Uptake of SGLT2i and Outcomes in Patients with Diabetes and Heart Failure: A Population-Based Cohort and a Specialized Clinic Cohort.

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are effective in adults with diabetes mellitus (DM) and heart failure (HF) based on randomized clinical trials. We compared SGLT2 inhibitor uptake and outcomes in two cohorts: a population-based cohort of all adults with DM and HF in Alberta, Canada and a specialized heart function clinic (HFC) cohort. METHODS: The population-based cohort was derived from linked provincial healthcare datasets. The specialized clinic cohort was created by chart review of consecutive patients prospectively enrolled in the HFC between February 2018 and August 2022. We examined the association between SGLT2 inhibitor use (modeled as a time-varying covariate) and all-cause mortality or deaths/cardiovascular hospitalizations. RESULTS: Of the 4,885 individuals from the population-based cohort, 64.2% met the eligibility criteria of the trials proving the effectiveness of SGLT2 inhibitors. Utilization of SGLT2 inhibitors increased from 1.2% in 2017 to 26.4% by January 2022. In comparison, of the 530 patients followed in the HFC, SGLT2 inhibitor use increased from 9.8% in 2019 to 49.1 % by March 2022. SGLT2 inhibitor use in the population-based cohort was associated with fewer all-cause mortality (aHR 0.51, 95%CI 0.41-0.63) and deaths/cardiovascular hospitalizations (aHR 0.65, 95%CI 0.54-0.77). However, SGLT2 inhibitor usage rates were far lower in HF patients without DM (3.5% by March 2022 in the HFC cohort). CONCLUSIONS: Despite robust randomized trial evidence of clinical benefit, the uptake of SGLT2 inhibitors in patients with HF and DM remains low, even in the specialized HFC. Clinical care strategies are needed to enhance the use of SGLT2 inhibitors and improve implementation.

Cost-Effectiveness of Radar Localisation Versus Wire Localisation for Wide Local Excision of Non-palpable Breast Cancer.

BACKGROUND: Wire localisation (WL) is the "gold standard" localisation technique for wide local excision (WLE) of non-palpable breast lesions but has disadvantages that have led to the development of wireless techniques. This study compared the cost-effectiveness of radar localisation (RL) to WL. METHODS: This was a single-institution study of 110 prospective patients with early-stage breast cancer undergoing WLE using RL with the SCOUT® Surgical Guidance System (2021-2023) compared with a cohort of 110 patients using WL. Margin status, re-excision rates, and surgery delays associated with preoperative localisation were compared. Costs from a third-party payer perspective in Australian dollars (AUD$) calculated by using microcosting, break-even point, and cost-utility analyses. RESULTS: A total of 110 WLEs using RL cost a total of AUD$402,281, in addition to the device cost of AUD$77,150. The average additional cost of a surgery delay was AUD$2318. Use of RL reduced the surgery delay rate by 10% (p = 0.029), preventing 11 delays with cost savings of AUD$25,496. No differences were identified in positive margin rates (RL: 11.8% vs. WL: 17.3%, p = 0.25) or re-excision rates (RL: 14.5% vs. WL: 21.8%, p = 0.221). In total, 290 RL cases are needed to break even. The cost of WLE using RL was greater than WL by AUD$567. There was a greater clinical benefit of 1.15 quality-adjusted life-years (QALYs) and an incremental cost-utility ratio of AUD$493 per QALY favouring RL. CONCLUSIONS: Routine use of RL was a more cost-effective intervention than WL. Close to 300 RL cases are likely needed to be performed to recover costs of the medical device. CLINICAL TRIAL REGISTRATION: ACTRN12624000068561.

Durability of radiofrequency ablation for long-segment and ultralong-segment Barrett's esophagus over 10 years.

