Median Lag Time Research Articles

Shoulder MRI lag times after implementation of the Affordable Care Act (ACA): a retrospective review

Background: With the Affordable Care Act (ACA), the challenge of expanding healthcare insurance to Americans without jeopardizing quality of care remains. This study was initiated to evaluate how the timing of magnetic resonance imaging (MRI) completion for shoulder pathology correlates with implementation of the ACA by comparing lag times between the initial visit and the date of MRI completion. In addition, the access to orthopaedic care after ACA implementation was evaluated by comparing shoulder MRI lag times among three cohorts based on insurer status. Methods: All shoulder and proximal upper extremity MRIs between 2009 and 2017 were reviewed, 5 yr before and 3 yr after ACA implementation. Patients were grouped into commercial, Medicare, and Medicaid cohorts. Average lag times for the pre- and post-ACA periods overall and among payor cohorts were calculated. Results: Included were 5900 MRIs, 1997 (33.8%) before and 3903 (66.2%) after ACA implementation. The difference in payor mix before and after ACA implementation was significantly different (P<0.001). Median lag time increased from 23 days pre-ACA to 31 days post-ACA (P<0.001). For commercial insurance, median lag time was 23 days pre-ACA compared with 28 days (P<0.001) post-ACA. Median lag time pre- and post-ACA in the Medicaid cohort was 8 days compared with 30.5 days (P<0.001), respectively. Pre- and post-ACA lag times in the Medicare cohort did not differ significantly (P=0.450). Conclusions: Lag times increased significantly after ACA implementation in patients with commercial and Medicaid insurance. This study provides valuable insight into unintended outcomes associated with the ACA legislation. Level of Evidence: Level III.

Clinicopathological Presentation of Retinoblastoma in Ethiopia

Introduction: The presenting symptoms of retinoblastoma in Ethiopia, as well as their relationship to the stage of the disease, are poorly understood, but they could be important as background knowledge for creating early detection initiatives. This study aimed to describe the clinical and histopathological characteristics of retinoblastoma among Ethiopian patients. Methods: A hospital-based cross-sectional analysis of all children with newly diagnosed retinoblastoma during the study period of May 2015 to December 2019, inclusive, who presented to a tertiary referral center during were included. Demographic, clinical, and histological characteristics were collected and descriptive statistics were done using SPSS Version 20.0 software. Results: A total of 217 patients (unilateral 84.3%, bilateral 15.7%) were studied. The median age at presentation was 29 months (34 months vs. 19.5 months in unilateral and bilateral cases, respectively, p < 0.001). Among all patients, 57.8% were male. Leukocoria was the most common presenting sign (37.3%) and followed by fungating mass (31.8%). Tumors were extraocular in 40.1% of cases. From the intraocular cases, 73.3% were advanced International Intraocular Retinoblastoma Classification Group D or E disease. Sixty-two (54.4%) of the eyes had high-risk pathological features. The median lag time was significantly shorter for intraocular versus extraocular cases (5 months vs. 12 months, respectively, p < 0.001). Conclusion: Our results show that the majority of Ethiopian children with retinoblastoma have delayed presentation and late stage at diagnosis. This suggests that national health promotion campaigns to increase public knowledge on the presenting signs of retinoblastoma may be critical to achieving early diagnosis. Furthermore, the development of standard management guidelines informed by this study will be helpful in managing the complex and advanced cases currently observed.

Assessment of scheduling for patients referred for an abnormal red reflex

Scheduling lag time is the time between the date of an appointment and the date an appointment was created in the scheduling system. We sought to determine the scheduling lag time in a pediatric ophthalmology clinic for children <8 years of age, referred by a primary care provider for an abnormal red reflex (ARR), cataract, leukocoria, or retinoblastoma. The median scheduling lag time was 1.8 days (IQR, 0.8-5.0). Of the 106 total appointments, 89 (84%) were completed as scheduled, 12 (11%) were canceled, and 5 (5%) were no-shows. Ten patients (12%) were never seen. There was a shorter scheduling lag time for completed visits (median, 1.1 days; IQR, 0.2-4.0) than canceled visits (median, 12.0 days; IQR, 3.1-48.5; P < 0.001). Monitoring of the scheduling lag time for urgent referrals may be a metric for quality improvement in pediatric ophthalmology.

