Diagnostic accuracy of community optometrists for age-related macular degeneration using colour fundus photographs: A pilot evaluation.

PURPOSE: The accurate diagnosis of age-related macular degeneration (AMD) represents an important step in delaying and preventing vision loss and achieving optimal patient care. Therefore, this pilot study aimed to estimate the diagnostic accuracy of community optometrists for identifying AMD using colour fundus photographs (CFPs) to support sample size calculations for subsequent definitive studies. METHODS: Five practising community optometrists were invited to classify a total of 1023 CFPs for the (1) presence of AMD, and, if applicable, (2) stage of AMD (early/intermediate/late geographic atrophy/late neovascular AMD). Diagnosis by referral centre clinicians formed the reference standard. Diagnostic accuracy was assessed by the area under the receiver operating characteristic curve (aROC). Sensitivity, specificity, positive and negative predictive values were also calculated. RESULTS: Of the 1023 CFPs included in the study, 226 images were of AMD and 797 images were of other ocular conditions or no abnormal findings. Participating community optometrists had a mean (SD) age of 30.2 (8.9) years, 60.0% (3/5) were female and the mean number of years practising in primary eye care was 5.4 (5.4) years. Community optometrists demonstrated excellent performance for diagnosing AMD, with an aROC of 0.86 (95% CI 0.83 to 0.89), sensitivity of 84.5% (95% CI 79.1 to 89.0) and specificity of 88.0% (95% CI 85.5 to 90.1). The aROC (95% CI) for diagnosing early, intermediate, late geographic atrophy and late neovascular AMD was 0.82 (0.73 to 0.91), 0.76 (0.72 to 0.81), 0.69 (0.49 to 0.90) and 0.55 (0.34 to 0.75), respectively. CONCLUSIONS: These results justify the need for an appropriately powered definitive study to assess community clinicians' diagnostic accuracy for AMD.

Optometrists' attitudes toward using OCT angiography lag behind other retinal imaging types.

PURPOSE: While optometrists' attitudes toward established retinal imaging types are generally positive, they are unknown for optical coherence tomography angiography (OCTA). We performed a cross-sectional survey to estimate attitudes toward OCTA and identify clinician and/or practice characteristics that influence them. METHODS: A paper-based survey was mailed to 252 randomly selected optometrists in Australia. Five-point Likert-scale items from a previous survey assessing attitudes toward new technology were included to probe respondent characteristics and attitudes toward retinal imaging. Performance expectancy attitudes toward OCTA were elicited by the statement 'I believe OCTA is useful in daily practice'. Mean scores out of five (mean [SD]) were rounded and mapped to appropriate descriptive statements. RESULTS: The response rate was 47% (118/252). The mean (SD) age of respondents was 44.0 (13.8) years and 50.8% (60/118) were female. Optometrists had 19.9 (14.0) years of clinical experience and 66.9% (79/118) worked at independent practices. In total, 8.5% (10/118) of respondents used OCTA to provide clinical care. Optometrists agreed that optical coherence tomography (OCT), colour fundus imaging, ultra-wide field imaging and fundus autofluorescence (mean scores 3.6-4.7 out of 5) were useful in daily practice but felt neutral about whether OCTA was useful (3.4 [0.8]). Optometrists believed that OCTA was less enjoyable to use (p < 0.0001), less endorsed by peers (p < 0.0001) and felt less confident that they had the knowledge to interpret OCTA (p < 0.0001) compared to other retinal imaging types. CONCLUSIONS: Optometrists are undecided on whether OCTA is useful in daily practice and had lower expectations that using OCTA would confer job performance benefits compared to other retinal imaging types. Further work is needed to advocate the benefits of using OCTA across the profession.

Drusen-aware model for age-related macular degeneration recognition.

