Achieving net-zero in the dry eye disease care pathway.

Climate change is a threat to human health and wellbeing across the world. In recent years, there has been a surge in awareness of this crisis, leading to many countries and organisations setting "net-zero" targets. This entails minimising carbon emissions and neutralising remaining emissions by removing carbon from the atmosphere. At the 2022 United Nations Climate Change Conference (COP27), commitments to transition away from fossil fuels and augment climate targets were underwhelming. It is therefore imperative for public and private sector organisations to demonstrate successful implementation of net-zero and set a precedent for the global political consensus. As a top 10 world employer, the United Kingdom National Health Service (NHS) has pledged to reach net-zero by 2045. The NHS has already taken positive steps forward, but its scale and complexity as a health system means stakeholders in each of its services must highlight the specifications for further progress. Dry eye disease is a chronic illness with an estimated global prevalence of 29.5% and an environmentally damaging care pathway. Moreover, environmental damage is a known aggravator of dry eye disease. Worldwide management of this illness generates copious amounts of non-recyclable waste, utilises inefficient supply chains and involves recurrent follow-up appointments and prescriptions. By mapping the dry eye disease care pathway to environmental impact, in this review we will highlight seven key areas in which reduced emissions and pollution could be targeted. Examining these approaches for improved environmental sustainability is critical in driving the transformation needed to preserve our health and wellbeing.

Comprehensive review of safety in Experimental Human Pneumococcal Challenge.

INTRODUCTION: Experimental Human Pneumococcal Challenge (EHPC) involves the controlled exposure of adults to a specific antibiotic-sensitive Streptococcus pneumoniae serotype, to induce nasopharyngeal colonisation for the purpose of vaccine research. The aims are to review comprehensively the safety profile of EHPC, explore the association between pneumococcal colonisation and frequency of safety review and describe the medical intervention required to undertake such studies. METHODS: A single-centre review of all EHPC studies performed 2011-2021. All recorded serious adverse events (SAE) in eligible studies are reported. An unblinded meta-analysis of collated anonymised individual patient data from eligible EHPC studies was undertaken to assess the association between experimental pneumococcal colonisation and the frequency of safety events following inoculation. RESULTS: In 1416 individuals (median age 21, IQR 20-25), 1663 experimental pneumococcal inoculations were performed. No pneumococcal-related SAE have occurred. 214 safety review events were identified with 182 (12.85%) participants presenting with symptoms potentially in keeping with pneumococcal infection, predominantly in pneumococcal colonised individuals (colonised = 96/658, non-colonised = 86/1005, OR 1.81 (95% CI 1.28-2.56, P = <0.001). The majority were mild (pneumococcal group = 72.7% [120/165 reported symptoms], non-pneumococcal = 86.7% [124/143 reported symptoms]). 1.6% (23/1416) required antibiotics for safety. DISCUSSION: No SAEs were identified directly relating to pneumococcal inoculation. Safety review for symptoms was infrequent but occurred more in experimentally colonised participants. Most symptoms were mild and resolved with conservative management. A small minority required antibiotics, notably those serotype 3 inoculated. CONCLUSION: Outpatient human pneumococcal challenge can be conducted safely with appropriate levels of safety monitoring procedures in place.

Clinical safety and efficacy of a preloaded monofocal hydrophobic acrylic intraocular lens in a real-world population.

