28232 research outputs found
Sort by
Predictive model for distal junctional kyphosis after cervical deformity surgery.
No full textBackground contextDistal junctional kyphosis (DJK) is a primary concern of surgeons correcting cervical deformity. Identifying patients and procedures at higher risk of developing this condition is paramount in improving patient selection and care.PurposeThe present study aimed to develop a risk index for DJK development in the first year after surgery.Study design/settingThis is a retrospective review of a prospective multicenter cervical deformity database.Patient samplePatients over the age of 18 meeting one of the following deformities were included in the study: cervical kyphosis (C2-7 Cobb angle>10°), cervical scoliosis (coronal Cobb angle>10°), positive cervical sagittal imbalance (C2-C7 sagittal vertical axis (SVA)>4 cm or T1-C6>10°), or horizontal gaze impairment (chin-brow vertical angle>25°).Outcome measuresDevelopment of DJK at any time before 1 year.MethodsDistal junctional kyphosis was defined by both clinical diagnosis (by enrolling surgeon) and post hoc identification of development of an angleResultsStatistical analysis included 101 surgical patients (average age: 60.1 years, 58.3% female, body mass index: 30.2) undergoing long cervical deformity correction (mean levels fused: 7.1, osteotomy used: 49.5%, approach: 46.5% posterior, 17.8% anterior, 35.7% combined). In 2 years after surgery, 6% of patients were diagnosed with clinical DJK; however, 23.8% of patients met radiographic definition for DJK. Patients with neurologic symptoms were at risk of DJK (odds ratio [OR]: 3.71, confidence interval [CI]: 0.11-0.63). However, no significant relationship was found between osteoporosis, age, and ambulatory status with DJK incidence. Baseline radiographic malalignments were the most numerous and strong predictors for DJK: (1) C2-T1 tilt>5.33 (OR: 6.94, CI: 2.99-16.14); (2) kyphosis36.4 (OR: 5.6, CI: 2.28-13.57); (5) C2-C7 SVA>56.3° (OR: 5.4, CI: 2.20-13.23); and (6) C4_Tilt>56.7 (OR: 5.0, CI: 1.90-13.1). Clinically, combined approaches (OR: 2.67, CI: 1.21-5.89) and usage of Smith-Petersen osteotomy (OR: 2.55, CI: 1.02-6.34) were the most important predictors of DJK.ConclusionsIn a surgical cohort of patients with cervical deformity, we found a 23.8% incidence of DJK. Different procedures and patient malalignment predicted incidence of DJK up to 1 year. Preoperative T1 slope-cervical lordosis, cervical kyphosis, SVA, and cervical lordosis all strongly predicted DJK at specific cut-off points. Knowledge of these factors will potentially help direct future study and strategy aimed at minimizing this potentially dramatic occurrence
Building a Decision Model to Estimate the Health and Economic Benefits of Targeted Mental Health Interventions to Improve ART Adherence among Young People Living with HIV in Tanzania
No full textYoung people living with HIV (YPLWH) constitute a growing proportion of the global population of people living with HIV but have less access to HIV testing, diagnosis, treatment, and face heightened mental health challenges. To address these challenges, targeted mental health and medication adherence interventions have been developed, including in Tanzania, which is home to 6% of the world's YPLWH. This study proposes a mathematical model to estimate the health and economic outcomes of mental health HIV adherence interventions targeting YPLWH in Tanzania.We developed a Markov model to predict the long-term health (Disability-Adjusted Life Years (DALY)) and economic outcomes (Value of a Statistical Life Year (VLSY)) of mental health HIV adherence interventions targeting YPLWH. We parameterized the model using outcomes data from the 2016-2020 Sauti ya Vijana randomized control trial (RCT) conducted in Moshi, Tanzania. Cost data were retrieved from a cost analysis of the same RCT and supplemented with data from published literature. The study is conducted from a health payer’s perspective, and the Willingness-To-Pay (WTP) per DALY averted was set to the 2021 Tanzanian GDP per capita (USD 1099.3). Costs and outcomes were modeled for ten years and discounted at an annual rate of 3%.
The findings suggest that the Sauti ya Vijana intervention modeled in this study is cost-effective at a WTP of USD 1099.3. The Incremental cost-effectiveness ratio for the intervention compared to the standard of care was USD 637.06 per DALY averted at a 3% discount rate. The benefit-to-cost ratio of the intervention was USD 26.54 in economic productivity for the intervention arm for every dollar spent on the intervention, and the net economic productivity benefit was USD 17,174.74 over a decade.
Mental health adherence interventions hold the promise of improving health outcomes amongst YPLWH. The mathematical model developed in this study is a valuable decision-making tool for policymakers regarding mental health adherence interventions targeting YPLWH in Tanzania. The model contributes to the global goal of achieving the UNAIDS 95-95-95 targets for YPLWH.
</p
Suppressyn localization and dynamic expression patterns in primary human tissues support a physiologic role in human placentation.
