Prehospital stroke care in Singapore.

ABSTRACT: Due to the narrow window of opportunity for stroke therapeutics to be employed, effectiveness of stroke care systems is predicated on the efficiency of prehospital stroke systems. A robust prehospital stroke system of care that provides a rapid and well-coordinated response maximises favourable poststroke outcomes, but achieving this presents a unique set of challenges dependent on demographic and geographical circumstances. Set in the context of a highly urbanised first-world nation with a rising burden of stroke, Singapore's prehospital stroke system has evolved to reflect the environment in which it operates. This review aims to characterise the current state of prehospital stroke care in Singapore, covering prehospital aspects of the stroke survival chain from symptom onset till arrival at the emergency department. We identify areas for improvement and innovation, as well as provide insights into the possible future of prehospital stroke care in Singapore.

Technology activated community first responders in Singapore: Real-world care delivery & outcome trends.

BACKGROUND: Community first responders (CFRs) strengthen the Chain of Survival for out-of-hospital cardiac arrest (OHCA) care. Considerable efforts have been invested in Singapore's CFR program, during the years 2016-2020, by developing an app-based activation system called myResponder. This paper reports on national CFR response indicators to evaluate the real-world impact of these efforts. METHODS: We matched data from the Singapore Civil Defence Force's CFR registry with the Pan Asian Resuscitation Outcomes Study (PAROS) registry data to calculate performance indicators. These included the number of CFRs receiving and accepting an issued alert per OHCA event. Also calculated were the fraction of OHCA events where CFRs received an issued alert, or accepted the alert, and arrived at the scene either before or after EMS. We also present trends of these indicators and compare the prevalence of these fractions between the CFR-attended and CFR-unattended OHCA events. RESULTS: Of 6577 alerted OHCA events, 42.7% accepted an alert, 50% of these arrived at the scene and 71% of them arrived before EMS. Almost all CFR response indicators improved over time even for the pandemic year (2020). The fraction of OHCA events where >2 CFRs received an alert increased from 62% to 96%; the same figure for accepting an alert did not change much but >2 CFRs arriving at the scene increased from 0% to 7.5%. The fraction of OHCA events with an automated external defibrillator applied and defibrillation performed by CFR increased from 4.2% to 10.3% and 1.6% to 3%, respectively. Statistically significant differences were observed in these indicators when CFR-attended and CFR-unattended OHCA events were compared. CONCLUSION: This real-world study shows that activating CFRs using mobile technology can improve community response to OHCA and are bearing fruit in Singapore at a national level. Some targets for improvement and future research are highlighted in this report.

Evaluating the outcome of screening for glaucoma using colour fundus photography-based referral criteria in a teleophthalmology screening programme for diabetic retinopathy.

AIMS: To evaluate the effectiveness of glaucoma screening using glaucoma suspect (GS) referral criteria assessed on colour fundus photographs in Singapore's Integrated Diabetic Retinopathy Programme (SiDRP). METHODS: A case-control study. This study included diabetic subjects who were referred from SiDRP with and without GS between January 2017 and December 2018 and reviewed at Singapore National Eye Centre. The GS referral criteria were based on the presence of a vertical cup-to-disc ratio (VCDR) of ≥0.65 and other GS features. The final glaucoma diagnosis confirmed from electronic medical records was retrospectively matched with GS status. The sensitivity, specificity and positive predictive value (PPV) of the test were evaluated. RESULTS: Of 5023 patients (2625 with GS and 2398 without GS) reviewed for glaucoma, 451 (9.0%, 95% CI 8.2% to 9.8%) were confirmed as glaucoma. The average follow-up time was 21.5±10.2 months. Using our current GS referral criteria, the sensitivity, specificity and PPV were 81.6% (95% CI 77.7% to 85.1%), 50.6% (95% CI 49.2% to 52.1%) and 14.0% (95% CI 13.4% to 14.7%), respectively, resulting in 2257 false positive cases. Increasing the VCDR cut-off for referral to ≥0.80, the specificity increased to 93.9% (95% CI 93.1% to 94.5%) but the sensitivity decreased to 11.3% (95% CI 8.5% to 14.6%), with a PPV of 15.4% (95% CI 12.0% to 19.4%). CONCLUSIONS: Opportunistic screening for glaucoma in a lower VCDR group could result in a high number of unnecessary referrals. If healthcare infrastructures are limited, targeting case findings on a larger VCDR group with high specificity will still be beneficial.

