Measuring training effectiveness of laboratory biosafety program offered at African Center for Integrated Laboratory Training in 22 President's Emergency Plan for AIDS Relief supported countries (2008-2014).

INTRODUCTION: The African Center for Integrated Laboratory Training (ACILT) in Johannesburg, South Africa offered a laboratory biosafety program to improve laboratory biosafety practices in 22 President's Emergency Plan for AIDS Relief (PEPFAR) supported countries. This manuscript evaluates the transference of newly gained knowledge and skills to the participants' place of employment for HIV and TB diagnostic laboratory programs. It also serves as a follow-on to a previously published manuscript that measured training effectiveness for all courses offered at ACILT. METHODS: ACILT offered 20 Laboratory Biosafety and Infrastructure courses (2008-2014), also referred as biosafety course/course comprising of 14 core laboratory safety elements to 402 participants from 22 countries. In 2015, participants received 22 e-questions divided into four categories: (1) Safety Policies, (2) Management's Engagement, (3) Safety Programs and (4) Assessments of Safety Practices to determine retrospectively the training effectiveness of biosafety practices in their place of employment 6 months before and after attending their course. We used Kirkpatrick model to assess the transference of knowledge, skills and obstructive factors. RESULTS: 20% (81/402) of the participants completed the e-questionnaire. The overall percentage of positive responses indicating implementation of new safety practices increased from 50% to 84%. Improvement occurred in all four categories after attending the course, with the greatest increases in Safety Policies (67-94%) and Safety Programs (43-91%). Creating a safety committee, allocating resources, and establishing a facility safety policy were important drivers for implementing and maintaining laboratory safety practices. In addition, accredited laboratories and countries with national safety regulations or policies had a higher percentage of improvements. The most reported challenges were inadequate funding and lack of management enforcement. CONCLUSIONS: PEPFAR and other partners' investments in training institutions, such as ACILT, were effective in building sustainable country ownership to strengthen biosafety practices and were leveraged to combat zoonotic diseases and COVID-19. Although support continues at the national/regional level, a standardized, coordinated and continent-wide sustainable approach to offer a biosafety program-like ACILT is missing. Continuous offerings of biosafety programs similar to ACILT could contribute to sustainable strengthening of laboratory biosafety, QMS and pandemic preparedness.

Pediatric glaucoma suspects: characteristics and outcomes.

PURPOSE: To determine the characteristics of children diagnosed with glaucoma suspect (GS) status, their clinical outcomes, and risk factors for progression to a diagnosis of glaucoma. METHODS: This was a retrospective sequential cohort study of children <18 years diagnosed as GS between 2013 and 2019, based on clinical (C-GS) and CGRN (CGRN-GS) criteria. Children with penetrating ocular trauma, steroid-response, treated ocular hypertension, and glaucoma at presentation were excluded. Outcomes included glaucoma, treated ocular hypertension, nonglaucomatous cupping (pseudoglaucomatous or physiologic), or persistent GS. Secondary outcomes were characteristics of children who progressed to glaucoma. RESULTS: A total of 887 children (mean age, 9.3 ± 4.7 years) were diagnosed as C-GS, because of optic nerve appearance (83%), family history (25%), ocular hypertension (15%), periocular lesion (4% [eg, Sturge-Weber]), blunt-trauma history (3%), ocular anomaly (2%), and systemic/genetic syndrome (1.5%). Outcomes among 487 children with one or more follow-up visits (mean, 1.7 ± 1.6 years) included 14 (3%) with glaucoma, 98 (20%) with physiologic cupping, 50 (10%) with prematurity-associated cupping, and 1 (0.2%) with treated ocular hypertension; 324 (67%) remained GS. Of children lost to follow-up, 116 (29%) were suspected physiologic or pseudoglaucomatous. Glaucoma diagnosis occurred at a mean age of 8.4 ± 5.5 years, based on elevated intraocular pressure (IOP; 79%), optical coherence tomography changes (43%), disk changes (21%), or field defects (14%). Risk factors for glaucoma were baseline IOP of ≥24 (P = 0.01) and periocular lesion (P = 0.008). Results from 773 children who met CGRN-GS criteria were similar. CONCLUSIONS: Risk of conversion to glaucoma diagnosis among children with glaucoma suspect status appears low. Baseline cup:disk ratio and family history of glaucoma were not predictive of glaucoma diagnosis. Baseline IOP >24 and presence of a periocular lesion carry higher risk.

