Epidemiology and treatment of invasive Bartonella spp. infections in the United States.

OBJECTIVES: Bartonella spp., renowned for cat-scratch disease, has limited reports of dissemination. Tissue and blood cultures have limitations in detecting this fastidious pathogen. Molecular testing (polymerase chain reaction, PCR) and cell-free DNA have provided an avenue for diagnoses. This retrospective observational multicenter study describes the incidence of disseminated Bartonella spp. and treatment-related outcomes. METHODS: Inclusion criteria were diagnosis of bartonellosis via diagnosis code, serology testing of blood, polymerase chain reaction (PCR) of blood, 16/18S tests of blood or tissue, cultures of blood or tissue, or cell-free DNA of blood or tissue from January 1, 2014, through September 1, 2021. Exclusions were patients who did not receive treatment, insufficient data on treatment course, absence of dissemination, or retinitis as dissemination. RESULTS: Patients were primarily male (n = 25, 61.0%), white (n = 28, 68.3%), with mean age of 50 years (SD 14.4), and mean Charlson comorbidity index of 3.5 (SD 2.1). Diagnosis was primarily by serology (n = 34, 82.9%), with Bartonella henselae (n = 40, 97.6%) as the causative pathogen. Treatment was principally doxycycline with rifampin (n = 17, 41.5%). Treatment failure occurred in 16 (39.0%) patients, due to escalation of therapy during treatment (n = 5, 31.3%) or discontinuation of therapy due to an adverse event or tolerability (n = 5, 31.3%). CONCLUSIONS: In conclusion, this is the largest United States-based cohort of disseminated Bartonella spp. infections to date with a reported 39% treatment failure. This adds to literature supporting obtaining multiple diagnostic tests when Bartonella is suspected and describes treatment options.

Evaluation of Sequential Oral Versus Intravenous Antibiotic Treatment of Enterococcus faecalis Bloodstream Infections.

BACKGROUND: Intravenous (IV) antibiotics have historically been considered standard of care for treatment of bloodstream infections (BSIs). Recent literature has shown sequential oral (PO) therapy to be noninferior to IV antibiotics for certain pathogens and disease states. However, a gap exists in the literature for BSI caused by Enterococcus faecalis. OBJECTIVE: To compare outcomes of definitive sequential PO therapy to definitive IV therapy in patients with E faecalis BSI. METHODS: Multicenter, retrospective, matched cohort study of adult patients with at least one blood culture positive for E faecalis from January 2017 to November 2022. Patients with polymicrobial BSI, concomitant infections requiring prolonged IV antibiotic therapy, those who did not receive antibiotic therapy, and those who died within 72 hours of index culture were excluded. Subjects were matched based on source of infection in a 2:1 (IV:PO) ratio. The primary outcome was a composite of all-cause mortality and treatment failure. Secondary outcomes included hospital length of stay (LOS), antibiotic duration, and 30-day readmission rate. RESULTS: Of the 186 patients who met criteria for inclusion, there was no statistically significant difference in the primary composite outcome for PO compared to IV therapy (14.5% vs 21.8%; OR 0.53 [0.23-1.25]) or 30-day readmission (17.5% vs 29%; OR 0.53 [0.25-1.13]). Hospital LOS was significantly longer in patients receiving IV-only therapy (6 days vs 14 days; P < 0.001). CONCLUSION AND RELEVANCE: Sequential oral therapy for E faecalis BSI had similar outcomes compared to IV-only treatment and may be considered in eligible patients.

Perioperative anaphylaxis and the principle of primum non nocere.

Perioperative anaphylaxis is a rare and unpredictable event that continues to cause patient harm. More work is needed to decrease the risk to patients through measures to limit sensitisation, optimise management and investigation, and ensure that patients are not inadvertently re-exposed to allergens. Robust epidemiological data such as that provided by the consecutive GERAP surveys over the past 30 yr have been invaluable in defining the problem, identifying emerging allergens, acting as a catalyst for change, and stimulating research.