Does witness type affect the chance of receiving bystander CPR in out-of-hospital cardiac arrest?

OBJECTIVES: The relationship between the bystander witness type and receipt of bystander CPR (BCPR) is not well understood. Herein we compared BCPR administration between family and non-family witnessed out-of-hospital cardiac arrest (OHCA). BACKGROUND: In many communities, interventions in the past decade have contributed to an increased receipt of BCPR, for example in Singapore from 15% to 60%. However, BCPR rates have plateaued despite sustained and ongoing community-based interventions, which may be related to gaps in education or training for various witness types. The purpose of this study was to investigate the association between witness type and BCPR administration. METHODS: Singapore data from 2010-2020 was extracted from the Pan-Asian Resuscitation Outcomes Study (PAROS) network registry (n = 25,024). All adult, layperson witnessed, non-traumatic OHCAs were included in this study. RESULTS: Of 10,016 eligible OHCA cases, 6,895 were family witnessed and 3,121 were non-family witnessed. After adjustment for potential confounders, BCPR administration was less likely for non-family witnessed OHCA (OR 0.83, 95% CI 0.75, 0.93). After location stratification, non-family witnessed OHCAs were less likely to receive BCPR in residential settings (OR 0.75, 95% CI 0.66, 0.85). In non-residential settings, there was no statistically significant association between witness type and BCPR administration (OR 1.11, 95% CI 0.88, 1.39). Details regarding witness type and bystander CPR were limited. CONCLUSION: This study found differences in BCPR administration between family and non-family witnessed OHCA cases. Elucidation of witness characteristics may be useful to determine populations that would benefit most from CPR education and training.

Generalized metabolic flux analysis framework provides mechanism-based predictions of ophthalmic complications in type 2 diabetes patients.

Chronic metabolic diseases arise from changes in metabolic fluxes through biomolecular pathways and gene networks accumulated over the lifetime of an individual. While clinical and biochemical profiles present just real-time snapshots of the patients' health, efficient computation models of the pathological disturbance of biomolecular processes are required to achieve individualized mechanistic insights into disease progression. Here, we describe the Generalized metabolic flux analysis (GMFA) for addressing this gap. Suitably grouping individual metabolites/fluxes into pools simplifies the analysis of the resulting more coarse-grain network. We also map non-metabolic clinical modalities onto the network with additional edges. Instead of using the time coordinate, the system status (metabolite concentrations and fluxes) is quantified as function of a generalized extent variable (a coordinate in the space of generalized metabolites) that represents the system's coordinate along its evolution path and evaluates the degree of change between any two states on that path. We applied GMFA to analyze Type 2 Diabetes Mellitus (T2DM) patients from two cohorts: EVAS (289 patients from Singapore) and NHANES (517) from the USA. Personalized systems biology models (digital twins) were constructed. We deduced disease dynamics from the individually parameterized metabolic network and predicted the evolution path of the metabolic health state. For each patient, we obtained an individual description of disease dynamics and predict an evolution path of the metabolic health state. Our predictive models achieve an ROC-AUC in the range 0.79-0.95 (sensitivity 80-92%, specificity 62-94%) in identifying phenotypes at the baseline and predicting future development of diabetic retinopathy and cataract progression among T2DM patients within 3 years from the baseline. The GMFA method is a step towards realizing the ultimate goal to develop practical predictive computational models for diagnostics based on systems biology. This tool has potential use in chronic disease management in medical practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00218-x.

Recent Advances in Clinical Applications of Imaging in Retinal Diseases.