The 24-h reporting of Gram stains from positive blood cultures contributes to physician's use of appropriate antimicrobials: Experience at a university hospital

Although recent technological advances for the diagnosis of bloodstream infection (BSI) provide rapid and accurate results, blood culture maintains a key role in the diagnosis of BSI. The objective of this study was to determine whether 24-h reporting by telephone to disclose the suspected microorganism based on the Gram stain morphology from positive blood cultures (first laboratory report) affects a physician's use of appropriate antimicrobials. A total of 627 (14%) out of 4413 blood samples, excluding duplicate samples from the same patient on the same day, were positive for blood cultures between January and December 2016. The contamination rate of blood cultures during the study period was 2.3%. Among 627 patients with positive blood cultures, 538 (86%) were receiving antibiotics at the time of the first laboratory report, of which 502 (80%) thereafter continued the same antimicrobials, and the remaining 36 (6%) were changed to appropriate antimicrobials after the first laboratory report. An additional 25 (4%) were newly administered appropriate antimicrobials after the first laboratory report, whereas an additional 21 (3%) were newly administered appropriate antimicrobials after infection control team (ICT)-intervention. The median time lag (interquartile ranges) from flagging culture bottles as positive to a physician's use of appropriate antimicrobials after the first laboratory report (4 h, 2–7) was significantly (p < 0.001) shorter than that after ICT-intervention (12 h, 10–17). During the study period, no cases of discrepancy between the Gram stain morphology in the first laboratory report and definitive identification of microorganisms in the final laboratory report were observed. Because the timing of flagging culture bottles as positive tends to fall outside normal working hours, immediate 24-h reporting by telephone to disclose the suspected microorganism based on the Gram stain morphology from positive blood cultures may contribute to an early recognition of bacteremia and the physician's use of appropriate antimicrobials.

Major bleeding during oral anticoagulant therapy associated with factor V activation by factor Xa

ObjectivePlasma thrombin generation (TG) provides important information on coagulation status; however, current TG output parameters do not predict major bleeding of patients on anticoagulants. We recently reported that factor V (FV) activation by factor X (FX)a contributes importantly to the initiation phase of TG. Here we investigated how this pathway varies in the normal population and whether FXa‐mediated activation of FV is associated with major bleeding in patients on anticoagulant therapy. ApproachWe employed TIX‐5, a specific inhibitor of FV activation by FXa, to estimate the contribution of FXa‐mediated FV activation to tissue factor (TF)–initiated TG. ResultsWe show that the contribution of this pathway to plasma TG varies considerably in the normal population, as measured by the time needed to form the first traces of thrombin (TG lag time; mean prolongation by TIX‐5 40%, range 0%–116%). Comparing patients on vitamin K antagonists (VKA) of the BLEED study (263 patients with and 538 patients without major bleeding), showed a marked prolongation in the median TG lag time in the presence of TIX‐5 in cases (12.83 versus 11.00 minutes, P = 0.0030), while the TG lag time without TIX‐5 only showed a minor although significant difference (5.83 vs. 5.67 minutes, P = 0.0198). The TIX‐5 sensitivity (lag time + TIX‐5/lag time + vehicle) in the upper quartile was associated with a 1.62‐fold (95% confidence interval 1.04–2.52) increased risk of major bleeding compared to the lowest quartile. ConclusionA greater dependence on FXa‐mediated activation of FV of TG is associated with increased risk of major bleeding during VKA therapy.

Analysis of Retracted Publications in The Biomedical Literature from Turkey.

BackgroundRetraction is a process for correcting the literature and provides a barrier to the dissemination of publications that include major faults or false-misleading data. The aim of this study was to examine the characteristics of retracted articles in the biomedical field sourced from Turkey.MethodsIn this descriptive cross-sectional study, all retracted publications from Turkey on PubMed were listed without date restriction. Data covering the article title, authors, publication date, retraction date, time between publication and retraction dates (in months), journal, article type, country of the corresponding author, peer review timeline (in days), reason for retraction, and subject area of the retracted item were recorded. Citation data were obtained using the Scopus database. The altmetric attention scores of the articles were recorded.ResultsA total of 102 articles were listed and after the implementation of exclusion criteria, 86 articles were included for analysis. The first retracted article was published in 2000 (n = 1), while the most retracted articles were published in 2020 (n = 11). The median time lag between publication and retraction was 10.33 (0.73–144.06) months. The main factors causing retraction were plagiarism (n = 23), duplication (n = 22) and error (n = 17). The total number of citations was 695. A total of 224 citations were in the pre-retraction period and 471 citations were in the post-retraction period.ConclusionThe retracted article counts showed a rising trend over the years. The leading causes of retraction for articles from Turkey were plagiarism, duplication, and error. It was found that the articles continued to be cited after the retraction. Researchers in Turkey should be educated on retraction, particularly plagiarism and duplication. Strategies should be developed to prevent articles from being cited after retraction.

Delays in initiating rabies post-exposure prophylaxis among dog bite victims in Wakiso and Kampala districts, Uganda.

