Lifelong Disability Research Articles

The Health and Economic Benefits of United States Investments in Measles and Rubella Control and Elimination

Background: Prior to measles vaccine introduction in 1963, measles virus caused hundreds of thousands of annual reported cases, which led to substantial US morbidity, mortality, and costs. Similarly, congenital rubella syndrome (CRS) led to highly visible and tragic lifelong disability for thousands of Americans, before rubella vaccine introduction in 1969. The US certified national virus transmission elimination of indigenous measles in 2000 and rubella in 2004. Methods: Applying an existing integrated transmission and economic model, this analysis characterizes the net benefits of US investments in measles (1963–2030) and rubella (1969–2030) immunization assuming continued high routine immunization coverage. Due to importation risks, the US maintains two doses of both vaccines in its routine immunization schedule. Results: This analysis estimates total US costs of 8.1 billion (economics reported in 2023 US dollars) for measles immunization for 1963–2023 and 14.1 billion for rubella immunization for 1969–2023. The analysis estimates an additional approximately 1.2 billion for measles immunization and 1.5 billion for rubella immunization expected for 2024–2030. Historical and future US investments prevented an estimated approximately 237 million measles infections, 228,000 measles deaths, 193 million rubella infections, and 166,000 CRS cases. These investments imply net benefits (from avoided treatment costs minus immunization costs) of approximately 310 billion for measles and 430 billion for rubella and CRS, even without incorporating avoided productivity losses and intangible costs. Conclusions: US investments in measles and rubella immunization continue to provide enormous savings of human and financial costs and to prevent substantial mortality and morbidity.

Daily functioning and (health-related) quality of life of young adult survivors of childhood bacterial meningitis.

Young adult survivors of childhood BM reported similar and even better levels of daily functioning, HRQoL, and overall QoL than age-matched Dutch reference scores. However, clinicians and healthcare workers should be mindful of poor mental and physical health of some survivors of childhood BM because these survivors also face problems with functioning in daily life. • Acute bacterial meningitis is a life-threatening infection which may lead to devastating lifelong disabilities. • Health-related quality of life is decreased in school-age survivors of bacterial meningitis. • The present study shows that HRQoL in survivors of childhood BM improves over time • However, especially poor mental health in adolescent and young adult survivors is associated with impaired functioning in daily life.

Bone health in crisis: Addressing Vitamin D deficiency in orthopedic practice

Vitamin D deficiency is increasingly recognized as a major contributor to musculoskeletal conditions, particularly in pediatric populations. This review focuses on the role of vitamin D in bone health, highlighting its deficiency as a key factor in the development of conditions such as rickets, osteomalacia, skeletal deformities, and an elevated risk of fractures. Vitamin D is essential for calcium and phosphate homeostasis, which are crucial for bone mineralization and growth. A deficiency disrupts these processes, leading to soft, weak bones and a range of orthopedic issues.Children with vitamin D deficiency often present with musculoskeletal pain, delayed growth, bowing of the legs, and recurrent fractures, all of which can have long-term consequences if not addressed early. Diagnostic approaches, including serum vitamin D measurement, radiographic evaluation, and bone mineral density assessment, are critical for timely identification. Treatment typically involves vitamin D supplementation, dietary adjustments, and lifestyle changes, such as increased exposure to sunlight.This review highlights the importance of early recognition and management of vitamin D deficiency within orthopedic practice to prevent severe musculoskeletal complications. By addressing this deficiency proactively, orthopedic practitioners can play a vital role in improving bone health and preventing lifelong orthopedic disabilities.

Genetic characterization of Neisseria meningitidis isolates recovered from patients with invasive meningococcal disease in Lithuania.