Nephrotoxic Risk Associated With Combination Therapy of Vancomycin and Piperacillin-Tazobactam in Critically Ill Patients With Chronic Kidney Disease.

Background: The combination of vancomycin and piperacillin-tazobactam (VPT) has been associated with acute kidney injury (AKI) in hospitalized patients when compared to similar combinations. Additional studies examining this nephrotoxic risk in critically ill patients have not consistently demonstrated the aforementioned association. Furthermore, patients with baseline renal dysfunction have been excluded from almost all of these studies, creating a need to examine the risk in this patient population. Methods: This was a retrospective cohort analysis of critically ill adults with baseline chronic kidney disease (CKD) who received vancomycin plus an anti-pseudomonal beta-lactam at Emory University Hospital. The primary outcome was incidence of AKI. Secondary outcomes included stage of AKI, time to development of AKI, time to return to baseline renal function, new requirement for renal replacement therapy, intensive care unit and hospital length of stay, and in-hospital mortality. Results: A total of 109 patients were included. There was no difference observed in the primary outcome between the VPT (50%) and comparator (58%) group (P = .4), stage 2 or 3 AKI (15.9% vs 6%; P = .98), time to AKI development (1.7 vs 2 days; P = .5), time to return to baseline renal function (4 vs 3 days; P = .2), new requirement for RRT (4.5% vs 1.5%; P = .3), ICU length of stay (7.3 vs 7.4 days; P = .9), hospital length of stay (19.3 vs 20.1 days; P = .87), or in-hospital mortality (15.9% vs 10.8%; P = .4). A significant difference was observed in the duration of antibiotic exposure (3.32 vs 2.62 days; P = .045 days). Conclusion: VPT was not associated with an increased risk of AKI or adverse renal outcomes. Our findings suggest that the use of this antibiotic combination should not be avoided in this patient population. More robust prospective studies are warranted to confirm these findings.

Lipidomic changes occurring in platelets during extended cold storage.

OBJECTIVES: Cold storage is being implemented as an alternative to conventional room-temperature storage for extending the shelf-life of platelet components beyond 5-7 days. The aim of this study was to characterise the lipid profile of platelets stored under standard room-temperature or cold (refrigerated) conditions. METHODS: Matched apheresis derived platelet components in 60% PAS-E/40% plasma (n = 8) were stored at room-temperature (20-24°C with agitation) or in the cold (2-6°C without agitation). Platelets were sampled on day 1, 5 and 14. The lipidome was assessed by ultra-pressure liquid chromatography ion mobility quadrupole time of flight mass spectrometry (UPLC IMS QToF). Changes in bioactive lipid mediators were measured by ELISA. RESULTS: The total phospholipid and sphingolipid content of the platelets and supernatant were 44 544 ± 2915 µg/mL and 38 990 ± 10 880 µg/mL, respectively, and was similar over 14 days, regardless of storage temperature. The proportion of the procoagulant lipids, phosphatidylserine (PS) and phosphatidylethanolamine (PE), increased by 2.7% and 12.2%, respectively, during extended cold storage. Cold storage for 14 days increased sphingomyelin (SM) by 4.1% and decreased ceramide by 1.6% compared to day 1. Further, lysophosphatidylcholine (LPC) species remained unchanged during cold storage for 14 days. The concentration of 12- and 15-hydroxyeicosatetraenoic acid (HETE) were lower in the supernatant of cold-stored platelets than room-temperature controls stored for 14 days. CONCLUSION: The lipid profile of platelets was relatively unchanged during storage for 5 days, regardless of temperature. However, during extended cold storage (14 days) the proportion of the procoagulant lipids, PS and PE, increased, while LPC and bioactive lipids were stable.

The feasibility and acceptability of a physician-led ICU follow-up service: A prospective cohort study.

