Assessment of Real-World Patient-Reported Outcomes in Patients Initiating Biologic Agents for the Treatment of Autoimmune Diseases: An Observational Study in Four Patient-Powered Research Networks.

Background: The most reliable and meaningful approach for inclusion of patient-reported outcomes (PROs) in the evaluation of real-world clinical effectiveness of biologics in the treatment of autoimmune diseases is u ncertain. This study aimed to assess and compare the proportions of patients who had abnormalities in PROs measuring important general health domains at the initiation of treatment with biologics, as well as the effects of baseline abnormalities on subsequent improvement. Methods: PROs were collected for patient participants with inflammatory arthritis, inflammatory bowel disease, and vasculitis using Patient-Reported Outcomes Measurement Information System instruments. Scores were reported as T-scores normalized to the general population in the United States. Baseline PROs scores were collected near the time of biologic initiation, and follow-up scores were collected 3 to 8 months later. In addition to summary statistics, the proportion of patients with PROs abnormalities (scores ≥5 units worse than the population norm) was determined. Baseline and follow-up scores were compared, and an improvement of ≥5 units was considered significant. Results: There was wide variation across autoimmune diseases in baseline PROs scores for all domains. For example, the proportion of participants with abnormal baseline pain interference scores ranged from 52% to 93%. When restricted to participants with baseline PROs abnormalities, the proportion of participants experiencing an improvement of ≥5 units was substantially higher. Conclusion: As expected, many patients experienced improvement in PROs following initiation of treatment with biologics for autoimmune diseases. Nevertheless, a substantial proportion of participants did not exhibit abnormalities in all PROs domains at baseline, and these participants appear less likely to experience improvement. For PROs to be reliably and meaningfully included in the evaluation of real-world medication effectiveness, more knowledge and careful consideration are needed to select the most appropriate patient populations and subgroups for inclusion and evaluation in studies measuring change in PROs.

"How PrEPared are you?": Knowledge of and attitudes toward PrEP among overseas-born and newly arrived gay, bisexual, and other men who have sex with men in Australia.

Introduction: Overseas-born and newly arrived gay and bisexual men and men who have sex with men (GBMSM) are at higher risk of acquiring HIV in comparison to Australian-born GBMSM. Pre-exposure prophylaxis (PrEP) is subsidized by the Australian government under Medicare, Australia's universal health insurance scheme, however many members of this population are Medicare-ineligible, which could prevent them from accessing PrEP. We wanted to explore participants' knowledge of and attitudes toward PrEP and their opinions of new PrEP modalities, namely injectable PrEP and PrEP implants. Methods: We conducted in-depth qualitative interviews between February 2021 to September 2021 with 22 overseas-born, newly arrived (<5 years in Australia) GBMSM of varying PrEP use. We asked their opinions of PrEP and their preferences of new PrEP modalities. Interviews were audio recorded and transcribed verbatim. We conducted a reflexive thematic analysis to interpret the data. Results: Participants' views reflect the intersections between systemic factors, such as Medicare ineligibility and the high cost of PrEP, with socio-cultural factors, such as lack of knowledge about PrEP, internalized stigma stemming from homo- and sex-negativity, and stigmatizing attitudes toward PrEP and PrEP users. For participants who were on PrEP, being community connected, having a positive relationship with doctors and nurses, and being informed of the option to purchase PrEP from overseas pharmacies at a low cost helped them to overcome some of these barriers. Additionally, there was a strong preference for injectable PrEP but not PrEP implants. Participants stressed the importance of providing a comprehensive information about PrEP specific to this population and to make PrEP free for all. Conclusions: We concluded that resources about PrEP specific to this population that address both systemic and socio-cultural factors are needed, and for these resources to be available in languages other than English. This is to coincide with on-going advocacy to increase the capacity of publicly funded sexual health clinics to provide multilingual PrEP services for people without Medicare, and to make PrEP free for all. These combined strategies have the potential to increase PrEP knowledge and uptake among this population.

Measuring Human Perception to Improve Handwritten Document Transcription.