Identifying unique barriers to implementing rural emergency department-based peer services for opioid use disorder through qualitative comparison with urban sites.

BACKGROUND: In an effort to address the current opioid epidemic, a number of hospitals across the United States have implemented emergency department-based interventions for engaging patients presenting with opioid use disorder. The current study seeks to address gaps in knowledge regarding implementation of a sub-type of such interventions, emergency department-based peer support services, in rural areas by comparing implementation of rural and urban programs that participated in Indiana's Recovery Coach and Peer Support Initiative (RCPSI). METHODS: We conducted a secondary analysis of qualitative semi-structured implementation interviews collected as part of an evaluation of 10 programs (4 rural and 6 urban) participating in the RCPSI. We conducted interviews with representatives from each program at 3 time points over the course of the first year of implementation. Our deductive coding process was guided by the Consolidated Framework for Implementation Research (CFIR) and an external context taxonomy. RESULTS: We identified key differences for rural programs corresponding to each of the 5 primary constructs in the coding scheme. (1) Intervention characteristics: rural sites questioned intervention fit with their context, required more adaptations, and encountered unexpected costs. (2) External context: rural sites were not appropriately staffed to meet patient needs, encountered logistical and legal barriers regarding patient privacy, and had limited patient transportation options. (3) Inner setting: rural sites lacked strong mechanisms for internal communication and difficulties integrating with pre-existing culture and climate. (4) Characteristics of individuals: some rural providers resisted working with peers due to pre-existing attitudes and beliefs. (5) Implementation process: rural sites spent more time identifying external partners and abandoned more components of their initial implementation plans. CONCLUSIONS: Findings demonstrate how rural programs faced greater challenges implementing emergency department-based peer services over time. These challenges required flexible adaptations to originally intended plans. Rural programs likely require flexibility to adapt interventions that were developed in urban settings to ensure success considering local contextual constraints that were identified by our analysis.

Navigating intersecting public health crises: a qualitative study of people with opioid use disorders' experiences during the COVID-19 pandemic.

BACKGROUND: The decades-long opioid epidemic and the more recent COVID-19 pandemic are two interacting events with significant public health impacts for people with opioid use disorder (OUD). Most published studies regarding the intersection of these two public health crises have focused on community, state, or national trends using pre-existing data. There is a need for complementary qualitative research aimed at identifying how people with opioid use disorder (OUD) are understanding, experiencing, and navigating this unprecedented time. The current study examines understandings and experiences of people with OUD while they have navigated these crises. METHODS: The study was guided by a pragmatic lens. We conducted brief semi-structured qualitative interviews with 25 individuals in Chicago, the majority of which had received methadone treatment during the pandemic. Thematic inductive analysis was guided by primary interview questions. RESULTS: The sample represents a high-risk group, being composed mostly of older non-Hispanic African American males and having considerable socioeconomic barriers. Themes demonstrate how individuals are keeping safe despite limited knowledge of COVID-19, how the pandemic has increased treatment motivation for some, how adaptations impacted treatment and recovery supports, how the availability social support had been reduced, and difficulties individuals had keeping or obtaining financial support. CONCLUSIONS: The findings can be useful for informing future public health response to ensure appropriate treatment access and supports are available. In particular are the need for treatment providers to ensure people with OUD receive appropriate and understandable health crisis-related information and ensuring funds are appropriately allocated to address mental health impacts of social isolation. Finally, there is a need for appropriate financial and infrastructure supports to ensure health and treatment access disparities are not exacerbated for those in greatest need.

Variation in brief treatment for substance use disorder: a qualitative investigation of four federally qualified health centers with SBIRT services.