BACKGROUND: Increased recognition of post-intensive care syndrome has led to widespread development of intensive care follow-up services internationally. OBJECTIVE: The objective of this study was to determine the feasibility and acceptability of an intensive care unit (ICU) follow-up clinic in Australia for patients and their caregivers and to describe satisfaction with this service. METHODS: This was a prospective cohort study in a mixed tertiary ICU in Australia. Eligible patients were adults admitted to the ICU for 7 days or more and/or ventilated for 48 h or more, as well as their primary caregiver. Patients and their primary caregivers were invited to attend a follow-up clinic 4-8 weeks after hospital discharge. The clinic appointment was attended by an ICU physician and nurse, with multidisciplinary support. Feasibility and acceptability were defined as the proportion of clinic attendance and frequency of interventions initiated at the clinic. Satisfaction was measured by a 5-point satisfaction survey (very dissatisfied to very satisfied). The burden of ongoing disease was reported via multiple validated instruments. RESULTS: From April 2020-July 2021, 386 patients met the inclusion criteria. Only 146 patients were approached for consent due to site staffing limitations. Eighty-three patients and 32 caregivers consented to attend the clinic. Seventy percent (54/77) of patients attended scheduled appointments and 50% (16/32) of caregivers. For patients, 23 medical referrals were made, 8 patients had medication changes, and 10 patients were offered social work support. Satisfaction surveys were completed by 65% (35/54) of attending patients; 97% (34) patients reported either being 'very satisfied' or 'satisfied' with the service. All responding caregivers (10) were either 'very satisfied' or 'satisfied' with the clinic. CONCLUSION: There were a large number of patients meeting the inclusion criteria to the ICU follow-up clinic, and clinic attendance was moderate for patients but lower for caregivers. Reported satisfaction with the service was high for both patients and their caregiver.

Rationale, evidence, and steps for implementation of medication for opioid use disorder treatment programs in HIV primary care settings.

As the opioid crisis continues to escalate, the management of patients with opioid use disorder has crossed over to the care of patients with chronic infectious diseases, specifically HIV, HBV, and HCV, typically managed in the primary care setting. Consensus guidelines recommend testing for HIV and hepatitis in persons who inject drugs at least annually, but high-risk sexual activity may put other patients at risk as well. Significant barriers to robust care of these patient populations include low rates of HIV and hepatitis testing, limited access to methadone treatment programs, lack of widespread knowledge of how to prescribe office-based opioid treatment, and ongoing stigma surrounding prescribing of HIV treatment and prophylaxis medications. Clinical pharmacists across ambulatory, infectious diseases, and opioid stewardship specialties have the opportunity to play a key role in the implementation and support of harm reduction and medication for opioid use disorder services in the outpatient setting. The goal of this article is to discuss the rationale and evidence for these services and provide a framework for implementation.

An evidence-based practice guideline of the National Society of Genetic Counselors for telehealth genetic counseling.

There are currently no practice guidelines available for genetic counseling using telehealth modalities. This evidence-based practice guideline was developed in response to increasing use of alternative service delivery models for genetic counseling, specifically telephone and video-based genetic counseling (telehealth genetic counseling or THGC). A recent systematic evidence review (SER) compared outcomes of THGC with in-person genetic counseling and found that for the majority of studied outcomes, THGC was a non-inferior and comparable service delivery model. The SER results were used to develop this guideline. The current and anticipated future use of THGC, including the influence of the COVID-19 pandemic, provides the context for this guideline. Recommendation: The Telehealth Practice Guideline author workgroup conditionally recommends telehealth genetic counseling, either via telephone or video, as a delivery method for genetic counseling. Depending on factors unique to individual healthcare systems and provider and patient populations, THGC may be the only service delivery model available or may be utilized in addition to other service delivery models including in-person genetic counseling. The evidence shows large desirable effects, minor undesirable effects, and increased equity for patients when THGC is available. THGC may reduce or remove existing barriers to patient access to genetic counseling, such as medical conditions and/or disabilities that may affect a patient's ability to travel, inflexible work or school schedules, and lack of reliable transportation, finances, or dependent care. THGC is likely acceptable to key groups impacted by its use and is feasible to implement. Certain patient populations may require additional resources or encounter more barriers in using telemedicine services in general. For these populations, THGC can still be a valuable option if solutions are available.