Background: Although rabies in dog bite patients is preventable through timely initiation of post-exposure prophylaxis (PEP), a number of barriers to achieving PEP exist. This study investigated the delays to initiation of PEP among dog bite patients in the emergency departments of two PEP centers in Uganda. Methods: A cross-sectional study was conducted among dog-bite patients that presented to two selected rabies PEP centers. A semi-structured questionnaire was used to collect data. Delay to receive PEP was defined as reporting for PEP beyond 24 hours after the bite event. Generalized linear models were used to calculate prevalence ratios and the 95% confidence intervals as a measure of association between delay and patient factors. Results: Out of 376 participants, just over half (53.5%) were males. The majority of participants (54.0%) were 15 years or older and 28.5% had no formal education. Just over three-quarters (77.9%) had category II dog bite wounds. Nearly 40% delayed to receive PEP, and median (inter quartile range) lag time between bite event and seeking medical care of 18 (41) hours. Compared to education level of secondary or above, patients with no formal education (adj. PR=4.06, 95% CI: 2.69 - 6.10) or primary education (adj.PR=2.15, 95% CI: 1.37 - 3.35), belonging to the lowest socio-economic tertile as compared to the highest (adj.PR=1.58, 95% CI: 1.10 - 2.28), knowing the owner of the biting dog (adj.PR=1.30, 95% CI: 1.02 - 1.65) and having category II wounds (adj.PR=2.31, 95% CI: 1.43 - 3.71) were all associated with delayed presentation for PEP. Conclusions and recommendations: Delays to receive PEP are common and are associated with poor level of education or low socio-economic status, knowledge of who the dog owner is and less severity of bite wounds. Seeking care irrespective of wound severity or knowledge of dog owner should be promoted.

Association of Premenopausal Bilateral Oophorectomy With Cognitive Performance and Risk of Mild Cognitive Impairment

The associations of bilateral oophorectomy among premenopausal women, age at oophorectomy, and use of estrogen therapy after oophorectomy with cognitive performance later in life remain controversial. To investigate whether women who underwent premenopausal bilateral oophorectomy were at increased risk of mild cognitive impairment (MCI) and experienced decreased global or domain-specific cognitive performance. This case-control study and cross-sectional study were made possible by combining data from the Mayo Clinic Study of Aging (MCSA) and the Rochester Epidemiology Project (REP) medical record-linkage system. The studies were conducted among a population-based sample in Olmsted County, Minnesota, consisting of 2732 women aged 50 to 89 years who participated in the MCSA study from 2004 to 2019 and underwent a clinical evaluation and comprehensive cognitive testing. Data were analyzed from January to May 2021. Medical record documentation of bilateral oophorectomy abstracted from a medical record-linkage system (ie, REP). Odds of MCI and global or domain-specific z scores on cognitive tests were measured at the first MCSA visit. The median (IQR) lag time between bilateral oophorectomy performed before menopause and before age 50 years and cognitive evaluation was 30 (22-38) years. Among 2732 women aged 50 to 89 years (median [IQR] age at evaluation, 74 [66-81] years) who participated in the MCSA, the case-control study included 283 women with MCI (10.4%) and 2449 women without cognitive impairment (89.6%). Bilateral oophorectomy before menopause and before age 46 years was associated with clinically diagnosed MCI (adjusted odds ratio [aOR], 2.21; 95% CI, 1.41-3.45; P < .001) compared with no bilateral oophorectomy. The presence of an association with MCI varied by surgical indication, with an association among 259 women with bilateral oophorectomy before menopause and before age 50 years for the indication of benign ovarian condition (aOR, 2.43; 95% CI, 1.36-4.33; P = .003) but not for cancer or no ovarian condition. The presence of an association did not vary by estrogen therapy after bilateral oophorectomy, with associations among women aged less than 46 years with estrogen therapy (aOR, 2.56; 95% CI, 1.24-5.31; P = .01) and without estrogen therapy (aOR, 2.05; 95% CI, 1.18-3.52; P = .01). The cross-sectional study included 625 women with a history of bilateral oophorectomy (median [IQR] age, 75 [70-82] years) and 2107 women without a history of bilateral oophorectomy (median [IQR] age, 73 [65-80] years). Premenopausal bilateral oophorectomy was performed before age 46 years among 161 women and was associated with decreased global cognition z score (β, -0.17; 95% CI, -0.32 to -0.03; P = .02), attention and executive domain z score (β, -0.21; 95% CI, -0.36 to -0.05; P = .009), and Short Test of Mental Status score (β, -0.51; 95% CI, -0.95 to -0.08; P = .02) compared with no bilateral oophorectomy. This study found that women who underwent bilateral oophorectomy before menopause had increased odds of MCI and poorer performance on cognitive tests approximately 30 years later compared with women who did not undergo bilateral oophorectomy.

Efficacy and Safety of Recombinant Factor IX-FIAV and Bypassing Agents in Thrombin Generation Analyses in Hemophilia A Patient Plasma: The FIVITAS Study

