103 research outputs found
Influence of health-system change on treatment burden: a systematic review
No full textBackground: Treatment burden is a patient-centred concept describing the effort required of people to look after their health and the impact this has on their functioning and wellbeing. High treatment burden is more likely for people with multiple long-term conditions (LTCs). Validated treatment burden measures exist, but have not been widely used in practice or as research outcomes. Aim: To establish whether changes in organisation and delivery of health systems and services improve aspects contributing to treatment burden for people with multiple LTCs. Design and setting: Systematic review of randomised controlled trials (RCTs) investigating the impact of system-level interventions on at least one outcome relevant to previously defined treatment burden domains among adults with ≥2 LTCs. Method The Embase, Ovid MEDLINE, and Web of Science electronic databases were searched for terms related to multimorbidity, system-level change, and treatment burden published between January 2010 and July 2021. Treatment burden domains were derived from validated measures and qualitative literature. Synthesis without meta-analysis (SWiM) methodology was used to synthesise results and study quality was assessed using the Cochrane risk-of-bias (version 2) tool. Results: The searches identified 1881 articles, 18 of which met the review inclusion criteria. Outcomes were grouped into seven domains. There was some evidence for the effect of system-level interventions on some domains, but the studies exhibited substantial heterogeneity, limiting the synthesis of results. Some concern over bias gave low confidence in study results. Conclusion: System-level interventions may affect some treatment burden domains. However, adoption of a standardised outcome set, incorporating validated treatment burden measures, and the development of standard definitions for care processes in future research would aid study comparability
Oxytocin effects on neural correlates of self-referential processing
No full textOxytocin (OT) influences how humans process information about others. Whether OT affects the processing of information about oneself remains unknown. Using a double-blind, placebo-controlled within-subject design, we recorded event-related potentials (ERPs) from adults during trait judgments about oneself and a celebrity and during judgments on word valence, after intranasal OT or placebo administration. We found that OT vs. placebo treatment reduced the differential amplitudes of a fronto-central positivity at 220-280 ms (P2) during self- vs. valence-judgments. OT vs. placebo treatment tended to reduce the differential amplitude of a late positive potential at 520-1000 ms (LPP) during self-judgments but to increase the differential LPP amplitude during other-judgments. OT effects on the differential P2 and LPP amplitudes to self- vs. celebrity-judgments were positively correlated with a measure of interdependence of self-construals. Thus OT modulates the neural correlates of self-referential processing and this effect varies as a function of interdependence.</p
Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome
No full textBackground: Detection of a retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), has recently been reported in 67% of patients with chronic fatigue syndrome. We have studied a total of 170 samples from chronic fatigue syndrome patients from two UK cohorts and 395 controls for evidence of XMRV infection by looking either for the presence of viral nucleic acids using quantitative PCR (limit of detection <16 viral copies) or for the presence of serological responses using a virus neutralisation assay.
Results: We have not identified XMRV DNA in any samples by PCR (0/299). Some serum samples showed XMRV neutralising activity (26/565) but only one of these positive sera came from a CFS patient. Most of the positive sera were also able to neutralise MLV particles pseudotyped with envelope proteins from other viruses, including vesicular stomatitis virus, indicating significant cross-reactivity in serological responses. Four positive samples were specific for XMRV.