BACKGROUND: Long-term durability data for radiofrequency ablation (RFA) to prevent esophageal adenocarcinoma in long-segment (LSBE) and ultralong-segment Barrett's esophagus (ULSBE) is lacking. This study aimed to determine 10-year cancer progression, eradication, and complication rates in LSBE and ULSBE patients treated with RFA. METHODS: Single-surgeon prospective database of patients with LSBE (≥ 3 to < 8 cm) and ULSBE (≥ 8 cm) who underwent RFA (2001-2021) were retrospectively analyzed. Ten-year cancer progression calculated with Kaplan-Meier analysis. Eradication rates, including complete remission of dysplasia (CR-D) and intestinal metaplasia (CR-IM), and rates of recurrence and complications, compared between LSBE and ULSBE groups. RESULTS: Ten years after starting treatment, the cancer rate was 14.3% in 56 patients. CR-D and CR-IM rates were 87.5% and 67.9%, respectively. Relapse rates from CR-D were 1.8% and 3.6% from CR-IM. Eradication rates for dysplasia in LSBE and ULSBE patients (90.6% versus 83.3%) and IM (71.9% versus 62.5%) were not significantly different. ULSBE patients required higher mean number of ablation sessions for IM eradication (4.7 versus 3.7, p = 0.032), while complication rates including strictures (4.2% versus 6.2%), perforation (0 versus 0), and bleeding (4.2% versus 3.1%), were similar between ULSBE and LSBE patients, respectively. On multivariate analysis, shorter Barrett's segment and baseline low-grade dysplasia were associated with increased likelihood for eradication of IM and dysplasia. A total number of ablation sessions or endoscopic resections ≥ 3 was associated with reduced likelihood for eradication. CONCLUSION: RFA was durable in maintaining dysplasia and IM eradication in both LSBE and ULSBE over 10 years, and with low complication rates. IM eradication was more difficult to achieve in ULSBE. Late development of cancer occurred in 14.3%.

Risk of lymph node metastasis in T1 esophageal adenocarcinoma: a meta-analysis.

Patients with early (T1) esophageal adenocarcinoma (EAC) are increasingly having definitive local therapy endoscopically. Endoscopic resection is not able to pathologically stage or treat lymph node metastasis (LNM). Accurate identification of patients having nodal metastasis is critical to select endoscopic therapy over surgery. This study aimed to define the risk of LNM in T1 EAC. A meta-analysis of studies of patients who underwent surgery and lymphadenectomy with assessment of LNM was performed according to PRISMA. Main outcome was probability of LNM in T1a and T1b disease. Secondary outcomes were risk factors for LNM and rate of LNM in submucosal T1b (SM1, SM2, and SM3) disease. Registered with PROSPERO (CRD42022341794). Twenty cohort studies involving 2264 patients with T1 EAC met inclusion criteria: T1a (857 patients) with 36 (4.2%) node positive and T1b (1407 patients) with 327 (23.2%) node positive. Subgroup analysis of T1b lesions was available in 10 studies (405 patients). Node positivity for SM1, SM2, and SM3 was 16.3%, 16.2%, and 29.4%, respectively. T1 substage (odds ratio [OR] 7.72, 95% confidence interval [CI] 4.45-13.38, P < 0.01), tumor differentiation (OR 2.82, 95% CI 2.06-3.87, P < 0.01), and lymphovascular invasion (OR 13.65, 95% CI 6.06-30.73, P < 0.01) were associated with LNM. T1a disease demonstrated a 4.2% nodal metastasis rate and T1b disease a rate of 23.2%. Endoscopic therapy should be reserved for T1a disease and perhaps select T1b disease, which has a moderately high rate of nodal metastasis. There were inadequate data to stratify T1b SM disease into 'low-risk' and 'high-risk' based on tumor differentiation and lymphovascular invasion.

Metabolic Engineering of Corynebacterium glutamicum for the Production of Flavonoids and Stilbenoids.

Flavonoids and stilbenoids, crucial secondary metabolites abundant in plants and fungi, display diverse biological and pharmaceutical activities, including potent antioxidant, anti-inflammatory, and antimicrobial effects. However, conventional production methods, such as chemical synthesis and plant extraction, face challenges in sustainability and yield. Hence, there is a notable shift towards biological production using microorganisms like Escherichia coli and yeast. Yet, the drawbacks of using E. coli and yeast as hosts for these compounds persist. For instance, yeast's complex glycosylation profile can lead to intricate protein production scenarios, including hyperglycosylation issues. Consequently, Corynebacterium glutamicum emerges as a promising alternative, given its adaptability and recent advances in metabolic engineering. Although extensively used in biotechnological applications, the potential production of flavonoid and stilbenoid in engineered C. glutamicum remains largely untapped compared to E. coli. This review explores the potential of metabolic engineering in C. glutamicum for biosynthesis, highlighting its versatility as a cell factory and assessing optimization strategies for these pathways. Additionally, various metabolic engineering methods, including genomic editing and biosensors, and cofactor regeneration are evaluated, with a focus on C. glutamicum. Through comprehensive discussion, the review offers insights into future perspectives in production, aiding researchers and industry professionals in the field.

