Introduction Religion and spirituality play important roles in the lives of many, including healthcare providers and their patients. The purpose of this study was to examine the relationships between ...religion, spirituality, and cultural competence of healthcare providers. Methods Physicians, residents, and medical students were recruited through social platforms to complete an electronically delivered survey, gathering data regarding demographics, cultural competency, religiosity, and spirituality. Four composite variables were created to categorize cultural competency: Patient Care Knowledge, Patient Care Skills/Abilities, Professional Interactions, and Systems Level Interactions. Study participants (n = 144) were grouped as Christian (n = 95)/non-Christian (n = 49) and highly religious (n = 62)/not highly religious (n = 82); each group received a score in the four categories. Wilcoxon rank sum and Chi-square tests were used for analysis of continuous and discrete variables. Results A total of 144 individuals completed the survey with the majority having completed medical school (n = 87), identifying as women (n = 108), white (n = 85), Christian (n = 95), and not highly religious (n = 82). There were no significant differences amongst Christian versus non-Christian groups or highly religious versus not highly religious groups when comparing their patient care knowledge (p = .563, p = .457), skills/abilities (p = .423, p = .51), professional interactions (p = .191, p = .439), or systems level interaction scores (p = .809, p = .078). Nevertheless, participants reported decreased knowledge of different healing traditions (90%) and decreased skills inquiring about religious/spiritual and cultural beliefs that may affect patient care (91% and 88%). Providers also reported rarely referring patients to religious services (86%). Conclusions Although this study demonstrated no significant impact of healthcare providers' religious/spiritual beliefs on the ability to deliver culturally competent care, it did reveal gaps around how religion and spirituality interact with health and healthcare. This suggests a need for improved cultural competence education.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The American Academy of Pediatrics recommends that extremely preterm infants receive mother's own milk (MOM) when available or pasteurized donor breast milk (DBM) when MOM is unavailable. The goal of ...this study was to determine whether DBM could be inoculated with MOM from mothers of preterm infants to restore the live microbiota (RM). Culture dependent and culture independent methods were used to analyze the fluctuations in the overall population and microbiome, respectively, of DBM, MOM, and RM samples over time. Using MOM at time = 0 (T0) as the target for the restoration process, this level was reached in the 10% (RM-10) and 30% (RM-30) mixtures after 4 h of incubation at 37°C, whereas, the larger dilutions of 1% (RM-1) and 5% (RM-5) after 8 h. The diversity indexes were similar between MOM and DBM samples, however, different genera were prevalent in each group. Interestingly, 40% of the bacterial families were able to expand in DBM after 4 h of incubation indicating that a large percentage of the bacterial load present in MOM can grow when transferred to DBM, however, no core microbiome was identified. In summary, the microbiome analyses indicated that each mother has a unique microbiota and that live microbial reestablishment of DBM may provide these microbes to individual mothers' infants. The agreement between the results obtained from the viable bacterial counts and the microbiome analyses indicate that DBM incubated with 10-30% v/v of the MOM for 4 h is a reasonable restoration strategy.
Summary
Liberibacter asiaticus is the prevalent causative pathogen of Huanglongbing or citrus greening disease, which has resulted in a devastating crisis in the citrus industry. A thorough ...understanding of this pathogen's physiology and mechanisms to control cell survival is critical in the identification of therapeutic targets. YbeY is a highly conserved bacterial RNase that has been implicated in multiple roles. In this study, we evaluated the biochemical characteristics of the L. asiaticus YbeY (CLIBASIA_01560) and assessed its potential as a target for antimicrobials. YbeYLas was characterized as an endoribonuclease with activity on 3′ and 5′ termini of 16S and 23S rRNAs, and the capacity to suppress the E. coli ΔybeY phenotype. We predicted the YbeYLas protein:ligand interface and subsequently identified a flavone compound, luteolin, as a selective inhibitor. Site‐directed mutagenesis was subsequently used to identify key residues involved in the catalytic activity of YbeYLas. Further evaluation of naturally occurring flavonoids in citrus trees indicated that both flavones and flavonols had potent inhibitory effects on YbeYLas. Luteolin was subsequently examined for efficacy against L. asiaticus in Huanglongbing‐infected citrus trees, where a significant reduction in L. asiaticus gene expression was observed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