Factor (F)IX-FIAV, a FIX variant with four amino acid substitutions that functions independently of the cofactor VIIIa, has been previously shown to ameliorate the hemophilia A (HA) phenotype in vivo [Quade-Lyssy et al. J. Thromb. Haemost. 2014]. Here we evaluated the efficacy of purified recombinant FIX-FIAV in severe, moderate, and mild hemophilia A patient plasma employing thrombin generation and intrinsic clotting activity (aPTT) analyses. The combination of FIX-FIAV with current hemophilia A therapeutics was used for preclinical safety assessment.Plasma was obtained from 21 HA patients, seven per HA phenotype, with a median age of 38 years [interquartile range (IQR) 27.5 - 49.5]. The plasma levels of FIX, FX, prothrombin, and antithrombin of all included patients were within the normal range. To determine the effect of FIX-FIAV on FXIa-triggered thrombin generation parameters (lag time, endogenous thrombin potential (ETP)), plasma was spiked with 100% (5 µg/ml in severe/mild) or 125% (6 µg/ml in moderate) FIX-FIAV prior to analysis. FIX-FIAV significantly shortened the lag time in all patient plasmas irrespective of disease severity (Figure 1) with an overall median of 4.4 min [IQR 3.6 - 6.9] in the absence of FIX-FIAV vs. 3.1 min [IQR 2.4 - 4.5] in the presence of FIX-FIAV (p<0.0001, Table 1). Similar observations were obtained following aPTT analyses: median clotting time of 115.5 sec [IQR 105 - 173.9] without vs. 97.7 sec [IQR 91.8 - 136.2] with 100% FIX-FIAV (p = 0.0039). Conversion of the thrombin generation lag time to FVIII-like activity using a FVIII calibration for each individual patient plasma revealed that FIX-FIAV mitigated the HA phenotype from severe to moderate, from moderate to mild, and from mild to normal (Table 1).Interestingly, following the addition of FIX-FIAV a minor but significant decrease in ETP was observed for non-severe HA patient plasma (p = 0.016 for mild and p = 0.016 for moderate), while FIX-FIAV increased the median ETP in severe HA plasma by 2.1-fold (p = 0.22) (Figure 2, Table 1). This may result from competition between the added FIX-FIAV and endogenous FIX for interaction with residual functional FVIII. In line with this, experiments performed in the presence of an anti-FVIII antibody that inhibits FVIII activity significantly enhanced the ETP in all patient plasmas (p = 0.016 for each individual severity, Figure 2) in addition to shortening the lag time (Figure 1).Next, we evaluated the combination of FIX-FIAV with bypassing agents (1 IU/mL aPCC or 1.5 mg/mL rFVIIa) in nine patient plasmas, three per phenotype. Addition of aPCC or rFVIIa to FIX-FIAV-spiked plasma did not significantly affect aPTT clotting times nor ETP values in comparison to adding aPCC or rFVIIa only, respectively. The median lag time shortened significantly, albeit modestly, for the combination of FIX-FIAV with aPCC in comparison to conditions with aPCC only: 5.2 min [IQR 3.0 - 6.4] vs. 5.5 min [IQR 3.6 - 7.7], p = 0.0078, respectively. Similar findings were obtained when combining FIX-FIAV with rFVIIa relative to rFVIIa only: median lag time 4.9 min [IQR 2.2 - 6.1] vs. 5.3 min [IQR 3.3 - 8.8], p = 0.0039. Hence, no substantial synergistic effect was observed when combining FIX-FIAV with bypassing agents aPCC or rFVIIa for HA. In contrast, combining approximate hemostatic levels (55 µg/ml) of emicizumab, a bispecific antibody mimicking FVIIIa, with FIX-FIAV resulted in a ~1.1-fold reduced lag time and ETP relative to emicizumab alone (p = 0.016 and p = 0.004 respectively). This is suggestive of a minor synergistic procoagulant effect, which is consistent with the FIX(a)-FX(a) bridging capacity of emicizumab.In conclusion, FIX-FIAV could serve as a potential treatment for hemophilia A as it mitigates the hemophilia A phenotype in patient plasma, also in the presence of an inhibitory anti-FVIII antibody. While further safety assessment is warranted, no severe procoagulant effects were observed for the combination of FIX-FIAV with conventional hemophilia A therapeutics. [Display omitted] DisclosuresRomano: Swedish Orphan Biovitrum B.V.: Other: Travel grant and aforementioned Research Funding in the form of the Young Investigator's Award 2020, Research Funding. Liu: uniQure Biopharma B.V.: Current Employment. McCreary: uniQure Biopharma B.V.: Ended employment in the past 24 months. Leebeek: Roche: Other: DSMB member of a study sponsored by Roche; uniQure Biopharma B.V.: Consultancy, Research Funding; Swedish Orphan Biovitrum B.V.: Other: Travel support, Research Funding; Biomarin: Consultancy; CSL Behring: Consultancy, Research Funding; Shire/Takeda: Consultancy, Research Funding. Bos: VarmX B.V.: Research Funding; uniQure Biopharma B.V.: Research Funding.

Delays in initiating rabies post-exposure prophylaxis among dog bite victims in Wakiso and Kampala districts, Uganda.

