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Permanent URI for this collectionhttps://hdl.handle.net/1807/100050

This collection contains a copy of open access articles published by U of T authors in Karger journals since March 2020. These copies are provided by the publisher as part of the transformative open access agreement between the University of Toronto and Karger Publishers.

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Efficacy and Safety of Intravitreal Faricimab in Neovascular Age-Related Macular Degeneration, Diabetic Macular Edema, and Retinal Vein Occlusion: A Meta-Analysis
(Karger, 2024-10-03) Nichani, Prem A H; Popovic, Marko M; Mihalache, Andrew; Pathak, Ananya; Muni, Rajeev H; Wong, David T W; Kertes, Peter J
Development of a Patient-Centered Pathway of Care for Retinoblastoma Patients: A Mixed-Methods Pilot Study
(S. Karger AG, 2024-07-17) Ristevski, Ivana; Flegg, Kaitlyn; Al-Hammadi, Mawj; Livingstone, Morgan; Dorna, Taline; Low, Leslie; Robert, Jill; Ulster, Alissa; Kletke, Stephanie; Mallipatna, Ashwin; Paton, Katherine; Dimaras, Helen
Treatments for Onychomycosis: A Bibliometric Analysis
(Karger, 2024-10) Gupta, Aditya K.; Taylor, Daniel; Polla Ravi, Shruthi; Wang, Tong; Talukder, Mesbah
Introduction: Oral antifungals were the earliest treatments to receive approval for the management of onychomycosis and have a long-standing record to support their efficacy. Topical antifungals and device-based treatments have been explored and some implemented in more recent years as alternatives to traditional oral antifungals. The present bibliometric analysis summarizes trends in publication frequency for onychomycosis treatment modalities over time and characterizes their body of literature in terms of types of studies available and relative level of evidence. Methods: A comprehensive literature search was performed using Web of Science and SCOPUS databases. Results: Covering all publications from 1970 to present day, our search identified oral therapeutics n = 295 articles (n = 63 randomized control trials [RCTs]), topical therapeutics n = 358 articles (n = 72 RCTs), and device-based treatments n = 158 articles (n = 37 RCTs). Spikes in research activity surround FDA approval of therapeutics for each treatment modality. Research activity within the last decade has focused on topical and device-based treatments. Evidence for efficacy of device-based treatments is lacking from relatively few high-quality RCTs. Conclusion: With growing concern for non-dermatophyte mold onychomycosis and terbinafine resistance, researchers should validate the efficacy and safety of device-based treatments with high-quality studies.
The Association between Retinal Thickness Fluctuations and Visual Outcomes under Anti-Vascular Endothelial Growth Factor Therapy: A Systematic Review and Meta-Analysis
(Karger, 2024-10) Pandya, Bhadra; Mihalache, Andrew; Hatamnejad, Amin; Grad, Justin; Popovic, Marko M; Wong, David T W
Introduction: The objective of this study was to examine the association between retinal thickness (RT) fluctuations and best corrected visual acuity (BCVA) in eyes with neovascular AMD, macular edema secondary to RVO, and DME treated with anti-VEGF therapy. Methods: A systematic search of Ovid MEDLINE, EMBASE, and the Cochrane Library was performed from January 2006 to March 2024. Studies comparing visual or anatomic outcomes of patients treated with anti-VEGF therapy, stratified by magnitudes of RT fluctuation, were included. ROBINS-I and Cochrane RoB 2 tools were used to assess risk of bias, and certainty of evidence was evaluated with GRADE criteria. Meta-analysis was performed with a random-effects model. Primary outcomes were final BCVA and change in BCVA relative to baseline. Results: 15,725 articles were screened; 15 studies were identified in the systematic review and 5 studies were included in the meta-analysis. Final ETDRS VA was significantly worse in eyes with the highest level of RT fluctuation (weighted mean difference [WMD] = 7.86 letters; 95% CI, 4.97, 10.74; p < 0.00001; I2 = 81%; 3,136 eyes). RT at last observation was significantly greater in eyes with high RT fluctuations (WMD = −27.35 μm; 95% CI, −0.04, 54.75; p = 0.05; I2 = 88%; 962 eyes). Conclusions: Final visual outcome is associated with magnitude of RT fluctuation over the course of therapy. It is unclear whether minimizing RT fluctuations would help optimize visual outcomes in patients treated with anti-VEGF therapy. These findings are limited by a small set of studies, risk of bias, and considerable heterogeneity.