BACKGROUND: This study was designed to evaluate visual, refractive and safety outcomes in eyes after they underwent phacoemulsification and implantation of a preloaded monofocal hydrophobic acrylic intraocular lens. METHODS: This was a single center observational study conducted at Ashford and St Peter's Hospitals NHS Foundation Trust, United Kingdom. Patients were included if they had cataract extraction with in-the-bag implantation of the EyeCee® One preloaded intraocular lens from August to October 2019. Pre-operative, surgery-related and 2 weeks and 3 months post-operative data was collected. Surgeons at this trust were then asked to complete a feedback form to evaluate their experience of implanting the EyeCee® One. RESULTS: One hundred fifty-two eyes were included in the study. Ninety-four (62%) of these eyes had cataract but no concomitant ocular pathology that could potentially affect visual acuity. Three months post-operatively, 98.7% of all eyes had monocular CDVA ≤0.3 logMAR. 100% of the eyes without concomitant ocular pathology achieved this target. The mean CDVA of all eyes in this study improved from 0.43 ± 0.43 logMAR pre-operatively, to 0.05 ± 0.11 logMAR post-operatively (p < 0.05). The mean sphere and spherical equivalent values showed significant improvements (p < 0.05) and (p < 0.05). There were no intraoperative complications and 1.3% of patients reported complications 2 weeks post-operatively. All of the participating surgeons said they would use the EyeCee® One again with 64% providing an overall rating of 'excellent' for their experience of implanting this intraocular lens. CONCLUSIONS: This study indicates excellent post-operative visual acuity and refractive outcomes in eyes after EyeCee® One implantation. This is accompanied with very little risk of intraoperative and post-operative complications.

A Meta-Analysis of Aspirin for the Primary Prevention of Cardiovascular Diseases in the Context of Contemporary Preventive Strategies.

BACKGROUND: The role of aspirin for primary prevention of cardiovascular diseases remains controversial, particularly in the context of contemporary aggressive preventive strategies. METHODS: Relevant randomized clinical trials were included, and risk ratios (RRs) were calculated using random-effects models. Additional moderator analyses were performed to compare the pooled treatment effects from recent trials (those reported after the guidelines of the National Cholesterol Education Program Third Adult Treatment Panel were published in 2001; thus, conducted on the background of contemporary preventive strategies) to the results of older trials. RESULTS: Data from 14 randomized controlled trials involving 164,751 patients were included. Aspirin use decreased myocardial infarction risk by 16% compared with placebo (RR 0.84; 95% confidence interval [CI], 0.75-0.94); however, in the moderator analyses, aspirin was not associated with a decreased risk of myocardial infarction in recent trials, but was in older trials (P-interaction = .02). Overall, aspirin use significantly increased the occurrence of major bleeding (RR 1.49; 95% CI, 1.32-1.69) and hemorrhagic stroke (RR 1.25; 95% CI, 1.01-1.54). In moderator analyses, the risk of major bleeding (P-interaction = .12) or hemorrhagic stroke (P-interaction = .44) with aspirin was not significantly different between the older and new trials. Differences between aspirin and placebo in the risks for all-cause stroke, cardiac death, and all-cause mortality were not found. CONCLUSIONS: In the context of contemporary primary prevention guidelines, the effect of aspirin on myocardial infarction risk was significantly attenuated, whereas its major bleeding and hemorrhagic stroke complications were retained. Therefore, in contemporary practice, routine use of aspirin for the primary prevention of cardiovascular events may have a net harmful effect.

Bivalirudin with a post-procedure infusion versus heparin monotherapy for the prevention of stent thrombosis.

OBJECTIVES: To evaluate the efficacy of post-primary percutaneous coronary intervention (PCI) bivalirudin infusion (at full PCI dose) to prevent stent thrombosis (ST) compared with heparin monotherapy. BACKGROUND: Early randomized controlled trials (RCTs) have shown that compared with heparin use, bivalirudin use during primary PCI is associated with an increased risk of ST. However, bivalirudin was stopped in those trials at the end of the procedure and glycoprotein IIb/IIIa inhibitors (GPIs) were routinely used with heparin. The increased risk of ST may be eliminated by continuing bivalirudin infusion post-procedure for few hours. Indeed, in most recent trials, a trend of lower ST risk has been observed with a post-procedure infusion of bivalirudin compared with heparin monotherapy (without the routine use of GPI). METHODS: Relevant RCTs were included and risk ratios (RRs) were calculated using random effect models. The primary outcome of interest was the risk of early definite ST. RESULTS: Four RCTs involving 13,505 patients were included in this meta-analysis. Compared with heparin monotherapy, bivalirudin (with a post-procedure infusion) was associated with a 55% decrease in the risk of early definite ST (RR: 0.45, 95% confidence interval: 0.23-0.85; P = 0.015). There was no difference in the risk of early ST between bivalirudin (with a post-procedure infusion) and heparin with GPI. CONCLUSIONS: For primary PCI, a bivalirudin-based anticoagulant strategy (with post procedure infusion) is associated with a lower risk of early definite ST compared with treatment with heparin monotherapy (without GPI).