Background: Although rabies in dog bite patients is preventable through timely initiation of post-exposure prophylaxis (PEP), a number of barriers to achieving PEP exist. This study investigated the delays to initiation of PEP among dog bite patients in the emergency departments of two PEP centers in Uganda. Methods: A cross-sectional study was conducted among dog-bite patients that presented to two selected rabies PEP centers. A semi-structured questionnaire was used to collect data. Delay to receive PEP was defined as reporting for PEP beyond 24 hours after the bite event. Generalized linear models were used to calculate prevalence ratios and the 95% confidence intervals as a measure of association between delay and patient factors. Results: Out of 376 participants, just over half (53.5%) were males. The majority of participants (54.0%) were 15 years or older and 28.5% had no formal education. Just over three-quarters (77.9%) had category II dog bite wounds. Nearly 40% delayed to receive PEP, and median (IQR) lag time between bite event and seeking medical care of 18 (41) hours. Compared to education level of secondary or above, patients with no formal education (adj. PR=4.06, 95% CI: 2.69 - 6.10) or primary education (adj.PR=2.15, 95% CI: 1.37 - 3.35), belonging to the lowest socio-economic tertile as compared to the highest (adj.PR=1.58, 95% CI: 1.10 - 2.28), knowing the owner of the biting dog (adj.PR=1.30, 95% CI: 1.02 - 1.65) and having category II wounds (adj.PR=2.31, 95% CI: 1.43 - 3.71) were all associated with delayed presentation for PEP. Conclusions and recommendations: Delays to receive PEP are common and are associated with poor level of education or low socio-economic status, knowledge of who the dog owner is and less severity of bite wounds. Seeking care irrespective of wound severity or knowledge of dog owner should be promoted.

Clinical picture and grouping of retinoblastoma at first presentation to a tertiary Hospital in Dar es Salaam: Implications for treatment outcomes

Objectives: To assess the clinical picture and grouping of retinoblastoma at first presentation to the oncology ward at Muhimbili National Hospital. Methods: A cross sectional descriptive hospital based study was conducted from April to December 2018. Seventy two patients who presented for the first time to Muhimbili National Hospital (MNH) with a diagnosis of retinoblastoma were consecutively sampled and recruited in the study. Visual acuity, horizontal corneal diameter, intraocular pressure, anterior and posterior segments of the eye were assessed and each eye was classified according to the International Classification of Retinoblastoma (ICRB) group. Ultrasonography, neuroimaging and histology were performed. Results: A total of 72 patients comprising of 90 affected eyes were recruited and analyzed: 39(54.2%) males and 33(45.8%) females. Majority of patients were residents of the Coastal and Lake Zones. Family history of Retinoblastoma was positive in only one patient. Fifty four (75.0%) patients had unilateral disease. Leukocoria (77.8%) and proptosis (41.7%) were the commonest first clinical signs noted by the family and health workers at MNH respectively. At MNH, both bilateral and unilateral cases presented with advanced disease of group E and extra ocular extension where 84(93.3%) eyes were indicated for enucleation. The median lag time from disease onset to presentation at MNH was 4 months. Conclusion: Leukocoria was the commonest first sign of retinoblastoma presentation at home. However, despite early presentation to primary health facilities, most patients presented to the tertiary centre of MNH late with advanced disease. Efforts to raise awareness on retinoblastoma to both health workers and the community are important for early case detection, referral, diagnosis and treatment in order to improve visual outcomes and survival rates of retinoblastoma patients.

The implications of lag times between nitrate leaching losses and riverine loads for water quality policy

Understanding the lag time between land management and impacts on riverine nitrate–nitrogen (N) loads is critical to understand when action to mitigate nitrate–N leaching losses from the soil profile may start improving water quality. These lags occur due to leaching of nitrate–N through the subsurface (soil and groundwater). Actions to mitigate nitrate–N losses have been mandated in New Zealand policy to start showing improvements in water quality within five years. We estimated annual rates of nitrate–N leaching and annual nitrate–N loads for 77 river catchments from 1990 to 2018. Lag times between these losses and riverine loads were determined for 34 catchments but could not be determined in other catchments because they exhibited little change in nitrate–N leaching losses or loads. Lag times varied from 1 to 12 years according to factors like catchment size (Strahler stream order and altitude) and slope. For eight catchments where additional isotope and modelling data were available, the mean transit time for surface water at baseflow to pass through the catchment was on average 2.1 years less than, and never greater than, the mean lag time for nitrate–N, inferring our lag time estimates were robust. The median lag time for nitrate–N across the 34 catchments was 4.5 years, meaning that nearly half of these catchments wouldn’t exhibit decreases in nitrate–N because of practice change within the five years outlined in policy.