IMPORTANCE: Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful ...vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SCD, particularly in children and participants treated with hydroxyurea. OBJECTIVE: To reassess the efficacy of poloxamer 188 for vaso-occlusive episodes. DESIGN, SETTING, AND PARTICIPANTS: Phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial conducted from May 2013 to February 2016 that included 66 hospitals in 12 countries and 60 cities; 388 individuals with SCD (hemoglobin SS, SC, S-β0 thalassemia, or S-β+ thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included. INTERVENTIONS: A 1-hour 100-mg/kg loading dose of poloxamer 188 intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194). MAIN OUTCOMES AND MEASURES: Time in hours from randomization to the last dose of parenteral opioids among all participants and among those younger than 16 years as a separate subgroup. RESULTS: Of 437 participants assessed for eligibility, 388 were randomized (mean age, 15.2 years; 176 45.4% female), the primary outcome was available for 384 (99.0%), 15-day follow-up contacts were available for 357 (92.0%), and 30-day follow-up contacts were available for 368 (94.8%). There was no significant difference between the groups for the mean time to last dose of parenteral opioids (81.8 h for the poloxamer 188 group vs 77.8 h for the placebo group; difference, 4.0 h 95% CI, −7.8 to 15.7; geometric mean ratio, 1.2 95% CI, 1.0-1.5; P = .09). Based on a significant interaction of age and treatment (P = .01), there was a treatment difference in time from randomization to last administration of parenteral opioids for participants younger than 16 years (88.7 h in the poloxamer 188 group vs 71.9 h in the placebo group; difference, 16.8 h 95% CI, 1.7-32.0; geometric mean ratio, 1.4 95% CI, 1.1-1.8; P = .008). Adverse events that were more common in the poloxamer 188 group than the placebo group included hyperbilirubinemia (12.7% vs 5.2%); those more common in the placebo group included hypoxia (12.0% vs 5.3%). CONCLUSIONS AND RELEVANCE: Among children and adults with SCD, poloxamer 188 did not significantly shorten time to last dose of parenteral opioids during vaso-occlusive episodes. These findings do not support the use of poloxamer 188 for vaso-occlusive episodes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01737814
Abstract
Background and Aims
The objective was to evaluate the pharmacokinetics, safety/tolerability, and efficacy of ustekinumab in children with moderately to severely active Crohn’s disease.
...Methods
In this Phase 1, multicentre, 16-week, double-blind, induction dose-ranging study NCT02968108, patients aged 2‐<18 years body weight ≥10 kg were randomised 1:1 to one of two weight range-based intravenous induction doses: 130 mg vs 390 mg in patients ≥40kg and 3 mg/kg vs 9 mg/kg in patients <40kg. At Week 8, all patients received a single subcutaneous ustekinumab maintenance dose of 90 mg in patients ≥40kg or 2 mg/kg in patients <40kg.
Results
A total of 44 patients were randomised and treated with ustekinumab n = 23 lower dose; n = 21 higher dose; median interquartile range age was 13.0 12–16 years. Pharmacokinetics were similar to those in adults with Crohn’s disease. However, serum ustekinumab concentrations were lower among those with body weight <40 kg compared with patients ≥40 kg and the reference Phase 3 adult population. Through Week 16, 73% of patients reported ≥1 adverse event 82.6% lower vs 62% higher dose; two discontinued due to adverse events one in each group. Serious adverse events occurred in 16% 26% lower, 5% higher dose, with Crohn’s disease exacerbation being the most frequent. At Week 16, 22%/29% lower/higher dose achieved clinical remission Paediatric Crohn’s Disease Activity Index ≤10.
Conclusions
The pharmacokinetics/safety profiles were generally consistent with those observed in adults with Crohn’s disease. These results suggest a different dosing regimen may be required for patients <40 kg from that employed in this study; additional pharmacokinetic analyses may be needed in this population.
Background
Mobile-bearing TKAs reportedly have no clinical superiority over fixed-bearing TKAs, but a potential benefit is improved polyethylene wear behavior.
Questions/purposes
We asked whether ...extent of damage and wear patterns would be less severe on retrieved mobile-bearing TKAs than on fixed-bearing TKAs and if correlations with patient demographics could explain differences in extent or locations of damage.
Methods
We performed damage grading and mapping of 48 mobile-bearing TKAs retrieved due to osteolysis/loosening, infection, stiffness, instability or malpositioning. Visual grading used stereomicroscopy to identify damage, and a grade was assigned based on extent and severity. Each damage mode was then mapped onto a photograph of the implant surface, and the area affected was calculated.
Results
Marked wear damage occurred on both surfaces, with burnishing, scratching, and pitting the dominant modes. Damage occurred over a large portion of both surfaces, exceeding the available articular borders in nearly 30% of implants. Wear of mobile-bearing surfaces included marked third-body debris. Damage on tibiofemoral and mobile-bearing surfaces was not correlated with patient BMI or component alignment. Damage on mobile-bearing surfaces was positively correlated with length of implantation and was greater in implants removed for osteolysis or instability than in those removed for stiffness or infection.
Conclusions
Each bearing surface in mobile-bearing implants was damaged to an extent similar to that in fixed-bearing implants, making the combined damage score higher than that for fixed-bearing implants. Mobile-bearing TKAs did not improve wear damage, providing another argument against the superiority of these implants over fixed-bearing implants.
Large angular deformities can be a challenge when performing primary total knee replacement. Some investigators have advocated the use of increased component constraint in these settings. The goal of ...this study was to determine the location and extent of damage to a consecutive series of retrieved constrained tibial inserts used in primary arthroplasty. There was significant post and articular damage in retrieved implants. Reliance on the polyethylene post for implant stability was associated with post and articular surface damage and may be a potential source of failure. Attempts to achieve implant stability using soft tissue techniques seem justified.
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