Rubella virus-associated necrotizing granulomatous inflammation with extensive eyelid, ocular, and orbital involvement.

We present a case of cutaneous granulomatous disease associated with rubella virus in a 4-year-old girl without an identifiable immunodeficiency. In this case, a combination of anti-inflammatory, anti-viral, and anti-neutrophil therapies successfully treated vision-threatening eyelid, conjunctival, scleral, and orbital inflammation.

Comparative transcriptomic responses of European and Japanese larches to infection by Phytophthora ramorum.

BACKGROUND AND OBJECTIVES: Phytophthora ramorum severely affects both European larch (EL) and Japanese larch (JL) trees as indicated by high levels of mortality particularly in the UK. Field observations suggested that EL is less severely affected and so may be less susceptible to P. ramorum than JL; however, controlled inoculations have produced inconsistent or non-statistically significant differences. The present study aimed to compare RNA transcript accumulation profiles in EL and JL in response to inoculation with P. ramorum to improve our understanding of their defence responses. METHODOLOGY: RNA-sequencing was carried out on bark tissues following the inoculation with P. ramorum of potted saplings in both EL and JL carried out under controlled environment conditions, with sampling at 1, 3, 10, and 25 days post inoculation in infected and control plants. RESULTS: All of the inoculated trees rapidly developed lesions but no statistically significant differences were found in lesion lengths between EL and JL. RNA-Sequencing comparing control and inoculate saplings identified key differences in differentially expressed genes (DEGs) between the two larch species. European larch had rapid induction of defence genes within 24 hours of infection followed by sustained expression until 25 days after inoculation. Results in JL were more varied; upregulation was stronger but more transient and represented fewer defence pathways. Gene enrichment analyses highlighted differences in jasmonate signalling and regulation including NPR1 upregulation in EL only, and specific aspects of secondary metabolism. Some DEGs were represented by multiple responsive copies including lipoxygenase, chalcone synthase and nucleotide-binding, leucine-rich-repeat genes. CONCLUSION: The variations between EL and JL in responsive DEGs of interest as potentially related to differences seen in the field and should be considered in the selection of trees for planting and future breeding.

Apathy and Depression as Predictors of Activities of Daily Living Following Stroke and Traumatic Brain Injuries in Adults: A Meta-Analysis.

Apathy and depression are common sequelae of acquired brain injury (ABI). Apathy is a syndrome characterized by diminished motivation and purposeful behaviours. Depression is a mood disorder featuring sadness, worthlessness, anhedonia and suicidal ideation. Both are associated negatively with activities of daily living (ADL), the skills required to fulfil basic and complex physical needs. However, the current literature's results are inconsistent and based on relatively small sample sizes. Furthermore, the unique and combined effects of apathy and depression as predictors of ADL have not yet been estimated. This is important, as both may have implications for planning rehabilitation after an ABI. Consequently, we aimed to estimate the association between apathy, depression and ADL in the stroke and traumatic brain injured population via meta-analysis and meta-analytic path-analysis. Based on the meta-analyses (N = 1,166 to N = 1,389), we estimated the following statistically significant bivariate effects: depression and apathy (r = .53, 95% CI: .42/.63), depression and ADL (r = -.27, 95% CI: -.43/-.11), apathy and ADL (r = -.41, 95% CI: -.51/-.31). A meta-analytic mediation model found that depression had a significant indirect effect onto ADL (ß = -.17, 95% CI: -.26/-.09), while apathy had a significant direct effect (ß = -.34, 95% CI: -.48/-.19) onto ADL (model R2 = .16). We interpreted the results to suggest that apathy and depression may impact adversely on engagement with ADL in people with ABI, although the potential influence of depression on ADL may occur primarily through its influence on apathy. Thus, greater focus on apathy by practitioners may be merited in cases with ABI.