Neisseria meningitidis is a gram-negative bacterium responsible for life-threatening invasive infections known as invasive meningococcal disease and is associated with high fatality rates and serious lifelong disabilities among survivors. This study aimed to characterize N. meningitidis isolates cultured from blood and cerebrospinal fluid collected between 2009 and 2021 in Lithuania, assess their genomic relationships with European strains, and evaluate the possibility of using a cost-effective method for strain characterization, thus improving the national molecular surveillance of invasive meningococcal disease. In total, 321 N. meningitidis isolates were collected and analyzed using multilocus restriction typing (MLRT). Amplification of the penA gene and restriction fragment length polymorphism analysis were performed to identify the modified penA genes. Based on the MLRT genotyping results, we selected 10 strains for additional analysis using whole-genome sequencing. The sequenced genomes were incorporated into a dataset of publicly available N. meningitidis genomes to evaluate genomic diversity and establish phylogenetic relationships within the Lithuanian and European circulating strains. We identified 83 different strains using MLRT genotyping. Genomic diversity of N. meningitidis genomes analysed revealed 21 different sequence types (STs) circulating in Lithuania. Among these, ST34 was the most prevalent. Notably, three isolates displayed unique combinations of seven housekeeping genes and were identified as novel STs: ST16969, ST16901, and ST16959. The analyzed strains were found to possess virulence factors not commonly found in N. meningitidis. Six distinct penA profiles were identified, each with different frequencies. In the present study, we also identified N. meningitidis strains with new penA, NEIS0123, NEIS1320, NEIS1525, NEIS1600, and NEIS1753 loci variants. In our study, using the cgMLST scheme, Minimum Spanning Tree (MST) analysis did not identify significant geographic relationships between Lithuanian N.meningitidis isolates and strains from Europe. Discussion: To our knowledge, this is the first study to employ whole genome sequencing (WGS) method for a comprehensive genetic characterization of invasive N. meningitidis isolates from Lithuania. This approach provides a more detailed and precise analysis of genomic relationships and diversity compared to prior studies relying on traditional molecular typing methods and antigen analysis.

7643 Acute blindness due to Metformin associated lactic acidosis

Abstract Disclosure: K.N. Pereira: None. K. Desai: None. T. Khan: None. S. Yong: None. Metformin, one of the most commonly prescribed oral hypoglycemic agents, effectively lowers basal and postprandial blood glucose. However, Metformin carries a black box warning for lactic acidosis, which is more common in setting of liver and kidney dysfunction. With an incidence rate of ∼ 4.3 cases per 100,000 patient-years, Metformin associated lactic acidosis (MALA) can present with nausea, vomiting, diarrhea, encephalopathy, hypothermia, respiratory failure and hypotension. Blindness is a rarely reported outcome of MALA. We present a case of a 48 year old intellectually disabled female with a history of type 2 diabetes (on Metformin) who presented with progressive encephalopathy insetting of intractable nausea and vomiting with poor oral intake, since starting lisinopril & rosuvastatin for newly diagnosed hypertension and hyperlipidemia. She was encephalopathic, hypothermic, hypotensive, tachycardic and tachypneic. Labs were notable for leukocytosis, AKI, hyperkalemia, elevated anion gap metabolic acidosis with a lactate of 13.6 and elevated lipase. She also tested positive for Influenza A. CT head showed no acute intracranial abnormality. CT chest, abdomen & pelvis was concerning for aspiration, multifocal pneumonia or a combination of both as well as acute interstitial pancreatitis. She was admitted to the ICU for further management including hemodialysis. She continued to have improving but persistent lactic acidosis despite multiple dialysis sessions. On day 5 of ICU stay, with resolution of her encephalopathy, she reported new onset complete bilateral painless vision loss. General eye and neurologic exam was unrevealing except for sluggishly reactive pupils to light. MRI brain showed an new acute 2 mm lacunar infarct in the right temporal lobe. Neurology ruled out stroke as the cause for her vision loss. Emergent ophthalmology evaluation revealed no retinopathy, macular edema, acute glaucoma or thromboembolic event. The new onset vision loss was suspected to be due to MALA due to persistent metabolic disturbances. Some animal studies have shown that retinal horizontal cells are sensitive to low pH, resulting in interruption of signal transmission to the visual neurons and consequent blindness. The presence of factors like metformin metabolites may contribute to impaired function of retinal cells.On extensive literature review it was noted that only 5 cases of vision loss associated with MALA have been reported. However, in these cases, vision loss was transient and reversed following correction of acidosis with dialysis. Our case highlights a rare consequence of MALA, which can be irreversible and cause lifelong disability. Presentation: 6/1/2024

Prenatal and postnatal antiviral therapies for the prevention and treatment of congenital cytomegalovirus infections.