Many diseases that cause visual impairment, as well as systemic conditions, manifest in the posterior segment of the eye. With the advent of high-speed, high-resolution, reliable, and noninvasive imaging techniques, ophthalmologists are becoming more dependent on ocular imaging for disease diagnosis, classification, and management in clinical practice. There are rapid advances on the indications of multimodal retinal imaging techniques, including the application of ultra-widefield fundus angiography, fundus autofluorescence, optical coherence tomography, as well as optical coherence tomography angiography. This review summarizes and highlights the clinical applications, latest indications, and interpretations of multimodal imaging in age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic macular edema, central serous chorioretinopathy, diabetic retinopathy, retinal vein occlusion, and uveitis.

Building a Machine Learning-based Ambulance Dispatch Triage Model for Emergency Medical Services.

Background: In charge of dispatching the ambulances, Emergency Medical Services (EMS) call center specialists often have difficulty deciding the acuity of a case given the information they can gather within a limited time. Although there are protocols to guide their decision-making, observed performance can still lack sensitivity and specificity. Machine learning models have been known to capture complex relationships that are subtle, and well-trained data models can yield accurate predictions in a split of a second. Methods: In this study, we proposed a proof-of-concept approach to construct a machine learning model to better predict the acuity of emergency cases. We used more than 360,000 structured emergency call center records of cases received by the national emergency call center in Singapore from 2018 to 2020. Features were created using call records, and multiple machine learning models were trained. Results: A Random Forest model achieved the best performance, reducing the over-triage rate by an absolute margin of 15% compared to the call center specialists while maintaining a similar level of under-triage rate. Conclusions: The model has the potential to be deployed as a decision support tool for dispatchers alongside current protocols to optimize ambulance dispatch triage and the utilization of emergency ambulance resources.

Evolution of Polypoidal Lesions after Treatment of Polypoidal Choroidal Vasculopathy.

Purpose: To evaluate the status and evolution of polypoidal lesions during the course of treatment of patients with symptomatic macular polypoidal choroidal vasculopathy (PCV). Design: Comparative cohort study of randomly selected patients from a multicenter, randomized controlled clinical trial. Participants: Thirty randomly selected patients from the EVEREST II study who were treated with combination ranibizumab and verteporfin photodynamic therapy (n = 15) or ranibizumab monotherapy (n = 15). Methods: All patients were randomized at baseline and treated with a standardized treatment protocol. Indocyanine green angiography (ICGA) images were graded at the central reading center at baseline and months 3, 6, 12, and 24. Polypoidal lesions present at baseline were overlaid on ICGA images at subsequent visits to determine if these remained perfused or had regressed completely. New polypoidal lesions occurring at subsequent visits were similarly tracked to detail the evolution of each polypoidal lesion. Main Outcome Measures: Complete polypoidal lesion regression over time. Results: Complete polypoidal lesion regression was higher in the combination therapy group compared with the monotherapy group at all visits (month 12, 12 of 15 patients [80%] vs. 5 of 14 patients [35.7%]; P = 0.016). Persistence of baseline polypoidal lesions was lower in the combination therapy group: 1 of 15 patients (6.7%) versus 7 of 14 patients (50%) in the monotherapy group at month 12. Recurrences of polypoidal lesions that had regressed completely at an earlier time point were uncommon: 0% in the combination therapy group and 1 patient each at months 6 and 12 in the monotherapy group. Fewer new polypoidal lesions (arising after the baseline visit) were found in the combination therapy group at all visits (combination therapy: 2 of 15 [13.3%] vs. monotherapy: 4 of 14 eyes [28.6%] at month 12). Total polypoidal lesion area was significantly smaller in the combination therapy group compared with the monotherapy group throughout the study (0.013 mm2 vs. 0.110 mm2; P < 0.01 at month 12). Conclusions: Combination therapy was associated with higher rates of complete polypoidal lesion regression and fewer persistent polypoidal lesions compared with monotherapy. Closed polypoidal lesions rarely reopened, regardless of the treatment.

PREDICTORS AND IMPORTANCE OF COMPLETE POLYPOIDAL LESION REGRESSION IN THE EVEREST II STUDY: Predictors of Polyp Regression in Polypoidal Choroidal Vasculopathy.