BACKGROUND: Brief treatment (BT) can be an effective, short-term, and low-cost treatment option for many people who misuse alcohol and drugs. However, inconsistent implementation is suggested to result in BT that often looks and potentially costs similar to regular outpatient care. Prior research is also rife with inconsistent operationalizations regarding the measurement of BT received by patients. As such, there is a need to more explicitly identify and document variations in BT practice. METHODS: A qualitative investigation of BT in four Federally Qualified Health Centers (FQHC) was undertaken as a sub study of a larger clinical trial. Researchers interviewed 12 staff (administrators and clinicians) involved in BT oversight, referral, or delivery within the four FQHCs. Data were analyzed following an inductive approach guided by the primary research questions. RESULTS: Findings demonstrate considerable differences in how BT was conceptualized and implemented within the FQHCs. This included a variety of ways in which BT was presented and described to patients that likely impacts how they perceive the BT they receive, including potentially not understanding they received substance use disorder treatment at all. CONCLUSIONS: The findings raise questions regarding the validity of prior research, demonstrating more objective definitions of BT and fidelity checklists are needed to ensure integrity of results. Future work in this area should seek to understand BT as practiced among a larger sample of providers and the direct experiences and perspectives of patients. There is also a need for more consistent implementation, quality assurance guidelines, and standardized stage of change assessments to aid practitioners.

Adaptations to Indiana's 21st Century Cures-funded recovery coaching initiative in the wake of COVID-19.

This brief commentary discusses how provider organizations from Indiana's Recovery Coach and Peer Support Initiative (RCPSI) adapted their practices in response to the COVID-19 pandemic and associated restrictions. The RCPSI, which is funded through the 21st Century Cures Act, placed peer recovery coaches (PRCs) in emergency departments (EDs) to link opioid overdose patients to medication for opioid use disorder. This commentary discusses how COVID-19 restrictions increased use of telehealth to replace in-person PRC contacts with patients, affected the timing of initial PRC contacts with patients, and led to allowances for Medicaid billing of recovery coach support sessions conducted via telehealth. Future research should further determine the effects of these changes on PRC services in the ED.

Syringe service program-based telemedicine linkage to opioid use disorder treatment: protocol for the STAMINA randomized control trial.

BACKGROUND: A key strategy for mitigating the current opioid epidemic is expanded access to medications for treating opioid use disorder (MOUD). However, interventions developed to expand MOUD access have limited ability to engage opioid users at higher levels of overdose risk, such as those who inject opioids. This paper describes the study protocol for testing STAMINA (Syringe Service Telemedicine Access for Medication-assisted Intervention through NAvigation), an intervention that engages high-risk opioid users at community-based syringe service programs (SSP) and quickly links them to MOUD using a telemedicine platform. METHODS: This randomized control trial will be conducted at three SSP sites in Chicago. All participants will complete an initial assessment with a provider from a Federally Qualified Health Center who can prescribe or refer MOUD services as appropriate. The control arm will receive standard referral to treatment and the intervention arm will receive immediate telemedicine linkage to the provider and (depending on the type of MOUD prescribed) provided transportation to pick up their induction prescription (for buprenorphine or naltrexone) or attend their intake appointment (for methadone). We aim to recruit a total of 273 participants over two years to provide enough power to detect a difference in our primary outcome of MOUD treatment linkage. Secondary outcomes include treatment engagement, treatment retention, and non-MOUD opioid use. Data will be collected using structured interviews and saliva drug tests delivered at baseline, three months, and six months. Fixed and mixed effects generalized linear regression analyses and survival analysis will be conducted to compare the probabilities of a successful treatment linkage between the two arms, days retained in treatment, and post-baseline opioid and other drug use. DISCUSSION: If successful, STAMINA's telemedicine approach will significantly reduce the amount of time between SSP clients' initial indication of interest in the medication and treatment initiation. Facilitating this process will likely lead to stronger additional treatment- and recovery-oriented outcomes. This study is also timely given the need for more rigorous testing of telemedicine interventions in light of temporary regulatory changes that have occurred during the COVID-19 pandemic. TRIAL REGISTRATION: ClinicalTrials.gov (Clinical Trials ID: NCT04575324 and Protocol Number: 1138-0420). Registered 29 September 2020. The study protocol is also registered on the Open Science Framework (DOI 10.17605/OSF.IO/4853 M).