Pathways to ovarian cancer diagnosis: a qualitative study.

BACKGROUND: Ovarian cancer is often diagnosed at a late stage, when survival is poor. Qualitative narratives of patients' pathways to ovarian cancer diagnoses may identify opportunities for earlier cancer detection and, consequently, earlier stage at diagnosis. METHODS: We conducted semi-structured interviews of ovarian cancer patients and survivors (n = 14) and healthcare providers (n = 11) between 10/2019 and 10/2021. Interviews focused on the time leading up to an ovarian cancer diagnosis. Thematic analysis was conducted by two independent reviewers using a two-phase deductive and inductive coding approach. Deductive coding used a priori time intervals from the validated Model of Pathways to Treatment (MPT), including self-appraisal and management of symptoms, medical help-seeking, diagnosis, and pre-treatment. Inductive coding identified common themes within each stage of the MPT across patient and provider interviews. RESULTS: The median age at ovarian cancer diagnosis was 61.5 years (range, 29-78 years), and the majority of participants (11/14) were diagnosed with advanced-stage disease. The median time from first symptom to initiation of treatment was 2.8 months (range, 19 days to 4.7 years). The appraisal and help-seeking intervals contributed the greatest delays in time-to-diagnosis for ovarian cancer. Nonspecific symptoms, perceptions of health and aging, avoidant coping strategies, symptom embarrassment, and concerns about potential judgment from providers prolonged the appraisal and help-seeking intervals. Patients and providers also emphasized access to care, including financial access, as critical to a timely diagnosis. CONCLUSION: Interventions are urgently needed to reduce ovarian cancer morbidity and mortality. Population-level screening remains unlikely to improve ovarian cancer survival, but findings from our study suggest that developing interventions to improve self-appraisal of symptoms and reduce barriers to help-seeking could reduce time-to-diagnosis for ovarian cancer. Affordability of care and insurance may be particularly important for ovarian cancer patients diagnosed in the United States.

Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder.

PURPOSE: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). METHODS: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers. RESULTS: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined. CONCLUSION: Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals.

The in vitro quality of X-irradiated platelet components in PAS-E is equivalent to gamma-irradiated components.

BACKGROUND: Blood components are irradiated to inactivate lymphocytes in an effort to prevent transfusion-associated graft versus host disease. Although gamma irradiators are commonly used, they are subjected to rigorous health, safety, and compliance regulations, compared with X-irradiators which have the advantage of only emitting radiation while the machine is switched on. While the effects of gamma irradiation on platelet components are well known, there is little or no data comparing the effects of X- and gamma-irradiation on the quality of these components. Therefore, this study examined the in vitro quality of platelet components (pooled and apheresis) following X- or gamma-irradiation. STUDY DESIGN AND METHODS: Whole-blood-derived (pooled) and apheresis platelet components in platelet additive solution (n = 20 pairs for each type) were irradiated (X vs. gamma). In vitro platelet quality was tested prior to irradiation (day 1) and subsequently on days 2, 5, and 7. Non-irradiated components were tested on day 5 in parallel as reference controls. Metabolic parameters, surface expression of glycoproteins and activation markers (CD62P and annexin-V binding), and agonist-induced aggregation were measured. RESULTS: All components met Council of Europe specifications. There were no statistical differences in any in vitro quality measurements between X- and gamma-irradiated pooled or apheresis platelet components. CONCLUSION: X- and gamma-irradiation have similar effects on the in vitro quality of stored blood components, indicating that either technology represents a suitable option for irradiation of platelet components.

Facilitators and Barriers to Developing, Implementing, and Evaluating Healthy Vending Policies in Four Cities.