Short-term versus long-term triple antithrombotic therapy for patients with coronary stents and requiring oral anticoagulation: a meta-analysis of randomized clinical trials.

BACKGROUND: The cornerstone therapy for patients with coronary stents is dual antiplatelet therapy (DAPT). In 5-10% of these patients, oral anticoagulation (OAC) is clearly indicated in addition to DAPT. However, the optimal duration of this triple antithrombotic therapy (TAT) remains uncertain. PATIENTS AND METHODS: Scientific databases and websites were searched for randomized clinical trials (RCTs). RCTs were included if patients undergoing coronary stent placements with additional indications of chronic OAC were randomly assigned to either short-term TAT or long-term TAT. Short-term TAT was defined as no more than 6 weeks of TAT, and long-term TAT was defined as 6-12 months of TAT RESULTS: Using data from three RCTs and 1883 patients, short-term TAT was associated with decreased rates of major adverse cardiovascular events, cardiac mortality, all-cause mortality, and any-bleeding events compared to long-term TAT, but similar rates of myocardial infarction, stroke, stent thrombosis, and thrombolysis in myocardial infarction major bleeding. Furthermore, in subgroup analysis, short-term TAT was associated with decreased rates of major adverse cardiovascular events, cardiac mortality, all-cause mortality, and any-bleeding compared to 12-month TAT, but similar rates compared to 6-month TAT. CONCLUSION: In patients who require chronic OAC therapy and undergo coronary stent placement, short-term TAT was associated with better efficacy and safety outcomes compared to long-term TAT.

Efficacy and Safety of Drug-Eluting Stents Optimized for Biocompatibility vs Bare-Metal Stents With a Single Month of Dual Antiplatelet Therapy: A Meta-analysis.

Importance: A significant number of patients receive bare-metal stents (BMSs) instead of drug-eluting stents (DESs) to shorten the duration of dual antiplatelet therapy (DAPT). Emerging evidence suggests that new-generation DESs, particularly those optimized for biocompatibility, may be more efficacious and safer than BMSs, even with a single month of DAPT after stent implantation. Objective: To evaluate the efficacy and safety of DESs compared with BMSs for coronary intervention with a single month of DAPT. Data Sources: Human studies found in PubMed, the Cochrane databases through April 2018, and reference lists of selected articles. Study Selection: Randomized clinical trials were included if they enrolled patients undergoing percutaneous coronary intervention and randomly assigned each patient to treatment with either DESs or BMSs. The additional inclusion criterion was use of only 1 month of DAPT poststent implantation. Data Extraction and Synthesis: Two reviewers independently extracted the data. Odds ratios (ORs) were calculated using random-effects models. Main Outcomes and Measures: The efficacy end points were major adverse cardiac events, myocardial infarction, target vessel revascularization, ischemia-driven target lesion revascularization, cardiac mortality, and all-cause mortality at 1 year. The safety outcomes were stent thrombosis and bleeding complications. Results: Data from 3 randomized clinical trials involving 3943 patients were included (2457 men [62.3%]; mean [SD] age ranging from 75.7 [9.3] years to 81.4 [4.3] years per trial subgroup). Coronary intervention with DESs reduced the rates for major adverse cardiac events (OR, 0.68 [95% CI, 0.57-0.82]; P < .001), target lesion revascularization (OR, 0.38 [95% CI, 0.22-0.67]; P = .001), target vessel revascularization (OR, 0.50 [95% CI, 0.38-0.65]; P < .001), and myocardial infarction (OR, 0.51 [95% CI, 0.31-0.83]; P = .01) compared with BMSs at 1 year. The incidence of stent thrombosis was also lower with DESs compared with BMSs (1.8% vs 2.8%), but this difference was not statistically significant in the random-effects model. Additionally, the 2 stent types did not differ in the risks of all-cause mortality, cardiac mortality, and bleeding. Conclusions and Relevance: In the limited number of randomized clinical trials comparing DESs with BMSs with shortened DAPT durations in patients who have high bleeding risk or are uncertain candidates for prolonged DAPT, coronary intervention with specific DESs optimized for biocompatibility is not only safe but also efficacious, even with only 1 month of DAPT.