Efficacy and Safety of Hydrocortisone, Ascorbic Acid, and Thiamine Combination Therapy for the Management of Sepsis and Septic Shock: A Systematic Review and Meta-Analysis of Randomised Controlled Trials
(Karger, 2024-10) Deng, Jiawen; Zuo, Qi Kang; Venugopal, Kaden; Hung, Jay; Zubair, Areeba; Blais, Sara; Porter, Victoria; Moskalyk, Myron; Heybati, Kiyan
Introduction: This systematic review aimed to assess the efficacy and safety of hydrocortisone, ascorbic acid, and thiamine (HAT) combination therapy in patients with sepsis and septic shock. Methods: We conducted a database search in MEDLINE, Embase, CENTRAL, Web of Science, and CNKI for randomised controlled trials (RCTs) comparing HAT against placebo/standard of care or against hydrocortisone in sepsis/septic shock patients. Outcomes included mortality, ICU/hospital length of stay (LOS), vasopressor durations, mechanical ventilation durations, change in SOFA at 72 h, and adverse events. RCT results were pooled in random-effects meta-analyses. Quality of evidence was assessed using GRADE. Results: Fifteen RCTs (N = 2,594) were included. At 72 h, HAT reduced SOFA scores from baseline (mean difference [MD] −1.16, 95% confidence interval [CI]: −1.58 to −0.74, I2 = 0%) compared to placebo/SoC, based on moderate quality of evidence. HAT also reduced the duration of vasopressor use (MD −18.80 h, 95% CI: −23.67 to −13.93, I2 = 64%) compared to placebo/SoC, based on moderate quality of evidence. HAT increased hospital LOS (MD 2.05 days, 95% CI: 0.15–3.95, I2 = 57%) compared to placebo/SoC, based on very low quality of evidence. HAT did not increase incidence of adverse events compared to placebo/SoC. Conclusions: HAT appears beneficial in reducing vasopressor use and improving organ function in sepsis/septic shock patients. However, its advantages over hydrocortisone alone remain unclear. Future research should use hydrocortisone comparators and distinguish between sepsis-specific and comorbidity- or care-withdrawal-related mortality.
Deep Brain Stimulation of the Globus Pallidus Internus in a Child with Refractory Dystonia due to L2-Hydroxyglutaric Aciduria
(Karger, 2024) Alamri, Abdullah; Breitbart, Sara; Warsi, Nebras; Rayco, Eriberto; Ibrahim, George; Fasano, Alfonso; Gorodetsky, Carolina
Introduction: L-2-hydroxyglutaric aciduria (L2HGA) is a rare neurometabolic disorder marked by progressive and debilitating psychomotor deficits. Here, we report the first patient with L2HGA-related refractory dystonia that was managed with deep brain stimulation to the bilateral globus pallidus internus (GPi-DBS). Case Presentation: We present a 17-year-old female with progressive decline in cognitive function, motor skills, and language ability which significantly impaired activities of daily living. Neurological exam revealed generalized dystonia, significant choreic movements in the upper extremities, slurred speech, bilateral dysmetria, and a wide-based gait. Brisk deep tendon reflexes, clonus, and bilateral Babinski signs were present. Urine 2-OH-glutaric acid level was significantly elevated. Brain MRI showed extensive supratentorial subcortical white matter signal abnormalities predominantly involving the U fibers and bilateral basal ganglia. Genetic testing identified a homozygous pathogenic mutation in the L-2-hydroxyglutarate dehydrogenase gene c. 164G>A (p. Gly55Asp). Following minimal response to pharmacotherapy, GPi-DBS was performed. Significant increases in mobility and decrease in dystonia were observed at 3 weeks, 6 months, and 12 months postoperatively. Conclusion: This is the first utilization of DBS as treatment for L2HGA-related dystonia. The resulting significant improvements indicate that pallidal neuromodulation may be a viable option for pharmaco-resistant cases, and possibly in other secondary metabolic dystonias.