Conclusions: No association between XMRV infection and CFS was observed in the samples tested, either by PCR or serological methodologies. The non-specific neutralisation observed in multiple serum samples suggests that it is unlikely that these responses were elicited by XMRV and highlights the danger of over-estimating XMRV frequency based on serological assays. In spite of this, we believe that the detection of neutralising activity that did not inhibit VSV-G pseudotyped MLV in at least four human serum samples indicates that XMRV infection may occur in the general population, although with currently uncertain outcomes
Baylor University vs. University of Utah; Oct. 20, 2024
No full textWomen\u27s Soccer game statistics; game bookAttendance: 778; Head Coach: Hideki NakadaWomen\u27s SoccerUtah 2; Baylor 0Baylor (7-7-4, 2-5-3) -vs- Utah (8-5-4, 5-3-2) 10/20/2024 at Salt Lake City (Ute Field (Old Soccer Field)) Date: 10/20/2024 Attendance: 778 Stadium: Ute Field (Old Soccer Field) Officials: Referee, Shane Butler Asst. Referee, Karsten Gilwald Asst. Referee, Joel Rincon Alt. Official, Brad Church Goals By Period Baylor Utah Baylor 0 Utah 2 Pos # Player SH SOG G A MIN Pos # Player Starters GK DEF DEF MID FWD FWD MID MID DEF DEF DEF FWD MID MID MID DEF FWD 1 3 4 5 9 11 14 17 22 27 28 Alvarez, Azul Vatter, Natalie Mabra, Paisley Leach, Skye Conrad, Callie Isgrig, Tyler McCullough, Theresa Merrill, Ashley Colberg, Ava Augustyn, Hallie Augustyn, Hannah Substitutes 2 Lockette, Alysiah 7 Merriam, Adriana 8 Hayes, Kai 10 Boughton, Hannah 26 Zimmerman, Kate 35 Staubach, Caroline Totals Goalkeepers Alvarez, Azul Totals 2 0 1 Total 0 2 SH SOG G A MIN Starters 0 1 0 0 2 1 0 2 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 90 90 32 90 63 90 52 74 90 90 33 GK DEF MID MID FWD FWD DEF DEF MID MID MID 1 1 0 0 1 0 9 0 1 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 38 31 58 12 30 27 990 DEF MID MID MID # 0 # 1 1 0 1 Minutes 90:00 GA 2 2 Saves 5 5 Shots By Period Baylor Utah 1 2 10 2 7 6 Total 9 16 Saves By Period Baylor Utah 3 0 2 2 5 2 0 2 3 6 7 8 13 15 18 20 23 Wardle, Kasey Granger, Maryn Blaylock, Brooklyn Dudley, Devi Bullock, Kelly Kaufusi, Taliana Bastone, Rachel Hetzel, Ava Blum, Lilliah O\u27Kane, Katie Callaway, Katie Substitutes 5 Blaylock, Callie 10 Lovell, Londyn 11 Matthews, Landen 24 Woods, Bella Totals Goalkeepers Wardle, Kasey Totals 0 0 0 0 4 2 0 0 2 4 1 0 0 0 0 2 0 0 0 2 2 0 0 0 0 0 1 0 0 0 1 0 0 0 0 0 1 0 1 0 0 0 1 0 90 90 90 90 86 53 90 90 76 87 45 0 0 0 3 16 0 0 0 1 7 0 0 0 0 2 0 0 0 0 3 8 20 7 68 990 Minutes 90:00 GA 0 0 Saves 2 2 Corner Kicks By Period Baylor Utah 1 3 1 2 7 0 Total 10 1 Fouls By Period Baylor Utah 2 5 4 6 6 11 Scoring Summary Time Team Goal Scorer Assist 17:35 UTAH Kelly Bullock Taliana Kaufusi , Devi Dudley 87:48 UTAH Lilliah Blum Katie O\u27Kane Description GOAL by UTAH Bullock, Kelly Assist by Kaufusi, Taliana and Dudley, Devi. GOAL by UTAH Blum, Lilliah Assist by O\u27Kane, Katie. Cautions and Ejections: 06:04 (YELLOW), #3 Natalie Vatter (BAY) 51:19 (YELLOW), #3 Brooklyn Blaylock (UTAH) 61:08 (YELLOW), #2 Maryn Granger (UTAH) Play By Play Time Team Play 00:00 00:00 01:36 06:04 06:04 06:04 06:04 09:45 11:51 16:11 16:50 17:35 UTAH BAY UTAH BAY UTAH BAY BAY BAY BAY BAY UTAH UTAH Wardle, Kasey at goalie for Utah Alvarez, Azul at goalie for Baylor Foul on O\u27Kane, Katie. Yellow card on BAY Vatter, Natalie. Foul on Callaway, Katie. Corner kick [06:04]. Corner kick [06:04]. Shot by BAY Conrad, Callie, out left. Corner kick [11:51]. BAY substitution: Hayes, Kai for Mabra, Paisley. Shot by UTAH Callaway, Katie. GOAL by UTAH Bullock, Kelly Assist by Kaufusi, Taliana and Dudley, Devi. 18:11 20:15 21:30 21:30 