PURPOSE: To evaluate the predictors of complete polypoidal lesion regression (CPREG) in polypoidal choroidal vasculopathy. METHODS: Post hoc analysis of EVEREST II-a 24-month, multicenter, randomized, controlled clinical trial of 322 patients with polypoidal choroidal vasculopathy, randomized to receive ranibizumab with or without photodynamic therapy. Images of indocyanine green angiography (ICGA) were graded by a central reading center. Multiple logistic regression analysis with significant baseline predictors then was conducted to assess adjusted odds ratios for CPREG at month (M) 12. RESULTS: Baseline ICGA characteristics were comparable between the treatment groups. Patients treated with combination therapy had higher odds of achieving CPREG at M12 (adjusted odds ratio = 4.64; 95% confidence interval, 2.85-7.55; P < 0.001) compared with those in the monotherapy group. Absence of polypoidal lesion pulsation on ICGA was also associated with CPREG at M12 (adjusted odds ratio = 2.62; 95% confidence interval, 1.32-5.21; P = 0.006). The presence of CPREG at M3 had higher odds of maintaining CPREG at M12 (adjusted odds ratio = 6.60; 95% confidence interval, 3.77-11.57; P < 0.001) compared with those with persistent polypoidal lesions. CONCLUSION: At M12, treatment with combination therapy was associated with higher probability of achieving CPREG than with ranibizumab monotherapy. The results contribute to the further understanding of the response of polypoidal lesions to treatment.

11C-Metomidate PET-CT versus adrenal vein sampling to subtype primary aldosteronism: a prospective clinical trial.

OBJECTIVE: Adrenal vein sampling (AVS) is recommended to subtype primary aldosteronism, but it is technically challenging. We compared 11C-Metomidate-PET-computed tomography (PET-CT) and AVS for subtyping of primary aldosteronism. METHODS: Patients with confirmed primary aldosteronism underwent both AVS and 11C-Metomidate PET-CT (post-dexamethasone). All results were reviewed at a multidisciplinary meeting to decide on final subtype diagnosis. Primary outcome was accuracy of PET versus AVS to diagnosis of unilateral primary aldosteronism based on post-surgical biochemical cure. Secondary outcome was accuracy of both tests to final subtype diagnosis. RESULTS: All 25 patients recruited underwent PET and successful AVS (100%). Final diagnosis was unilateral in 22 patients, bilateral in two and indeterminate in one due to discordant lateralization. Twenty patients with unilateral primary aldosteronism underwent surgery, with 100% complete biochemical success, and 75% complete/partial clinical success. For the primary outcome, sensitivity of PET was 80% [95% confidence interval (95% CI): 56.3-94.3] and AVS was 75% (95% CI: 50.9-91.3). For the secondary outcome, sensitivity and specificity of PET was 81.9% (95% CI: 59.7-94.8) and 100% (95% CI: 15.8-100), and AVS was 68.2% (95% CI: 45.1-86.1) and 100% (95% CI: 15.8-100), respectively. Twelve out of 20 (60%) patients had both PET and AVS lateralization, four (20%) PET-only, three (15%) AVS-only, while one patient did not lateralize on PET or AVS. Post-surgery outcomes did not differ between patients identified by either test. CONCLUSION: In our pilot study, 11C-Metomidate PET-CT performed comparably to AVS, and this should be validated in larger studies. PET identified patients with unilateral primary aldosteronism missed on AVS, and these tests could be used together to identify more patients with unilateral primary aldosteronism. VIDEO ABSTRACT: http://links.lww.com/HJH/B918.

Neovascular Age-Related Macular Degeneration (nAMD): A Review of Emerging Treatment Options.

