Displaying publications 1 - 20 of 36 in total

Abstract:
Sort:
  1. Lim AY, Segarra I, Chakravarthi S, Akram S, Judson JP
    BMC Pharmacol., 2010;10:14.
    PMID: 20950441 DOI: 10.1186/1471-2210-10-14
    BACKGROUND: Sunitinib, a tyrosine kinase inhibitor to treat GIST and mRCC may interact with paracetamol as both undergo P450 mediated biotransformation and P-glycoprotein transport. This study evaluates the effects of sunitinib-paracetamol coadministration on liver and renal function biomarkers and liver, kidney, brain, heart and spleen histopathology. ICR male mice (n = 6 per group/dose) were administered saline (group-A) or paracetamol 500 mg/kg IP (group-B), or sunitinib at 25, 50, 80, 100, 140 mg/kg PO (group-C) or coadministered sunitinib at 25, 50, 80, 100, 140 mg/kg PO and paracetamol IP at fixed dose 500 mg/kg (group-D). Paracetamol was administered 15 min before sunitinib. Mice were sacrificed 4 h post sunitinib administration.
    RESULTS: Group-A serum ALT and AST levels were 14.29 ± 2.31 U/L and 160.37 ± 24.74 U/L respectively and increased to 249.6 ± 222.7 U/L and 377.1 ± 173.6 U/L respectively in group-B; group-C ALT and AST ranged 36.75-75.02 U/L and 204.4-290.3 U/L respectively. After paracetamol coadministration with low sunitinib doses (group-D), ALT and AST concentrations ranged 182.79-221.03 U/L and 259.7-264.4 U/L respectively, lower than group-B. Paracetamol coadministration with high sunitinib doses showed higher ALT and AST values (range 269.6-349.2 U/L and 430.2-540.3 U/L respectively), p < 0.05. Hepatic histopathology showed vascular congestion in group-B; mild congestion in group-C (but lesser than in group-B and D). In group-D, at low doses of sunitinib, lesser damage than in group-B occurred but larger changes including congestion were observed at high sunitinib doses. BUN levels were higher (p < 0.05) for group-B (33.81 ± 5.68 mg/dL) and group-D (range 35.01 ± 6.95 U/L to 52.85 ± 12.53 U/L) compared to group-A (15.60 ± 2.17 mg/dL) and group-C (range 17.50 ± 1.25 U/L to 26.68 ± 6.05 U/L). Creatinine remained unchanged. Renal congestion and necrosis was lower in group-C than group-B but was higher in group-D (p > 0.05). Mild cardiotoxicity occurred in groups B, C and D. Brain vascular congestion occurred at high doses of sunitinib administered alone or with paracetamol. Hepatic and renal biomarkers correlated with histopathology signs.
    CONCLUSIONS: Paracetamol and sunitinib coadministration may lead to dose dependent outcomes exhibiting mild hepatoprotective effect or increased hepatotoxicity. Sunitinib at high doses show renal, cardiac and brain toxicity. Liver and renal function monitoring is recommended.
  2. Jones DJW, Harris JP, Butler LT, Vaux EC
    Physiol Behav, 2017 03 15;171:1-6.
    PMID: 28025091 DOI: 10.1016/j.physbeh.2016.12.029
    We investigated an effect of end-stage renal disease (ESRD) on the visual system by measuring the ability of 21 patients to perceive depth in the random dot stereograms and circles of the Randot Test. To control for other factors which might influence performance on the tests of stereopsis, patients were compared with healthy controls matched for age, years of education, IQ, and general cognitive ability. Vernier acuity (thought to reflect mainly central processing) and Landolt acuity (more sensitive to retinal and optical abnormalities) were also measured, but the study did not include a formal ophthalmological examination. All controls could perceive depth in random dot stereograms, whereas 9/21 patients could not. Patients who could perceive depth had worse stereoacuity than did their matched controls. The patient group as a whole had worse Vernier and Landolt acuities than the controls. The stereoblind patient subgroup had similar Vernier acuity to the stereoscopic subgroup, but worse Landolt acuity, and was more likely to have peripheral vascular disease. We conclude that ESRD had affected structures both within the eye, and within the visual brain. However, the similarity of Vernier acuity and difference of Landolt acuity in the stereoblind and stereoscopic patient subgroups suggest that the differences in stereoscopic ability arise from abnormalities in the eyes rather than in the brain.
  3. Nadarajah VD, Min RG, Judson JP, Jegasothy R, Ling EH
    J Obstet Gynaecol Res, 2009 Oct;35(5):855-63.
    PMID: 20149032 DOI: 10.1111/j.1447-0756.2009.01037.x
    To establish baseline levels of maternal plasma soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) among normotensive Malaysian mothers and to compare the marker levels between normotensives and mothers with gestational hypertension (GH).
  4. Zain ZM, O'Neill RD, Lowry JP, Pierce KW, Tricklebank M, Dewa A, et al.
    Biosens Bioelectron, 2010 Feb 15;25(6):1454-9.
    PMID: 19945264 DOI: 10.1016/j.bios.2009.10.049
    D-serine has been implicated as a brain messenger, promoting not only neuronal signalling but also synaptic plasticity. Thus, a sensitive tool for D-serine monitoring in brain is required to understand the mechanisms of D-serine release from glia cells. A biosensor for direct fixed potential amperometric monitoring of D-serine incorporating mammalian D-amino acid oxidase (DAAO) immobilized on a Nafion coated poly-ortho-phenylenediamine (PPD) modified Pt-Ir disk electrode was therefore developed. The combined layers of PPD and Nafion enhanced the enzyme activity and biosensor efficiency by approximately 2-fold compared with each individual layer. A steady state response time (t(90%)) of 0.7+/-0.1s (n=8) and limit of detection 20+/-1 nM (n=8) were obtained. Cylindrical geometry showed lower sensitivity compared to disk geometry (61+/-7 microA cm(-2) mM(-1), (n=4), R(2)=0.999). Interference by ascorbic acid (AA), the main interference species in the central nervous system and other neurochemical electroactive molecules was negligible. Implantation of the electrode and microinjection of D-serine into rat brain striatal extracellular fluid demonstrated that the electrode was capable of detecting D-serine in brain tissue in vivo.
  5. Jones DJ, Harvey K, Harris JP, Butler LT, Vaux EC
    J Clin Nurs, 2018 Jan;27(1-2):193-204.
    PMID: 28498615 DOI: 10.1111/jocn.13871
    AIMS AND OBJECTIVES: While haemodialysis is an effective treatment for end-stage renal disease, the requirements and restrictions it imposes on patients can be onerous. The aim of this study was to obtain UK National Health Service patients' perspectives on the challenges arising from haemodialysis with the intention of identifying potential improvements.