Drug-induced Urinary Retention: An Analysis of a National Spontaneous Adverse Drug Reaction Reporting Database

BackgroundNumerous drugs have been associated with urinary retention (UR), but updated information on drugs that may induce UR is limited. ObjectiveTo evaluate drug-induced UR using the Italian spontaneous adverse drug reactions (ADRs) reporting database. Design, setting, and participantsWe selected all suspected spontaneous reports of drug-induced UR collected into the Italian spontaneous reporting system (SRS) database from its inception to June 30, 2019. Outcome measurements and statistical analysisThe Mantel-Haenszel χ2 test and the Mann-Whitney U test were performed for statistical comparisons of categorical and continuous variables, respectively. As a measure of disproportionality, we calculated the reporting odds ratios (RORs) with corresponding 95% confidence intervals using a statistical case/noncase methodology. Results and limitationsA total of 506 383 ADR reports were received in the Italian SRS database during the study period. Of these, 421 reports (0.1%) included UR-related ADRs, for a total of 497 suspected drugs. The median (interquartile range [IQR]) age of patients experiencing UR was 67 (47–77) yr. Overall, 174 (41.3%) ADR reports were considered serious. One-third of male patients experiencing UR suffered from benign prostatic hyperplasia, followed by diabetes mellitus (N = 58, 13.8%), and bladder-related disorders (N = 21, 5.0%). The median lag time between the start of drug treatment and UR onset was 7 (IQR 1–47.5) d. Overall, a statistically significant ROR was reported for 39 individual drugs, and for five (12.8%) of them (dapagliflozin, gabapentin, lithium, celecoxib, and piroxicam) UR was not described in their summary of product characteristics. Limitations include under-reporting and selective over-reporting of suspected ADRs and lacking information on the number of drug users. ConclusionsA disproportionality analysis identified five potentially new UR signals for dapagliflozin, gabapentin, lithium, celecoxib, and piroxicam, requiring further evaluation. Patient summaryIn this analysis of the Italian spontaneous reporting system database, we found new urinary retention signals, requiring further evaluation, for dapagliflozin, gabapentin, lithium, celecoxib, and piroxicam.

P-EP026. Clinical profile of children with west syndrome: A retrospective chart review

Introduction. This study was intended to document the clinical profile and treatment outcome of West syndrome in children attending a tertiary care center in Northern India. Methods. Data were collected by a retrospective chart review of children diagnosed with West syndrome between January 2017 to January 2018. Information was recorded pertaining to the age at onset and presentation, etiology, and associated co-morbidities; results of electroencephalography (EEG) and neuroimaging; treatment given; and final outcome. The following drugs were used for treatment: ACTH (n=7), prednisolone (n=17), vigabatrin (n=25), sodium valproate (n=28), clonazepam (n=30), and levetiracetam (n=13) and modified Atkins diet (n=7). The response was categorized as spasm cessation, partial improvement (>50% improvement), or no improvement. Results. Records of 30 children (21 boys) were analyzed. The mean (SD) age at onset was 4 (3, 6.5) months. The median lag time to treatment was 5 (2,14) months. Eight (26%) were premature, 2 (7%) were SGA, birth asphyxia in 56%, neonatal encephalopathy in 62%. EEG findings were compatible with hypsarrhythmia in 13 (43.3%) children and 9 (30%) had modified hypsarrythmia. MRI finding was periventricular leucomalacia (54.1%), cystic encephalomalacia (13.8%), normal MRI (20.7%) and 1 had arrested hydrocephalus. There was no improvement with valproate (93%), clonazepam (89%) and levetiracetam (78%). Cessation of spasm was achieved with vigabatrin (28 %), prednisolone (38.2%) and ACTH (42.8%). Hypsarrhythmia resolved with presence of background and other epileptiform abnormalities in 34 children. Conclusion. The present research highlights limited role of sodium valporate, levetiracetam and clonazepam in initial management of children with West syndrome. However, further studies with larger sample size are required before concluding its limited role.

Long-term outcome of patients with inflammatory cardiomyopathies implanted with cardiac defibrillators: a single centre experience

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Arrhythmia management remains a challenge in patients with inflammatory cardiomyopathies and little is known about the clinical characteristics affecting the arrhythmia burden on the long term. Purpose To identify clinical predictors of ICD therapies among patients with inflammatory cardiomyopathies. Methods We included all ICD patients implanted in our centre over the last 10 years in a context of inflammatory cardiomyopathy. For each patient, data from implant, device checks and clinical follow-ups were retrospectively collected. Results A total of 16 patients were identified (11 males, age at implant 50 ± 13 years). Based on the revised 2019 Japanese Circulation Society criteria, a diagnosis of cardiac sarcoidosis was established in all cases. Secondary prevention of sudden cardiac death was the indication for ICD implant in 50% of the patients. In 5 cases a CRT-D device was implanted because of concomitant left ventricular systolic dysfunction and a high grade AV block. During a median follow-up of 5.0 (0.9-6.6) years, 9 patients (56%) received ≥ 1 appropriate ICD treatment for ventricular tachycardia (VT) episodes (ATP only in 3 cases, ATP and shocks in 6 cases) with a median time lag from implant of 65.5 (57.0-314.8) days. Of these 9 patients, 6 were initially implanted for secondary prevention of sudden cardiac death. At the time of ICD therapies, 8 patients were under immunosuppressive treatment and 3 under antiarrhythmic drugs. A cardiac 18F-FDG PET scan was performed in 7 patients and an abnormal FDG uptake, compatible with an active inflammatory status, was documented in all cases. After optimisation of antiarrhythmic drugs, a VT ablation procedure was performed in 3 patients during the first 6 months following the ICD treatment because of recurrent VT. In another 3 patients, a VT ablation was performed 2-5 years after the first ICD treatment and was associated to stereotactic radiotherapy to achieve VT control. Conclusion In our series, patients affected by inflammatory cardiomyopathy and implanted with an ICD for secondary prevention of sudden cardiac death appear to be at high risk of ICD treatment especially during the first months after implantation. This could be the consequence of a more aggressive underlying inflammatory substrate, especially during the first phases of the disease, whereas the occurrence of VT episodes at later stage appear to be more scar-related. However, further studies on larger populations are required to confirm these observations.