Neovascular age-related macular degeneration (nAMD) is a common world-wide cause of visual loss. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are an effective means to treat nAMD and reduce its impact on vision compared to either sham treatment or photodynamic therapy. Currently, the approved anti-VEGF drugs include ranibizumab, aflibercept and brolucizumab. In addition, bevacizumab, used as an off-label drug, and has been shown to be effective in treating nAMD. While anti-VEGF agents are effective, its limitations include the requirement for frequent, often monthly injections, and the need for long-term treatment of nAMD. These present significant burdens on the healthcare system and on the patients. In addition, reviews of patients with nAMD treated with anti-VEGF have reported deterioration of vision over time with progression of geographic atrophy. These limitations are partly addressed by exploring different treatment regimens that reduce the frequency of treatments. Newer anti-VEGF drugs have been shown in Phase III clinical trials to have injection intervals as long as 12 or even 16 weeks for a proportion of patients. There is research on newer drugs that affect other pathways, such as the angiopoietin pathway, which may impact nAMD by extending the treatment interval and reducing the burden of treatment. Other measures include the use of sustained-release implants that release the drug regularly over a period of time, and can be refilled periodically, as well as hydrogel platforms that serve to release the drug. The use of biosimilars will also serve to reduce the cost of treatment for nAMD. A new frontier of gene therapy, primarily targeting genes involved in the transduction of retinal cells to produce anti-VEGF proteins intraocularly, also opens a new avenue of therapeutic approaches that can be used for treatment. This review paper will discuss both current treatment options and the newer treatments under development.

Multicentre, randomised clinical trial comparing intravitreal aflibercept monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) for the treatment of polypoidal choroidal vasculopathy.

PURPOSE: To compare the efficacy and safety of intravitreal aflibercept (IVA) monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) (IVA+RF-PDT) for the treatment of polypoidal choroidal vasculopathy (PCV). METHODS AND ANALYSIS: Multicentred, double-masked, randomised controlled trial to compare the two treatment modalities. The primary outcome of the study is to compare the 52-week visual outcome of IVA versus IVA+RF PDT. One hundred and sixty treatment-naïve patients with macular PCV confirmed on indocyanine green angiography will be recruited from three centres in Singapore. Eligible patients will be randomised (1:1 ratio) into one of the following groups: IVA monotherapy group-aflibercept monotherapy with sham photodynamic therapy (n=80); combination group-aflibercept with RF-PDT (n=80). Following baseline visit, all patients will be monitored at 4 weekly intervals during which disease activity will be assessed based on best-corrected visual acuity (BCVA), ophthalmic examination findings, optical coherence tomography (OCT) and angiography where indicated. Eyes that meet protocol-specified retreatment criteria will receive IVA and sham/RF-PDT according to their randomisation group. Primary endpoint will be assessed as change in BCVA at week 52 from baseline. Secondary endpoints will include anatomical changes based on OCT and dye angiography as well as safety assessment. Additionally, we will be collecting optical coherence tomography angiography data prospectively for exploratory analysis. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the ICH E6 guidelines of Good Clinical Practice and the applicable regulatory requirements. Approval from the SingHealth Centralised Institutional Review Board has been sought prior to commencement of the study. TRIAL REGISTRATION NUMBER: NCT03941587.

Assessment of the Macular Microvasculature in High Myopes With Swept Source Optical Coherence Tomographic Angiography.

Background: The risk of pathologic myopia (PM) increases with worsening myopia and may be related to retinal microvasculature alterations. To evaluate this, we analyzed the macular microvasculature of myopes with swept source-optical coherence tomographic angiography (SS-OCTA) in adolescent and young adult Singaporeans. Methods: This is a prevalent case-control study including 93 young Chinese from the Strabismus, Amblyopia and Refractive error in Singaporean children (STARS, N = 45) study and the Singapore Cohort Study of Risk Factors for Myopia (SCORM, N = 48) studies. Macular vessel density (VD) measurements were obtained from 3 × 3 mm SS-OCTA scans and independently assessed using ImageJ. These measurements were compared between individuals with non-high myopia [non-HM, N = 40; SE >-5.0 diopter (D)] and HM (SE ≤-5.0D, N = 53). Results: The mean macular VD was 40.9 ± 0.6% and 38.2 ± 0.5% in the non-HM and HM, groups, respectively (p = 0.01 adjusted for age and gender). Mean FAZ area in the superficial layer was 0.22 ± 0.02 mm2 in the HM group, which was smaller compared to non-HM group (0.32 ± 0.03 mm2, p = 0.04). Mean deep FAZ area was similar between the two groups (0.45 ± 0.03 mm2 and 0.48 ± 0.04 mm2 in the HM and non-HM groups, respectively, p = 0.70). Conclusions: VD was lower and superficial FAZ area was smaller, in adolescents and young adults with HM compared to non-HM. These findings require validation in prospective studies to assess their impact on the subsequent development of PM.