In this paper, we consider how to incorporate psychophysical measurements of human visual perception into the loss function of a deep neural network being trained for a recognition task, under the assumption that such information can reduce errors. As a case study to assess the viability of this approach, we look at the problem of handwritten document transcription. While good progress has been made towards automatically transcribing modern handwriting, significant challenges remain in transcribing historical documents. Here we describe a general enhancement strategy, underpinned by the new loss formulation, which can be applied to the training regime of any deep learning-based document transcription system. Through experimentation, reliable performance improvement is demonstrated for the standard IAM and RIMES datasets for three different network architectures. Further, we go on to show feasibility for our approach on a new dataset of digitized Latin manuscripts, originally produced by scribes in the Cloister of St. Gall in the the 9th century.

An AAV-based, room-temperature-stable, single-dose COVID-19 vaccine provides durable immunogenicity and protection in non-human primates.

The SARS-CoV-2 pandemic has affected more than 185 million people worldwide resulting in over 4 million deaths. To contain the pandemic, there is a continued need for safe vaccines that provide durable protection at low and scalable doses and can be deployed easily. Here, AAVCOVID-1, an adeno-associated viral (AAV), spike-gene-based vaccine candidate demonstrates potent immunogenicity in mouse and non-human primates following a single injection and confers complete protection from SARS-CoV-2 challenge in macaques. Peak neutralizing antibody titers are sustained at 1 year and complemented by functional memory T cell responses. The AAVCOVID vector has no relevant pre-existing immunity in humans and does not elicit cross-reactivity to common AAVs used in gene therapy. Vector genome persistence and expression wanes following injection. The single low-dose requirement, high-yield manufacturability, and 1-month stability for storage at room temperature may make this technology well suited to support effective immunization campaigns for emerging pathogens on a global scale.

Barriers and facilitators to pre-exposure prophylaxis among African migrants in high income countries: a systematic review.

Background The aim of this review is to explore acceptability, barriers, and facilitators to PrEP use among African migrants in high-income countries. METHODS: A systematic review was conducted to explore reasons that contribute to low PrEP uptake in this population. Three online databases, abstracts from key conferences and reference lists of relevant studies articles published between the 2 July 2018 and 3 March 2019 were searched. Narrative synthesis was performed on quantitative data and thematic synthesis was performed on qualitative data. RESULTS: Of 1779 titles retrieved, two cross-sectional studies (United States (US) (n = 1), United Kingdom (UK) (n = 1)) and six qualitative studies (US (n = 2), UK (n = 3), Australia (n = 1)) met inclusion criteria. PrEP acceptability was reported in one cross-sectional article and two qualitative articles. Cross-sectional studies measured acceptability and willingness to use PrEP; in one study, 46% of African migrant men found PrEP use acceptable, and following PrEP education, another study categorised 60% of participants as willing to use PrEP if it were cost-free. Qualitative studies reported mixed acceptability, with higher acceptability reported for serodiscordant couples. Barriers and facilitators to PrEP use were coded into five themes: cultural aspects of stigma; knowledge gap in health literacy; risks unrelated to HIV transmission; practical considerations for PrEP use; and the impact of PrEP use on serodiscordant couples. CONCLUSIONS: Several common barriers to PrEP use, including stigma, health literacy and risk perception and cost, were identified. Findings were limited by there being no published data on uptake. Additional work is needed to understand PrEP acceptability and uptake among African migrants.

Immunogenicity of an AAV-based, room-temperature stable, single dose COVID-19 vaccine in mice and non-human primates.

The SARS-CoV-2 pandemic has affected more than 70 million people worldwide and resulted in over 1.5 million deaths. A broad deployment of effective immunization campaigns to achieve population immunity at global scale will depend on the biological and logistical attributes of the vaccine. Here, two adeno-associated viral (AAV)-based vaccine candidates demonstrate potent immunogenicity in mouse and nonhuman primates following a single injection. Peak neutralizing antibody titers remain sustained at 5 months and are complemented by functional memory T-cells responses. The AAVrh32.33 capsid of the AAVCOVID vaccine is an engineered AAV to which no relevant pre-existing immunity exists in humans. Moreover, the vaccine is stable at room temperature for at least one month and is produced at high yields using established commercial manufacturing processes in the gene therapy industry. Thus, this methodology holds as a very promising single dose, thermostable vaccine platform well-suited to address emerging pathogens on a global scale.