Submacular and Intraretinal Fluid Associated with Arteritic Anterior Ischemic Optic Neuropathy
(Karger, 2024-06) Solish, Danielle; Micieli, Jonathan
Introduction: Anterior ischemic optic neuropathy (AION) is an ischemic disorder of the optic nerve and a common cause of acute, painless, permanent vision loss. It is divided into two types: arteritic AION (AAION) and non-arteritic anterior ischemic optic neuropathy (NAION). Although subretinal fluid associated with optic disc edema has been reported in cases of NAION, it is rarely described in AAION. Case Presentation: An 86-year-old female with a history of polymyalgia rheumatica presented with sudden vision loss in the left eye. Initial examination revealed left pallid optic disc edema with peripapillary hemorrhages. Optical coherence tomography (OCT) of the left macula showed intraretinal and submacular fluid. The patient was started on 50 mg of oral prednisone daily. The diagnosis of giant cell arteritis (GCA) was later confirmed with a positive temporal artery biopsy. Three weeks after presentation, an OCT was completed which demonstrated complete resolution of the intraretinal and submacular fluid. Although the presence of both intraretinal and subretinal fluid has been previously documented in cases of NAION, it is rarely reported in a patient with GCA. Conclusion: This is a newly described case of subretinal and intraretinal fluid in a patient with AAION. We postulate that the pathophysiology behind this is mediated by associated choroidal ischemia leading to altered permeability. OCT is an important imaging modality allowing for signs of GCA to be better characterized.
From Hair Loss to Vision Loss: Minoxidil-Associated CRVO in a Young Female
(Karger, 2024-03) Pickel, Lauren; Ji, Patrick Xiang; Abdelazim, Amr; Sivachandran, Nirojini
Introduction: Central retinal vein occlusion (CRVO) is a common retinal vascular disorder that is most often seen in older adults and individuals with vascular risk factors. Case Presentation: We report a case of CRVO with cystoid macular edema (CME) in a young, otherwise healthy patient taking minoxidil for hair loss. The patient had no known vascular risk factors, and a comprehensive coagulability workup was negative. The CRVO with CME resolved without intervention upon cessation of minoxidil. Conclusion: Possible mechanisms for minoxidil-associated retinal vascular disorders are explored. Thorough medication histories and the consideration of possible adverse drug events in patients without traditional risk factors are recommended.
The Relationship between Neurobiological Function and Inflammation in Depressed Children and Adolescents: A Scoping Review
(Karger, 2024-06) Schumacher, Anett; Muha, Jessica; Campisi, Susan C; Bradley-Ridout, Glyneva; Lee, Andy C H; Korczak, Daphne J
Introduction: Neurobiological dysfunction is associated with depression in children and adolescents. While research in adult depression suggests that inflammation may underlie the association between depression and brain alterations, it is unclear if altered levels of inflammatory markers provoke neurobiological dysfunction in early-onset depression. The aim of this scoping review was to provide an overview of existing literature investigating the potential interaction between neurobiological function and inflammation in depressed children and adolescents. Methods: Systematic searches were conducted in six databases. Primary research studies that included measures of both neurobiological functioning and inflammation among children (≤18 years) with a diagnosis of depression were included. Results: Four studies (240 participants; mean age 16.0 ± 0.6 years, 62% female) meeting inclusion criteria were identified. Studies primarily examined the inflammatory markers interleukin 6, tumor necrosis factor alpha, C-reactive protein, and interleukin 1 beta. Exploratory whole brain imaging and analysis as well as region of interest approaches focused on the anterior cingulate cortex, basal ganglia, and white matter tracts were conducted. Most studies found correlations between neurobiological function and inflammatory markers; however, depressive symptoms were not observed to moderate these effects. Conclusions: A small number of highly heterogeneous studies indicate that depression may not modulate the association between altered inflammation and neurobiological dysfunction in children and adolescents. Replication in larger samples using consistent methodological approaches (focus on specific inflammatory markers, examine certain brain areas) is needed to advance the knowledge of potential neuro-immune interactions early in the course of depression.