Implementation of peer recovery coach services for opioid overdose patients in emergency departments in Indiana: findings from an informal learning collaborative of stakeholders.

The Recovery Coach and Peer Support Initiative (RCPSI) in Indiana focused on implementing peer recovery coaches (PRCs) to engage opioid overdose patients in emergency department (ED) settings and promote entry into recovery services. State workers and researchers organized an informal learning collaborative primarily through teleconference meetings with representatives of 11 health service vendors to support implementation. This study presents qualitative analysis of the teleconference meeting discussions that guided RCPSI implementation to display how the informal learning collaborative functioned to support implementation. This informal learning collaborative model can be applied in similar situations where there is limited guidance available for a practice being implemented by multidisciplinary teams. Authors conducted a thematic analysis of data from 32 stakeholder teleconference meetings held between February 2018 and April 2020. The analysis explored the function of these collaborative teleconferences for stakeholders. Major themes representing functions of the meetings for stakeholders include: social networking; executing the implementation plan; identifying and addressing barriers and facilitators; educating on peer recovery services and target population; and working through data collection. During the last 2 months of meetings, stakeholders discussed how the COVID-19 pandemic created multiple barriers but increased use of telehealth for recovery services. Teleconference meetings served as the main component of an informal learning collaborative for the RCPSI through which the vendor representatives could speak with each other and with organizers as they implemented the use of PRCs in EDs.

Deciphering the role of ttrA and pduA genes for Salmonella enterica serovars in a chicken infection model.

Salmonella enterica serovars use self-induced intestinal inflammation to increase electron acceptor availability and to obtain a growth advantage in the host gut. There is evidence suggesting that the ability of Salmonella to use tetrathionate and 1,2-propanediol provides an advantage in murine infection. Thus, we present here the first study to evaluate both systemic infection and faecal excretion in commercial poultry challenged by Salmonella Enteritidis (SE) and S. Typhimurium (STM) harbouring deletions in ttrA and pduA genes, which are crucial to the metabolism of tetrathionate and 1,2-propanediol, respectively. Mutant strains were excreted at higher rates when compared to the wild-type strains. The highest rates were observed with white egg-layer and brown egg-layer chicks (67.5%), and broiler chicks (56.7%) challenged by SEΔttrAΔpduA, and brown egg-layer chicks (64.8%) challenged by STMΔttrAΔpduA. SEΔttrAΔpduA presented higher bacterial counts in the liver and spleen of the three chicken lineages and caecal contents from the broiler chickens, whereas STMΔttrAΔpduA presented higher counts in the liver and spleen of the broiler and brown-egg chickens for 28 days post-infection (P < 0.05). The ttrA and pduA genes do not appear to be major virulence determinants in faecal excretion or invasiveness for SE and STM in chickens. RESEARCH HIGHLIGHTSttrA and pudA do not impair gut colonization or systemic infection in chicks.Mutant strains were present in higher numbers in broilers than in laying chicks.Mutants of SE and STM showed greater pathogenicity in broiler chicks than layers.

The $74,973 Question: Are Medicare Beneficiaries Informed Users of Private Medical Care Contracts?

Health-care providers are allowed to opt-out of Medicare, privately contract with beneficiaries, and require that beneficiaries pay the full cost of services. Responses from a nationally representative sample of Medicare beneficiaries reveal that they lack the knowledge necessary to make informed decisions regarding such contracts. For example, only 4.6% of participants knew the correct answer to a real-life $74,973 question, leaving a full 95.4% vulnerable to paying a large bill, even a $74,973 bill, they should not pay. In addition to advocating that Medicare effectively monitor private medical care contracts, social workers should educate beneficiaries and/or their caregivers on the implications of entering into such contracts or refer them to their State Health Insurance Assistance Program or Senior Medicare Patrol program for expert guidance.