INTRODUCTION: The purpose of this study was to build an automated age-related macular degeneration (AMD) colour fundus photography (CFP) recognition method that incorporates confounders (other ocular diseases) and normal age-related changes by using drusen masks for spatial feature supervision. METHODS: A range of clinical sources were used to acquire 7588 CFPs. Contrast limited adaptive histogram equalisation was used for pre-processing. ResNet50 was used as the backbone network, and a spatial attention block was added to integrate prior knowledge of drusen features into the backbone. The evaluation metrics used were sensitivity, specificity and F1 score, which is the harmonic mean of precision and recall (sensitivity) and area under the receiver-operating characteristic (AUC). Fivefold cross-validation was performed, and the results compared with four other methods. RESULTS: Excellent discrimination results were obtained with the algorithm. On the public dataset (n = 6565), the proposed method achieved a mean (SD) sensitivity of 0.54 (0.09), specificity of 0.99 (0.00), F1 score of 0.62 (0.06) and AUC of 0.92 (0.02). On the private dataset (n = 1023), the proposed method achieved a sensitivity of 0.92 (0.02), specificity of 0.98 (0.01), F1 score of 0.92 (0.01) and AUC of 0.98 (0.01). CONCLUSION: The proposed drusen-aware model outperformed baseline and other vessel feature-based methods in F1 and AUC on the AMD/normal CFP classification task and achieved comparable results on datasets that included other diseases that often confound classification. The method also improved results when a five-category grading protocol was used, thereby reflecting discriminative ability of the algorithm within a real-life clinical setting.

Attitudes of optometrists towards artificial intelligence for the diagnosis of retinal disease: A cross-sectional mail-out survey.

PURPOSE: Artificial intelligence (AI)-based systems have demonstrated great potential in improving the diagnostic accuracy of retinal disease but are yet to achieve widespread acceptance in routine clinical practice. Clinician attitudes are known to influence implementation. Therefore, this study aimed to identify optometrists' attitudes towards the use of AI to assist in diagnosing retinal disease. METHODS: A paper-based survey was designed to assess general attitudes towards AI in diagnosing retinal disease and motivators/barriers for future use. Two clinical scenarios for using AI were evaluated: (1) at the point of care to obtain a diagnostic recommendation, versus (2) after the consultation to provide a second opinion. Relationships between participant characteristics and attitudes towards AI were explored. The survey was mailed to 252 randomly selected practising optometrists across Australia, with repeat mail-outs to non-respondents. RESULTS: The response rate was 53% (133/252). Respondents' mean (SD) age was 42.7 (13.3) years, and 44.4% (59/133) identified as female, whilst 1.5% (2/133) identified as gender diverse. The mean number of years practising in primary eye care was 18.8 (13.2) years with 64.7% (86/133) working in an independently owned practice. On average, responding optometrists reported positive attitudes (mean score 4.0 out of 5, SD 0.8) towards using AI as a tool to aid the diagnosis of retinal disease, and would be more likely to use AI if it is proven to increase patient access to healthcare (mean score 4.4 out of 5, SD 0.6). Furthermore, optometrists expressed a statistically significant preference for using AI after the consultation to provide a second opinion rather than during the consultation, at the point-of-care (+0.12, p = 0.01). CONCLUSIONS: Optometrists have positive attitudes towards the future use of AI as an aid to diagnose retinal disease. Understanding clinician attitudes and preferences for using AI may help maximise its clinical potential and ensure its successful translation into practice.

Toxicity evaluation of prolonged convection-enhanced delivery of small-molecule kinase inhibitors in naïve rat brainstem.

PURPOSE: Convection-enhanced delivery (CED), a local drug delivery technique, is typically performed as a single session and drug concentrations therefore decline quickly post CED. Prolonged CED (pCED) overcomes this problem by performing a long-term infusion to maintain effective drug concentrations for an extended period. The purpose of the current study was to assess the toxicity of using pCED to deliver single and multi-drug therapy in naïve rat brainstem. METHODS: Sixteen rats underwent pCED of three small-molecule kinase inhibitors in the pons. Single and multi-drug combinations were delivered continuously for 7 days using ALZET mini-osmotic pumps (model 2001, rate of 1 µl/h). Rats were monitored daily for neurological signs of toxicity. Rats were sacrificed 10 days post completion of infusion, and appropriate tissue sections were analyzed for histological signs of toxicity. RESULTS: Two rats exhibited signs of neurological deficits, which corresponded with diffuse inflammation, necrosis, and parenchymal damage on histological analysis. The remaining rats showed no neurological or histological signs of toxicity. CONCLUSION: The neurological deficits in the two rats were likely due to injury from physical force, such as cannula movement post insertion and subsequent encephalitis. The remaining rats showed no toxicity and therefore brainstem targeting using pCED to infuse single and multi-drug therapy was well tolerated in these rats.

Toxicity evaluation of convection-enhanced delivery of small-molecule kinase inhibitors in naïve mouse brainstem.