Social Media Misinformation about Pregnancy and COVID-19 Vaccines: A Systematic Review
(Karger, 2024-06) Malik, Mahnoor; Bauer-Maison, Natasha; Guarna, Giuliana; D'Souza, Rohan D
Objective: The objectives of this study were to identify common social media misconceptions about COVID-19 vaccination in pregnancy, explain the spread of misinformation, and identify solutions to guide clinical practice and policy. Methodology: A systematic review was conducted and the databases Embase and Medline were searched from December 2019 to February 8, 2023, using terms related to social media, pregnancy, COVID-19 vaccines and misinformation. The inclusion criteria were original research studies that discussed misinformation about COVID-19 vaccination during pregnancy on social media. The exclusion criteria were review articles, no full text, and not published in English. Two independent reviewers conducted screening, extraction, and quality assessment. Results: Our search identified 76 articles, of which 3 fulfilled eligibility criteria. Included studies were of moderate and high quality. The social media platforms investigated included Facebook, Google Searches, Instagram, Reddit, TikTok, and Twitter. Misinformation was related to concerns regarding vaccine safety, and its association with infertility. Misinformation was increased due to lack of content monitoring on social media, exclusion of pregnant women from early vaccine trials, lack of information from reputable health sources on social media, and others. Suggested solutions were directed at pregnancy care providers (PCPs) and public health/government. Suggestions included: (i) integrating COVID-19 vaccination information into antenatal care, (ii) PCPs and public health should increase their social media presence to disseminate information, (iii) address population-specific vaccine concerns in a culturally relevant manner, and others. Conclusion: Increased availability of information from reputable health sources through multiple channels could increase COVID-19 vaccine uptake in the pregnant population and help combat misinformation.
Optimizing Post-Acute Coronary Syndrome Dyslipidemia Management: Insights from the North American Acute Coronary Syndrome Reflective III
(Karger, 2024-06) Alanezi, Meshal; Yan, Andrew T; Tan, Mary K; Bourgeois, Ronald; Malek-Marzban, Peiman; Beharry, Rani; Alkurtass, Suhaib; Gyenes, Gabor T; Nadeau, Pierre-Louis; Nwadiaro, Nduka; Jedrzkiewicz, Sean; Gao, Dongsheng; Chandna, Harish; Nelson, William B; Goodman, Shaun G
Introduction: Despite contemporary practice guidelines, a substantial number of post-acute coronary syndrome (ACS) patients fail to achieve guideline-recommended LDL-C thresholds. Our study aimed to investigate this guideline recommendations-to-practice care gap. Specifically, we aimed to identify opportunities where additional lipid-lowering therapies are indicated and explore reasons for the non-prescription of guideline-recommended therapies. Methods: ACS patients with LDL-C ≥1.81 mmol/L (70 mg/dL) despite maximally tolerated statin ± ezetimibe therapy (including those intolerant of ≥2 statins) were enrolled 1–12 months post-event from 27 Canadian and US sites from September 2018 to October 2020 and followed up for three visits during the 12 months post-event. We determined the proportion of patients who did not achieve Canadian/US guideline-recommended LDL-C thresholds, the number of patients who would have been eligible for additional lipid-lowering therapies, and reasons behind lack of escalation in lipid-lowering therapies when indicated. Individual patient and aggregate practice feedback, including guideline-recommended intensification suggestions, were provided to each physician. Results: Of the 248 patients enrolled in the pilot study (median age 64 [57, 73] years, 31.5% female and STEMI 27.4%), 75.4% were on high-intensity statins on the first visit. A total of 18.5% of those who attended all 3 visits had an LDL-C measured only at the first visit which was above the threshold. After 1 year of follow-up, 51.9% of patients achieved LDL-C thresholds at either visit 2 or 3. In the context of feedback reminding physicians about guideline-directed LDL-C-modifying therapy in their individual participating patients, we observed an increase in the use of ezetimibe and PCSK9 inhibitor therapy at 3–12 months. This was associated with a significant lowering of the mean LDL-C (from 2.93 mmol/L [baseline] to 2.09 mmol/L [3–6 months] to 1.87 mmol/L [6–12 months]) and a significantly greater proportion of patients (from 0% [baseline] to 38.6% [3–6 months] to 53.4% [6–12 months]) achieving guideline-recommended LDL-C thresholds. The most prevalent reasons behind the non-intensification of LDL-C-lowering therapy with ezetimibe and/or PCSK9i were LDL-C levels being close to target, the pre-existing use of other lipid-lowering therapies, patient refusal, and cost. Conclusion: Although most patients post-ACS were on high-intensity statin therapy, almost 50% failed to achieve guideline-recommended LDL-C thresholds by 1-year follow-up. Furthermore, additional lipid-lowering therapies in this high-risk group were underprescribed, and this might be linked to several factors including potential gaps in physician knowledge, treatment inertia, patient refusal, and cost.