24:34 25:48 28:41 30:37 31:18 32:33 32:40 32:45 35:13 35:31 36:25 36:35 36:59 37:41 38:14 38:28 40:14 40:28 41:29 45:00 45:00 UTAH BAY UTAH BAY UTAH BAY UTAH UTAH UTAH UTAH BAY UTAH UTAH UTAH UTAH BAY UTAH UTAH BAY BAY UTAH UTAH UTAH 0 0 Shot by UTAH Kaufusi, Taliana, out left. Foul on Vatter, Natalie. UTAH substitution: Woods, Bella for Kaufusi, Taliana. BAY substitution: Lockette, Alysiah for McCullough, Theresa. Foul on Dudley, Devi. BAY substitution: Staubach, Caroline for Conrad, Callie. Shot by UTAH Bullock, Kelly, out left. UTAH substitution: Lovell, Londyn for Callaway, Katie. Shot by UTAH Bullock, Kelly, out left. Shot by UTAH Blum, Lilliah, bottom left, saved by Alvarez, Azul. BAY substitution: Zimmerman, Kate for Augustyn, Hannah. Shot by UTAH Woods, Bella, bottom left, saved by Alvarez, Azul. Foul on Hetzel, Ava. Foul on Blum, Lilliah. UTAH substitution: Blaylock, Callie for Blum, Lilliah. Foul on Leach, Skye. Corner kick [36:59]. Shot by UTAH O\u27Kane, Katie, out left. Shot by BAY Lockette, Alysiah, out top left. BAY substitution: Merriam, Adriana for Merrill, Ashley. Shot by UTAH Woods, Bella, out top left. UTAH substitution: Matthews, Landen for Bullock, Kelly. Shot by UTAH O\u27Kane, Katie, bottom center, saved by Alvarez, Azul. End of period [45:00]. Start of 2nd period [45:00]. FOR BAY: , #1 Alvarez, Azul, #3 Vatter, Natalie, #8 Hayes, Kai, #5 Leach, Skye, #9 Conrad, Callie, #11 Isgrig, Tyler, #14 McCullough, Theresa, #17 Merrill, Ashley, #22 Colberg, Ava, #27 Augustyn, Hallie, #26 Zimmerman, Kate. FOR UTAH: , #0 Wardle, Kasey, #2 Granger, Maryn, #3 Blaylock, Brooklyn, #6 Dudley, Devi, #7 Bullock, Kelly, #24 Woods, Bella, #13 Bastone, Rachel, #15 Hetzel, Ava, #8 Kaufusi, Taliana, #20 O\u27Kane, Katie, #18 Blum, Lilliah. UTAH substitution: Bullock, Kelly for Matthews, Landen. UTAH substitution: Kaufusi, Taliana for Blaylock, Callie. UTAH substitution: Blum, Lilliah for Lovell, Londyn. BAY substitution: Conrad, Callie for Staubach, Caroline. BAY substitution: McCullough, Theresa for Lockette, Alysiah. BAY substitution: Merrill, Ashley for Merriam, Adriana. Shot by UTAH O\u27Kane, Katie, out top. Corner kick [49:12]. Shot by BAY Zimmerman, Kate, out top. Foul on Hayes, Kai. Shot by UTAH Bullock, Kelly, bottom center, saved by Alvarez, Azul. Yellow card on UTAH Blaylock, Brooklyn. Shot by BAY Merrill, Ashley, out top. Corner kick [53:23]. Foul on Colberg, Ava. Shot by UTAH Woods, Bella. Foul on Hetzel, Ava. Baylor 0, Utah 1 45:00 BAY 45:00 45:00 45:00 45:00 45:00 45:00 45:00 48:34 49:12 49:45 50:20 51:10 51:19 52:41 53:23 54:08 57:46 58:32 UTAH UTAH UTAH UTAH BAY BAY BAY UTAH BAY BAY BAY UTAH UTAH BAY BAY BAY UTAH UTAH 58:58 59:29 61:08 61:28 62:52 63:33 64:55 66:46 67:15 67:48 68:33 69:06 72:00 72:53 73:37 74:02 74:58 74:58 74:58 74:58 75:25 75:25 75:29 78:15 79:47 80:29 80:36 80:48 82:34 83:52 85:29 85:36 86:17 86:38 87:48 UTAH UTAH UTAH UTAH BAY UTAH BAY BAY BAY BAY UTAH BAY BAY UTAH BAY UTAH BAY BAY BAY BAY UTAH UTAH UTAH UTAH UTAH BAY BAY BAY UTAH BAY BAY UTAH UTAH BAY UTAH Foul on O\u27Kane, Katie. Offside against Utah. Yellow card on UTAH Granger, Maryn. UTAH substitution: Callaway, Katie for Kaufusi, Taliana. BAY substitution: Boughton, Hannah for Zimmerman, Kate. Foul on O\u27Kane, Katie. BAY substitution: Merriam, Adriana for Merrill, Ashley. BAY substitution: Staubach, Caroline for Conrad, Callie. Foul on Merriam, Adriana. Foul on Merriam, Adriana. Foul on Granger, Maryn. Corner kick [69:06]. Corner kick [72:00]. UTAH substitution: Matthews, Landen for O\u27Kane, Katie. Shot by BAY Vatter, Natalie, out top left. Offside against Utah. BAY substitution: Conrad, Callie for Hayes, Kai. BAY substitution: Merrill, Ashley