Association Between Third-Trimester Tdap Immunization and Neonatal Pertussis Antibody Concentration.

Importance: Immunization with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in the United States during weeks 27 through 36 of pregnancy to prevent life-threatening infant pertussis. The optimal gestation for immunization to maximize concentrations of neonatal pertussis toxin antibodies is unknown. Objective: To determine pertussis toxin antibody concentrations in cord blood from neonates born to women immunized and unimmunized with Tdap vaccine in pregnancy and optimal gestational age for immunization to maximize concentrations of neonatal antibodies. Design, Setting, and Participants: Prospective, observational, cohort study of term neonates in Houston, Texas (December 2013-March 2014). Exposures: Tdap immunization during weeks 27 through 36 of pregnancy or no Tdap immunization. Main Outcomes and Measures: Primary outcome was geometric mean concentrations (GMCs) of pertussis toxin antibodies in cord blood of Tdap-exposed and Tdap-unexposed neonates and proportions of Tdap-exposed and Tdap-unexposed neonates with pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher, cutoffs representing quantifiable antibodies or levels that may be protective until the infant immunization series begins. Secondary outcome was the optimal gestation for immunization to achieve maximum pertussis toxin antibodies. Results: Six hundred twenty-six pregnancies (mean maternal age, 29.7 years; 41% white, 27% Hispanic, 26% black, 5% Asian, 1% other; mean gestation, 39.4 weeks) were included. Three hundred twelve women received Tdap vaccine at a mean gestation of 31.2 weeks (range, 27.3-36.4); 314 were unimmunized. GMC of neonatal cord pertussis toxin antibodies from the Tdap-exposed group was 47.3 IU/mL (95% CI, 42.1-53.2) compared with 12.9 IU/mL (95% CI, 11.7-14.3) in the Tdap-unexposed group, for a GMC ratio of 3.6 (95% CI, 3.1-4.2; P < .001). More Tdap-exposed than Tdap-unexposed neonates had pertussis toxin antibody concentrations of 15 IU/mL or higher (86% vs 37%; difference, 49% [95% CI, 42%-55%]), 30 IU/mL or higher (72% vs 17%; difference, 55% [95% CI, 49%-61%]), and 40 IU/mL or higher (59% vs 12%; difference, 47% [95% CI, 41%-54%]); P < .001 for each analysis. GMCs of pertussis toxin antibodies were highest when Tdap vaccine was administered during weeks 27 through 30 and declined thereafter, reaching a peak at week 30 (57.3 IU/mL [95% CI, 44.0-74.6]). Conclusions and Relevance: Immunization with Tdap vaccine during the third trimester of pregnancy, compared with no immunization, was associated with higher neonatal concentrations of pertussis toxin antibodies. Immunization early in the third trimester was associated with the highest concentrations.

Clinical evaluation and validation of laboratory methods for the diagnosis of Bordetella pertussis infection: Culture, polymerase chain reaction (PCR) and anti-pertussis toxin IgG serology (IgG-PT).