Bacterial Skin Dysbiosis in Darier Disease
(Karger, 2024-06) Reiter, Ofer; Leshem, Avner; Alexander-Shani, Rivka; Brandwein, Michael; Cohen, Yotam; Yeshurun, Algit; Ziv, Michael; Elinav, Eran; Hodak, Emmilia; Dodiuk-Gad, Roni P
Introduction: Darier disease is a rare inherited disease with dominant skin manifestations including keratotic papules and plaques on sebaceous and flexural areas. Secondary infection of skin lesions is common, and Staphylococcus aureus commonly colonizes these lesions. The aim of the study was to characterize the bacterial microbiome of cutaneous Darier lesions compared to normal-looking skin and disease severity. Methods: All patients with a history of Darier followed up at Emek Medical Center were invited to participate in the study. Patients that did not use antibiotics in the past month and signed informed consent had four skin sites sampled with swabs: scalp, chest, axilla, and palm. All samples were analyzed for bacterial microbiome using 16S rDNA sequencing. Results: Two hundred and eighty microbiome samples obtained from lesional and non-lesional skin of the scalp, chest, axilla, and palm of 42 Darier patients were included in the analysis. The most abundant bacterial genera across all skin sites were Propionibacterium, Corynebacterium, Paracoccus, Micrococcus, and Anaerococcus. Scalp and chest lesions featured a distinct microbiome configuration that was mainly driven by an overabundance of Staphylococci species. Patients with more severe disease exhibited microbiome alterations in the chest, axilla, and palm compared with patients with only mild disease, driven by Peptoniphilus and Moryella genera in scalp and palmar lesions, respectively. Conclusion:Staphylococci were significantly associated with Darier lesions and drove Darier-associated dysbiosis. Severity of the disease was associated with two other bacterial genera. Whether these associations also hold a causative role and may serve as a therapeutic target remains to be determined and requires further investigation.
Public Opinions and Attitudes toward Noninvasive Prenatal Testing on Reddit: Content and Sentiment Analysis
(Karger, 2024-02) Xiao, Bowen; Yan, Joyce; Hayeems, Robin Z
Introduction: Noninvasive prenatal testing (NIPT) can be used to detect fetal chromosomal abnormalities early in pregnancy. As eligibility criteria broaden and screening targets expand, gauging public acceptability of NIPT becomes increasingly important. Leveraging social media as a rich source of public discourse, the purpose of this study was to understand public opinions and attitudes toward NIPT on the social media platform Reddit. Methods: We applied content and natural language processing techniques (i.e., sentiment analysis) to textual data collected from 4 Reddit communities focusing on the NIPT content posted from September 2012 to September 2022 (367 posts and 7,822 comments in total). Results: Content analysis findings indicated that social media users consider NIPT to be worthwhile. Reasons NIPT was perceived to be not worthwhile related to unwanted anxiety, and the fact that NIPT results would not change anything about their approach to pregnancy were also expressed. The sentiment analysis identified more positive than negative emotions; the mean sentiment scores ranged from 0.48 to 1.22, depending on the specific Lexicon used. Specific emotions (i.e., trust, fear) were also identified. Conclusion: Our novel approach to understanding public perception and attitudes toward NIPT yielded results that are consistent with conventional patient-oriented research methods. These findings may not only contribute to ongoing improvements in prenatal patient care, research, and policy but also indicate that sentiment analysis applied to social media data can serve as a suitable means to assess public acceptability of NIPT, particularly as public dialogue on this topic increases over time.