Association Between Vaccination Status and Outcomes in Patients Admitted to the ICU With COVID-19.

OBJECTIVES: Although COVID-19 vaccines can reduce the need for intensive care unit admission in COVID-19, their effect on outcomes in critical illness remains unclear. We evaluated outcomes in vaccinated patients admitted to the ICU with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the association between vaccination and booster status on clinical outcomes. DESIGN: Retrospective cohort. SETTING AND PATIENTS: All patients were admitted to an ICU between January 2021 (after vaccination was available) and July 2022 with a diagnosis of COVID-19 based on a SARS-CoV-2 polymerase chain reaction test in Alberta, Canada. INTERVENTIONS: None. MEASUREMENT: The propensity-matched primary outcome of all-cause in-hospital mortality was compared between vaccinated and unvaccinated patients, and vaccinated patients were stratified by booster dosing. Secondary outcomes were mechanical ventilation (MV) duration ICU length of stay (LOS). MAIN RESULTS: The study included 3,293 patients: 743 (22.6%) were fully vaccinated (54.6% with booster), 166 (5.0%) were partially vaccinated, and 2,384 (72.4%) were unvaccinated. Unvaccinated patients were more likely to require invasive MV (78.4% vs 68.2%), vasopressor use (71.1% vs 66.6%), and extracorporeal membrane oxygenation (2.1% vs 0.5%). In a propensity-matched analysis, in-hospital mortality was similar (31.8% vs 34.0%, adjusted odds ratio [OR], 1.25; 95% CI, 0.97-1.61), but median duration MV (7.6 vs 4.7 d; p < 0.001) and ICU LOS (6.6 vs 5.2 d; p < 0.001) were longer in unvaccinated compared to fully vaccinated patients. Among vaccinated patients, greater than or equal to 1 booster had lower in-hospital mortality (25.5% vs 40.9%; adjusted OR, 0.50; 95% CI, 0.0.36-0.68) and duration of MV (3.8 vs 5.6 d; p = 0.025). CONCLUSIONS: Nearly one in four patients admitted to the ICU with COVID-19 after widespread COVID-19 vaccine availability represented a vaccine-breakthrough case. Mortality risk remains substantial in vaccinated patients and similar between vaccinated and unvaccinated patients after the onset of critical illness. However, COVID-19 vaccination is associated with reduced ICU resource utilization and booster dosing may increase survivability from COVID-19-related critical illness.

Novel Dual Tracer Indocyanine Green and Radioisotope Versus Gold Standard Sentinel Lymph Node Biopsy in Breast Cancer: The GREENORBLUE Trial.

BACKGROUND: The methods for sentinel lymph node (SLN) biopsy in breast cancer have been variable in type and number of tracers. Some units have abandoned the use of blue dye (BD) due to adverse reactions. Fluorescence-guided biopsy with indocyanine green (ICG) is a relatively novel technique. This study compared the clinical efficacy and costs between novel dual tracer ICG and radioisotope (ICG-RI) with "gold standard" BD and radioisotope (BD-RI). METHODS: Single-surgeon study of 150 prospective patients with early breast cancer undergoing SLN biopsy (2021-2022) using ICG-RI compared with a retrospective cohort of 150 consecutive previous patients using BD-RI. Number of SLNs identified, rate of failed mapping, identification of metastatic SLNs, and adverse reactions were compared between techniques. Cost-minimisation analysis performed by using Medicare item numbers and micro-costing analysis. RESULTS: Total number of SLNs identified with ICG-RI and BD-RI was 351 and 315, respectively. Mean number of SLNs identified with ICG-RI and BD-RI was 2.3 (standard deviation [SD] 1.4) and 2.1 (SD 1.1), respectively (p = 0.156). There were no cases of failed mapping with either dual technique. Metastatic SLNs were identified in 38 (25.3%) ICG-RI patients compared with 30 (20%) BD-RI patients (p = 0.641). There were no adverse reactions to ICG, whereas four cases of skin tattooing and anaphylaxis were associated with BD (p = 0.131). ICG-RI cost an additional AU$197.38 per case in addition to the initial cost for the imaging system. CLINICAL TRIAL REGISTRATION:  ACTRN12621001033831. CONCLUSIONS: Novel tracer combination, ICG-RI, provided an effective and safe alternative to "gold standard" dual tracer. The caveat was the significantly greater costs associated with ICG.

