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Search Results for all work with filters:

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Article

Patient and caregiver determinants of patient quality of life and caregiver strain in left ventricular assist device therapy

by Julie T. Bidwell; Karen S. Lyons; James O. Mudd; Kathleen L. Grady; Jill M. Gelow; Shirin O. Hiatt; Christopher V. Chien; Christopher S. Lee

2018

Subjects
  • Health Sciences, Nursing
  • Health Sciences, General
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Abstract:Close

Background--Although current guidelines emphasize the importance of social support to the success of left ventricular assist device (LVAD) therapy, few studies examine the influence of the caregiver on patient outcomes or quantify the impact of LVAD caregiving on caregiver outcomes. The purpose of this analysis was to identify patient and caregiver determinants of patient quality of life (QOL) and caregiver strain in response to LVAD therapy. Methods and Results--Data on patients receiving LVAD therapy and their caregivers (n=50 dyads) were prospectively collected pre-implantation and 1, 3, and 6 months post-implantation. Growth curve modeling was used to describe change in patient QOL (Kansas City Cardiomyopathy Questionnaire) and caregiver strain (Multidimensional Caregiver Strain Index). Patient QOL improved most in the first month (β=23.22±3.76, P < 0.001), followed by gradual gains over 6 months (β=1.90±0.64, P<0.01). Caregivers experienced worsening of strain in the first month (β=4.30±1.42, P < 0.01), followed by gradual resolution to pre-implantation levels by 6 months (β=-0.71±0.23, P < 0.01). Worse pre-implantation patient symptoms were associated with greater improvement in patient QOL (β=0.53±0.19, P < 0.01) but worsening caregiver strain (β=0.15±0.07, P=0.04). Better relationship quality was associated with greater improvement in patient QOL (β=14.39±5.85, P=0.01) and less pre-implantation caregiver strain (β=-9.31±2.28, P < 0.001). Nonspousal caregivers experienced less pre-implantation strain (β=-8.60±3.10, P=0.01), and patients with nonspousal caregivers had less improvement in QOL (β=-3.70±1.62, P=0.02). Conclusions--A combination of patient and caregiver characteristics predicts patient and caregiver response to LVAD therapy. Including caregiver factors in future studies may be helpful in developing interventions that improve patient and caregiver outcomes, together.

Article

Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants

by Dale L. Phelps; Robert M. Ward; Rick L. Williams; Tracy L. Nolen; Kristi L. Watterberg; William Oh; Michael Goedecke; Richard A. Ehrenkranz; Timothy Fennell; Brenda B. Poindexter; C. Michael Cotten; Mikko Hallman; Ivan D. Frantz; Roger G. Faix; Kristin M. Zaterka-Baxter; Abhik Das; M. Bethany Ball; Conra B. Lacy; Michele C. Walsh; Waldemar A. Carlo; Pablo J. Sanchez; Edward F. Bell; Seetha Shankaran; David Carlton; Patricia R. Chess; Rosemary D. Higgins

2016

Subjects
  • Health Sciences, General
  • Health Sciences, Pharmacology
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Background: Preterm infants with respiratory distress syndrome (RDS) given inositol had reduced bronchopulmonary dysplasia (BPD), death and severe retinopathy of prematurity (ROP). We assessed the safety and pharmacokinetics of daily inositol to select a dose providing serum levels previously associated with benefit, and to learn if accumulation occurred when administered throughout the normal period of retinal vascularization. Methods: Infants ≤ 29 wk GA (n = 122, 14 centers) were randomized and treated with placebo or inositol at 10, 40, or 80 mg/kg/d. Intravenous administration converted to enteral when feedings were established, and continued to the first of 10 wk, 34 wk postmenstrual age (PMA) or discharge. Serum collection employed a sparse sampling population pharmacokinetics design. Inositol urine losses and feeding intakes were measured. Safety was prospectively monitored. Results: At 80 mg/kg/d mean serum levels reached 140 mg/l, similar to Hallman's findings. Levels declined after 2 wk, converging in all groups by 6 wk. Analyses showed a mean volume of distribution 0.657 l/kg, clearance 0.058 l/kg/h, and half-life 7.90 h. Adverse events and comorbidities were fewer in the inositol groups, but not significantly so. Conclusion: Multiple dose inositol at 80 mg/kg/d was not associated with increased adverse events, achieves previously effective serum levels, and is appropriate for investigation in a phase III trial.