Transformation of Australian Community Pharmacies Into Good Clinical Practice Compliant Trial Pharmacies for HIV Pre-Exposure Prophylaxis.

Background: In Australia, clinical trial drugs are conventionally dispensed through clinical trial pharmacies only, while community pharmacies dispense drugs approved by Australia's regulatory body. A large HIV pre-exposure prophylaxis study aimed to deliver clinical trial drug through community pharmacies to improve convenience and mimic real world prescribing. This paper describes the process of making community trials compliant with good clinical practice and reports outcomes of delivering clinical trial drug through community pharmacies. Methods: Eight community and four clinical trial pharmacies across three Australian states were approached to participate. A good clinical practice checklist was generated and pharmacies underwent a number of changes to meet clinical trial pharmacy requirements prior to study opening. Changes were made to community pharmacies to make them compliant with good clinical trial practice including; staff training, structural changes, and implementing monitoring of study drug and prescribing practices. Study drug was ordered through standard clinical trial processes and dispensed from study pharmacies by accredited pharmacists. Throughout the trial, record logs for training, prescriber signature and delegation, temperature, participant, and drug accountability were maintained at each pharmacy. The study team monitored each log and delivered on-site training to correct protocol variations. Results: Each pharmacy that was approached agreed to participate. All community pharmacies achieved good clinical practice compliance prior to dispensing study drug. Over the course of the study, 20,152 dispensations of study drug occurred, 83% of these occurred at community pharmacies. Only 2.0% of dispensations had an error, and errors were predominantly minor. On five occasions a pharmacist who was not accredited dispensed study drug. Conclusions: Community based pharmacies can undergo training and modifications to achieve good clinical practice compliance and dispense clinical trial study drug. Community based pharmacies recorded few variations from study protocol. Community based pharmacies offer a useful alternative to clinical trial pharmacies to increase convenience for study participants and expanded use of these pharmacies should be considered for large clinical trials, including HIV prevention trials.

Interest in Switching to On-Demand HIV Pre-Exposure Prophylaxis (PrEP) Among Australian Users of Daily PrEP: An Online Survey.

We surveyed 970 PrEPX study participants to evaluate interest in switching from daily to on-demand PrEP in a study setting. Interested respondents (n = 469, 48%) more commonly reported PrEP cessation (adjusted odds ratio [aOR], 3.0; P < .001), difficulty with adherence (aOR, 1.6; P = .029), infrequent sex (aOR, 3.7; P < .001), and toxicity concerns (aOR, 2.7; P < .001).

Association of HIV Preexposure Prophylaxis With Incidence of Sexually Transmitted Infections Among Individuals at High Risk of HIV Infection.

Importance: Emerging evidence suggests that risk of bacterial sexually transmitted infections (STIs) increases among gay and bisexual men following initiation of HIV preexposure prophylaxis (PrEP). Objective: To describe STI incidence and behavioral risk factors among a cohort of predominantly gay and bisexual men who use PrEP, and to explore changes in STI incidence following PrEP commencement. Design, Setting, and Participants: The Pre-exposure Prophylaxis Expanded (PrEPX) Study, a multisite, open-label intervention study, was nested within the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) clinic network. A total of 4275 participants were enrolled (July 26, 2016-April 1, 2018) in Victoria, Australia. Of these, 2981 enrolled at 5 ACCESS clinics (3 primary care, 1 sexual health, and 1 community-based HIV rapid testing service), had at least 1 follow-up visit, and were monitored until April 30, 2018. Exposures: Upon enrollment, participants received daily oral tenofovir disoproxil fumurate and emtricitabine for HIV PrEP, quarterly HIV and STI testing, and clinical monitoring. Main Outcomes and Measures: The primary outcome was incidence of chlamydia, gonorrhea, or syphilis. Incidence rates and hazard ratios describing behavioral risk factors of STI diagnosis were calculated. Incidence rate ratios (IRRs), adjusted for change in testing frequency, described changes in STI incidence from 1-year preenrollment to study follow-up among participants with preenrollment testing data (n = 1378). Results: Among the 2981 individuals (median age, 34 years [interquartile range, 28-42]), 98.5% identified as gay or bisexual males, 29% used PrEP prior to enrollment, 89 (3%) withdrew and were censored at date of withdrawal, leaving 2892 (97.0%) enrolled at final follow-up. During a mean follow-up of 1.1 years (3185.0 person-years), 2928 STIs were diagnosed among 1427 (48%) participants (1434 chlamydia, 1242 gonorrhea, 252 syphilis). STI incidence was 91.9 per 100 person-years, with 736 participants (25%) accounting for 2237 (76%) of all STIs. Among 2058 participants with complete data for multivariable analysis, younger age, greater partner number, and group sex were associated with greater STI risk, but condom use was not. Among 1378 participants with preenrollment testing data, STI incidence increased from 69.5 per 100 person-years prior to enrollment to 98.4 per 100 person-years during follow-up (IRR, 1.41 [95% CI, 1.29-1.56]). After adjusting for testing frequency, the increase in incidence from 1 year preenrollment to follow-up was significant for any STI (adjusted IRR, 1.12 [95% CI, 1.02-1.23]) and for chlamydia (adjusted IRR, 1.17 [95% CI, 1.04-1.33]). Conclusions and Relevance: Among gay and bisexual men using PrEP, STIs were highly concentrated among a subset, and receipt of PrEP after study enrollment was associated with an increased incidence of STIs compared with preenrollment. These findings highlight the importance of frequent STI testing among gay and bisexual men using PrEP.