A scoping review of asthma and machine learning.

OBJECTIVE: The objective of this study was to determine the extent of machine learning (ML) application in asthma research and to identify research gaps while mapping the existing literature. DATA SOURCES: We conducted a scoping review. PubMed, ProQuest, and Embase Scopus databases were searched with an end date of September 18, 2020. STUDY SELECTION: DistillerSR was used for data management. Inclusion criteria were an asthma focus, human participants, ML techniques, and written in English. Exclusion criteria were abstract only, simulation-based, not human based, or were reviews or commentaries. Descriptive statistics were presented. RESULTS: A total of 6,317 potential articles were found. After removing duplicates, and reviewing the titles and abstracts, 102 articles were included for the full text analysis. Asthma episode prediction (24.5%), asthma phenotype classification (16.7%), and genetic profiling of asthma (12.7%) were the top three study topics. Cohort (52.9%), cross-sectional (20.6%), and case-control studies (11.8%) were the study designs most frequently used. Regarding the ML techniques, 34.3% of the studies used more than one technique. Neural networks, clustering, and random forests were the most common ML techniques used where they were used in 20.6%, 18.6%, and 17.6% of studies, respectively. Very few studies considered location of residence (i.e. urban or rural status). CONCLUSIONS: The use of ML in asthma studies has been increasing with most of this focused on the three major topics (>50%). Future research using ML could focus on gaps such as a broader range of study topics and focus on its use in additional populations (e.g. location of residence).Supplemental data for this article is available online at http://dx.doi.org/ .

Microorganisms for Ginsenosides Biosynthesis: Recent Progress, Challenges, and Perspectives.

Ginsenosides are major bioactive compounds present in the Panax species. Ginsenosides exhibit various pharmaceutical properties, including anticancer, anti-inflammatory, antimetastatic, hypertension, and neurodegenerative disorder activities. Although several commercial products have been presented on the market, most of the current chemical processes have an unfriendly environment and a high cost of downstream processing. Compared to plant extraction, microbial production exhibits high efficiency, high selectivity, and saves time for the manufacturing of industrial products. To reach the full potential of the pharmaceutical resource of ginsenoside, a suitable microorganism has been developed as a novel approach. In this review, cell biological mechanisms in anticancer activities and the present state of research on the production of ginsenosides are summarized. Microbial hosts, including native endophytes and engineered microbes, have been used as novel and promising approaches. Furthermore, the present challenges and perspectives of using microbial hosts to produce ginsenosides have been discussed.

CRISPR-Cas system in microbial hosts for terpenoid production.

Terpenoids represent the largest group of secondary metabolites with variable structures and functions. Terpenoids are well known for their beneficial application in human life, such as pharmaceutical products, vitamins, hormones, anticancer drugs, cosmetics, flavors and fragrances, foods, agriculture, and biofuels. Recently, engineering microbial cells have been provided with a sustainable approach to produce terpenoids with high yields. Noticeably, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) system has emerged as one of the most efficient genome-editing technologies to engineer microorganisms for improving terpenoid production. In this review, we summarize the application of the CRISPR-Cas system for the production of terpenoids in microbial hosts such as Escherichia coli, Saccharomyces cerevisiae, Corynebacterium glutamicum, and Pseudomonas putida. CRISPR-Cas9 deactivated Cas9 (dCas9)-based CRISPR (CRISPRi), and the dCas9-based activator (CRISPRa) have been used in either individual or combinatorial systems to control the metabolic flux for enhancing the production of terpenoids. Finally, the prospects of using the CRISPR-Cas system in terpenoid production are also discussed.

Impact of low health literacy on patients' health outcomes: a multicenter cohort study.