Stroke risk reassessment and oral anticoagulant initiation in primary care patients with atrial fibrillation: A ten-year follow-up.

To examine the change in stroke risk over time and determine the proportion of patients with atrial fibrillation (AF) who were initiated on an oral anticoagulant (OAC) as their stroke risk increased from low/moderate to high, using the Australian general practice data set, MedicineInsight. A total of 2296 patients diagnosed with AF between 1 January 2007 and 31 December 2008, aged 18years or older and not initiated on an OAC before 2009, were included. We assessed the change in stroke risk and the proportion of patients who had a recorded prescription of an OAC, each year from 1 January 2009 to 31 December 2018. At baseline, 23.9%, 22.9% and 53.2% were categorised as being at low (score=0), moderate (score=1) and high stroke risk (score≥2), respectively, using the sexless CHA2 DS2 -VASc (CHA2 DS2 -VA) score. Overall, the CHA2 DS2 -VA score increased by a mean of 1.34 (95% confidence interval, 1.29-1.39) points over the study period. Nearly two-thirds of patients (65%, 412/632) whose stroke risk changed from baseline low/moderate to high were subsequently prescribed an OAC. The median (interquartile range) lag time from becoming high stroke risk to having OAC initiation was 2 (5) years. Nearly one-third of patients reclassified as being at high risk of stroke during the study period were not prescribed OAC therapy. Furthermore, the delay in OAC initiation following classification as being at high risk was a median of 2years, suggesting that more frequent stroke reassessment is needed.

Clinical profile of children with West syndrome: A retrospective chart review.

Background:This study was intended to document the clinical profile and treatment outcome of West syndrome in children attending a tertiary care centre in Northern India.Methods:Data were collected by a retrospective chart review of children diagnosed with West syndrome between January 2017 to January 2018. Information was recorded pertaining to the age at onset and presentation, etiology, and associated co-morbidities; results of electroencephalography (EEG) and neuroimaging; treatment given; and final outcome. The following drugs were used for treatment: ACTH (n = 7), prednisolone (n = 17), vigabatrin (n = 25), sodium valproate (n = 28), clonazepam (n = 30), and levetiracetam (n = 13) and modified Atkins diet (n = 7). The response was categorized as spasm cessation, partial improvement (>50% improvement), or no improvement.Results:Records of 30 children (21 boys) were analyzed. The median (IQR) age at onset was 4 (3, 6.5) months. The median (IQR) lag time to treatment was 5 (2,14) months. Eight (26%) were premature, 2 (7%) were small for gestational age, birth asphyxia in 56%, neonatal encephalopathy in 62%. EEG findings were hypsarrhythmia in 13 (43.3%) children and modified hypsarrhythmia in 9 (30%) children. MRI finding was periventricular leukomalacia (54.1%), cystic encephalomalacia (13.8%), normal MRI (20.7%) and one had arrested hydrocephalus. There was no improvement with valproate (93%), clonazepam (89%), levetiracetam (78%). Cessation of spasm was achieved with vigabatrin (28%), prednisolone (38.2%), ACTH (42.8%). Hypsarrhythmia resolved with improvement in of background and other epileptiform abnormalities in 17 children.Conclusion:The present research highlights favourable response of West syndrome to oral steroids, vigabatrin and ACTH with limited role of conventional antiepileptic drugs like sodium valporate, levetiracetam and clonazepam. Primary care physician plays a vital role in early recognition and treatment of epileptic spasm.

Kilonova Luminosity Function Constraints Based on Zwicky Transient Facility Searches for 13 Neutron Star Merger Triggers during O3