Congenital cytomegalovirus infection (cCMV) is the leading infectious cause of sensorineural hearing loss and lifelong neurodevelopmental disabilities. Studies suggest antiviral therapy can prevent fetal infection after maternal primary infection, as well as halt the progression of hearing loss and neurodevelopmental disabilities in newborns with symptomatic cCMV. With growing worldwide momentum on early detection and diagnosis of cCMV, this review describes the exciting recent advances in antiviral therapies in CMV infected pregnant mothers and babies, as well as emerging evidence on anti-CMV vaccines. New opportunities for prenatal and neonatal interventions have driven a rising interest in screening and identification of asymptomatic CMV infection. Routine screening of pregnant women to identify primary infection in first trimester is now advocated in Western Europe but has yet to be examined from a public health perspective in other regions. Evidence is emerging for maternal valaciclovir therapy to prevent fetal infection after a maternal primary CMV infection in the first trimester of pregnancy. For those infants who are born with symptomatic cCMV, a 6-month course of valganciclovir, started within the first 4 weeks of life, and possibly up to 13 weeks of life, is the current recommended therapy. However, there is unclear evidence for the benefit of treatment for asymptomatic cCMV and cCMV with isolated hearing loss. Research to identify more effective antivirals and an effective CMV vaccine continues. More research is needed to determine the region-specific applicability of the new European recommendations for routine CMV screening in pregnancy. Areas of uncertainty in postnatal management include timing of initiation, duration of treatment and identifying pediatric subgroups that benefit from modification of the standard treatment recommendations.

Tethered cord prevalence among patients with prenatal or postnatal myelomeningocele repair.

Myelomeningocele (MMC) is a severe form of spina bifida characterized by spinal cord extrusion into a cerebrospinal fluid (CSF) filled sac which may lead to lifelong disability. Repair of these lesions have classically occurred shortly after birth, but more recently, prenatal myelomeningocele repair techniques have been elucidated. This study aimed to investigate the outcome of surgery, particularly with subsequent spinal cord tethering, in patients with prenatal myelomeningocele closure and those with postnatal repair surgery. In this retrospective study which assessed patients from April 2002 to April 2020, the data of 18 total patients with MMC were reviewed. Nine patients from each group were included, closed prenatally or postnatally, respectively. Demographic information including age and sex, birth week, infant comorbidities, presence of dermoid or lipoma, cutaneous stigmata, total number and timing of detethering procedures, presence of Chiari malformation, and need for VPS was obtained. Eighteen patients including nine infants closed prenatally and nine infants with myelomeningoceles closed postnatally were reviewed. The mean age was 4 ± 3years and 6.22 ± 2.4 in prenatal and postnatal retrospectively. There was a significant relationship between the number of detethering procedures (p-value = 0.03) and the need for a ventriculoperitoneal shunt (VPS) (p-value = 0.01) between the groups, with the prenatal closure group having lower rates of each. There was no significant difference between the groups in regard to the mean age at the detethering procedure (p = 0.4), sex (p = 0.09), birth week (p = 0.8), comorbidities (p = 0.8), presence of intraspinal dermoid or lipoma (p = 0.09), presence of cutaneous stigma (p = 0.08), Chiari (p = 0.6), fatty filum (p = 0.08), syrinx (p = 0.4), bone anomaly (p = 0.4), and spina bifida neurological scale (p = 0.66). There was a significant relationship between the two groups in terms of the number of detethering procedures, and the need for VPS. Our data represents a possible difference in the need for detethering surgeries and ventriculoperitoneal shunt placements between patients with prenatal and postnatal myelomeningocele closures.