PURPOSE: Diffuse intrinsic pontine gliomas (DIPGs) are inoperable and lethal high-grade gliomas lacking definitive therapy. Platelet-derived growth factor receptor (PDGFR) and its downstream signaling molecules are the most commonly overexpressed oncogenes in DIPG. This study tested the effective concentration of PDGFR pathway inhibitors in cell culture and then toxicity of these small-molecule kinase inhibitors delivered to the mouse brainstem via convection-enhanced delivery (CED) for potential clinical application. METHODS: Effective concentrations of small-molecule kinase inhibitors were first established in cell culture from a mouse brainstem glioma model. Sixteen mice underwent CED, a local drug delivery technique, of saline or of single and multidrug combinations of dasatinib (2 M), everolimus (20 M), and perifosine (0.63 mM) in the pons. Animals were kept alive for 3 days following the completion of infusion. RESULTS: No animals displayed any immediate or delayed neurological deficits postoperatively. Histological analysis revealed edema, microgliosis, acute inflammation, and/or axonal injury in the experimental animals consistent with mild acute drug toxicity. CONCLUSIONS: Brainstem CED of small-molecule kinase inhibitors in the mouse did not cause serious acute toxicities. Future studies will be necessary to evaluate longer-term safety to prepare for potential clinical application.

Diagnostic accuracy of OCTA and OCT for myopic choroidal neovascularisation: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: The purpose of this project was to systematically review and meta-analyse studies assessing the diagnostic accuracy of optical coherence tomography angiography (OCTA) and optical coherence tomography (OCT) for myopic choroidal neovascularisation (mCNV). Fluorescein angiography (FA) was accepted as the reference standard. METHODS: PUBMED and EMBASE were searched from inception to March 2021 for studies evaluating the test accuracy of OCTA and/or OCT for diagnosing mCNV. The Preferred Reporting Items for Systematic Reviews and Meta-analyses of Diagnostic Test Accuracy Studies guideline was followed, and the Grading of Recommendations, Assessment, Development and Evaluation approach was used to frame clinical recommendations. Pooled estimates of test accuracy were obtained using a bivariate model. RESULTS: Of 410 studies assessed for eligibility, 3 studies were identified that compared OCTA to FA and 3 studies were identified that compared spectral domain (SD) OCT to FA. All studies had at least one major methodological flaw leading to an overall high risk of bias. On meta-analysis, the pooled sensitivity of OCTA was 0.89 (95% CI 0.78-0.94) and pooled specificity was 0.93 (95% CI 0.79-0.98). The pooled sensitivity of SD-OCT was 0.99 (95% CI 0.91-1.00). Due to uncertainty in individual studies, the pooled specificity of SD-OCT could not be estimated. CONCLUSIONS: OCTA can reliably diagnose mCNV in clinically suspected patients, however, SD-OCT may not reliably establish a positive diagnosis of mCNV. Future large, prospective studies with improvements in conduct and reporting are needed to strengthen these clinical recommendations.

A steamed broccoli sprout diet preparation that reduces colitis via the gut microbiota.

Sulforaphane is a bioactive metabolite with anti-inflammatory activity and is derived from the glucosinolate glucoraphanin, which is highly abundant in broccoli sprouts. However, due to its inherent instability its use as a therapeutic against inflammatory diseases has been limited. There are few studies to investigate a whole food approach to increase sulforaphane levels with therapeutic effect and reduce inflammation. In the current study, using a mouse model of inflammatory bowel disease, we investigated the ability of steamed broccoli sprouts to ameliorate colitis and the role of the gut microbiota in mediating any effects. We observed that despite inactivation of the plant myrosinase enzyme responsible for the generation of sulforaphane via steaming, measurable levels of sulforaphane were detectable in the colon tissue and feces of mice after ingestion of steamed broccoli sprouts. In addition, this preparation of broccoli sprouts was also capable of reducing chemically-induced colitis. This protective effect was dependent on the presence of an intact microbiota, highlighting an important role for the gut microbiota in the metabolism of cruciferous vegetables to generate bioactive metabolites and promote their anti-inflammatory effects.

Clinical decision support in primary care for better diagnosis and management of retinal disease.