    BACKGROUND: Depression rates are particularly high in those with end-stage renal disease; however, there is limited insight into the range of stressors associated with haemodialysis treatment within the National Health Service contributing to such high rates, particularly those of a cognitive or psychological nature.

    DESIGN: A qualitative approach was used to obtain rich, patient-focused data; one-to-one semi-structured interviews were conducted with twenty end-stage renal disease at a UK National Health Service centre.

    METHODS: Patients were interviewed during a typical haemodialysis session. Thematic analysis was used to systematically interpret the data. Codes were created in an inductive and cyclical process using a constant comparative approach.

    RESULTS: Three themes emerged from the data: (i) fluctuations in cognitive/physical well-being across the haemodialysis cycle, (ii) restrictions arising from the haemodialysis treatment schedule, (iii) emotional impact of haemodialysis on the self and others. The findings are limited to predominantly white, older patients (median = 74 years) within a National Health Service setting.

    CONCLUSIONS: Several of the experiences reported by patients as challenging and distressing have so far been overlooked in the literature. A holistic-based approach to treatment, acknowledging all aspects of a patient's well-being, is essential if optimal quality of life is to be achieved by healthcare providers.

    RELEVANCE TO CLINICAL PRACTICE: The findings can be used to inform future interventions and guidelines aimed at improving patients' treatment adherence and outcomes, for example, improved reliable access to mental health specialists.