Article

Multi-method assessment of patients with febrile illness reveals over-diagnosis of malaria in rural Uganda

by Ria R. Ghai; Mary I. Thurber; Azza El El Bakry; Colin A. Chapman; Tony L. Goldberg

2016

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, General
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Background Health clinics in rural Africa are typically resource-limited. As a result, many patients presenting with fever are treated with anti-malarial drugs based only on clinical presentation. This is a considerable issue in Uganda, where malaria is routinely over-diagnosed and over-treated, constituting a wastage of resources and an elevated risk of mortality in wrongly diagnosed patients. However, rapid diagnostic tests (RDTs) for malaria are increasingly being used in health facilities. Being fast, easy and inexpensive, RDTs offer the opportunity for feasible diagnostic capacity in resource-limited areas. This study evaluated the rate of malaria misdiagnosis and the accuracy of RDTs in rural Uganda, where presumptive diagnosis still predominates. Specifically, the diagnostic accuracy of “gold standard” methods, microscopy and PCR, were compared to the most feasible method, RDTs. Methods Patients presenting with fever at one of two health clinics in the Kabarole District of Uganda were enrolled in this study. Blood was collected by finger prick and used to administer RDTs, make blood smears for microscopy, and blot Whatman FTA cards for DNA extraction, polymerase chain reaction (PCR) amplification, and sequencing. The accuracy of RDTs and microscopy were assessed relative to PCR, considered the new standard of malaria diagnosis. Results A total of 78 patients were enrolled, and 31 were diagnosed with Plasmodium infection by at least one method. Comparing diagnostic pairs determined that RDTs and microscopy performed similarly, being 92.6 and 92.0 % sensitive and 95.5 and 94.4 % specific, respectively. Combining both methods resulted in a sensitivity of 96.0 % and specificity of 100 %. However, both RDTs and microscopy missed one case of non-falciparum malaria (Plasmodium malariae) that was identified and characterized by PCR and sequencing. In total, based on PCR, 62.0 % of patients would have been misdiagnosed with malaria if symptomatic diagnosis was used. Conclusions Results suggest that diagnosis of malaria based on symptoms alone appears to be highly inaccurate in this setting. Furthermore, RDTs were very effective at diagnosing malaria, performing as well or better than microscopy. However, only PCR and DNA sequencing detected non-P. falciparum species, which highlights an important limitation of this test and a treatment concern for non-falciparum malaria patients. Nevertheless, RDTs appear the only feasible method in rural or resource-limited areas, and therefore offer the best way forward in malaria management in endemic countries.

Article

Screening a large pediatric cohort with GH deficiency for mutations in genes regulating pituitary development and GH secretion: Frequencies, phenotypes and growth outcomes

by Werner F. Blum; Jurgen Klammt; Serge Amselem; Heike M. Pfaeffle; Marie Legendre; Marie-Laure Sobrier; Marie-Pierre Luton; Christopher J. Child; Christine Jones; Alan G. Zimmermann; Charmian A. Quigley; Gordon B. Cutler; Cheri L. Deal; Jan Lebl; Ron G. Rosenfeld; John Parks; Roland W. Pfaeffle