Misdiagnosis of retinal disease is a common problem in primary care that can lead to irreversible vision loss and false-positive referrals, resulting in inappropriate use of health services. Clinical decision support systems describe tools that leverage information technology to provide timely recommendations that assist clinicians in the decisions they make about the care of a patient. They, therefore, have the potential to reduce the rate of misdiagnosis by promoting evidence-based medicine and more effective and efficient healthcare. This narrative review aims to support primary care practitioners in better understanding the current and emerging capacity of clinical decision support systems in eye care. Different types of clinical decision support systems are discussed, using current examples and evidence from the available literature to demonstrate how they may improve diagnostic effectiveness and aid the management of retinal disease. Comments are made on the future directions of clinical decision support in primary eye care and the potential applications of artificial intelligence.

Gut Microbiota Modulate CD8 T Cell Responses to Influence Colitis-Associated Tumorigenesis.

There is increasing evidence that gut microbiome perturbations, also known as dysbiosis, can influence colorectal cancer development. To understand the mechanisms by which the gut microbiome modulates cancer susceptibility, we examine two wild-type mouse colonies with distinct gut microbial communities that develop significantly different tumor numbers using a mouse model of inflammation-associated tumorigenesis. We demonstrate that adaptive immune cells contribute to the different tumor susceptibilities associated with the two microbial communities. Mice that develop more tumors have increased colon lamina propria CD8+ IFNγ+ T cells before tumorigenesis but reduced CD8+ IFNγ+ T cells in tumors and adjacent tissues compared with mice that develop fewer tumors. Notably, intratumoral T cells in mice that develop more tumors exhibit increased exhaustion. Thus, these studies suggest that microbial dysbiosis can contribute to colon tumor susceptibility by hyperstimulating CD8 T cells to promote chronic inflammation and early T cell exhaustion, which can reduce anti-tumor immunity.

The first crystal structures of a family 19 class IV chitinase: the enzyme from Norway spruce.

Chitinases help plants defend themselves against fungal attack, and play roles in other processes, including development. The catalytic modules of most plant chitinases belong to glycoside hydrolase family 19. We report here x-ray structures of such a module from a Norway spruce enzyme, the first for any family 19 class IV chitinase. The bi-lobed structure has a wide cleft lined by conserved residues; the most interesting for catalysis are Glu113, the proton donor, and Glu122, believed to be a general base that activate a catalytic water molecule. Comparisons to class I and II enzymes show that loop deletions in the class IV proteins make the catalytic cleft shorter and wider; from modeling studies, it is predicted that only three N-acetylglucosamine-binding subsites exist in class IV. Further, the structural comparisons suggest that the family 19 enzymes become more closed on substrate binding. Attempts to solve the structure of the complete protein including the associated chitin-binding module failed, however, modeling studies based on close relatives indicate that the binding module recognizes at most three N-acetylglucosamine units. The combined results suggest that the class IV enzymes are optimized for shorter substrates than the class I and II enzymes, or alternatively, that they are better suited for action on substrates where only small regions of chitin chain are accessible. Intact spruce chitinase is shown to possess antifungal activity, which requires the binding module; removing this module had no effect on measured chitinase activity.

Monitoring of serum prolactin in pediatric patients with cystic fibrosis who are receiving domperidone.

BACKGROUND: Since 2003, it has been routine practice at Children's and Women's Health Centre of British Columbia to monitor serum levels of prolactin in pediatric patients with cystic fibrosis who are receiving domperidone. Although a pharmacologic relationship between domperidone and prolactin has been documented in the literature, there is no information about routine monitoring of prolactin, and guidance on interpretation of prolactin values is lacking. OBJECTIVES: To characterize how prolactin levels were being used in monitoring patients with cystic fibrosis who were receiving domperidone therapy at this institution, to evaluate the need for this practice, and to formulate recommendations accordingly. METHODS: A chart review was conducted for pediatric patients with cystic fibrosis who had been receiving domperidone therapy and whose serum prolactin levels had been monitored between June 1, 2001, and October 1, 2005. RESULTS: A total of 219 samples had been drawn, from 49 patients, for determination of prolactin level. Of these, 100 (45.7%) were above the normal range. Of the values above the normal range, 86 (86%) led to no dosage adjustment of domperidone and 14 (14%) led to either a decrease in dose or discontinuation of therapy. None of the elevated prolactin levels were associated with supratherapeutic doses of domperidone. CONCLUSION: The role of routine monitoring of prolactin in this patient population requires further study. In particular, more information is needed about prolactin levels in pediatric patients and the relationship of prolactin level to domperidone dose.

Crystal structures of a family 19 chitinase from Brassica juncea show flexibility of binding cleft loops.