Vending machines are a common source of low-nutrient, energy-dense snacks, and beverages. Many cities are beginning to adopt healthy vending policies in public areas, but evidence regarding best practices for developing, implementing, and evaluating these healthy vending polices is limited. This study used a mixed-methods, multiple case study design to examine healthy vending policies and initiatives in four cities. Data were collected between August 2017 and December 2017. Research staff worked with a designated contact person to coordinate site visits to each city where observations of the vending machines were conducted. Semistructured interviews were conducted with multiple stakeholders from each site and documents, including policies, vendor contracts, and nutrition standards, were reviewed. The following elements were identified as being essential to a healthy vending policy or initiative: having a champion and support from leadership, internal and external partnerships, and clear communication. Conducting regular compliance checks of the vending machines and the ability to obtain sales data, especially pre- and post-healthy vending policy sales data, continues to be a challenge. Stakeholders across all cities reported that concerns about profit-loss from the vendor and city revenue and procurement departments are barriers to adopting healthy vending policies. More research and evaluation are needed, as results are mixed regarding the impact on overall revenue/profits. This study yielded a variety of resources and "lessons learned" from those who have developed and implemented healthy vending policies and initiatives. This information should be used by others looking to influence healthier snacking behaviors through vending machines.

Test-retest reliability and sample size estimates after MRI scanner relocation.

OBJECTIVE: Many factors can contribute to the reliability and robustness of MRI-derived metrics. In this study, we assessed the reliability and reproducibility of three MRI modalities after an MRI scanner was relocated to a new hospital facility. METHODS: Twenty healthy volunteers (12 females, mean age (standard deviation) â€‹= â€‹41 (11) years, age range [25-66]) completed three MRI sessions. The first session (S1) was one week prior to the 3T GE HDxt scanner relocation. The second (S2) occurred nine weeks after S1 and at the new location; a third session (S3) was acquired 4 weeks after S2. At each session, we acquired structural T1-weighted, pseudo-continuous arterial spin labelled, and diffusion tensor imaging sequences. We used longitudinal processing streams to create 12 summary MRI metrics, including total gray matter (GM), cortical GM, subcortical GM, white matter (WM), and lateral ventricle volume; mean cortical thickness; total surface area; average gray matter perfusion, and average diffusion tensor metrics along principal white matter pathways. We compared mean MRI values and variance at the old scanner location to multiple sessions at the new location using Bayesian multi-level regression models. K-fold cross validation allowed identification of important predictors. Whole-brain analyses were used to investigate any regional differences. Furthermore, we calculated within-subject coefficient of variation (wsCV), intraclass correlation coefficient (ICC), and dice similarity index (SI) of cortical segmentations across scanner relocation and within-site. Additionally, we estimated sample sizes required to robustly detect a 4% difference between two groups across MRI metrics. RESULTS: All global MRI metrics exhibited little mean difference and small variability (bar cortical gray matter perfusion) both across scanner relocation and within-site repeat. T1- and DTI-derived tissue metrics showed â€‹< â€‹|0.3|% mean difference and <1.2% variance across scanner location and <|0.4|% mean difference and <0.8% variance within the new location, with between-site intraclass correlation coefficient (ICC) â€‹> â€‹0.80 and within-subject coefficient of variation (wsCV) â€‹< â€‹1.4%. Mean cortical gray matter perfusion had the highest between-session variability (6.7% [0.3, 16.7], estimate [95% uncertainty interval]), and hence the smallest ICC (0.71 [0.44,0.92]) and largest wsCV (13.4% [5.4, 18.1]). No global metric exhibited evidence of a meaningful mean difference between scanner locations. However, surface area showed evidence of a mean difference within-site repeat (between S2 and S3). Whole-brain analyses revealed no significant areas of difference between scanner relocation or within-site. For all metrics, we found no support for a systematic difference in variance across relocation sites compared to within-site test-retest reliability. Necessary sample sizes to detect a 4% difference between two independent groups varied from a maximum of n â€‹= â€‹362 per group (cortical gray matter perfusion), to total gray matter volume (n â€‹= â€‹114), average fractional anisotropy (n â€‹= â€‹23), total gray matter volume normalized by intracranial volume (n â€‹= â€‹19), and axial diffusivity (n â€‹= â€‹3 per group). CONCLUSION: Cortical gray matter perfusion was the most variable metric investigated (necessitating large sample sizes to identify group differences), with other metrics showing substantially less variability. Scanner relocation appeared to have a negligible effect on variability of the global MRI metrics tested. This manuscript reports within-site test-retest variability to act as a tool for calculating sample size in future investigations. Our results suggest that when all other parameters are held constant (e.g., sequence parameters and MRI processing), the effect of scanner relocation is indistinguishable from within-site variability, but may need to be considered depending on the question being investigated.