Longitudinal Frailty Transitions in Adults Aging with Intellectual Disability

Abstract Background Adults with Intellectual Disability (ID) are a vulnerable population, experiencing high rates of polypharmacy and multimorbidity, and experiencing early mortality. Lifelong functional and intellectual disability can complicate frailty measurement. To date, no studies have examined long term frailty transitions in this complex group. The aim of this study was to examine longitudinal frailty transitions, with the hope of distinguishing frailty from disability. Methods This study was conducted using The Intellectual Disability Supplement to the Irish Longitudinal Study of Aging (IDS-TILDA). It followed 745 adults with ID across 4 waves of data collection between 2010 and 2021. Frailty was measured at each wave using an ID-specific Frailty Index. Scores were classified into the following states: Non-Frail, Pre-Frail, Frail, Missing and Dead. Transitions are demonstrated visually using alluvial plots, created using the ggalluvial package in R. Multistate Markov Modelling was used to calculate transition probabilities between states across subsequent waves. Results Frailty transitions were common across the 4 waves. Both positive (decreasing frailty) and negative (increasing frailty) transitions were seen. There was a 6.8% probability of transitioning from Frail to Pre-Frail, and a 10.5% probability of transitioning from Pre-Frail to Non-Frail. The probabilities of negative transitions were higher than positive transitions. The probability of transitioning to death was higher in higher frailty states: Non-Frail = 2.6%, Pre-Frail = 5.1%, Frail = 19.3%. Compared to the general population, positive transitions were less likely. Conclusion This is the first study to demonstrate transitions in frailty states in adults with ID. To date, singe time-point studies of frailty in ID have faced the struggle of distinguishing frailty from underlying disability. For adults with ID, lifelong disability is expected to be relatively static. The dynamism captured here points to frailty as a distinct entity experienced by this group. Efforts are needed to better manage frailty in this vulnerable cohort.

"Motherhood forced me to cope with my disability": identity intersection among mothers with physical disabilities.

Although motherhood plays a meaningful role in the formation of a woman's identity, most studies have focused on the process of identity transformation in the transition to motherhood among non-disabled women; less is known about this process among women with physical disabilities who become mothers. The present study aimed to understand and describe the subjective experiences of Israeli women with lifelong physical disabilities in their motherhood journey from the perspective of the intersection of their motherhood and disability identities, and from the disability studies approach. Semi-structured interviews were conducted with 20 Israeli mothers with visible lifelong physical disabilities who live in the community and raise their children. Three themes emerged from the interviews: (1) the decision to become a mother: Coping with the disability identity for the first time; (2) The FIRST 3 years: Depending on others as limiting their motherhood identity; (3) after age three: Balancing the motherhood and disability identities. The transition to motherhood led to identity transformation among women with physical disabilities. Becoming a mother increased the tension between dependence and independence in the context of disability, which also influenced the intersection of their motherhood and disability identities and their wellbeing. Practitioners should provide emotional support to mothers with disabilities and help them embrace the positive aspects of each identity and strike a balance between them.

Paediatric low-grade glioma: the role of classical pathology in integrated diagnostic practice.

Low-grade gliomas are a cause of severe and often life-long disability in children. Pathology plays a key role in their management by establishing the diagnosis, excluding malignant alternatives, predicting outcomes and identifying targetable genetic alterations. Molecular diagnosis has reshaped the terrain of pathology, raising the question of what part traditional histology plays. In this review, we consider the classification and pathological diagnosis of low-grade gliomas and glioneuronal tumours in children by traditional histopathology enhanced by the opportunities afforded by access to comprehensive genetic and epigenetic characterisation.

Effect of Nesting and Swaddling on Sleep Duration of Preterm Neonate Hospitalized at Tertiary Care Centre of Eastern Nepal

Background: All preterm neonates’ sleep is disturbed during hospitalization period due to various stressful environmental factors and human error and without focusing in individual developmental care. This impacts neonatal neurological development as well as normal growth resulting lifelong disabilities. Thus, modification of the environment by intervening developmental care could minimize the iatrogenic effect and neuro-developmental delay by decreasing stressful environment. This study was conducted to assess the effect of nesting and swaddling on sleep duration of preterm neonates during hospitalization at B.P.Koirala Instituted of Health sciences (BPKIHS). Methods: True experimental (post-test control design) study conducted among 36 preterm neonates, admitted in Nursery and Neonatal Unit of BPKIHS. The objective of this study was to assess the effect of nesting and swaddling on sleep duration. Consecutive sampling technique was used for total sample size then after random allocation is applied for creates the samples into two groups: experimental and control. Performa was used to collect socio-demographic characteristics. Sleep duration was recorded in self-administer observation form base on the observational behavior characteristics scoring of neonatal sleep by AASM (American Academy of sleep Medicine). As intervention, nesting and swaddling were performed in experimental group, then the sleep was video-recorded for 2 hours for each neonate. Finally, data were analyzed using descriptive and inferential statistics. Results: Among the enrolled neonates, there were 23 male (63.9%) and 13 female (36.1%) preterm. There was significant difference in sleep duration between experimental and control group. The mean ± SD of sleep duration was 59.22 ± 22.61 minute in experimental group and 39.50 ± 8.06 minute in control with p-value 0.001. The mean sleep duration was not associated with other selected study variables except the performed intervention. Conclusions: Nesting and Swaddling can be used as convenient and effective method to increase neonatal sleep duration or rest period.