Brassica juncea chitinase is an endo-acting, pathogenesis-related protein that is classified into glycoside hydrolase family 19, with highest homology (50-60%) in its catalytic domain to class I plant chitinases. Here we report X-ray structures of the chitinase catalytic domain from wild-type (apo, as well as with chloride ions bound) and a Glu234Ala mutant enzyme, solved by molecular replacement and refined at 1.53, 1.8 and 1.7 A resolution, respectively. Confirming our earlier mutagenesis studies, the active-site residues are identified as Glu212 and Glu234. Glu212 is believed to be the catalytic acid in the reaction, whereas Glu234 is thought to have a dual role, both activating a water molecule in its attack on the anomeric carbon, and stabilizing the charged intermediate. The molecules in the various structures differ significantly in the conformation of a number of loops that border the active-site cleft. The differences suggest an opening and closing of the enzyme during the catalytic cycle. Chitin is expected to dock first near Glu212, which will protonate it. Conformational changes then bring Glu234 closer, allowing it to assist in the following steps. These observations provide important insights into catalysis in family 19 chitinases.

Bronchial constriction and inhaled colistin in cystic fibrosis.

STUDY OBJECTIVE: Inhaled colistin is used for the treatment of Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients despite reports of chest tightness and bronchospasm. The main objective of the study was to assess whether bronchospasm occurred in pediatric CF patients with or without clinical evidence of airway hyperreactivity. DESIGN AND METHODS: A prospective placebo-controlled clinical trial with crossover design was devised using challenge tests with 75 mg colistin in 4 mL saline solution and a placebo solution of the same osmolarity using a breath-enhanced nebulizer for administration. Subjects were recruited as follows: high risk (HR) for bronchospasm due to a personal history of recurrent wheezing, a family history of asthma and/or atopy, or bronchial lability, as demonstrated in pulmonary function tests; or low risk (LR) without these characteristics. RESULTS: The mean FEV(1) (expressed as the mean [+/- SD] fall from baseline) of the HR group (n = 12) fell 12 +/- 9% after placebo was administered, and fell 17 +/- 10% after colistin was administered. For the LR group (n = 8), the mean FEV(1) fell 9 +/- 4% following placebo administration and 13 +/- 8% following colistin administration. There was a greater number of subjects in the HR group compared to the LR group, which had a mean fall in FEV(1) of >/= 15% (p < 0.01) after inhaling colistin. The differences between placebo and colistin therapy in the LR group were not significant. CONCLUSION: The results demonstrated that colistin can cause bronchospasm, particularly in those patients with coexisting CF and asthma.

Evaluation of bronchial constriction in children with cystic fibrosis after inhaling two different preparations of tobramycin.

OBJECTIVES: This randomized, double-blind, cross-over study evaluated the risk of bronchoconstriction with two preparations of inhaled tobramycin in children with cystic fibrosis (CF) infected with Pseudomonas aeruginosa with and without airway hyperreactivity. DESIGN: Of 19 children with CF (age range, 7 to 16 years) with mild-to-moderate pulmonary disease, 10 children were at high risk (HR) for bronchospasm (family history of asthma and previous response to bronchodilators) and 9 children were at low risk (LR) for bronchospasm (no family history of asthma or previous response to bronchodilators). Two solutions of tobramycin were administered: (1) 80 mg in a 2-mL vial diluted with 2 mL of saline solution containing the preservatives phenol and bisulfites (IV preparation); and (2) 300 mg in a preservative-free preparation in a 5-mL solution. Following a bronchodilator-free period of 12 h, the patients inhaled either one or the other preparation in random order on two different occasions, 2 weeks apart. RESULTS: Prechallenge and postchallenge results for the LR group showed a percentage of fall in FEV(1) (DeltaFEV(1)) of 12 +/- 9% (mean +/- SD) for the IV preparation, compared to 4 +/- 5% for the preservative-free preparation (p = 0.046). An DeltaFEV(1) of > 10% was seen in six of nine patients for the IV preparation and in one of nine patients for preservative-free preparation. For the HR group, the DeltaFEV(1) was 17 +/- 13% for the IV-preparation group, compared to 16 +/- 12% for the preservative-free group (p = 0.4). In this group, equal numbers of patients (8 of 10 patients) had an DeltaFEV(1) > 10% after inhaling each preparation. The largest DeltaFEV(1) was 44% (HR group with the preservative-free preparation that forced the early termination of inhalation). CONCLUSIONS: Both preparations caused significant bronchoconstriction in the HR group, and the preservative-containing IV preparation caused more bronchospasm in LR group than the preservative-free solution. Heightened airway reactivity in children with CF places them at risk of bronchospasm from inhalation therapy.