2018

Subjects
  • Health Sciences, General
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Background: Pituitary development and GH secretion are orchestrated by multiple genes including GH1, GHRHR, GLI2, HESX1, LHX3, LHX4, PROP1, POU1F1, and SOX3. We aimed to assess their mutation frequency and clinical relevance in children with severe GH deficiency (GHD). Methods: The Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS; Clinical Trial Registry Number: NCT01088412) was a prospective, open-label, observational research program for pediatric patients receiving GH treatment, conducted in 30 countries between 1999 and 2015. The study included a sub-study to investigate mutations in the genes listed above. PCR products from genomic blood cell DNA were analyzed by Sanger sequencing. DNA variants were classified as pathogenic according to the recommendations of the American College of Medical Genetics and Genomics. Demographic, auxologic, and endocrine data at baseline and during GH treatment were documented and related to the genotyping results. Findings: The analysis comprised 917 patients. In 92 patients (10%) 33 mutations were found, 16 previously described and 17 novel (52%). Mutation carriers were significantly younger, shorter, and more slowly growing than non-carriers. In general, their peak values in GH stimulation tests were very low; however, in 15/77 (20%) patients with GH1, PROP1, and SOX3 mutations they were only moderately diminished (3-6 μg/L). Two patients with a GH1 mutation developed TSH deficiency and one ADH deficiency. Using logistic multi-regression analysis, significant indicators of a mutation were combined pituitary hormone deficiency, greater patient-parent height difference (SDS), low GH peak, and young age. Final height SDS gain in mutation carriers (mean ± SD 3.4 ± 1.4) was greater than in non-carriers (2.0 ± 1.4; P <.001) and in patients with non-GHD short stature. Interpretation: DNA testing for mutations in children with severe GHD shows a positive finding in approximately 10%. Phenotypes of mutation carriers can be variable. The benefit for clinical practice justifies DNA testing as an important component in the diagnostic work-up of patients with severe GHD. Fund: Eli Lilly and Company, Indianapolis, IN, USA. ClinicalTrials.com registration: NCT01088412.

Article

Association of Single Nucleotide Polymorphisms (SNPs) in CCR6, TAGAP and TNFAIP3 with Rheumatoid Arthritis in African Americans

by Elizabeth A. Perkins; Dawn Landis; Zenoria L. Causey; Yuanqing Edberg; Richard J. Reynolds; Laura B. Hughes; Doyt L Conn; Peter K. Gregersen; Robert P. Kimberly; Jeffrey C. Edberg; S. Louis Bridges, Jr.

2012

Subjects
  • Health Sciences, Immunology
  • Health Sciences, General
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Objective: We previously reported an analysis of single nucleotide polymorphisms (SNPs) in three validated European rheumatoid arthritis (RA) susceptibility loci, TAGAP, TNFAIP3, and CCR6 in African-Americans with RA. Unexpectedly, the disease-associated alleles were different in African-Americans than in Europeans. In an effort to better define their contribution, we performed additional SNP genotyping in these genes. Methods: Seven SNPs were genotyped in 446 African Americans with RA and 733 African American controls. Differences in minor allele frequency between cases and controls were analyzed after controlling for global proportion of European admixture, and pairwise linkage disequilibrium (LD) was estimated among the SNPs. Results: Three SNPs were significantly associated with RA: TNFAIP3 rs719149 A allele (OR (95% CI) 1.22 (1.03–1.44) (p =0.02); TAGAP rs1738074 G allele OR 0.75 (0.63–0.89), (p =0.0012); and TAGAP rs4709267 G allele 0.74 (0.60–0.91), (p =0.004). Pairwise LD between the TAGAP SNPs was low (R2=0.034). The haplotype containing minor alleles for both TAGAP SNPs was uncommon (4.5%). After conditional analysis on each TAGAP SNP, its counterpart remained significantly associated with RA (rs1738074 for rs4709267 p=0.00001; rs4709267 for rs1738074 p=0.00005), suggesting independent effects. Conclusions: SNPs in regulatory regions of TAGAP and an intronic SNP (TNFAIP3) are potential susceptibility loci in African Americans. Pairwise LD, haplotype analysis, and SNP conditioning analysis suggest that these two SNPs in TAGAP are independent susceptibility alleles. Additional fine mapping of this gene and functional genomic studies of these SNPs should provide additional insight into the role of these genes in RA.