QTc Interval Prolongation Is Independently Associated with FGF23 and Predicts Mortality in Predialysis Chronic Kidney Disease
(Karger, 2024) Sikaneta, Tabo; Ho, Natalie; Bellasi, Antonio; Mahdavi, Sara; Taskapan, Hulya; Svendrovski, Anton; Makanjee, Bhavanesh; Roberts, Jason; Wu, George; Nathoo, Bharat; Tam, Paul
Introduction: QTc interval prolongation is increasingly frequent as chronic kidney disease (CKD) advances and predicts death in dialysis. However, predictors and mortality risk in predialysis CKD are understudied. FGF23 induces left ventricular hypertrophy (LVH) which is associated with QTc interval prolongation and death, suggesting a possible pathway from FGF23 to death that entails LVH and QTc prolongation. We looked for links between FGF23 and prolonged QTc intervals mediated by LVH and for deaths associated with QTc prolongation in a prospective observational cohort of patients with predialysis CKD. Methods: Participants underwent protocolized baseline and semiannual FGF23 testing, baseline and study end echocardiograms, and baseline and annual electrocardiograms over 3 years. Results: A total of 2,254 participants (34.1% female; mean age: 68.7 years; mean glomerular filtration: rate 41.4 mL/min/m2) enrolled in the study. Baseline LVH (left ventricular mass index >131 g/m2 [>100 g/m2 if female]) was present in 10.8% and prolonged QTc intervals (≥500 ms) in 1.5% of participants. One hundred thirty-eight (6.1%) participants died during the study. In generalized mixed-effects regression, each unit increase in the natural log of FGF23 – but not LVH – predicted an odds ratio of 1.76 (1.15, 2.70, p = 0.009) for prolonged QTc intervals independently of 15 other covariates. Mediation analysis showed that only 13% of FGF23’s total effect on prolonged QTc intervals was mediated by LVH. Patients with prolonged QTc intervals had higher unadjusted (log rank p < 0.001) and adjusted (hazard ratio: 2.06 [1.08, 3.92, p = 0.028]) mortality rates than those with QTc intervals <500 ms. Discussion: QTc interval prolongation ≥500 ms was prospectively associated with FGF23 independently of LVH and with increased mortality risk in patients with predialysis CKD.
Cannabis-Induced Gastrointestinal Tract Symptoms in the Adult Population: A Systematic Review
(Karger, 2024) Senderovich, Helen; Meaney, Christopher; Vashishtha, Srishti
Cannabinoid usage is widespread in the self-management of various medical ailments. However, adverse effects have been reported with use, especially pertaining to the gastrointestinal system in adults and aged patients. These range from nausea, vomiting, bloating, or abdominal pain. This systematic review of previously reported cannabis-induced gastrointestinal symptoms in the adult population from the literature provides an analysis of relevant data to enhance knowledge and awareness of this topic.
Anti-Inflammatory Effects of Japanese Herbal Medicine Hochuekkito in a Mouse Model of Acute Exacerbation of Chronic Obstructive Pulmonary Disease
(Karger, 2024-04) Fukuda, Kensuke; Matsuzaki, Hirotaka; Hiraishi, Yoshihisa; Miyashita, Naoya; Ishii, Takashi; Yuki, Masaaki; Isago, Hideaki; Tamiya, Hiroyuki; Mitani, Akihisa; Saito, Akira; Jo, Taisuke; Nagase, Takahide
Introduction: The traditional Japanese herbal medicine hochuekkito (TJ-41) has been reported to ameliorate systemic inflammation and malnutrition in patients with chronic obstructive pulmonary disease (COPD). TJ-41 has also been known to have preventive effects against influenza virus infection. However, its role in the acute exacerbation of COPD (AECOPD) remains to be elucidated. Our previous study established a murine model of viral infection-associated AECOPD that was induced by intratracheal administration of porcine pancreatic elastase (PPE) and polyinosinic-polycytidylic acid [poly(I:C)]. Here, we used this model and investigated the effects of TJ-41 in AECOPD. Methods: Specific pathogen-free C57BL/6J mice were used. A COPD model was induced by treating mice intratracheally with PPE on day 0. To generate the murine model of AECOPD, poly(I:C) was administered intratracheally following PPE treatment on days 22–24. Mice were sacrificed and analyzed on day 25. Mice were fed a diet containing 2% TJ-41 or a control diet. Results: Daily oral intake of TJ-41 significantly decreased the numbers of neutrophils and lymphocytes in the bronchoalveolar lavage fluid (BALF), which was accompanied by decreased transcripts of CXC chemokines involved in neutrophil migration, viz., Cxcl1 and Cxcl2, in whole lung homogenates and reduced Cxcl2 concentration in BALF. Conclusion: This study demonstrates the anti-inflammatory effects of TJ-41 in a mouse model of AECOPD, suggesting the effectiveness of TJ-41 for the management of COPD. Clinical investigations evaluating the therapeutic efficacy of TJ-41 in AECOPD would be meaningful.