Abstract We present a systematic search for optical counterparts to 13 gravitational wave (GW) triggers involving at least one neutron star during LIGO/Virgo’s third observing run (O3). We searched binary neutron star (BNS) and neutron star black hole (NSBH) merger localizations with the Zwicky Transient Facility (ZTF) and undertook follow-up with the Global Relay of Observatories Watching Transients Happen (GROWTH) collaboration. The GW triggers had a median localization area of 4480 deg2, a median distance of 267 Mpc, and false-alarm rates ranging from 1.5 to 10−25 yr−1. The ZTF coverage in the g and r bands had a median enclosed probability of 39%, median depth of 20.8 mag, and median time lag between merger and the start of observations of 1.5 hr. The O3 follow-up by the GROWTH team comprised 340 UltraViolet/Optical/InfraRed (UVOIR) photometric points, 64 OIR spectra, and three radio images using 17 different telescopes. We find no promising kilonovae (radioactivity-powered counterparts), and we show how to convert the upper limits to constrain the underlying kilonova luminosity function. Initially, we assume that all GW triggers are bona fide astrophysical events regardless of false-alarm rate and that kilonovae accompanying BNS and NSBH mergers are drawn from a common population; later, we relax these assumptions. Assuming that all kilonovae are at least as luminous as the discovery magnitude of GW170817 (−16.1 mag), we calculate that our joint probability of detecting zero kilonovae is only 4.2%. If we assume that all kilonovae are brighter than −16.6 mag (the extrapolated peak magnitude of GW170817) and fade at a rate of 1 mag day−1 (similar to GW170817), the joint probability of zero detections is 7%. If we separate the NSBH and BNS populations based on the online classifications, the joint probability of zero detections, assuming all kilonovae are brighter than −16.6 mag, is 9.7% for NSBH and 7.9% for BNS mergers. Moreover, no more than &lt;57% (&lt;89%) of putative kilonovae could be brighter than −16.6 mag assuming flat evolution (fading by 1 mag day−1) at the 90% confidence level. If we further take into account the online terrestrial probability for each GW trigger, we find that no more than &lt;68% of putative kilonovae could be brighter than −16.6 mag. Comparing to model grids, we find that some kilonovae must have M ej &lt; 0.03 M ⊙, X lan &gt; 10−4, or ϕ &gt; 30° to be consistent with our limits. We look forward to searches in the fourth GW observing run; even 17 neutron star mergers with only 50% coverage to a depth of −16 mag would constrain the maximum fraction of bright kilonovae to &lt;25%.

Retinoblastoma in Children Older than 6 Years of Age

Objective: The aim of this work was to study the clinical and histopathology features and treatment outcome in retinoblastoma cases presenting at an older age (>6 years). Design: This was a retrospective study. We recruited 48 retinoblastoma patients who were treated at our institute over 7 consecutive years and were older than 6 years at presentation. Methods: Medical records were reviewed for data, including age at diagnosis, gender, laterality, family history, lag time, first symptom, misdiagnosis, clinical findings, grade and stage of disease at diagnosis, treatment, outcome, and follow-up status. Histopathology slides were reviewed and assessed for the presence of histopathological high-risk features (HRF) for metastasis. The main outcome measures were the frequency of atypical clinical features like hyphema, pseudohypopyon, glaucoma, cataract, vitreous hemorrhage, and phthisis, and misdiagnosis, prior intervention, stage of disease at presentation, and treatment outcome. Results: In total, 48/610 (7.8%) patients were older than 6 years, with a median age of 7 years (range 6–31). Retinoblastoma was bilateral in 7 cases. The most common initial symptom was white reflex followed by a decrease in vision. The median lag time was 9 months. Fourteen cases (29.2%) were misdiagnosed, with endophthalmitis the most common misdiagnosis. Twenty-six (54%) patients had intraocular disease, 12 (25%) had locally advanced disease, and 10 (21%) had metastatic disease at presentation. Overall, 67% (14/21) of the eyes that were enucleated upfront for presumed intraocular disease had histopathological HRF. At last follow-up, 31/36 (86%) who were treated were alive and healthy, while 5 (14%) patients had disease progression. Conclusions: This is the largest study of older age retinoblastoma and shows that it forms a significant percentage of retinoblastoma in developing countries, is misdiagnosed in one-third of cases, and may present at an advanced stage in 46% of cases.

Excisional penetrating keratoplasty for fungal interface keratitis after endothelial keratoplasty: surgical timing and visual outcome.

In this paper, we describe two cases of fungal interface infectious keratitis (IIK) developed after endothelial keratoplasty (EK) who underwent delayed therapeutic penetrating keratoplasty (TPK) with a poor visual outcome. Furthermore, we conducted a review of the literature and analyzed the visual outcomes of TPK in relation to the time from IIK diagnosis. We searched the literature for fungal IIK cases occurred after EK and treated by TPK. We identified 17 cases of fungal IIK, mostly caused by Candida spp. (88%). Infection was diagnosed at a median time of 21 (range 1-90days) days after EK. The median lag time between infection diagnosis and TPK was 30 (range 7-393) days. The median distance corrected visual acuity (DCVA) measured 4-12months after surgery was 20/40 (range 20/200-20/20). When TPK was performed within one month from diagnosis, the final median DCVA was 20/30 (range 20/100-20/20), with 83% of patients achieving ≥ 20/40 vision. When TPK was carried out later, the final median DCVA was 20/50 (range 20/200-20/22) with 44% of patients achieving ≥ 20/40 vision. One patient in the early surgery and four patients in the late surgery group showed postoperative DCVA ≤ 20/100 despite clear grafts. TPK with removal of the sequestered infection is advocated as a safe and effective measure to treat a post-EK infection. Early surgery allows a reduced exposure time to infection and therefore may result in better visual outcomes and lower risk of complications caused by prolonged inflammation.