Article

Cyclone idai as a trigger for pellagra outbreak in nhamatanda, mozambique: A case-control study

by Vánio A Mugabe; Arlete Mahumane; Cynthia S Baltazar; Érika V Rossetto; Crescêncio S Nhabomba; Neusa Fataha; Unicia Nyamula; Angélica Sotomane; Wilson Irugula; Benigno Canze; Osvaldo F Inlamea; Uriel Kitron; Guilherme S Ribeiro; Eduardo S Gudo

2021

Subjects
  • Health Sciences, General
  • Health Sciences, Public Health
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In mid-June 2019, 3 months after cyclone Idai landfall in Mozambique, health authorities of Nhamatanda district reported an outbreak of Pellagra. Applying a mixed-method protocol, we carried out an investigation to characterize cases of pellagra, identify the associated factors for the outbreak using a case-control study, and explore the perceived impact on food security (availability, access, and usage) before and after Idai.Wecollected data from 121 cases and 121 controls and conducted in-depth interviews with 69 heads of households. The cases were more likely to be female (P < 0.01) and less educated (P < 0.01) than controls. Insufficient consumption of chicken and peanut before cyclone Idai arrival were statistically associated with pellagra (P < 0.05). From interviewed households' heads, 51% were experiencing food shortages even before the cyclone hit. Cyclone Idai served as a trigger to reduce niacin consumption below the threshold that protected Nhamatanda population from pellagra and caused a ≈2,300 case (707.9/100,000 inhabitants) outbreak.

Article

Massive Splenomegaly and Pancytopenia: It's a Hairy Situation.

by Sarah M Clark; Farmin Samareh-Jahani; Munir A Chaudhuri

2020

Subjects
  • Health Sciences, Medicine and Surgery
  • Health Sciences, General
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A 33-year-old previously healthy Middle Eastern male presented to the emergency department with four weeks of progressively worsening fatigue, dyspnea on exertion, night sweats, and a 10-pound weight loss after suffering a self-limiting viral upper respiratory illness. He was found to be profoundly anemic and thrombocytopenic with normal white blood cell count with a lymphocytic predominance. His anemia was refractory to red blood cell transfusions, to which he developed hyperbilirubinemia. A CT scan revealed hepatomegaly and massive splenomegaly associated with multi-station abdominopelvic lymphadenopathy. A peripheral blood smear revealed several lymphocytes with hairy cell features and bone marrow biopsy revealed hypercellularity with interstitial infiltration by mature lymphoid cells. Flow cytometry confirmed the diagnosis of hairy cell leukemia (HCL) and this patient was initiated on cladribine chemotherapy. This case illustrates the uniqueness of this patient presenting within a short time course, at an atypical age, and with uncommon features for HCL including lymphadenopathy, hepatomegaly, and petechial skin rash. This case also highlights an important point regarding the management of severe anemia in the acute setting while undergoing splenic sequestration. His lack of response to red blood cell transfusions highlights the need for more research on the use of transfusions in patients who are not current surgical candidates for splenectomy.

Article

EUS-guided drainage of pancreatic fluid collection with a Hot AXIOS stent in a patient with pancreatitis following distal pancreatectomy (with video)

by Lianyong Li; Sarah Cristofaro; Changmin Qu; Shuwen Liang; Xiaoyu Li; Qiang Cai

2018

Subjects
  • Health Sciences, General
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Article

Structural domains in RNAi

by Robert E. Collins; Xiaodong Cheng

2005

Subjects
  • Chemistry, Biochemistry
  • Health Sciences, General
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Structural and biochemical studies have begun to elucidate the pathway of RNA silencing that leads to the formation of the RISC complex. The outstanding feature of this pathway is the precise recognition and processing of double-stranded RNA. We present a review of recent structures that illustrate the molecular mechanisms contributing to these two related functions, highlighting models of Drosha, Dicer, and RISC function.

Conference

Differential induction of activation and apoptosis by TCR signaling in sooty mangabeys and rhesus macaques

by S. Yu; K. Rogers; Francois Villinger; A. Kaur

2012-09-13

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, General
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