Comparison of Polypoidal Choroidal Vasculopathy Lesion Sizes Measured on Multicolor Imaging and Indocyanine Green Angiography.

Purpose: To evaluate the areas of lesion components of polypoidal choroidal vasculopathy (PCV) measured using multicolor imaging compared to indocyanine green angiography (ICGA). Methods: In a prospective study of 50 consecutive treatment-naïve PCV patients, multicolor imaging and ICGA were performed. The images were independently graded by reading center-certified retinal specialists to confirm the diagnosis of PCV and identify lesion components. The areas of the respective lesion components were compared. Results: The mean age of the participants was 67.8 years. PCV was diagnosed in 96% of eyes using multicolor imaging. The mean numbers of polypoidal lesions identified using ICGA and multicolor were 4.0 and 2.1, respectively (P < 0.001), with mean total polypoidal lesion areas of 0.32 mm2 versus 0.30 mm2 (P = 0.727). The area of the branching vascular network (BVN) on ICGA was 7.8 mm2 compared to 5.7 mm2 on multicolor imaging (P = 0.289). Patients with four or more polypoidal lesions on ICGA had larger differences in total lesion area between ICGA and multicolor imaging (4.07 vs. -0.70 mm2, p = 0.039). Those with total lesion area ≥ 2.0 mm2 on ICGA had larger differences in mean polypoidal lesion number compared to those with smaller areas (2.2 vs. 0.5; P = 0.026). Conclusions: Multicolor imaging is a useful, noninvasive adjunct for detecting PCV lesion components, revealing lesion areas similar to but generally smaller than those seen on ICGA. This is important to consider when making treatment decisions with different imaging modalities. Translational Relevance: New features seen on multicolor imaging can aid in the diagnosis and treatment of PCV.

Non-ICGA treatment criteria for Suboptimal Anti-VEGF Response for Polypoidal Choroidal Vasculopathy: APOIS PCV Workgroup Report 2.

PURPOSE: To develop and validate OCT and color fundus photography (CFP) criteria in differentiating polypoidal choroidal vasculopathy (PCV) from typical neovascular age-related macular degeneration (nAMD) in eyes with suboptimal response to anti-vascular endothelial growth factor (VEGF) monotherapy and to determine whether OCT alone can be used to guide photodynamic therapy (PDT) treatment. DESIGN: Clinical study evaluating diagnostic accuracy. PARTICIPANTS: Patients with nAMD who received 3-month anti-VEGF monotherapy but had persistent activity defined as subretinal fluid or intraretinal fluid at month 3 assessments. METHODS: In phase 1, international retina experts evaluated OCT and CFP of eyes with nAMD to identify the presence or absence of features due to PCV. The performance of individual and combinations of these features were compared with ICGA. In phase 2, these criteria were applied to an independent image set to assess generalizability. In a separate exercise, retinal experts drew proposed PDT treatment spots using only OCT and near-infrared (NIR) images in eyes with PCV and persistent activity. The location and size of proposed spot were compared with ICGA to determine the extent of coverage of polypoidal lesions (PLs) and branching neovascular network (BNN). MAIN OUTCOME MEASURES: Sensitivity and specificity of CFP and OCT criteria to differentiate PCV from nAMD and accuracy of coverage of OCT-guided PDT compared with ICGA. RESULTS: In eyes with persistent activity, the combination of 3 non-ICGA-based criteria (sharp-peaked pigment epithelial detachment [PED], subretinal pigment epithelium [RPE] ring-like lesion, and orange nodule) to detect PCV showed good agreement compared with ICGA, with an area under the receiver operating characteristic curve of 0.85. Validation using both an independent image set and assessors achieved an accuracy of 0.77. Compared with ICGA, the OCT-guided PDT treatment spot covered 100% of PL and 90% of the BNN. CONCLUSIONS: In nAMD eyes with persistent activity, OCT and CFP can differentiate PCV from typical nAMD, which may allow the option of adjunct PDT treatment. Furthermore, OCT alone can be used to plan adjunct PDT treatment without the need for ICGA, with consistent and complete coverage of PL.