Short Term Outcome of Writer’s Cramp in Children - A Case Series

Background: Focal task-specific dystonia of the hand is unusual in childhood. Childhood dystonia can result in lifelong disability and thus represents a significant diagnostic and rehabilitation challenge. A detailed clinical evaluation and comprehensive work-up to rule out treatable causes of focal dystonia are mandatory for establishing a therapeutic strategy. We reported 4 cases of writer. s cramp with earliest age of onset. Our aim was to focus on early detection, proper evaluation and management of writer’s cramp to ensure better quality of life of an affected child. J Com Med Col Teachers Asso Jan 2024; 28(1): 33-36

Pain hypersensitivity, sensorimotor impairment, and decreased muscle force in a novel rat model of radiation-induced peripheral neuropathy.

Radiation-induced peripheral neuropathy is a rare, but serious complication often resulting in profound morbidity, life-long disability, and chronic debilitating pain. Unfortunately, this type of peripheral neuropathy is usually progressive, and almost always irreversible. To date, a standardized rat model of radiation-induced peripheral neuropathy has not been established. The purpose of the present study was to examine neuropathic pain, sensorimotor impairment, and muscle force parameters following the administration of a clinically relevant radiation dose in a rat model. Ten rats were randomly assigned to one of two experimental groups: (1) radiation and (2) sham-radiated controls. Radiated animals were given a clinically relevant dose of 35 Gray (Gy) divided into five daily doses of 7 Gy/day. This regimen represents a human equivalent dose of 70 Gy, approximating the same dosage utilized for radiotherapy in oncologic patients. Sham-radiated controls were anesthetized and placed in the radiation apparatus but were not given radiation. All animals were tested for baseline values in both sensorimotor and pain behavioral tests. Sensorimotor testing consisted of the evaluation of walking tracks with the calculation of the Sciatic Functional Index (SFI). Pain-related behavioral measures consisted of mechanical allodynia (von Frey test), cold allodynia (Acetone test), and thermal allodynia (Hargreaves test). Animals were tested serially over an 8-week period. At the study endpoint, electrophysiological and muscle force assessments were completed, and histomorphometric analysis was performed on all sciatic nerves. Animals that underwent radiation treatment displayed significantly greater pain hypersensitivity to mechanical stimulation as compared to sham radiated controls from weeks 4 to 8 of testing. SFI values indicated sensorimotor impairments in the overground gait of radiated animals as compared to non-radiated animals. Furthermore, radiated animals displayed reduced twitch and tetanic muscle force when compared to sham radiated controls. A clinically relevant human equivalent dose of fractionated 35 Gy in rats established significant pain hypersensitivity, impairments in sensorimotor locomotion, and decreased muscle force capacity. This novel rodent model of radiation-induced peripheral neuropathy can be utilized to assess the potential efficacy of therapeutic treatments to either prevent or remediate this clinically debilitating condition.

Clinical characteristics and outcomes of perinatal stroke in Australia: Population-based longitudinal study.

Perinatal stroke is one of the main causes of hemiplegia and seizure disorder. This study aimed to analyse the clinical characteristics and outcomes of perinatal stroke in a cohort of Australian children for its early detection. A population-based prospective longitudinal study on perinatal stroke up to 2 years of age, was conducted from 2017 to 2019. Eighty-seven children with perinatal stroke included 79% (69/87) acute and 21% (18/87) presumed perinatal stroke. Seventy-four per cent (51/69) acute symptomatic perinatal strokes presented in the first 3 days of life and 78% (14/18) presumed perinatal strokes presented by 6 months of age. 62% had an arterial stroke, 29% had a venous stroke and 5% had a combined arterial and venous stroke. Unexpectedly, 35% (24/69) acute symptomatic perinatal stroke had only respiratory symptoms and 50% (9/18) presumed perinatal stroke were asymptomatic. The incidence of cerebral palsy was 29% (20/69) with acute symptomatic perinatal stroke and 72% (13/18) with presumed perinatal stroke. The first week of a child's life is the most critical period in terms of lifelong disability from perinatal stroke. Recognising diverse clinical presentations will ensure early diagnosis and timely intervention treatments.