Protocol for an HIV Pre-exposure Prophylaxis (PrEP) Population Level Intervention Study in Victoria Australia: The PrEPX Study.

Background: Pre-exposure prophylaxis (PrEP) is the use of HIV anti-retroviral therapy to prevent HIV transmission in people at high risk of HIV acquisition. PrEP is highly efficacious when taken either daily, or in an on-demand schedule. In Australia co-formulated tenofovir-emtricitabine is registered for daily use for PrEP, however, this co-formulation is not listed yet on the national subsidized medicines list. We describe a study protocol that aims to demonstrate if the provision of PrEP to up to 3800 individuals at risk of HIV in Victoria, Australia reduces HIV incidence locally by 25% generally and 30% among GBM. Methods: PrEPX is a population level intervention study in Victoria, Australia in which generic PrEP will be delivered to 3800 individuals for up to 36 months. Study eligibility is consistent with the recently updated 2017 Australian PrEP guidelines. Participants will attend study clinics, shared care clinics, or outreach clinics for quarterly HIV/STI screening, biannual renal function tests and other clinical care as required. Study visits and STI diagnoses will be recorded electronically through the ACCESS surveillance system. At each study visit participants will be invited to complete behavioral surveys that collect demographics and sexual risk data. Diagnosis and behavioral data will be compared between PrEPX participants and other individuals testing within the ACCESS surveillance system. A subset of participants will complete in depth surveys and interviews to collect attitudes, beliefs and acceptability data. Participating clinics will provide clinic level data on implementation and management of PrEPX participants. The population level impact on HIV incidence will be assessed using Victorian HIV notification data. Discussion: This study will collect evidence on the real world impact of delivery of PrEP to 3800 individuals at risk of acquiring HIV in Victoria. This study will provide important information for the broader implementation of PrEP planning upon listing of the tenofovir-emtricitabine on the national subsidized list of medicines. The study is registered on the Australian New Zealand Clinical Trials Registry (ACTRN12616001215415).

Evaluation of Preexposure (PrEP) Eligibility Criteria, Using Sexually Transmissible Infections as Markers of Human Immunodeficiency Virus (HIV) Risk at Enrollment in PrEPX, a Large Australian HIV PrEP Trial.