Virtual Pharmacy: An Integrated Collaborative Redesign Targeting Medication-Related Problems in Patients with Chronic Kidney Disease
(Karger, 2024) Ong, Stephanie W; Kitchlu, Abhijat; Cherney, David Z I; Leung, Karen; Chan, Christopher T M
Introduction: Collaborative management of kidney disease relies on coordinated and effective partnerships between multiple providers. Siloed traditional health systems often result in delays, barriers to treatment access, and inefficient monitoring. Methods: We conducted a 1-year observational mixed-methods study. We included all consecutive referrals except for patients without telephone access. We assessed 4 domains of outcomes: (1) patient and caregiver experience, (2) provider experience (e.g., physicians and pharmacists), (3) clinical outcomes specific to medication-related outcomes (e.g., adherence, adverse drug events [ADEs]), and (4) value and efficiency (i.e., medication access, defined as time to treatment and resolution of medication reimbursement issues). Results: Sixty-five patients were referred to the integrated virtual pharmacy (iVRx) model. Most (72%) patients were male. Patients had a median (min, max) age of 60 (27, 85) years and were taking 8 (4, 13) medications. Compared with traditional care delivery models, medication access improved for 56% of participants. Direct home delivery of medication resulted in 91% of patients receiving prescriptions within 2 days of a nephrologist visit. During more than 2,000 pharmacist-patient encounters, 208 ADEs were identified that required clinician intervention to prevent patient harm. When these ADEs were classified by severity, 53% were mild, 45% were moderate (e.g., delaying dose titration in patients initiated on glucagonlike peptide 1 (GLP-1) agonists due to intolerable gastrointestinal side effects), and the remaining 2% of ADEs were severe, meaning clinical intervention was required to prevent a serious outcome (e.g., uncontrolled blood pressure, prevention of acute kidney injury). Nephrologists reported high satisfaction with iVRx, citing efficiency, timely response, and collaboration with pharmacists as key facilitators. Of the 65 patient participants, 98% reported being extremely satisfied. Conclusions: The iVRx is an acceptable and feasible clinical strategy. Our pilot program was associated with improved kidney care by increasing medication access for patients and avoiding potential harms associated with ADEs.
Neuropsychological Assessments of Cognitive Impairment in Major Depressive Disorder: A Systematic Review and Meta-Analysis with Meta-Regression
(Karger, 2024-01) Rhee, Taeho Greg; Shim, Sung Ryul; Manning, Kevin J; Tennen, Howard A; Kaster, Tyler S; d'Andrea, Giacomo; Forester, Brent P; Nierenberg, Andrew A; McIntyre, Roger S; Steffens, David C
Cognitive dysfunction or deficits are common in patients with major depressive disorder (MDD). The current study systematically reviews and meta-analyzes multiple domains of cognitive impairment in patients with MDD.