  6. Zarkasi KZ, Taylor RS, Abell GC, Tamplin ML, Glencross BD, Bowman JP
    Microb Ecol, 2016 Apr;71(3):589-603.
    PMID: 26780099 DOI: 10.1007/s00248-015-0728-y
    To better understand salmon GI tract microbial community dynamics in relation to diet, a feeding trial was performed utilising diets with different proportions of fish meal, protein, lipid and energy levels. Salmon gut dysfunction has been associated with the occurrence of casts, or an empty hind gut. A categorical scoring system describing expressed digesta consistency was evaluated in relation to GI tract community structure. Faster growing fish generally had lower faecal scores while the diet cohorts showed minor differences in faecal score though the overall lowest scores were observed with a low protein, low energy diet. The GI tract bacterial communities were highly dynamic over time with the low protein, low energy diet associated with the most divergent community structure. This included transiently increased abundance of anaerobic (Bacteroidia and Clostridia) during January and February, and facultatively anaerobic (lactic acid bacteria) taxa from February onwards. The digesta had enriched populations of these groups in relation to faecal cast samples. The majority of samples (60-86 %) across all diet cohorts were eventually dominated by the genus Aliivibrio. The results suggest that an interaction between time of sampling and diet is most strongly related to community structure. Digesta categorization revealed microbes involved with metabolism of diet components change progressively over time and could be a useful system to assess feeding responses.
  7. Louis JP, Wood AM, Lockwood G, Ho MR, Ferguson E
    Psychol Assess, 2018 Sep;30(9):1199-1213.
    PMID: 29672073 DOI: 10.1037/pas0000567
    Negative schemas have been widely recognized as being linked to psychopathology and mental health, and they are central to the Schema Therapy (ST) model. This study is the first to report on the psychometric properties of the Young Positive Schema Questionnaire (YPSQ). In a combined community sample (Manila, Philippines, n = 559; Bangalore, India, n = 350; Singapore, n = 628), we identified a 56-item, 14-factor solution for the YPSQ. Multigroup confirmatory factor analysis supported the 14-factor model using data from two other independent samples: an Eastern sample from Kuala Lumpur, Malaysia (n = 229) and a Western sample from the United States (n = 214). Construct validity was demonstrated with the Young Schema Questionnaire 3 Short Form (YSQ-S3) that measures negative schemas, and divergent validity was demonstrated for 11 of the YPSQ subscales with their respective negative schema counterparts. Convergent validity of the 14 subscales of YPSQ was demonstrated with measures of personality dispositions, emotional distress, well-being, trait gratitude, and humor styles. Positive schemas also showed incremental validity over and above negative schemas for these same measures, thus demonstrating that both positive and negative schemas are separate constructs that relate in unique ways to mental health. Implications for using both the YPSQ and the YSQ-S3 scales in tandem in ST as well as cultural nuances from the use of Asian samples were discussed. (PsycINFO Database Record
  8. Zarkasi KZ, Taylor RS, Glencross BD, Abell GCJ, Tamplin ML, Bowman JP
    Res. Microbiol., 2017 Oct;168(8):751-759.
    PMID: 28728852 DOI: 10.1016/j.resmic.2017.07.003
    In this study, microbial community dynamics were assessed within a simple in vitro model system in order to understand those changes influenced by diet. The abundance and diversity of bacteria were monitored within different treatment slurries inoculated with salmon faecal samples in order to mimic the effects of dietary variables. A total of five complete diets and two ingredients (plant meal) were tested. The total viable counts (TVCs) and sequencing data revealed that there was very clear separation between the complete diets and the plant meal treatments, suggesting a dynamic response by the allochthonous bacteria to the treatments. Automated ribosomal intergenic spacer analysis (ARISA) results showed that different diet formulations produced different patterns of fragments, with no separation between the complete diets. However, plant-based protein ingredients were clearly separated from the other treatments. 16S rRNA Illumina-based sequencing analysis showed that members of the genera Aliivibrio, Vibrio and Photobacterium became predominant for all complete diets treatments. The plant-based protein ingredient treatments only sustained weak growth of the genus Sphingomonas. In vitro based testing of diets could be a useful strategy to determine the potential impact of either complete feeds or ingredients on major fish gastrointestinal tract microbiome members.
  9. Wu Y, Levis B, Ioannidis JPA, Benedetti A, Thombs BD, DEPRESsion Screening Data (DEPRESSD) Collaboration
    Psychother Psychosom, 2021;90(1):28-40.
    PMID: 32814337 DOI: 10.1159/000509283
    INTRODUCTION: Three previous individual participant data meta-analyses (IPDMAs) reported that, compared to the Structured Clinical Interview for the DSM (SCID), alternative reference standards, primarily the Composite International Diagnostic Interview (CIDI) and the Mini International Neuropsychiatric Interview (MINI), tended to misclassify major depression status, when controlling for depression symptom severity. However, there was an important lack of precision in the results.