A comprehensive meta-analysis of randomized controlled trials comparing drug-eluting stents with bare-metal stents in saphenous vein graft interventions.

BACKGROUND: Several large randomized controlled trials (RCTs) have proven the superiority of drug-eluting stents (DESs) over bare-metal stents (BMSs) for native coronary stenosis. However, RCTs comparing DESs with BMSs for SVG lesions have predominantly been small in size and have yielded conflicting results. Therefore, we conducted an updated comprehensive meta-analysis of RCTs comparing DESs versus BMSs for SVG interventions using the largest sample size to date. METHODS: Scientific databases and websites were searched to find RCTs. Data from six RCTs involving 1,582 patients were included. Pooled risk ratios (RRs) were calculated using random-effects models. The primary outcome of this meta-analysis was target vessel revascularization (TVR). The secondary outcomes were major adverse cardiac events (MACEs), myocardial infarction (MI), stent thrombosis, all-cause mortality, and cardiac mortality. RESULTS: Data from six RCTs involving 1,582 patients were included. Saphenous vein graft interventions with DESs reduced TVR (RR, 0.52; 95% CI, 0.30-0.88; P = 0.017) and MACE rate (RR, 0.60; 95% CI, 0.42-0.87; P = 0.007) compared to BMSs. No difference between the stents were found in rates of MI (RR, 0.69; 95% CI, 0.43-1.10; P = 0.123), stent thrombosis (RR, 0.61; 95% CI, 0.27-1.41; P = 0.255), all-cause mortality (RR, 1.13; 95% CI, 0.74-1.71; P = 0.554), or cardiac mortality. CONCLUSION: For SVG intervention, the MACE rate was lower for DESs compared to BMSs, driven primarily by decreased non-MI-related TVR. Rates of MI, all-cause mortality, cardiac mortality, and stent thrombosis were not different between the stents.

A comprehensive meta-analysis of stem cell therapy for chronic angina.

BACKGROUND: A substantial proportion of patients with coronary artery disease do not achieve complete revascularization and continue to experience refractory angina despite optimal medical therapy. Recently, stem cell therapy has emerged as a potential therapeutic option for these patients. However, findings of individual trials have been scrutinized because of their small sample sizes and lack of statistical power. Therefore, we conducted an updated comprehensive meta-analysis of available randomized controlled trials (RCTs) with the largest sample size ever reported on this subject. HYPOTHESIS: In patients with chronic angina stem cell therapy improves clinical outcomes. METHODS: Scientific databases and websites were searched for RCTs. Data were independently collected by 2 investigators, and disagreements were resolved by consensus. Data from 10 trials including 658 patients were analyzed. RESULTS: Stem cell therapy improved Canadian Cardiovascular Society angina class (risk ratio: 1.53, 95% CI: 1.09 to 2.15, P = 0.013), exercise capacity (standardized mean difference [SMD]: 0.56, 95% CI: 0.23 to 0.88, P = 0.001), and left ventricular ejection fraction (SMD: 0.63, 95% CI: 0.27 to 1.00, P = 0.001) compared with placebo. It also decreased anginal episodes (SMD: -1.21, 95% CI: -2.40 to -0.02, P = 0.045) and myocardial perfusion defects (SMD: -0.70, 95% CI: -1.11 to -0.29, P = 0.001). However, no improvements in all-cause mortality were observed after a relatively short follow-up. CONCLUSIONS: In patients with chronic angina on optimal medical therapy, stem cell therapy improves symptoms, exercise capacity, and left ventricular ejection fraction. These findings warrant confirmation using larger trials.