Background: To determine participants' human immunodeficiency virus (HIV) risk, the Australian preexposure prophylaxis (PreEPX) trial used 6 eligibility criteria derived from the US Centers for Disease Control and Prevention PrEP guidelines. Participants who fulfilled no eligibility criteria could be enrolled if clinically assessed to need PrEP. This study evaluated whether PREPX eligibility criteria correlated with biological HIV risk markers-namely, syphilis, anorectal chlamydia, or anorectal gonorrhea (sexually transmitted infections [STIs]). Methods: We calculated adjusted odds ratios (aORs) to assess whether eligibility criteria predicted STI diagnoses at enrollment. Results: We included 1774 participants, of whom 10.2% tested positive for STIs. Eligibility criteria predicted STI diagnoses as follows: (1) aOR 2.5 (95% confidence interval [CI], 1.4-4.4) for condomless anal intercourse (CLAI) with an HIV-positive regular sexual partner (RSP) with detectable viral load; (2) aOR 1.8 (95% CI, 1.3-2.5) for receptive CLAI with casual sexual partners; (3) aOR 1.8 (95% CI, 1.3-2.5) for previous STIs; (4) aOR 2.1 (95% CI, 1.4-3.0) for methamphetamine use; (5) aOR 0.8 (95% CI, .6-1.1) for unsuccessful condom use; and (6) aOR 1.0 (95% CI, .7-1.4) for insertive CLAI when uncircumcised. Of participants enrolled outside eligibility criteria, 7.1% had STIs. Conclusions: Eligibility criteria 1-4 predicted diagnoses of STIs, but eligibility criteria 5 and 6 did not. Our findings support the use of PrEP eligibility criteria recommended in current guidelines. Participants enrolled outside the eligibility criteria had substantial prevalence of STIs, suggesting that people who request PrEP but do not fulfill eligibility criteria may nonetheless need PrEP.

Recumbent Stepper Submaximal Test response is reliable in adults with and without stroke.

PURPOSE: The purpose of the present study was to determine the reliability of the exercise response (predicted peak VO2) using the total body recumbent stepper (TBRS) submaximal exercise test in: 1) healthy adults 20-70 years of age and 2) adults participating in inpatient stroke rehabilitation. We hypothesized that the predicted peak VO2 (Visit 1) would have an excellent relationship (r > 0.80) to predicted peak VO2 (Visit 2). We also wanted to test whether the exercise response at Visit 1 and Visit 2 would be significantly different. METHODS: Healthy adults were recruited from the Kansas City metro area. Stroke participants were recruited during their inpatient rehabilitation stay. Eligible participants completed 2 TBRS submaximal exercise tests between 24 hours and 5 days at similar times of day. RESULTS: A total of 70 participants completed the study. Healthy adults (n = 50) were 36 M, 38.1 ± 10.1 years and stroke participants (n = 20) were 15 M, 62.5 ± 11.8 years of age. The exercise response was reliable for healthy adults (r = 0.980, p<0.01) and stroke participants (r = 0.987, p<0.01) between Visit 1 and Visit 2. Repeated Measures ANOVA showed a significant difference in predicted values between the two visits for healthy adults (47.2 ± 8.4 vs 47.7 ± 8.5 mL∙kg-1∙min-1; p = 0.04) but not for stroke participants (25.0 ± 9.9 vs 25.3 ± 11.4 mL∙kg-1∙min-1; p = 0.65). CONCLUSION: These results suggest that the exercise response is reliable using the TBRS submaximal exercise test in this cohort of healthy adults and stroke participants.

Comparing non-occupational post-exposure prophylaxis drug regimens for HIV: insights from a linked HIV surveillance system.

Background International non-occupational post-exposure prophylaxis (NPEP) guidelines recommend routine use of three drug NPEP regimens, despite absence of evidence for greater prevention efficacy compared with two drug regimens. This study examines the potential for excess HIV seroconversions among high-risk men who have sex with men (MSM) reporting receptive anal intercourse with a source of unknown HIV serostatus (RAIU) following a two-drug versus a three-drug NPEP regimen. METHODS: Data for MSM in the Victorian NPEP service database between 10 August 2005 and 31 December 2012 were linked with all Victorian HIV notifications up to 31 December 2013. The primary outcome was NPEP failure following NPEP presentation among MSM reporting RAIU, stratified by the number of drugs prescribed. RESULTS: Among 1482 MSM reporting 2002 episodes of RAIU and prescribed two- or three-drug NPEP, 70 seroconverted to HIV, but only 19 were considered possible NPEP failures. HIV diagnosis incidence among men reporting RAIU was 1.2/100 person years (PY) (95%CI=1.0-1.6); 1.1/100 PY (95%CI=0.8-1.4) among MSM prescribed two drugs and 2.2/100 PY (95%CI=1.4-3.7) among MSM prescribed three drugs (P<0.01). Of the 19 possible NPEP failures, 13 (0.7%) were prescribed two drugs and six (2.7%) three drugs (P<0.001). CONCLUSIONS: This study suggests that two-drug NPEP regimens do not result in excess seroconversions compared with three-drug regimens when used following RAIU. Clinical services should carefully consider their use of three drug NPEP and whether resources might be better invested in other prevention strategies, particularly pre-exposure prophylaxis (PrEP).