    OBJECTIVE: To compare the odds of the major depression classification based on the SCID, CIDI, and MINI.

    METHODS: We included and standardized data from 3 IPDMA databases. For each IPDMA, separately, we fitted binomial generalized linear mixed models to compare the adjusted odds ratios (aORs) of major depression classification, controlling for symptom severity and characteristics of participants, and the interaction between interview and symptom severity. Next, we synthesized results using a DerSimonian-Laird random-effects meta-analysis.

    RESULTS: In total, 69,405 participants (7,574 [11%] with major depression) from 212 studies were included. Controlling for symptom severity and participant characteristics, the MINI (74 studies; 25,749 participants) classified major depression more often than the SCID (108 studies; 21,953 participants; aOR 1.46; 95% confidence interval [CI] 1.11-1.92]). Classification odds for the CIDI (30 studies; 21,703 participants) and the SCID did not differ overall (aOR 1.19; 95% CI 0.79-1.75); however, as screening scores increased, the aOR increased less for the CIDI than the SCID (interaction aOR 0.64; 95% CI 0.52-0.80).

    CONCLUSIONS: Compared to the SCID, the MINI classified major depression more often. The odds of the depression classification with the CIDI increased less as symptom levels increased. Interpretation of research that uses diagnostic interviews to classify depression should consider the interview characteristics.