Metformin attenuates white matter injury in neonatal mice through activating NRF2/HO-1/NF-κB pathway

White matter injury (WMI) is a major form of brain injury that occurs in preterm infants and develops into lifelong disabilities, including cerebral palsy, impaired cognitive function, and psychiatric disorders. Metformin (MET) has been reported to have neuroprotective effects. However, whether MET is responsible for neuroprotection against WMI remains unclear. In this study, we established a WMI model in neonatal mice to explore the neuroprotective effects of MET and attempted to elucidate its potential mechanisms. Our results showed that MET increased the expression of myelin basic protein (MBP), oligodendrocyte transcription factor 2 (Olig2), and CC1, improved the thickness and density of the myelin sheath, and reduced oxidative stress and microglial infiltration after chronic hypoxia induction. Moreover, MET improved memory, learning, and motor abilities as well as relieved anxiety-like behaviors in mice with WMI. These protective effects of MET may involve the upregulation of the nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1(HO-1)/NF-κB pathway related protein expressions. In addition, the NRF2 inhibitor ML385 could significantly reverse the effects of MET. In conclusion, this study suggested that MET attenuated chronic hypoxia-induced WMI through activating the NRF2/HO-1/NF-κB pathway, indicating that MET might be a promising therapeutic option for WMI.

Modified MacIntosh (Over-the-Top Iliotibial Band Autograft) Technique for Pediatric Anterior Cruciate Ligament Reconstruction Using Knotless All-Suture Anchor Fixation

Anterior cruciate ligament (ACL) injury is a significant cause of injury among pediatric patients with an increasing incidence. ACL insufficiency can lead to lifelong disability as further joint deterioration occurs in the form of meniscal and subsequently chondral pathology. Techniques for pediatric ACL reconstruction can broadly be classified as physeal-sparing and non–physeal-sparing. Bone age is frequently used when deciding which technique to employ. Patients are candidates for physeal-sparing, over-the-top iliotibial band reconstruction (i.e., modified MacIntosh II) when they have >4 years remaining before skeletal maturity. The modified Macintosh procedure provides both intra- and extra-articular rotational and translational constraint. This Technical Note describes the senior author’s modified MacIntosh technique using knotless all-suture anchor fixation in a suture staple technique to mitigate risk of physeal damage.

Cost-effectiveness of screening for developmental dysplasia of the hip in Karachi, Pakistan using a universally applicable cost-effectiveness model

IntroductionDevelopmental dysplasia of the hip (DDH) is a congenital anomaly of the hip socket that can lead to lifelong disability and pain when left untreated. DDH is a good candidate...

Critical thresholds of long-pressure reactivity index and impact of intracranial pressure monitoring methods in traumatic brain injury