for Staubach, Caroline. BAY substitution: Lockette, Alysiah for McCullough, Theresa. BAY substitution: Mabra, Paisley for Boughton, Hannah. UTAH substitution: O\u27Kane, Katie for Callaway, Katie. UTAH substitution: Kaufusi, Taliana for Matthews, Landen. Foul on Woods, Bella. Shot by UTAH Kaufusi, Taliana. UTAH substitution: Lovell, Londyn for Blum, Lilliah. Shot by BAY Isgrig, Tyler, right woodwork. Shot by BAY Conrad, Callie, top, saved by Wardle, Kasey. Corner kick [80:48]. Shot by UTAH O\u27Kane, Katie, bottom left, saved by Alvarez, Azul. Corner kick [83:52]. Shot by BAY Merrill, Ashley, out right. UTAH substitution: Blum, Lilliah for Lovell, Londyn. Offside against Utah. Corner kick [86:38]. GOAL by UTAH Blum, Lilliah Assist by O\u27Kane, Katie. Baylor 0, Utah 2 87:58 UTAH 88:06 BAY 90:00 0 Foul on Hetzel, Ava. Shot by BAY Merriam, Adriana, top, saved by Wardle, Kasey. End of period [90:00]
Influences on young people's physical activity in Scotland : a socio-ecological approach
No full textAim: I describe the original contribution my work has made to understanding individual, social and environmental influences on physical activity among young people in Scotland. The work I present is based on six publications from five studies.
Design/Methodology/Approach: Two studies used quantitative methods and include a 5-year longitudinal study and a cross-sectional pupil and school-level study. Data were collected through self-administered questionnaires. Three studies used qualitative methods including focus group discussions, photography and descriptive writing. All studies involved adolescents (10-15 years) attending schools in Scotland.
Key Findings: My longitudinal evidence showed significant gender and developmental effects through early-mid adolescence, particularly at the primary-secondary school transition. While boys reported higher levels of physical activity than girls at all ages, baseline physical activity was a significant predictor of later activity levels for both genders. The importance of social influences was evident across my research. Survey data showed boys to report
higher peer support, parental support and independent play than girls. Among both genders, peer, paternal and maternal support decreased with age, whereas independent play increased. Time spent with friends was particularly important and was further highlighted in qualitative findings. Being with friends was a benefit of active travel to school, walking, and general physical activity.
Other factors influencing physical activity included proximity and access to local facilities, and the school environment. Most notable was the importance of cost and value for money. In general, pupils were satisfied with school facilities, but felt time for physical education (PE) could be increased. Among adolescent girls, survey data showed the best predictor of physical activity to be hours allocated to PE in fourth year of secondary school. Provision of PE and extra-curricular clubs are likely to be of greater importance to girls’ participation than schools facilities. Longitudinal data showed girls reporting lower levels of perceived competence, self-esteem and physical self-worth than boys at each age. Furthermore, girls’ physical perceptions decreased markedly over time, whereas among boys, only perceived competence decreased, while global esteem increased. Influences on physical activity participation were shown to be context specific, e.g. pupils reported not having bicycle storage as a barrier to cycling to school. Walking was a popular activity among girls, although areas in which walking took place, and reasons for walking could differ between geographical locations.