Safety of Thoracentesis and Tube Thoracostomy in Patients With Uncorrected Coagulopathy: A Systematic Review and Meta-analysis.

BACKGROUND: Thoracentesis and tube thoracostomy are common procedures with bleeding risks, but existing guidelines may be overly conservative. We reviewed the evidence on the safety of thoracentesis and tube thoracostomy in patients with uncorrected coagulopathy. RESEARCH QUESTION: Is it safe to perform thoracentesis and tube thoracostomy in patients with uncorrected coagulopathy? STUDY DESIGN AND METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. PubMed and Embase were searched from inception through December 31, 2019. Included studies involved patients with uncorrected coagulopathy because of disease (eg, thrombocytopenia, liver cirrhosis, kidney failure) or drugs (eg, antiplatelets, anticoagulants). Relevant outcomes were major bleeding and mortality. RESULTS: Eighteen studies (5,134 procedures) were included. Using random-effects meta-analysis, the pooled major bleeding and mortality rate was 0 (95% CI, 0%-1%). No publication bias was found. Excluding six studies that were in abstract form, meta-analysis of the remaining 12 full articles showed that the pooled major bleeding and mortality rate also was 0 (95% CI, 0%-2%). Subgroup analysis performed for patients with uncorrected coagulopathy resulting from disease or drugs showed similar results. INTERPRETATION: Among patients with uncorrected coagulopathy who underwent thoracentesis or tube thoracostomy, major bleeding and mortality complications were uncommon. Our results suggest that in appropriately selected patients, thoracentesis or tube thoracostomy can be performed safely. TRIAL REGISTRY: PROSPERO; No.: CRD42020152226; URL: www.crd.york.ac.uk/prospero/.

RANIBIZUMAB WITH OR WITHOUT VERTEPORFIN PHOTODYNAMIC THERAPY FOR POLYPOIDAL CHOROIDAL VASCULOPATHY: Predictors of Visual and Anatomical Response in the EVEREST II Study.

PURPOSE: To evaluate the demographic and imaging factors at baseline and Month 3 (M3) that predict visual or anatomical responses at Month 12 (M12) in the EVEREST-II study for polypoidal choroidal vasculopathy. METHODS: Post-hoc analysis of 322 participants in the EVEREST-II study. Patient factors, best-corrected visual acuity (BCVA), treatment, and imaging parameters at baseline and M3 were evaluated with respect to outcomes at M12 using univariate and multivariable analysis. RESULTS: Younger age (P < 0.001) and lower baseline BCVA (P < 0.001) were associated with higher BCVA gains at M12. Smaller baseline polypoidal lesion area was associated with higher BCVA gains at M12 only in the ranibizumab monotherapy arm (P = 0.008). Central subfield thickness at M3, area of branching vascular network at M3, BCVA at M3, and age were associated with change in BCVA from M3 at M12. Higher odds of fluid-free retina at M12 were associated with lower baseline central subfield thickness (P = 0.006), treatment with combination therapy (baseline and M3 models; P < 0.001), and absence of subretinal fluid at M3 (P < 0.001). CONCLUSION: Several imaging parameters at baseline and M3 can predict treatment outcome. The interaction between treatment arm and total polypoidal lesion area suggests this feature may assist selecting between initial ranibizumab monotherapy or combination therapy.

Adolescent with facial swelling.

BackgroundA previously well 15-year-old girl presented with a 2-month history of facial swelling that progressively worsened to involve the neck. There was associated dyspnoea, orthopnoea, headache and throat discomfort. Two weeks before presentation, the patient had an episode of fever for 5 days. On examination, vital signs were within normal limits. Swelling, plethora and venous distension of the face and neck were apparent (figure 1).