  10. Velligan DI, Weiden PJ, Sajatovic M, Scott J, Carpenter D, Ross R, et al.
    J Clin Psychiatry, 2009;70 Suppl 4:1-46; quiz 47-8.
    PMID: 19686636
    OBJECTIVES: Poor adherence to medication treatment can have devastating consequences for patients with mental illness. The goal of this project was to develop recommendations for addressing adherence problems to improve patient outcomes.
    METHODS: The editors identified important topics and questions concerning medication adherence problems in serious mental illness that are not fully addressed in the literature. A survey was developed containing 39 questions (521 options) asking about defining nonadherence, extent of adherence problems in schizophrenia and bipolar disorder, risk factors for nonadherence, assessment methods, and interventions for specific types of adherence problems. The survey was completed by 41 (85%) of the 48 experts to whom it was sent. Results of the literature review and survey were used to develop recommendations for assessing and improving adherence in patients with serious mental illness.
    RESULTS: ASSESSING ADHERENCE: The experts endorsed percentage of medication not taken as the preferred method of defining adherence, with 80% or more of medication taken endorsed as an appropriate cut-off for adherence in bipolar disorder and schizophrenia. Although self- and physician report are the most common methods used to assess adherence in clinical settings, they are often inaccurate and may underestimate nonadherence. The experts recommend that, if possible, clinicians also use more objective measures (e.g., pill counts, pharmacy records, and, when appropriate, serum levels such as are used for lithium). Use of a validated self-report scale may help improve accuracy.
    SCOPE OF THE PROBLEM: The majority of the experts believed the average patient with schizophrenia or bipolar disorder in their practices takes only 51%-70% of prescribed medication. FACTORS ASSOCIATED WITH NONADHERENCE: The experts endorsed poor insight and lack of illness awareness, distress associated with specific side effects or a general fear of side effects, inadequate efficacy with persistent symptoms, and believing medications are no longer needed as the most important factors leading to adherence problems in schizophrenia and bipolar disorder. The experts considered weight gain a side effect that is very likely to lead to adherence problems in patients with schizophrenia and bipolar disorder; sedation was considered a more important contributor to adherence problems in bipolar disorder than schizophrenia. The experts rated persistent positive or negative symptoms in schizophrenia and persistent grandiosity and manic symptoms in bipolar disorder as the most important symptomatic contributors to adherence problems in these illnesses.
    INTERVENTIONS: It is important to identify the specific factors that may be contributing to a patient's adherence problems in order to customize interventions to target those problems. Multiple problems may be involved, requiring a combination of interventions.
    CONCLUSIONS: Adherence problems are complex and multidetermined. The experts recommended customized interventions focused on the underlying causes.
  11. Schratz A, Pineda MF, Reforma LG, Fox NM, Le Anh T, Tommaso Cavalli-Sforza L, et al.
    Adv Parasitol, 2010;72:79-107.
    PMID: 20624529 DOI: 10.1016/S0065-308X(10)72004-2
    Ethnic minority groups (EMGs) are often subject to exclusion, marginalization and poverty. These characteristics render them particularly vulnerable to neglected diseases, a diverse group of diseases that comprise bacteria, ecto-parasites, fungi, helminths and viruses. Despite the health policy relevance, only little is known of the epidemiological profile of neglected diseases among EMGs. We reviewed country data from Australia, Cambodia, Lao People's Democratic Republic, Malaysia, the Philippines and Vietnam and found several overlaps between regions with high proportions of EMG population and high prevalence rates of neglected diseases (infections with soil-transmitted helminths, filarial worms, schistosomes, food-borne trematodes and cestodes). While the links are not always clearly evident and it is impossible to establish correlations among highly aggregated data without control variables-such as environmental factors-there appear indeed to be important linkages between EMGs, socio-economic status and prevalence of neglected diseases. Some determinants under consideration are lack of access to health care and general health status, poverty and social marginalization, as well as education and literacy. Further research is needed to deepen the understanding of these linkages and to determine their public health and socio-economic significance. In particular, there is a need for more data from all countries in the Western Pacific Region that is disaggregated below the provincial level. Selected case studies that incorporate other control variables-such as risk factors from the physical environment-might be useful to inform policy makers about the feasibility of prevention and control interventions that are targeted at high-risk EMGs.
  12. Lewis HIJ, Jin X, Guo B, Lee S, Jung H, Kodati SH, et al.
    Sci Rep, 2023 Jun 19;13(1):9936.
    PMID: 37336988 DOI: 10.1038/s41598-023-36744-7
    Al0.85Ga0.15As0.56Sb0.44 has recently attracted significant research interest as a material for 1550 nm low-noise short-wave infrared (SWIR) avalanche photodiodes (APDs) due to the very wide ratio between its electron and hole ionization coefficients. This work reports new experimental excess noise data for thick Al0.85Ga0.15As0.56Sb0.44 PIN and NIP structures, measuring low noise at significantly higher multiplication values than previously reported (F = 2.2 at M = 38). These results disagree with the classical McIntyre excess noise theory, which overestimates the expected noise based on the ionization coefficients reported for this alloy. Even the addition of 'dead space' effects cannot account for these discrepancies. The only way to explain the low excess noise observed is to conclude that the spatial probability distributions for impact ionization of electrons and holes in this material follows a Weibull-Fréchet distribution function even at relatively low electric-fields. Knowledge of the ionization coefficients alone is no longer sufficient to predict the excess noise properties of this material system and consequently the electric-field dependent electron and hole ionization probability distributions are extracted for this alloy.
  13. Tan MC, Yeo YH, San BJ, Suleiman A, Lee JZ, Chatterjee A, et al.
    J Am Heart Assoc, 2024 Apr 16;13(8):e030895.
    PMID: 38587138 DOI: 10.1161/JAHA.123.030895
    BACKGROUND: Percutaneous heart valve procedures have been increasingly performed over the past decade, yet real-world mortality data on valvular heart disease (VHD) in the United States remain limited.