No full textWe previously identified suppressyn (SUPYN), a placental protein that negatively regulates the cell fusion essential for trophoblast syncytialization via binding to the trophoblast receptor for syncytin-1, ASCT2, and hypothesized that SUPYN may thereby regulate cell-cell fusion in the placenta. Here, we redefine in vivo SUPYN localization using specific monoclonal antibodies in a rare early placental sample, showing SUPYN localization in villous and extravillous trophoblast subtypes, the decidua and even in placental debris in the maternal vasculature. In human trophoblast cell lines, we show SUPYN alters ASCT2 glycosylation within the secretory pathway and that this binding is associated with inhibition of cell fusion. Using newly-optimized trophoblast isolation protocols that allow tracking of ex vivo cell fusion, we present transcription and translation dynamics of fusion-related proteins over 96 hours in culture and the effects of changes in ambient oxygen levels on these processes. We report converse syncytin-1 and SUPYN transcriptional and translational responses to surrounding oxygen concentrations that suggest both are important in the effects of hypoxia and hyperoxia on placental syncytialization. Our results suggest that SUPYN's anti-fusogenic properties may be exerted at several sites in the maternal body and its dysregulation may be associated with diseases of abnormal placentation
<i>Salmonella</i> Typhi Vi capsule prime-boost vaccination induces convergent and functional antibody responses.
No full textVaccine development to prevent Salmonella Typhi infections has accelerated over the past decade, resulting in licensure of new vaccines, which use the Vi polysaccharide (Vi PS) of the bacterium conjugated to an unrelated carrier protein as the active component. Antibodies elicited by these vaccines are important for mediating protection against typhoid fever. However, the characteristics of protective and functional Vi antibodies are unknown. In this study, we investigated the human antibody repertoire, avidity maturation, epitope specificity, and function after immunization with a single dose of Vi-tetanus toxoid conjugate vaccine (Vi-TT) and after a booster with plain Vi PS (Vi-PS). The Vi-TT prime induced an IgG1-dominant response, whereas the Vi-TT prime followed by the Vi-PS boost induced IgG1 and IgG2 antibody production. B cells from recipients who received both prime and boost showed evidence of convergence, with shared V gene usage and CDR3 characteristics. The detected Vi antibodies showed heterogeneous avidity ranging from 10 μM to 500 pM, with no evidence of affinity maturation after the boost. Vi-specific antibodies mediated Fc effector functions, which correlated with antibody dissociation kinetics but not with association kinetics. We identified antibodies induced by prime and boost vaccines that recognized subdominant epitopes, indicated by binding to the de–O-acetylated Vi backbone. These antibodies also mediated Fc-dependent functions, such as complement deposition and monocyte phagocytosis. Defining strategies on how to broaden epitope targeting for S. Typhi Vi and enriching for antibody Fc functions that protect against typhoid fever will advance the design of high-efficacy Vi vaccines for protection across diverse populations
Under Correction of Sagittal Deformities Based on Age-adjusted Alignment Thresholds Leads to Worse Health-related Quality of Life Whereas Over Correction Provides No Additional Benefit.
No full textStudy designRetrospective review of prospectively-collected database.ObjectiveThis study aims to compare 2-year clinical outcomes of patients who underwent surgical reconstructions based on their achievement to age-adjusted alignment ideals.Summary of background dataRecent research in sagittal plane has proposed age-adjusted alignment thresholds. However, the impact of these thresholds on postoperative health-related quality of life (HRQOL) is yet to be investigated.MethodsPatients were included if they were more than 18-years old and underwent surgical correction of adult spinal deformity with a complete 2-year follow-up. Patients were stratified into three groups based on achievement of age-adjusted thresholds in pelvic tilt (PT), pelvic incidence minus lumbar lordosis (PI-LL), and sagittal vertical axis (SVA). First group included patients who reached the exact age-adjusted threshold ± 10 years (MATCHED), other two groups included patients who were over corrected (OVER), and under corrected (UNDER). Clinical outcomes including actual value and offset from age-adjusted Oswestry Disability Index, Short-Form-36 (SF-36) -physical component summary, and Scoliosis Research Society-22r (SRS-22r) were compared between groups at 2 years follow-up.ResultsA total of 343 patients (mean, 57 yrs and 83% females) were included. Sagittal profile of the population was: PT = 23.6°, SVA = 65.8 mm, and PI-LL = 15.6°. At 2-year follow-up, there was significant improvement in all sagittal modifiers with 25.7%, 24.3%, and 33.1% of the patients matching their age alignment targets in terms of PT, PI-LL, and SVA, respectively. For PT and PI-LL, the three groups (MATCHED, OVER, and UNDER) had comparable values and offsets from age-adjusted patient reported outcome. However, for SVA groups, patients in UNDER had significantly worse HRQOL than the two other groups. Patients in PT, PI-LL, and SVA UNDER groups were significantly younger than the other groups, P ConclusionAt 2 years after adult spinal deformity surgical treatment, only 24.3% to 33.1% of the patients reached age-adjusted alignment thresholds. Those under corrected in SVA demonstrated worse clinical outcomes. No significant improvements were found between matched and overcorrected patients, with overcorrection being an established risk for proximal junctional kyphosis. These results further emphasize the need for patient specific operative planning.Level of evidence3
Digital Medicine System in Veterans With Severe Mental Illness: Feasibility and Acceptability Study.
