart rate characteristics (HRC) parameters) and clinical applications (physiological and pathological conditions, responses lack of consistency in analysis methods applied. Specific guidelines for HRV analyses in neonates are needed to allow for comparisons between studies.

The Kyushu and Okinawa Population Study (KOPS) was established to investigate gene-environmental interactions in non-communicable diseases in Japan. Besides collecting blood samples and anthropometric measurements, we also obtained medical histories, psychological status and lifestyle habits, including physical activities and dietary patterns.

KOPS is a community-based prospective cohort study and consists of participants from four southwestern areas in Japan. Baseline surveys were conducted between 2004 and 2007 (wave 1), and 2009 and 2012 (wave 2) at the sites of municipality-based health check-ups. A total of 17 077 participants were included, comprising 10 697 participants of wave 1 and 6380 participants of wave 2; the median age in both groups was 61 years. Among them, 3006 individuals participated in both wave 1 and wave 2 surveys.

We have focused on either risk or confounding factors for non-communicable diseases. We have assessed the clinical utility of the newly developed biomarkers for impairemarkers and the gene-environmental interactions using prospective data.

We plan to investigate further the clinical utility of the newly developed biomarkers and the gene-environmental interactions using prospective data.

To investigate the effect of clinical, methodological and logistic factors on operating room (OR) efficiency in the surgical management of primary rhegmatogenous retinal detachment (RRD).

Monocentric retrospective register cohort study.

Single tertiary centre in the western region of Austria.

We audited patients diagnosed with primary RRD who were treated between January 2014 and August 2019. In total, 783 eyes of 776 consecutive patients were included in this study. Various risk factors affecting OR time efficiency and anatomical success after pars plana vitrectomy (PPV) procedures and scleral buckle (SB) surgery were analysed.

OR efficiency was the primary outcome measure. Secondary outcome measures were the primary success rate after PPV procedures and SB surgery.

PPV was performed in 641 (81.9%) eyes and SB surgery in 142 (18.1%) eyes. Mean surgical times in PPV and SB under retrobulbar anaesthesia (RA) were 74.0 (±32.6) min and 62.1 (±24.6) min (p<0.001), respectively, while under general dent clinical (giant tear, PVR-C, advanced detachment), methodological (PPV vs SB) and logistic (GA vs RA, after-hours setting and surgeon experience) factors to improve the success rate and surgical management planning of RRD accurately while optimising OR resources and staff efficiency.

Vitamin D deficiency is associated with chronic obstructive pulmonary disease (COPD). We examined the cross-sectional association between 25-hydroxyvitamin D (25(OH)D) and lung function impairment and assessed whether vitamin D deficiency is related to long-term mortality in those with impaired lung function.

Prospective study SETTING General practices in the UK.

3575 men aged 60-79 years with no prevalent heart failure.

Airway obstruction and mortality. The Global Initiative on Obstructive Lung diseases (GOLD) spirometry criteria was used to define airway obstruction.

During the follow-up period of 20 years, there were 2327 deaths (114 COPD deaths). Vitamin D deficiency was defined as serum 25(OH)D levels<10 ng/mL; insufficiency as 25(OH)D 10-19 ng/mL; sufficient as 25(OH)D>20 ng/mL. In cross-sectional analysis, vitamin D deficiency was more prevalent in those with moderate COPD (FEV/FVC <70% and FEV

50 to <80%; FEV

, forced expiratory volume in 1 s and FVC, forced vital capacity) anD were more likely to be vitamin D deficient than those with normal lung function. Vitamin D deficiency is associated with increased all-cause mortality in older men with no lung impairment as well as in those with restrictive or obstructive lung impairment.

Multimorbidity is the simultaneous occurrence of several (chronic) diseases. Persons living with multimorbidity not only have complex care needs, but the burden of care often has a negative impact on their family lives, leisure time and professional activities. The aim of this project is to systematically review the literature to assess how multimorbidity affects the everyday lives of middle-aged persons, and to find out what abilities and resources help in the development of coping strategies to overcome the challenges of living with it.