BACKGROUND: This study aims to assess the health literacy of medical patients admitted to hospitals and examine its correlation with patients' emergency department visits, hospital readmissions, and durations of hospital stay. METHODS: This prospective cohort study recruited patients admitted to the general internal medicine units at the two urban tertiary care hospitals. Health literacy was measured using the full-length Test of Functional Health Literacy in Adults. Logistic regression analyses were performed to examine the correlation between health literacy and the desired outcomes. The primary outcome of interest of this study was to determine the correlation between health literacy and emergency department revisit within 90 days of discharge. The secondary outcomes of interest were to assess the correlation between health literacy and length of stay and hospital readmission within 90 days of discharge. RESULTS: We found that 50% had adequate health literacy, 32% had inadequate, and 18% of patients had marginal health literacy. Patients with inadequate health literacy were more likely to revisit the emergency department as compared to patients with adequate health literacy (odds ratio: 3.0; 95% Confidence Interval: 1.3-6.9, p = 0.01). In patients with inadequate health literacy, the mean predicted probability of emergency department revisits was 0.22 ± 0.11 if their education level was some high school or less and 0.57 ± 0.18 if they had completed college. No significant correlation was noted between health literacy and duration of hospital stay or readmission. CONCLUSIONS: Only half of the patients admitted to the general internal medicine unit had adequate health literacy. Patients with low health literacy, but high education, had a higher probability of emergency department revisits.

ASSESSING THE ACCURACY OF A LARGE OBSERVATIONAL REGISTRY OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the accuracy of an observational database that tracks real-world treatment outcomes for neovascular age-related macular degeneration. METHODS: We audited 245 randomly sampled eyes from 189 patients with 3,356 visits from 11 doctors in the Fight Retinal Blindness! DATABASE: Sex, birth year, previous treatments received, treatment, and visual acuity were validated against the clinical notes. Error rates, the proportion of missed visits (the number of visits present in the patient record but not entered into Fight Retinal Blindness!), the level of agreement using Cohen's kappa (κ) and intraclass correlation coefficients, and positive and negative predictive values were calculated. A visual acuity error was defined as an absolute difference of ≥5 letters. RESULTS: The overall error rate was 3.5% (95% confidence interval: 3.1-3.9). The error rate for visual acuity was 5.1% (95% confidence interval: 4.2-5.9) and <5% for the remaining fields. The level of agreement for each field ranged from good to excellent (κ or intraclass correlation ≥ 0.75). The positive predictive value and negative predictive value for visits were 99% and 89%, respectively. The proportion of missed visits was 10.2%. CONCLUSION: Accuracy of the Fight Retinal Blindness! database was good (>95%). The rate of missed visits was high, possibly due to the high burden of retrospective data entry or patients switching practitioners during treatment.

Characterization of Poor Visual Outcomes of Neovascular Age-related Macular Degeneration Treated with Anti-Vascular Endothelial Growth Factor Agents.

PURPOSE: To investigate the incidence, characteristics, and baseline predictors of poor visual outcomes in eyes with neovascular age-related macular degeneration (nAMD) receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents in daily clinical practice. DESIGN: Observational study. PARTICIPANTS: Treatment-naive eyes starting anti-VEGF therapy for nAMD between 2007 and 2012 tracked in the Fight Retinal Blindness! registry. Eyes had sustained ≥15 letters of loss from baseline without recovery of visual acuity (VA) at final end point. A subgroup analysis included eyes that sustained ≥30 letters of loss. Controls had not sustained ≥15 letters of loss. METHODS: Kaplan-Meier curves estimated time to first development of loss of ≥15 letters. Cox proportional hazards models evaluated predictors of loss of ≥15 letters. MAIN OUTCOME MEASURES: The proportion of eyes with sustained VA loss within 5 years, the time to development of sustained VA loss, and baseline predictors of sustained VA loss. RESULTS: There were 1760 eyes in total and 856 eyes that completed 5 years follow-up. The proportion of eyes with sustained VA loss of ≥15 letters at 5 years was 22.9% (95% confidence interval [CI], 20.7%-25.1%) and VA loss of ≥30 letters was 10.8% (95% CI, 9.1%-12.5%). Factors independently associated with higher incidence of sustained ≥15-letter loss included age >80 years (odds ratio [OR], 1.33 for patients >80 years vs. ≤80 years; 95% CI, 1.05-1.69; P = 0.02), fewer injections (OR, 0.97 per injection; 95% CI, 0.96-0.98; P = 0.0005), and more visits at which the choroidal neovascularization was graded as active (OR, 1.97 for eyes in upper quartile of active visits vs. eyes in lowest quartile of active visits; 95% CI, 1.39-2.79; P = 0.0001). Baseline VA ≥70 letters was associated with reduced risk of sustained ≥30-letter loss (OR, 0.61; 95% CI, 0.38-0.98; P = 0.04). Baseline angiographic lesion criteria were not significantly associated with sustained VA loss. CONCLUSIONS: Twenty-three percent of eyes with nAMD developed sustained VA loss of ≥15 letters over 5 years of anti-VEGF therapy. Baseline predictors of poor outcomes provide more accurate assessment of the potential benefit from anti-VEGF therapy.