No full textBackgroundSuboptimal medication adherence is a significant problem for patients with serious mental illness. Measuring medication adherence through subjective and objective measures can be challenging, time-consuming, and inaccurate.ObjectiveThe primary purpose of this feasibility and acceptability study was to evaluate the impact of a digital medicine system (DMS) among Veterans (patients) with serious mental illness as compared with treatment as usual (TAU) on medication adherence.MethodsThis open-label, 2-site, provider-randomized trial assessed aripiprazole refill adherence in Veterans with schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder. We randomized 26 providers such that their patients either received TAU or DMS for a period of 90 days. Semistructured interviews with patients and providers were used to examine the feasibility and acceptability of using the DMS.ResultsWe enrolled 46 patients across 2 Veterans Health Administration sites: 21 (46%) in DMS and 25 (54%) in TAU. There was no difference in the proportion of days covered by medication refill over 3 and 6 months (0.82, SD 0.24 and 0.75, SD 0.26 in DMS vs 0.86, SD 0.19 and 0.82, SD 0.21 in TAU, respectively). The DMS arm had 0.85 (SD 0.20) proportion of days covered during the period they were engaged with the DMS (mean 144, SD 100 days). Interviews with patients (n=14) and providers (n=5) elicited themes salient to using the DMS. Patient findings described the positive impact of the DMS on medication adherence, challenges with the DMS patch connectivity and skin irritation, and challenges with the DMS app that affected overall use. Providers described an overall interest in using a DMS as an objective measure to support medication adherence in their patients. However, providers described challenges with the DMS dashboard and integrating DMS data into their workflow, which decreased the usability of the DMS for providers.ConclusionsThere was no observed difference in refill rates. Among those who engaged in the DMS arm, the proportion of days covered by refills were relatively high (mean 0.85, SD 0.20). The qualitative analyses highlighted areas for further refinement of the DMS.Trial registrationClinicalTrials.gov NCT03881449; https://clinicaltrials.gov/ct2/show/NCT03881449
The Chado Natural Diversity module: a new generic database schema for large-scale phenotyping and genotyping data.
No full textLinking phenotypic with genotypic diversity has become a major requirement for basic and applied genome-centric biological research. To meet this need, a comprehensive database backend for efficiently storing, querying and analyzing large experimental data sets is necessary. Chado, a generic, modular, community-based database schema is widely used in the biological community to store information associated with genome sequence data. To meet the need to also accommodate large-scale phenotyping and genotyping projects, a new Chado module called Natural Diversity has been developed. The module strictly adheres to the Chado remit of being generic and ontology driven. The flexibility of the new module is demonstrated in its capacity to store any type of experiment that either uses or generates specimens or stock organisms. Experiments may be grouped or structured hierarchically, whereas any kind of biological entity can be stored as the observed unit, from a specimen to be used in genotyping or phenotyping experiments, to a group of species collected in the field that will undergo further lab analysis. We describe details of the Natural Diversity module, including the design approach, the relational schema and use cases implemented in several databases
The Saviorism of Melinda Gates: Eugenics, Philanthrocapitalism, and the Perils of ‘Western’ Feminisms
No full textIn this thesis, I aim to historically analyze and explicate long-lasting issues with philanthropic programs, specifically their health programs, by using Melinda Gates and her family planning programs at the Gates Foundation as a case study for the harms of philanthrocapitalism. Philanthrocapitslism was initially defined by Matthew Bishop and Michael Green in their book Philanthrocapitalism: How the Rich Can Save the World (2008) as a form of philanthropy conducted through a capitalist business-model by entrepreneurs. In addition to looking at the dangers of Melinda Gates’ philanthrocapitalism, this thesis also focuses on the specific history of family planning programs and outlines its history with eugenics to show how this history continues to shape Gates’ family planning programs. I analyze examples from the Population Council, a population control organization founded by eugenicists and funded by the Rockefeller and Ford Foundations among others. Comparing the Population Council’s eugenic research and programs to Melinda Gates’ work in the Gates Foundation, I show the throughlines between past eugenic movements and her work today. Finally, I do a close reading of Melinda Gates’ word choices in her book The Moment of Lift (2019), TedTalk, and the Gates Discovery Center, a public museum in Seattle, to dissect the saviorism underlying her philanthropic work. I connect the saviorism in her work to past and current philanthropy foundations as well as contextualizing her language choices as examples of Western feminist frameworks. Overall, this thesis shows the issues underlying Melinda Gates’ family planning programs by connecting them to past racist, imperialist programs of a similar nature