We will systematically search for studies reporting on the everyday life experiences of middle-aged persons (30-60 years) with multimorbidity (≥2 chronic conditions) in MEDLINE, CINAHL, PsycINFO, Social Sciences Citation Index, Social Sciences Citation Index Expanded, PSYNDEX and The Cochrane Library from inception. We will include all primary studies that use quantitative, qualitative and mixed methodologies, irrespective of publication date/study setting.Two independent reviewers will screen titles/abstracts/full texts, extract data from the selected studies and present evidence in terms of study/population characteristics, data collection method and the phenomenon of interest, that is, everyday life experiences of middle-aged persons with multimorbidity. Risk of bias will be independently assessed by two reviewers using the Mixed Methods Appraisal Tool. We will use a convergent integrated approach on qualitative/quantitative studies, whereby information will be synthesised narratively and, if possible, quantitatively.

Ethical approval is not required due to the nature of the proposed systematic review. Results from this research will be disseminated at relevant (inter)national conferences and via publication in peer-reviewed journals.

CRD42021226699.

CRD42021226699.

Lay consultation is the process of discussing a symptom or an illness with lay social network members. This can have positive or negative consequences on health-seeking behaviours. Understanding how consultation with lay social networks works in informal urban settlements of low-income and middle-income countries (LMICs) is important to enable health and policy-makers to maximise its potential to aid healthcare delivery and minimise its negative impacts. This study explored the composition, content and consequences of lay consultation in informal urban settlements of LMICs.

systematic review.

Six key public health and social science databases, Google Scholar and reference lists of included studies were searched for potential articles.

Papers that described discussions with lay informal social network members during symptoms or illness experiences.

Quality assessment was done using the Mixed Methods Appraisal Tool. Data were analysed and synthesised using a stepwise thematic synthesis approach involving two steps identifying themes within individual studies and synthesising themes across studies.

13 studies were included in the synthesis. Across the studies, three main categories of networks consulted during illness kin, non-kin associates and significant community groups. Of these, kin networks were the most commonly consulted. The content of lay consultations were asking for suggestions, negotiating care-seeking decisions, seeking resources and non-disclosure due to personal or social reasons. Lay consultations positively and negatively impacted access to formal healthcare and adherence to medical advice.

Lay consultation is mainly sought from social networks in immediate environments in informal urban settlements of LMICs. Policy-makers and practitioners need to utilise these networks as mediators of healthcare-seeking behaviours.

CRD42020205196.

CRD42020205196.

Maternity care providers play an essential role in supporting women to breast feed. It is critical that their professional associations limit influence from breastmilk substitute (BMS) manufacturers. Aims of this study were (i) to examine whether maternity care provider associations had policy or positions statements addressing BMS marketing and (ii) to explore the type of funding received by these associations.

An online cross-sectional review.

National or regional maternity provider professional associations in Australia, New Zealand, the USA, Canada and the UK.

Twenty-eight maternity care provider (obstetricians, midwives, nurses and others involved in perinatal care) professional association websites.

Websites were examined from November 2019 to October 2020.

Evidence of BMS industry funding and policy or position statements addressing acceptance of funding from industries such as BMS.

Policies addressing the BMS industry were found for 14 associations (50%). UK-based associations (5/5, 100%ations had policies addressing BMS marketing. BMS industry support can create conflicts of interest that can threaten efforts to support, protect and promote breast feeding. Healthcare provider associations should avoid BMS funding and at a minimum have policy or position statements addressing BMS marketing.

Youth suicide is a significant public health priority, and is the second leading cause of death among young people between 15 and 29 years of age. An emerging intervention in suicide prevention programming with youth is peer support. Although increasingly used in other settings, the evidence for peer support interventions in youth suicide prevention remains nascent. This article presents a protocol for a scoping review aimed at systematically mapping the current evidence on peer support for youth suicide prevention.

Arksey and O’Malley’s scoping review framework will guide the review methods. The search strategy will be developed with guidance from a health sciences librarian. Multiple databases (Medline, Embase, PsycINFO, Cumulative Index for Nursing and Allied Health Literature) and grey literature will be identified using terms related to peer support and youth suicide prevention. Publication date restrictions will not be applied. All identified records of published literature will be collated and uploaded to a systematic review management software, Covidence, for review and selection.