Prevalence and associated factors for self-reported asthma in a Canadian population: The Canadian Community Health Survey, 2014.

BACKGROUND: Asthma prevalence is increasing among adults, yet limited information regarding the association between adult asthma and environmental and personal exposures is available using large nationally representative population-based survey. OBJECTIVE: To determine the prevalence of asthma and associated factors for self-reported asthma in a Canadian population aged 12 years and older by using the Canadian Community Health Survey (CCHS) 2014 cross-sectional cohort. METHODS: We used data from the 2014 CCHS. Asthma was determined through self-reported health professional diagnosis. Information regarding covariates of importance, such as socio-economic status, life style variables, was obtained. A weighted logistic regression analysis was performed with appropriate technique for clustering effects. RESULTS: Estimated self-reported asthma prevalence of 8.1% in the greater than 12 years old Canadian population was observed. We found that a substantial proportion of Canadians (aged 12 and older) reported having asthma and geographical differences and differences between specific provinces in asthma prevalence. Women had higher prevalence of asthma than men, but the relationship depended on age and body mass index (BMI). Interactions between household income and smoking status were observed to predict the probability of asthma. CONCLUSIONS: Additional studies are needed to determine which factors influence the asthma prevalence between sex, BMI as well as smoking status and household income and its interactions with each other.

Genome-guided exploration of metabolic features of Streptomyces peucetius ATCC 27952: past, current, and prospect.

Streptomyces peucetius ATCC 27952 produces two major anthracyclines, doxorubicin (DXR) and daunorubicin (DNR), which are potent chemotherapeutic agents for the treatment of several cancers. In order to gain detailed insight on genetics and biochemistry of the strain, the complete genome was determined and analyzed. The result showed that its complete sequence contains 7187 protein coding genes in a total of 8,023,114 bp, whereas 87% of the genome contributed to the protein coding region. The genomic sequence included 18 rRNA, 66 tRNAs, and 3 non-coding RNAs. In silico studies predicted ~ 68 biosynthetic gene clusters (BCGs) encoding diverse classes of secondary metabolites, including non-ribosomal polyketide synthase (NRPS), polyketide synthase (PKS I, II, and III), terpenes, and others. Detailed analysis of the genome sequence revealed versatile biocatalytic enzymes such as cytochrome P450 (CYP), electron transfer systems (ETS) genes, methyltransferase (MT), glycosyltransferase (GT). In addition, numerous functional genes (transporter gene, SOD, etc.) and regulatory genes (afsR-sp, metK-sp, etc.) involved in the regulation of secondary metabolites were found. This minireview summarizes the genome-based genome mining (GM) of diverse BCGs and genome exploration (GE) of versatile biocatalytic enzymes, and other enzymes involved in maintenance and regulation of metabolism of S. peucetius. The detailed analysis of genome sequence provides critically important knowledge useful in the bioengineering of the strain or harboring catalytically efficient enzymes for biotechnological applications.

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration: a meta-analysis of randomized controlled trials.