Fast Appearance Modeling for Automatic Primary Video Object Segmentation.

Automatic segmentation of the primary object in a video clip is a challenging problem as there is no prior knowledge of the primary object. Most existing techniques thus adapt an iterative approach for foreground and background appearance modeling, i.e., fix the appearance model while optimizing the segmentation and fix the segmentation while optimizing the appearance model. However, these approaches may rely on good initialization and can be easily trapped in local optimal. In addition, they are usually time consuming for analyzing videos. To address these limitations, we propose a novel and efficient appearance modeling technique for automatic primary video object segmentation in the Markov random field (MRF) framework. It embeds the appearance constraint as auxiliary nodes and edges in the MRF structure, and can optimize both the segmentation and appearance model parameters simultaneously in one graph cut. The extensive experimental evaluations validate the superiority of the proposed approach over the state-of-the-art methods, in both efficiency and effectiveness.

Inner and inter label propagation: salient object detection in the wild.

In this paper, we propose a novel label propagation-based method for saliency detection. A key observation is that saliency in an image can be estimated by propagating the labels extracted from the most certain background and object regions. For most natural images, some boundary superpixels serve as the background labels and the saliency of other superpixels are determined by ranking their similarities to the boundary labels based on an inner propagation scheme. For images of complex scenes, we further deploy a threecue-center-biased objectness measure to pick out and propagate foreground labels. A co-transduction algorithm is devised to fuse both boundary and objectness labels based on an inter propagation scheme. The compactness criterion decides whether the incorporation of objectness labels is necessary, thus greatly enhancing computational efficiency. Results on five benchmark data sets with pixelwise accurate annotations show that the proposed method achieves superior performance compared with the newest state-of-the-arts in terms of different evaluation metrics.

Adaptive Metric Learning for Saliency Detection.

In this paper, we propose a novel adaptive metric learning algorithm (AML) for visual saliency detection. A key observation is that the saliency of a superpixel can be estimated by the distance from the most certain foreground and background seeds. Instead of measuring distance on the Euclidean space, we present a learning method based on two complementary Mahalanobis distance metrics: 1) generic metric learning (GML) and 2) specific metric learning (SML). GML aims at the global distribution of the whole training set, while SML considers the specific structure of a single image. Considering that multiple similarity measures from different views may enhance the relevant information and alleviate the irrelevant one, we try to fuse the GML and SML together and experimentally find the combining result does work well. Different from the most existing methods which are directly based on low-level features, we devise a superpixelwise Fisher vector coding approach to better distinguish salient objects from the background. We also propose an accurate seeds selection mechanism and exploit contextual and multiscale information when constructing the final saliency map. Experimental results on various image sets show that the proposed AML performs favorably against the state-of-the-arts.

Functional and evolutionary characterization of the CONSTANS gene family in short-day photoperiodic flowering in soybean.

CONSTANS (CO) plays a central role in photoperiodic flowering control of plants. However, much remains unknown about the function of the CO gene family in soybean and the molecular mechanisms underlying short-day photoperiodic flowering of soybean. We identified 26 CO homologs (GmCOLs) in the soybean genome, many of them previously unreported. Phylogenic analysis classified GmCOLs into three clades conserved among flowering plants. Two homeologous pairs in Clade I, GmCOL1a/GmCOL1b and GmCOL2a/GmCOL2b, showed the highest sequence similarity to Arabidopsis CO. The mRNA abundance of GmCOL1a and GmCOL1b exhibited a strong diurnal rhythm under flowering-inductive short days and peaked at dawn, which coincided with the rise of GmFT5a expression. In contrast, the mRNA abundance of GmCOL2a and GmCOL2b was extremely low. Our transgenic study demonstrated that GmCOL1a, GmCOL1b, GmCOL2a and GmCOL2b fully complemented the late flowering effect of the co-1 mutant in Arabidopsis. Together, these results indicate that GmCOL1a and GmCOL1b are potential inducers of flowering in soybean. Our data also indicate rapid regulatory divergence between GmCOL1a/GmCOL1b and GmCOL2a/GmCOL2b but conservation of their protein function. Dynamic evolution of GmCOL regulatory mechanisms may underlie the evolution of photoperiodic signaling in soybean.