Lifetime Economic Burden of Crohn's Disease and Ulcerative Colitis by Age at Diagnosis.

BACKGROUND & AIMS: Understanding the burden of Crohn's disease (CD) and ulcerative colitis (UC) is important for measuring treatment value. We estimated lifetime health care costs incurred by patients with CD or UC by age at diagnosis. METHODS: We collected data from 78,620 patients with CD, 85,755 with UC, and propensity score-matched control subjects from the Truven Health MarketScan insurance claims databases (2008‒2015). Total medical (inpatient, outpatient) and pharmacy costs were captured. Cost variations over a lifetime were estimated in cost-state Markov models by age at diagnosis, adjusted to 2016 U.S. dollars and discounted at 3% per annum. We measured lifetime total and lifetime incremental cost (the difference between costs of CD or UC patients vs matched controls). RESULTS: For CD, the lifetime incremental cost was $707,711 among patients who received their diagnosis at 0‒11 years, and $177,614 for patients 70 years or older, averaging $416,352 for a diagnosis at any age. Lifetime total cost was $622,056, consisting of outpatient ($273,056), inpatient ($164,298), pharmacy ($163,722), and emergency room (ER) ($20,979) costs. For UC, the lifetime incremental cost was $369,955 among patients who received their diagnosis at 0‒11 years, and $132,396 for individuals 70 years or older, averaging $230,102 for a diagnosis at any age. Lifetime total cost was $405,496, consisting of outpatient ($163,670), inpatient ($123,190), pharmacy ($105,142), and ER ($13,493) costs. Therefore, the prevalent populations of patients with CD or UC in the United States in 2016 are expected to incur lifetime total costs of $498 billion and $377 billion, respectively. CONCLUSIONS: Using a Markov model, we estimated lifetime costs for patients with CD or UC to exceed previously published estimates. Individuals who receive a diagnosis of CD or UC at an early age (younger than 11 years) incur the highest lifetime cost burden. Advancing management strategies may significantly improve patient outcomes and reduce lifetime health care spending.

De novo variants of NR4A2 are associated with neurodevelopmental disorder and epilepsy.

PURPOSE: This study characterizes the clinical and genetic features of nine unrelated patients with de novo variants in the NR4A2 gene. METHODS: Variants were identified and de novo origins were confirmed through trio exome sequencing in all but one patient. Targeted RNA sequencing was performed for one variant to confirm its splicing effect. Independent discoveries were shared through GeneMatcher. RESULTS: Missense and loss-of-function variants in NR4A2 were identified in patients from eight unrelated families. One patient carried a larger deletion including adjacent genes. The cases presented with developmental delay, hypotonia (six cases), and epilepsy (six cases). De novo status was confirmed for eight patients. One variant was demonstrated to affect splicing and result in expression of abnormal transcripts likely subject to nonsense-mediated decay. CONCLUSION: Our study underscores the importance of NR4A2 as a disease gene for neurodevelopmental disorders and epilepsy. The identified variants are likely causative of the seizures and additional developmental phenotypes in these patients.