Do in-line respiratory filters protect patients? Comparing bacterial removal efficiency of six filters.

With all pulmonary function diagnostic and respiratory therapy equipment, cross-infection has always been a concern, especially in the cystic fibrosis population, in whom pulmonary function tests are done routinely. The aim of this study was to identify and compare the bacterial removal efficiency (BRE, ability of a filter to remove microorganisms) of six different filters used in hospital settings: Microgard (MG), Spirobac (SB), PALL (PL), and KOKO (KK), used in the pulmonary function laboratory; and Clear-Guard (CG) and Respigard (RG), used in ventilator circuits. Filters were tested in both saturated and nonsaturated conditions. A Pseudomonas aeruginosa suspension of 1 x 10(4) to 1 x 10(8) CFU/mL was nebulized onto each filter. A blood agar plate was held immediately downstream from the filter. Colony-forming units (CFU) were then counted after 24 hr of incubation. A peak flow was applied across the spirometry filters. Bacterial thresholds of the filters were also identified (concentration of bacteria at which a filter no longer has 100% BRE). There was a significant difference in BRE among the six filters in saturated states when challenged with 1 x 10(4) CFU/mL (MG, KK, CG, and RG, 100%; SB, 98.8%; PL, 42.7%; P = 0.003). There was no significant difference between saturated and nonsaturated states, or after application of a peak flow. Filter thresholds were significantly different (KK 1 x 10(8), MG 1 x 10(7), CG 1 x 10(6), RG 1 x 10(5), and SB and PL <1 x 10(4) CFU/mL). In conclusion, when all filters are exposed to the same extreme challenges, significant differences exist in their ability to remove bacteria.

Phenotype of Pseudomonas aeruginosa isolates causing corneal infection between 1997 and 2000.

PURPOSE: To investigate the relationship between functional phenotype of and the associated human corneal infection. METHODS: This was an experimental pilot study of patients presenting with corneal infections at the Jules Stein Eye Institute with presumed infection during the period from 12/30/97 to 9/1/00. Thirteen patients were admitted to the study based on positive identification of the causative pathogen as and patient consent. Data were collected (including bacterial cultures, lens wear schedule and care, gender and age, completed history questionnaire, clinical photographs). Statistical analysis of possible correlations was performed. Phenotypes of were determined, and clinical factors associated with infection were explored. RESULTS: Both invasive and cytotoxic phenotypes of were isolated in equal proportion. Cytotoxic strains and invasive strains were found to be associated with patients younger than 50 years of age and older than 50 years of age, respectively. CONCLUSIONS: remains a significant pathogen in corneal infection, especially during contact lens wear. The age of the patient may influence the phenotype of causing infection. Since invasive and cytotoxic strains have different effects on corneal cells, treatment of the infection might require different approaches depending on this phenotype of the causative bacteria.

Utility of anti-xa monitoring in children receiving enoxaparin for therapeutic anticoagulation.

Although enoxaparin is used to treat thromboembolism in children, current treatment guidelines are largely extrapolated from adults. The objectives of this study were to determine: i) correlation between enoxaparin dose and anti-factor Xa (anti-Xa) level, ii) intra-patient variability, and iii) whether dose or anti-Xa level is a predictor of outcomes. A retrospective chart review was conducted on all hospitalized patients receiving enoxaparin in a tertiary care pediatric institution. Simple linear regression, coefficient of variation (CV), and Student's t-test were used to analyze the objectives. Eighty treatment courses with interpretable anti-Xa levels were analyzed. Mean patient age was 6.5 years. Mean enoxaparin dose was 1.10 mg/kg q12h. Correlation between initial dosing and anti-Xa level was poor; R(2) = 0.0307 and 0.0237 for patients > 2 months with and without cardiac or renal diseases, respectively. Four out of seven patients ≤ 2 months of age compared to 4/32 patients > 2 months had a CV > 40%. Similarly, 4/12 cardiac patients compared to 4/27 non-cardiac patients had a CV > 40%. Neither dose nor anti-Xa level predicted treatment success or adverse reactions (P > .05). These results suggest a need to reexamine the use of anti-Xa levels for guiding enoxaparin therapy. Further prospective studies are warranted to clarify whether routine or selective anti-Xa monitoring should be recommended in pediatric patients.