    METHODS AND RESULTS: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database among patients ≥15 years old from 1999 to 2020. VHD and its subtypes were listed as the underlying cause of death. We calculated age-adjusted mortality rate (AAMR) per 100 000 individuals and determined overall trends by estimating the average annual percent change using the Joinpoint regression program. Subgroup analyses were performed based on demographic and geographic factors. In the 22-year study, there were 446 096 VHD deaths, accounting for 0.80% of all-cause mortality (56 014 102 people) and 2.38% of the total cardiovascular mortality (18 759 451 people). Aortic stenosis recorded the highest mortality of VHD-related death in both male (109 529, 61.74%) and female (166 930, 62.13%) populations. The AAMR of VHD has declined from 8.4 (95% CI, 8.2-8.5) to 6.6 (95% CI, 6.5-6.7) per 100 000 population. Similar decreasing AAMR trends were also seen for the VHD subtypes. Men recorded higher AAMR for aortic stenosis and aortic regurgitation, whereas women had higher AAMR for mitral stenosis and mitral regurgitation. Mitral regurgitation had the highest change in average annual percent change in AAMR.

    CONCLUSIONS: The mortality rate of VHD among the US population has declined over the past 2 decades. This highlights the likely efficacy of increasing surveillance and advancement in the management of VHD, resulting in improved outcomes.

  14. Graham NS, Hammond JP, Lysenko A, Mayes S, O Lochlainn S, Blasco B, et al.
    Plant Cell, 2014 Jul;26(7):2818-30.
    PMID: 25082855 DOI: 10.1105/tpc.114.128603
    Although Ca transport in plants is highly complex, the overexpression of vacuolar Ca(2+) transporters in crops is a promising new technology to improve dietary Ca supplies through biofortification. Here, we sought to identify novel targets for increasing plant Ca accumulation using genetical and comparative genomics. Expression quantitative trait locus (eQTL) mapping to 1895 cis- and 8015 trans-loci were identified in shoots of an inbred mapping population of Brassica rapa (IMB211 × R500); 23 cis- and 948 trans-eQTLs responded specifically to altered Ca supply. eQTLs were screened for functional significance using a large database of shoot Ca concentration phenotypes of Arabidopsis thaliana. From 31 Arabidopsis gene identifiers tagged to robust shoot Ca concentration phenotypes, 21 mapped to 27 B. rapa eQTLs, including orthologs of the Ca(2+) transporters At-CAX1 and At-ACA8. Two of three independent missense mutants of BraA.cax1a, isolated previously by targeting induced local lesions in genomes, have allele-specific shoot Ca concentration phenotypes compared with their segregating wild types. BraA.CAX1a is a promising target for altering the Ca composition of Brassica, consistent with prior knowledge from Arabidopsis. We conclude that multiple-environment eQTL analysis of complex crop genomes combined with comparative genomics is a powerful technique for novel gene identification/prioritization.
  15. Aboul-Soud MAM, Ashour AE, Challis JK, Ahmed AF, Kumar A, Nassrallah A, et al.
    Plants (Basel), 2020 Sep 30;9(10).
    PMID: 33008079 DOI: 10.3390/plants9101295
    Organic fractions and extracts of willow (Salix safsaf) leaves, produced by sequential solvent extraction as well as infusion and decoction, exhibited anticancer potencies in four cancerous cell lines, including breast (MCF-7), colorectal (HCT-116), cervical (HeLa) and liver (HepG2). Results of the MTT assay revealed that chloroform (CHCl3) and ethyl acetate (EtOAc)-soluble fractions exhibited specific anticancer activities as marginal toxicities were observed against two non-cancerous control cell lines (BJ-1 and MCF-12). Ultra-high-resolution mass spectrometry Q-Exactive™ HF Hybrid Quadrupole-Orbitrap™ coupled with liquid chromatography (UHPLC) indicated that both extracts are enriched in features belonging to major phenolic and purine derivatives. Fluorescence-activated cell sorter analysis (FACS), employing annexin V-FITC/PI double staining indicated that the observed cytotoxic potency was mediated via apoptosis. FACS analysis, monitoring the increase in fluorescence signal, associated with oxidation of DCFH to DCF, indicated that the mechanism of apoptosis is independent of reactive oxygen species (ROS). Results of immunoblotting and RT-qPCR assays showed that treatment with organic fractions under investigation resulted in significant up-regulation of pro-apoptotic protein and mRNA markers for Caspase-3, p53 and Bax, whereas it resulted in a significant reduction in amounts of both protein and mRNA of the anti-apoptotic marker Bcl-2. FACS analysis also indicated that pre-treatment and co-treatment of human amniotic epithelial (WISH) cells exposed to the ROS H2O2 with EtOAc fraction provide a cytoprotective and antioxidant capacity against generated oxidative stress. In conclusion, our findings highlight the importance of natural phenolic and flavonoid compounds with unparalleled and unique antioxidant and anticancer properties.
  16. Huang LM, Schibler A, Huang YC, Tai A, Chi H, Chieng CH, et al.
    Influenza Other Respir Viruses, 2023 Jul;17(7):e13176.
    PMID: 37502622 DOI: 10.1111/irv.13176
    BACKGROUND: Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available.