A Meta-Analysis of Neuropsychological Predictors of Outcome Following Stroke and Other Non-Traumatic Acquired Brain Injuries in Adults.

A number of cognitive abilities have been reported to predict outcome following a non-traumatic acquired brain injury (ABI) in adults. However, the results are inconsistent. Furthermore, the unique and combined capacity of these cognitive abilities to predict ABI outcome has not been evaluated. Consequently, we employed meta-analysis and multiple regression to evaluate the capacity of various neuropsychological domains to predict two separate outcome variables in adults: (1) activities of daily living; and (2) quality of life. Based on the activities of daily living meta-analysis (N = 2384), we estimated the following significant bivariate effects: memory (r = .31, 95% CI: .20/.41]), language (r = .33, 95% CI:.26/.40), attention (r = .38, 95% CI: .30/.46]), executive functions (r = .29, 95% CI: .19/.39]), and visuospatial abilities (r = .41, 95% CI: .34/ .48). Based on the quality of life meta-analysis (N = 1037), we estimated the following significant bivariate effects: memory (r = .12, 95% CI: .03/.20]), language (r = .19, 95% CI: .06/ .32), attention (r = .30, 95% CI: .16/.44]), executive functions (r = .24, 95% CI: .12/.37) and visuospatial/constructional abilities (r = .30, 95% CI: .14/.46). Meta-analytic structural equation modelling (metaSEM) identified two significant, unique predictors of activities of daily living, attention and visuospatial abilities, and the model accounted for 21% of the variance (multiple R2 = .21, 95%CI: .16/.26). For the corresponding quality of life metaSEM, no statistically significant unique predictors were identified, however, a significant multiple correlation was observed, multiple R2 = .11 (95%CI: 04/.18). We conclude that practitioners may be able to predict, with some degree of accuracy, functional outcome following a stroke and other non-traumatic ABI in adults. We also provide some critical commentary on the nature and quality of the measures used in this area of research to represent the cognitive dimensions of interest.

Freezing expired platelets does not compromise in vitro quality: An opportunity to maximize inventory potential.

BACKGROUND AND OBJECTIVES: Cryopreservation provides an option for long-term storage of platelet concentrates. While platelets are usually frozen as soon as practical after collection (within 2 days), the ability to freeze units at a later stage of the shelf life may improve inventory management. As such, the aim of this study was to determine the impact of freezing platelets approaching expiry (Day 5/6). MATERIALS AND METHODS: Two ABO-matched buffy coat-derived platelets (30% plasma/70% platelet additive solution) were pooled and split to produce matched pairs (n = 8 pairs). Platelets were frozen on Day 1 after collection (cryopreserved platelets [CPPs]) or Day 5 or 6 (expired-CPPs) at -80°C with 5% to 6% dimethyl sulfoxide. In vitro platelet quality was tested before freezing and after thawing and reconstitution in plasma. RESULTS: The majority of prefreeze parameters were equivalent for all platelet units (Day 1 vs. Day 5 or 6). Expired-CPPs had a higher mean postthaw platelet recovery (82 ± 4%) compared to CPPs (75 ± 4%; p = 0.0021). Cryopreservation resulted in a loss of surface glycoproteins (glycoprotein (GP) Ibα, GPIIb, GPVI), an increase in activation markers (phosphatidylserine and P-selectin) and microparticle release, compared to unfrozen platelets. However, the cryopreservation-induced changes were equivalent in CPPs and expired-CPPs. Functionality was measured by thromboelastography and was similar between expired-CPPs (R-time: 5.3 ± 0.3) and CPPs (R-time: 5.4 ± 0.5; p = 0.7094). CONCLUSION: The phenotype and functional profile of platelets frozen at expiry were similar to platelets frozen 1 day following collection. These data suggest that expired platelets may represent a suitable starting material for cryopreservation.