BackgroundModerate-to-severe traumatic brain injury (TBI) has a global mortality rate of about 30%, resulting in acquired life-long disabilities in many survivors. To potentially improve outcomes in this TBI population, the management of secondary injuries, particularly the failure of cerebrovascular reactivity (assessed via the pressure reactivity index; PRx, a correlation between intracranial pressure (ICP) and mean arterial blood pressure (MAP)), has gained interest in the field. However, derivation of PRx requires high-resolution data and expensive technological solutions, as calculations use a short time-window, which has resulted in it being used in only a handful of centers worldwide. As a solution to this, low resolution (longer time-windows) PRx has been suggested, known as Long-PRx or LPRx. Though LPRx has been proposed little is known about the best methodology to derive this measure, with different thresholds and time-windows proposed. Furthermore, the impact of ICP monitoring on cerebrovascular reactivity measures is poorly understood. Hence, this observational study establishes critical thresholds of LPRx associated with long-term functional outcome, comparing different time-windows for calculating LPRx as well as evaluating LPRx determined through external ventricular drains (EVD) vs intraparenchymal pressure device (IPD) ICP monitoring.MethodsThe study included a total of n = 435 TBI patients from the Karolinska University Hospital. Patients were dichotomized into alive vs. dead and favorable vs. unfavorable outcomes based on 1-year Glasgow Outcome Scale (GOS). Pearson’s chi-square values were computed for incrementally increasing LPRx or ICP thresholds against outcome. The thresholds that generated the greatest chi-squared value for each LPRx or ICP parameter had the highest outcome discriminatory capacity. This methodology was also completed for the segmentation of the population based on EVD, IPD, and time of data recorded in hospital stay.ResultsLPRx calculated with 10–120-min windows behaved similarly, with maximal chi-square values ranging at around a LPRx of 0.25–0.35, for both survival and favorable outcome. When investigating the temporal relations of LPRx derived thresholds, the first 4 days appeared to be the most associated with outcomes. The segmentation of the data based on intracranial monitoring found limited differences between EVD and IPD, with similar LPRx values around 0.3.ConclusionOur work suggests that the underlying prognostic factors causing impairment in cerebrovascular reactivity can, to some degree, be detected using lower resolution PRx metrics (similar found thresholding values) with LPRx found clinically using as low as 10 min-by-minute samples of MAP and ICP. Furthermore, EVD derived LPRx with intermittent cerebrospinal fluid draining, seems to present similar outcome capacity as IPD. This low-resolution low sample LPRx method appears to be an adequate substitute for the clinical prognostic value of PRx and may be implemented independent of ICP monitoring method when PRx is not feasible, though further research is warranted.

Aging Well With a Lifelong Disability: A Scoping Review.

Existing literature highlights notable health and social inequalities for people aging with a lifelong disability and the need for research to better understand how we can support this group to age well. This scoping review mapped existing literature related to "aging well" in people with lifelong disabilities. Five scientific databases and gray literature sources were searched for studies related to "aging well" and "lifelong disability" (defined as a disability that a person had lived with since birth or early childhood). We identified 81 studies that discussed aging well with a lifelong disability, with most (70%) focusing on intellectual disabilities. Two themes captured existing research on aging well with a lifelong disability: (1) framing aging well with a lifelong disability, which included the ways that people with lifelong disability, their supporters, and existing research frame aging well for this group and (2) supporting people to age well with a lifelong disability, which involves the micro-, meso-, and macro-level factors where research suggests interventions to facilitate aging well could be situated. This synthesis highlights how aging well is currently framed in the literature and where interventions to improve aging well in this group could be situated. Literature highlights the importance of considering multilevel interventions to improve aging well. Evidence gaps include the lack of research conducted with groups other than those with intellectual disabilities and the need for more research examining aging well interventions.

Immunizing Mice with Influenza Virus-like Particles Expressing the Leishmania amazonensis Promastigote Surface Antigen Alleviates Inflammation in Footpad.

Cutaneous leishmaniasis (CL) is a tropical disease endemic in many parts of the world. Characteristic clinical manifestations of CL include the formation of ulcerative skin lesions that can inflict life-long disability if left untreated. Although drugs are available, they are unaffordable and out of reach for individuals who need them the most. Developing a highly cost-efficient CL vaccine could address this problem but such a vaccine remains unavailable. Here, we developed a chimeric influenza virus-like particle expressing the Leishmania amazonensis promastigote surface antigen (LaPSA-VLP). LaPSA-VLPs were self-assembled in Spodoptera frugiperda insect cell lines using the baculovirus expression system. After characterizing the vaccines and confirming successful VLP assembly, BALB/c mice were immunized with these vaccines for efficacy assessment. Sera acquired from mice upon subcutaneous immunization with the LaPSA-VLP specifically interacted with the L. amazonensis soluble total antigens. LaPSA-VLP-immunized mice elicited significantly greater quantities of parasite-specific IgG from the spleens, popliteal lymph nodes, and footpads than unimmunized mice. LaPSA-VLP immunization also enhanced the proliferation of B cell populations in the spleens of mice and significantly lessened the CL symptoms, notably the footpad swelling and IFN-γ-mediated inflammatory response. Overall, immunizing mice with the LaPSA-VLPs prevented mice from developing severe CL symptoms, signifying their developmental potential.