    METHODS: This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment.

    RESULTS: No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group.

    CONCLUSIONS: AK0529 was well tolerated in hospitalized RSV-infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score.

    CLINICAL TRIALS REGISTRATION: NCT02654171.

  17. Oei JL, Saugstad OD, Lui K, Wright IM, Smyth JP, Craven P, et al.
    Pediatrics, 2017 01;139(1).
    PMID: 28034908 DOI: 10.1542/peds.2016-1452
    BACKGROUND AND OBJECTIVES: Lower concentrations of oxygen (O2) (≤30%) are recommended for preterm resuscitation to avoid oxidative injury and cerebral ischemia. Effects on long-term outcomes are uncertain. We aimed to determine the effects of using room air (RA) or 100% O2 on the combined risk of death and disability at 2 years in infants <32 weeks' gestation.

    METHODS: A randomized, unmasked study designed to determine major disability and death at 2 years in infants <32 weeks' gestation after delivery room resuscitation was initiated with either RA or 100% O2 and which were adjusted to target pulse oximetry of 65% to 95% at 5 minutes and 85% to 95% until NICU admission.

    RESULTS: Of 6291 eligible patients, 292 were recruited and 287 (mean gestation: 28.9 weeks) were included in the analysis (RA: n = 144; 100% O2: n = 143). Recruitment ceased in June 2014, per the recommendations of the Data and Safety Monitoring Committee owing to loss of equipoise for the use of 100% O2. In non-prespecified analyses, infants <28 weeks who received RA resuscitation had higher hospital mortality (RA: 10 of 46 [22%]; than those given 100% O2: 3 of 54 [6%]; risk ratio: 3.9 [95% confidence interval: 1.1-13.4]; P = .01). Respiratory failure was the most common cause of death (n = 13).

    CONCLUSIONS: Using RA to initiate resuscitation was associated with an increased risk of death in infants <28 weeks' gestation. This study was not a prespecified analysis, and it was underpowered to address this post hoc hypothesis reliably. Additional data are needed.

  18. Ong WL, Schouwenburg MG, van Bommel ACM, Stowell C, Allison KH, Benn KE, et al.
    JAMA Oncol, 2017 May 01;3(5):677-685.
    PMID: 28033439 DOI: 10.1001/jamaoncol.2016.4851
    A major challenge in value-based health care is the lack of standardized health outcomes measurements, hindering optimal monitoring and comparison of the quality of health care across different settings globally. The International Consortium for Health Outcomes Measurement (ICHOM) assembled a multidisciplinary international working group, comprised of 26 health care providers and patient advocates, to develop a standard set of value-based patient-centered outcomes for breast cancer (BC). The working group convened via 8 teleconferences and completed a follow-up survey after each meeting. A modified 2-round Delphi method was used to achieve consensus on the outcomes and case-mix variables to be included. Patient focus group meetings (8 early or metastatic BC patients) and online anonymized surveys of 1225 multinational BC patients and survivors were also conducted to obtain patients' input. The standard set encompasses survival and cancer control, and disutility of care (eg, acute treatment complications) outcomes, to be collected through administrative data and/or clinical records. A combination of multiple patient-reported outcomes measurement (PROM) tools is recommended to capture long-term degree of health outcomes. Selected case-mix factors were recommended to be collected at baseline. The ICHOM will endeavor to achieve wide buy-in of this set and facilitate its implementation in routine clinical practice in various settings and institutions worldwide.
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links