Pars Plana Vitrectomy with or without Internal Limiting Membrane Peel for Epiretinal Membrane: A Systematic Review and Meta-Analysis
(Karger, 2024-02) Mihalache, Andrew; Huang, Ryan S; Ahmed, Haleema; Patil, Nikhil S; Popovic, Marko M; Kertes, Peter J; Muni, Rajeev H
Background: The safety and effectiveness of pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling remains poorly understood for the treatment of epiretinal membrane (ERM). Objectives: Our study aims to compare the safety and effectiveness of PPV with and without ILM peeling for ERM. Methods: A systematic literature search was conducted on Ovid MEDLINE, Embase, Cochrane Library, and Google Scholar from January 2000 to January 2023 for comparative studies reporting visual and anatomical outcomes for patients with ERM that received PPV with or without ILM peeling. Primary outcomes included best-corrected visual acuity (BCVA) at last study observation and change in BCVA from baseline. Secondary outcomes included retinal thickness (RT) at last study observation, change in RT from baseline, risk of ERM recurrence, and adverse events. A random-effects meta-analysis was performed. Risk of bias of randomized controlled trials was assessed using the Risk of Bias 2 tool of observational studies using the Risk of Bias in Non-randomized Studies of Interventions-I tool. The certainty of evidence of outcomes was evaluated using Grading of Recommendations, Assessment, Development and Evaluation criteria. Results: Nineteen studies reporting on 1,291 eyes at baseline were included. PPV with and without ILM peel achieved a similar BCVA at last study observation (p = 0.68) and change in BCVA from baseline (p = 0.79). These findings remained consistent irrespective of whether simultaneous phacoemulsification was performed. PPV with ILM peel achieved a significantly lower incidence of ERM recurrence (risk ratio [RR] = 0.26, 95% CI = [0.13, 0.51], p < 0.0001) and additional surgery (RR = 0.17, 95% CI = [0.04, 0.74], p = 0.02) compared to PPV without ILM peel. Conclusion: PPV with and without ILM peel achieved a similar BCVA at last study observation in ERM patients. Patients treated with PPV and ILM peel also had a reduced risk of ERM recurrence and lower reoperation risk. These conclusions are associated with a moderate certainty of evidence and potential for bias from multiple non-randomized studies.
Intravitreal Triamcinolone Acetonide for Diabetic Macular Edema and Macular Edema Secondary to Retinal Vein Occlusion: A Meta-Analysis
(Karger, 2024-02) Mihalache, Andrew; Hatamnejad, Amin; Patil, Nikhil S; Popovic, Marko M; Kertes, Peter J; Cruz-Pimentel, Miguel; Muni, Rajeev H
Background: The comparative safety and efficacy of different doses of intravitreal triamcinolone acetonide (IVTA) for diabetic macular edema (DME) and macular edema (ME) secondary to retinal vein occlusion (RVO) is unclear. Objectives: This meta-analysis aimed to compare the safety and efficacy of different doses of IVTA in this setting. Methods: A systematic literature search for randomized clinical trials (RCTs) was conducted on Cochrane Library, Ovid MEDLINE, and EMBASE from January 2005 to May 2022. Studies that reported on patients with DME or ME secondary to RVO that received treatment with different doses of IVTA were included. A random-effects meta-analysis was performed. Cochrane’s Risk of Bias Tool 2 was used to assess the risk of bias, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines were used to assess certainty of evidence. Results: Five RCTs reporting on 1,041 eyes at baseline were included in this meta-analysis. In eyes with ME secondary to RVO, high-dose (4 mg) IVTA achieved a significantly better change in best-corrected visual acuity (WMD = −4.75 ETDRS letters, 95% CI = [−7.73, −1.78], p = 0.002) and reduction in retinal thickness (WMD = −93.02 μm, 95% CI = [−153.23, −32.82], p = 0.002) at months 4–6 compared to low-dose (1–2 mg) IVTA. However, high-dose IVTA had a higher risk of intraocular pressure-related adverse events (RR = 2.99, 95% CI = [1.05, 8.50], p = 0.04) and cataract surgery (RR = 5.67, 95% CI = [3.09, 10.41], p < 0.00001) than low-dose IVTA in eyes with ME secondary to RVO. These efficacy and safety differences in high-dose and low-dose IVTA were not observed in DME eyes. Conclusions: The RCT evidence in this setting is limited. High-dose IVTA achieved greater improvements in visual acuity and reductions in retinal thickness than low-dose IVTA at months 4–6. However, high-dose IVTA had a less favorable safety profile than low-dose IVTA. The significance of these outcomes was based on patients with ME secondary to RVO, but not DME.

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