INTRODUCTION: The appropriate use of clinically accurate diagnostic tests is essential for the detection of pertussis, a poorly controlled vaccine-preventable disease. The purpose of this study was to estimate the sensitivity and specificity of different diagnostic criteria including culture, multi-target polymerase chain reaction (PCR), anti-pertussis toxin IgG (IgG-PT) serology, and the use of a clinical case definition. An additional objective was to describe the optimal timing of specimen collection for the various tests. METHODS: Clinical specimens were collected from patients with cough illness at seven locations across the United States between 2007 and 2011. Nasopharyngeal and blood specimens were collected from each patient during the enrollment visit. Patients who had been coughing for ≤ 2 weeks were asked to return in 2-4 weeks for collection of a second, convalescent blood specimen. Sensitivity and specificity of each diagnostic test were estimated using three methods-pertussis culture as the "gold standard," composite reference standard analysis (CRS), and latent class analysis (LCA). RESULTS: Overall, 868 patients were enrolled and 13.6% were B. pertussis positive by at least one diagnostic test. In a sample of 545 participants with non-missing data on all four diagnostic criteria, culture was 64.0% sensitive, PCR was 90.6% sensitive, and both were 100% specific by LCA. CRS and LCA methods increased the sensitivity estimates for convalescent serology and the clinical case definition over the culture-based estimates. Culture and PCR were most sensitive when performed during the first two weeks of cough; serology was optimally sensitive after the second week of cough. CONCLUSIONS: Timing of specimen collection in relation to onset of illness should be considered when ordering diagnostic tests for pertussis. Consideration should be given to including IgG-PT serology as a confirmatory test in the Council of State and Territorial Epidemiologists (CSTE) case definition for pertussis.

Simultaneous Versus Sequential Ptosis and Strabismus Surgery in Children.

PURPOSE: The authors sought to compare the clinical outcomes of simultaneous versus sequential ptosis and strabismus surgery in children. METHODS: Retrospective, single-center cohort study of children requiring both ptosis and strabismus surgery on the same eye. Simultaneous surgeries were performed during a single anesthetic event; sequential surgeries were performed at least 7 weeks apart. Outcomes were ptosis surgery success (margin reflex distance 1 ≥ 2 mm, good eyelid contour, and good eyelid crease); strabismus surgery success (ocular alignment within 10 prism diopters of orthophoria and/or improved head position); surgical complications; and reoperations. RESULTS: Fifty-six children were studied, 38 had simultaneous surgery and 18 sequential. Strabismus surgery was performed first in 38/38 simultaneous and 6/18 sequential cases. Mean age at first surgery was 64 months, with mean follow up 27 months. A total of 75% of children had congenital ptosis; 64% had comitant strabismus. A majority of ptosis surgeries were frontalis sling (59%) or Fasanella-Servat (30%) procedures. There were no significant differences between simultaneous and sequential groups with regards to surgical success rates, complications, or reoperations (all p > 0.28). CONCLUSIONS: In the first comparative study of simultaneous versus sequential ptosis and strabismus surgery, no advantage for sequential surgery was seen. Despite a theoretical risk of postoperative eyelid malposition or complications when surgeries were performed in a combined manner, the rate of such outcomes was not increased with simultaneous surgeries. Performing ptosis and strabismus surgery together appears to be clinically effective and safe, and reduces anesthesia exposure during childhood.

Progress towards Bait Station Integration into Oral Rabies Vaccination Programs in the United States: Field Trials in Massachusetts and Florida.

Bait stations for distribution of oral rabies vaccine baits are designed for rabies management in highly-developed areas where traditional distribution of oral rabies vaccine baits may be difficult. As part of national efforts to contain and eliminate the raccoon (Procyon lotor) variant of the rabies virus (raccoon rabies) in the eastern United States, the United States Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services program, distributed vaccine baits by bait stations experimentally and operationally in Massachusetts during 2006-present, and in Florida during 2009⁻2015. In Massachusetts, a rabies virus-neutralizing antibody (RVNA) response of 42.1% for raccoons captured in areas baited with high density bait stations during 2011⁻2015 was achieved, compared with 46.2% in areas baited by hand, suggesting the continuation of this as a strategy for the oral rabies vaccination (ORV) program there, and for similar locations. Non-target competition for vaccine baits is problematic, regardless of distribution method. In Massachusetts, bait station visitation rates for targeted raccoons and non-target opossums (Didelphis virginiana) were similar (1.18:1) during 2006⁻2009 (p > 0.05). Bait station modifications for reducing non-target uptake were tested, and in Massachusetts, reduced non-target bait access was achieved with two design alternatives (p < 0.001). However, no difference was noted between the control and these two alternative designs in Florida. Due to ongoing trials of new vaccines and baits, the bait station performance of an adenovirus rabies glycoprotein recombinant vaccine bait, ONRAB® bait (Artemis Technologies, Guelph, ON, Canada) and a vaccinia-rabies glycoprotein recombinant vaccine bait, RABORAL V-RG®bait (Merial Limited, Athens, GA, USA), was compared. While uptake of the ONRAB bait was greater in Massachusetts (p < 0.001) in this limited trial, both types performed equally well in Florida. Since bait station tampering or theft as well as potential human bait contacts has been problematic, performance of camouflaged versus unpainted white bait stations was analyzed in terms of internal temperatures and maintaining a stable bait storage environment. In Massachusetts, camouflaged bait station interiors did not reach higher average temperatures than plain white bait stations in partially- or fully-shaded locations, while in Florida, camouflaged bait stations were significantly warmer in light exposure categories (p < 0.05). As ORV operations expand into more heavily-urbanized areas, bait stations will be increasingly important for vaccine bait distribution, and continued refinements in the strategy will be key to that success.