BACKGROUND: To evaluate the relative efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) agents for the treatment of neovascular age-related macular degeneration (AMD). METHODS: Systematic literature review identifying RCTs comparing anti-VEGF agents to another treatment published before June 2016. Efficacy assessed by mean change in best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline at up to 2 years followup. Safety assessed by proportions of patients with death, arteriothrombotic and venous thrombotic events, and at least one serious systemic adverse event at up to 2 years of followup. RESULTS: Fifteen RCTs selected for meta-analysis (8320 patients). Two trials compared pegaptanib, and three trials compared ranibizumab versus control. Eight trials compared bevacizumab with ranibizumab. Two trials compared aflibercept with ranibizumab. There were no significant differences between bevacizumab and ranibizumab for BCVA at 1 or 2 years (weighted mean difference = - 0.57, 95% CI - 1.55 to 0.41, P = 0.25 and weighted mean difference = - 0.76, 95% CI - 2.25 to 0.73, P = 0.32, respectively). Ranibizumab was more effective in reducing CMT at 1 year (weighted mean difference = 4.49, 95% CI 1.13 to 7.84, P = 0.009). Risk ratios comparing rates of serious systemic adverse events at 1 and 2 years were slightly out of favour for bevacizumab. Aflibercept compared with ranibizumab demonstrated similar mean change in BCVA, reduction in CMT, and safety at 1 year. CONCLUSIONS: Bevacizumab and ranibizumab had equivalent efficacy for BCVA, while ranibizumab had greater reduction in CMT and less rate of serious systemic adverse events. Aflibercept and ranibizumab had comparable efficacy for BCVA and CMT. This provides information to balance comparable effects on vision and risk of adverse events between anti-VEGF agents.

Simultaneous, same-anaesthetic bilateral total knee arthroplasty has low mortality and complication rates.

PURPOSE: The benefits of simultaneous bilateral total knee arthroplasty (SBTKR) include reduced hospital costs, single anaesthetic exposure and in many cases is also the patient's preference. Despite these potential benefits, risk-adversity with respect to assumed complications and mortality make it difficult for the orthopaedic surgeon and patient to make an informed decision. This study aimed to address the inconsistencies and lack of consensus in previous literature regarding the short-term complications and clinical safety of SBTKR in patients with end-stage knee osteoarthritis (OA). METHODS: A cohort of 950 knees (475 patients) undergoing surgery between 2008 and 2013 was extracted from a prospectively collected clinical database and retrospectively linked to the Australian Joint Replacement Registry and hospital records. Patients underwent sequential SBTKR by their treating surgeon under one anaesthetic. Basic demographic data and outcome data including complications and mortality were collected. All data were analyzed using descriptive statistics only. RESULTS: A total of 413 patients and 826 knees were included. The average age of the cohort was 70 years with range between 46 and 88 years. 50% of patients were female. The overall mortality rate during the study follow-up period was 1.9%, with an average time to death postoperatively of 23.8 months. There were no cases of acute postoperative mortality (< 6 weeks). Medical complication rates were low. CONCLUSIONS: In contrast to the higher mortality and complication rates suggested in previous literature, this study has demonstrated that SBTKR is safe, with low mortality and complication rates under the current surgical protocol. LEVEL OF EVIDENCE: IV.

Prevalence, risk factors, and clinical outcomes of atopic and nonatopic asthma among rural children.

BACKGROUND: Because of time and cost constraints, objective classification of atopic and nonatopic asthma has been limited in large epidemiologic studies. However, as we try to better understand exposure-outcome associations and ensure appropriate treatment of asthma, it is important to focus on phenotype-defined asthma classification. OBJECTIVE: To compare atopic and nonatopic asthma in rural children with regard to risk factors and clinical outcomes. METHODS: We conducted a cross-sectional study in rural Saskatchewan, Canada, in 2011. Parents of 6- to 14-year-old children completed a health and exposure survey. Skin prick tests were completed in a subsample of 529 children. Asthma was based physician diagnosis. Asthma status was defined as no asthma, nonatopic asthma, and atopic asthma. RESULTS: Asthma prevalence was 14.7% of which 32.1% of cases were atopic. After adjustment, early respiratory illness and a family history of asthma were predictors of childhood asthma, regardless of atopic status (P < .05). Being overweight and having a dog in the home were associated with an increased risk of nonatopic asthma (P < .05). A mother with a history of smoking increased the risk of atopic asthma (P = .01). Compared with those with nonatopic asthma, in the past 12 months, children with atopic asthma were more likely to report a sneezy, runny, or blocked nose or have shortness of breath (odds ratio >2), whereas those with nonatopic asthma were more likely to have parents who missed work (odd ratio >3). Those with nonatopic asthma had significantly lower forced expiratory volume in 1 second compared w2ith those with atopic asthma. CONCLUSION: Exposures may contribute differentially to atopic and nonatopic asthma and result in differential clinical presentation or burden. The study of these characteristics is important for etiologic understanding and management decisions.