Hemodynamic consequences of ketamine vs etomidate for endotracheal intubation in the air medical setting.

OBJECTIVE: Recent drug shortages have required the occasional replacement of etomidate for endotracheal intubation (ETI) by helicopter emergency medical services (HEMS), with ketamine. The purpose of this study was to assess whether there was an association between ketamine vs etomidate use as the main ETI drug, with hemodynamic or clinical (airway) end points. METHODS: This retrospective study used data entered into medical records at the time of HEMS transport. Subjects, 50 ketamine and 50 etomidate, were accrued from 3 US HEMS programs. The study period was from August 2011 through May 2012. Data collection included demographics, diagnostic category, ETI drugs use, ETI success, and complications. Hemodynamic parameters were assessed for up to 2 sets of vital signs before airway management and up to 5 sets of post-ETI vital signs. Significance was defined at the P < .05 level. RESULTS: Patients on ketamine and etomidate were similar (P > .05) with respect to age, sex, scene/interfacility mission type, trauma vs nontrauma, neuromuscular blocking agent use, and rates of coadministration of fentanyl or midazolam. All patients had successful airway placement. Peri-ETI hypoxemia was seen in 10% of etomidate and 16% of ketamine cases (P = .55). The pre-ETI and post-ETI were similar between the ketamine and etomidate groups with respect to systolic blood pressure and heart rate at every vital signs assessment after ETI. CONCLUSION: Initial assessment of ETI success and complication rates, as well as peri-ETI hemodynamic changes, suggests no concerning complications associated with large-scale replacement of etomidate with ketamine as the major airway management drug for HEMS.

Central scotoma without prodromal illness caused by Bartonella henselae neuroretinitis.

This case report describes Bartonella henselae neuroretinitis in a 26-year-old woman who presented to the emergency department with unilateral central scotoma and no prodromal symptoms, a unique presentation of this disease. B henselae, a gram-negative bacteria, is the cause of cat scratch disease. Cat scratch disease (CSD) is a self-limiting illness, which typically presents with regional lymphadenopathy, fever, and small skin lesions in associationwith a cat scratch or bite. The mostcommon ocular manifestations of cat scratch disease are Parinaud oculoglandular syndrome and neuroretinitis. All prior reported cases of CSD neuroretinitis presented with prodromal symptoms, not vision loss alone.

HIV seroconversions among male non-occupational post-exposure prophylaxis service users: a data linkage study.

BACKGROUND: Despite widespread prescription of non-occupational post-exposure prophylaxis (NPEP) in Victoria, little is known about subsequent HIV acquisition among NPEP users. We linked the Victorian NPEP Service (VNPEPS) database and the Victorian HIV Surveillance Registry to determine the number, incidence rate and predictive factors of HIV seroconversions among users of the VNPEPS. METHODS: Records from male patients that received NPEP in the VNPEPS database (n = 1420) between January 2001 and February 2008 were linked with all entries in the Victorian HIV Surveillance Registry up to May 2008. RESULTS: Sixty-one men who presented to the VNPEPS were identified as HIV seropositive; 16 of these were diagnosed at initial presentation for NPEP. The incidence of HIV seroconversion in males who were HIV seronegative at first presentation for NPEP was 1.27 (95% confidence interval 0.95-1.70) per 100 person-years. There was no association between HIV seroconversion and number of NPEP presentations or age. The median age of seroconversion was 34.6 years. CONCLUSION: The incidence of HIV infection among men presenting to the VNPEPS is slightly lower than the HIV incidence in NPEP users in a recent Australian cohort study of men who have sex with men, but higher than HIV incidence in general gay male populations. Frequency of NPEP use was not associated with risk of HIV seroconversion. Examination of risk behaviour before and after NPEP use in this population is required to further assess the impact of NPEP availability and use on HIV incidence rates and risk behaviour in Australia.