Evaluation of Commercial Assays for Single-Point Diagnosis of Pertussis in the US.

BACKGROUND: Pertussis serodiagnosis is increasingly being used in the United States despite the lack of a US Food and Drug Administration-approved, commercially available assay. To better understand the utility of these assays in diagnosing pertussis, serology assays were evaluated for analytical parameters and clinical accuracy. METHODS: Forty-three antigen-antibody combinations were evaluated for single-point diagnosis of pertussis. Serum panels included sera from laboratory-confirmed cases, an international reference standard, and healthy donors. Phase I panel (n = 20) of sera was used to assess precision, linearity, and accuracy; Phase II panel (n = 226) followed with positive percent agreement (PPA) and negative percent agreement (NPA) estimates. Analytical analyses included coefficients of variation (CV) and concordance correlation coefficients (rc). RESULTS: Intra-analyst variability was found to be relatively low among samples per assay, with only 6% (78 of 1240) having CV >20%, primarily with the highly concentrated immunoglobulin (Ig)G anti-pertussis toxin (PT) specimens and IgM assays. The rc measurements to assess linearity ranged between 0.282 and 0.994, 0.332 and 0.999, and -0.056 and 0.482 for IgA, IgG, and IgM, respectively. Analytical accuracy for calibrated IgG anti-PT assays was 86%-115%. The PPA and NPA varied greatly for all assays; PPA/NPA ranges for IgA, IgG, and IgM assays, with culture and/or polymerase chain reaction positivity as control, were 29-90/13-100, 26-96/27-100, and 0-73/42-100, respectively. In IgG assays, mixing filamentous hemagglutinin antigen with PT increased PPA but decreased NPA. CONCLUSIONS: Seroassays varied substantially under both analytical and clinical parameters; however, those that were calibrated to a reference standard were highly accurate. Our findings support incorporation of calibrated pertussis seroassays to the pertussis case definition for improved diagnosis and surveillance.

Timely implementation of a retinopathy of prematurity telemedicine system.

PURPOSE: To examine the feasibility of a retinopathy of prematurity (ROP) telemedicine evaluation system of providing timely feedback to a neonatal intensive care unit (NICU) with at-risk premature infants. METHODS: This was a prospective observational study of premature infants with birth weights of <1251 g in five NICUs in the United States. Infants scheduled for clinically indicated ROP evaluations underwent indirect ophthalmoscopic examinations and digital imaging on the same day. Imaging was performed by nonphysician retinal imagers. Times required were determined from obtaining digital images of both eyes to submission via web-based system to a secure server for grading by trained readers at a central reading center to sending back grading results to the clinical center. RESULTS: A total of 1,642 image sets of eyes of 292 infants were obtained, from 823 imaging sessions. The mean turnaround time from submission of image sets of both eyes to return of the grading results to the clinical center was 10.1 ± 11.3 hours (standard deviation), with a median of 12.0 hours (1st quartile, 0.9 hours; 3rd quartile, 16 hours). Overall, 95.5% of gradings (95% CI, 93.9%-96.7%) were returned within 24 hours. Subgroup analyses found, for image sets submitted to the reading center before 2 p.m. Eastern Standard Time, median time to report was 1.7 hours (1st quartile, 0.7 hours; 3rd quartile, 15.5 hours) compared with those submitted after 2pm (median, 14.1 hours; 1st quartile, 11.2, hours; 3rd quartile, 16.3 hours). CONCLUSIONS: An ROP telemedicine approach can provide timely feedback to the NICU regarding the detection of potentially serious ROP and thus referral to an ophthalmologist for examination and consideration of treatment.

Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss.

PURPOSE: To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. METHODS: Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. RESULTS: Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. CONCLUSIONS: Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC.

Uveitis Reactivation in Children Treated With Tumor Necrosis Factor Alpha Inhibitors.

PURPOSE: To evaluate reactivation of pediatric uveitis during/following treatment with tumor necrosis factor alpha inhibition (anti-TNFα). DESIGN: Retrospective cohort study. METHODS: We assessed the incidence of uveitis reactivation in children ≤18 years who had achieved uveitis quiescence under anti-TNFα. Survival analysis was used to calculate reactivation rates while still on (primary outcome), and following discontinuation of (secondary outcome), anti-TNFα. Potential predictive factors were assessed. RESULTS: Among 50 children observed to develop quiescence of uveitis under anti-TNFα, 39 met criteria to be "at risk" of the primary (19 for the secondary) outcome. 60% were female, ∼half had juvenile idiopathic arthritis, and most were treated with infliximab. Overall, the estimated proportion relapsing within 12 months was 27.8% (95% confidence interval [CI]: 15.9%-45.8%); the estimated probability of reactivation was higher following (63.8% [95% CI: 38.9%-87.7%]) vs before (21.6% [95% CI: 10.8%-40.2%]) anti-TNFα discontinuation. Among those who discontinued anti-TNFα, the likelihood of reactivation was higher for those treated with adalimumab vs infliximab (hazard ratio [HR] 13.4, P = .01, 95% CI: 2.2-82.5) and those with older age at uveitis onset (HR 1.3, P = .09, 95% CI: 1.0-1.7). The duration of suppression, on medication, did not significantly affect the likelihood of reactivation when quiescence was maintained for ≥1.5 years. CONCLUSIONS: Approximately 75% of children remaining on anti-TNFα following achievement of uveitis quiescence remain quiescent at 1 year. However, most reactivate following anti-TNFα discontinuation. These results suggest that infliximab more often is followed by remission, off medication, than adalimumab. The data do not suggest that maintenance of suppression for more than 1.5 years decreases the reactivation risk.

Retinal Structure in Cobalamin C Disease: Mechanistic and Therapeutic Implications.

PURPOSE: To describe the retinal structure in a patient with cobalamin C (cblC) disease. METHODS: A 13-year-old male patient diagnosed with cblC disease during a perinatal metabolic screening prompted by jaundice and hypotony underwent ophthalmic examinations, electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT). RESULTS: The patient carried a homozygous (c.271dupA) mutation in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. At age 3 months he had a normal eye exam. A pigmentary maculopathy progressed to chorioretinal atrophy from 5-10 months. ERG at 7 months was normal. A nystagmus remained stable since the age of 2 years. At age 13, visual acuity was 20/250 (right eye) and 20/400 (left eye), with a +5.00 D correction, a level of vision maintained since first measurable at age 5 years. SD-OCT showed bilateral macular coloboma-like lesions; there was also a thickened surface layer with ganglion cell layer thinning. Photoreceptor outer segment loss and thinning of the outer nuclear layer (ONL) transitioned to regions with no discernible ONL with a delaminated, thickened, inner retina. CONCLUSIONS: A thick surface layer near the optic nerve resembling an immature retina and an initially normal macula that rapidly developed coloboma-like lesions suggest there may be an interference with retinal/foveal development in cblC, a mechanism of maculopathy that may be shared by other early onset retinal degenerations. Photoreceptor loss and inner retinal remodeling confirm associated photoreceptor degeneration.