Trends, predictors and outcomes of ischemic stroke and intracranial hemorrhage in patients with a left ventricular assist device.

BACKGROUND: Patients with a left ventricular assist device (LVAD) are at a higher risk of ischemic stroke (IS) and intracranial hemorrhage (ICH). There is limited data available on risk factors and outcomes associated with IS and ICH in LVAD patients. METHODS: All patients >18 years of age with an LVAD were identified based on the U.S. Nationwide Inpatient Sample (NIS) database from the year 2007 to 2011. Patients with a discharge diagnosis of IS were compared to those without IS. In a separate analysis, patients with a discharge diagnosis of ICH were compared to patients without ICH. Trends, predictors and outcomes of IS and ICH were analyzed using a multivariate regression model. RESULTS: Out of 17,323 discharges with a primary diagnosis of heart failure with LVAD, 624 (3.6%) patients had a co-diagnosis of IS and 387 (2.2%) had a co-diagnosis of ICH. From 2007 to 2011, the discharge diagnosis of heart failure with LVAD increased from 946 to 5,540, but the proportion of patients with IS remained about 3.4%, while the incidence of ICH decreased from 3.8% in 2007 to a plateau of around 2.2% in the following years. After adjusting for potential confounders, increasing Charlson Comorbidity Index (CCI) score was an independent predictor of IS and ICH. In-hospital mortality was four-fold higher in the IS group (odds ratio: 4.2; 95% CI: 2.3-7.6; P<0.0001) and 18-fold higher in the ICH group (OR: 18; 95% CI: 9-34, P<0.0001). Renal disease (OR: 5.3; CI: 1.3-22.1; P=0.02), liver disease (OR: 4.9; CI: 1.1-21.2; P=0.03) and abnormal coagulation profile (OR: 4.8; CI: 1.6-14.4; P=0.01) were independent predictors of mortality in LVAD patients with IS. Presence of diabetes mellitus (OR 4.3, P=0.1) and liver disease (or 2.8, P=0.2) showed trends towards predicting mortality in LVAD patients with ICH but did not reach statistical significance. CONCLUSIONS: Increasing comorbidity burden significantly increases the risk of both IS and ICH with LVAD. In our cohort, the incidence of IS and ICH increases the mortality 4- and 18-fold, respectively. Renal disease, liver disease and abnormal coagulation profile were independent predictors of mortality in LVAD patients with IS.

Permanent pacemaker insertion in patients with conduction abnormalities post transcatheter aortic valve replacement: a review and proposed guidelines.

Conduction abnormalities are a common and serious complication of transcatheter aortic valve replacement (TAVR) with well-established predictive factors. Current guidelines are not concrete, leaving several questions unanswered about indications, timing and risks of pacemaker implantation post-TAVR. In this review article, we discuss current guidelines, predictors of pacemaker implantation, clinical implications of this procedure and our recommendations for reducing the pacemaker implantation rate post-TAVR.

Access site complications in transcutaneous aortic valve replacement: frequency, outcomes, prevention, and treatment.

Aortic stenosis (AS) is a common cause of valvular heart disease with heavy disease burden in elderly patients. It is present in almost 7% of patients older than 65. The mortality rate increases significantly once it becomes symptomatic with average life expectancy of around 1-year. Symptoms include angina, syncope, or heart failure. This requires either surgical or transcutaneous replacement. Transcutaneous aortic valve replacement (TAVR) use has increased in recent years from high risk patients to now even including intermediate risk patients. With the increased number of procedures performed, one of the consequences is access site complications. These complications can lead to increased hospitalization, cost, infections, and eventually worse outcomes. In this manuscript, we provide a comprehensive review discussing the consequences, outcomes, frequency, predictors and some possible solutions to these complications set forth in these studies.