Conclusions: In line with the socio-ecological model, my findings demonstrate the complex interaction of individual, social and environmental factors on physical activity participation among young people. They highlight the need for all sectors to work together in developing the most suitable interventions, considering the activity, its context and the population being targeted
How distinctive are indigenous ways of achieving influence? a comparative study of guanxi, wasta, jeitinho, and pulling strings
No full textThe purpose of the study was to investigate the cultural specificity of guanxi, wasta, and jeitinho, each of which has been identified as an indigenous process of informal influence. Students in Brazil, China, Lebanon, and the United Kingdom were presented with three scenarios derived from each of the nations sampled. They rated the extent to which each scenario was representative of the locally indigenous process, the typicality for their culture of the events portrayed in the scenarios, and the extent to which these interpersonal exchanges were perceived positively. While each type of scenario was perceived as representative and typical in its culture of origin, each was also perceived as somewhat typical by respondents in additional locations. Informal influence processes may vary between cultures more in frequency than in quality. Rated scenario positivity was significantly predicted by respondents' values. The United Kingdom-based process of pulling strings was rated as typical in all locations and was more positively evaluated than the other influence processes by all respondents. It is concluded that in addition to the pragmatic value of these concepts locally, their comparative testing can contribute to the development of culture-general models of social influence processes. © The Author(s) 2012.Ali AJ, 2006, ROUT GLOB HUM RESOUR, P79; Aycan Z., 2008, SCI ADV INDIGENOUS C, P445; Barbosa L, 2006, JEITINHO BRASILEIRO; Bass BM, 1997, AM PSYCHOL, V52, P130, DOI 10.1037-0003-066X.52.2.130; Bolino MC, 2008, J MANAGE, V34, P1080, DOI 10.1177-0149206308324325; Bond MH, 2004, J CROSS CULT PSYCHOL, V35, P548, DOI 10.1177-0022022104268388; Bond R, 1996, PSYCHOL BULL, V119, P111, DOI 10.1037-0033-2909.119.1.111; Chen CC, 2004, ORGAN SCI, V15, P200, DOI 10.1287-orsc.1030.0047; Chen XP, 2004, ASIA PACIFIC J MANAG, V21, P305, DOI DOI 10.1023-B:APJM.0000036465.19102.D5; Cunningham R. B., 1993, WASTA HIDDEN FORCE M; Doi T., 1973, ANATOMY DEPENDENCE; Duarte F, 2006, ORGANIZATION, V13, P509, DOI 10.1177-1350508406065103; Dunfee TW, 2001, J BUS ETHICS, V32, P191, DOI 10.1023-A:1010766721683; EARLEY PC, 1993, ACAD MANAGE J, V36, P319, DOI 10.2307-256525; Earley P.C., 1989, ADM SCI Q, V34, P661; El-Said H., 2001, MANAGEMENT INT BUSIN, P65; Farh JL, 1998, ORGAN SCI, V9, P471, DOI 10.1287-orsc.9.4.471; Fox Kate, 2004, WATCHING ENGLISH HID; Gregg G. S., 2005, MIDDLE E CULTURAL PS; Hess David J., 1995, BRAZILIAN PUZZLE CUL, P35; Hofstede G., 2001, CULTURES CONSEQUENCE; House R., 2004, LEADERSHIP CULTURE O; Hwang K. K., 2010, HDB CHINESE PSYCHOL, P479; Kim U., 2006, INDIGENOUS CULTURAL, P1; Law KS, 2000, INT J HUM RESOUR MAN, V11, P751; Mellahi K., 2003, INT J CROSS CULTURAL, V3, P369, DOI 10.1177-1470595803003003007; Schwartz SH, 2001, J CROSS CULT PSYCHOL, V32, P519, DOI 10.1177-0022022101032005001; Schwartz SH, 2001, J CROSS CULT PSYCHOL, V32, P268, DOI 10.1177-0022022101032003002; Schwartz Shalom H, 2004, COMP CULTURES DIMENS, P43; Sinha D., 1997, HDB CROSS CULTURAL P, VI, P129; Smith P. B., 1997, HDB CROSS CULTURAL P, V3, P77; Smith PB, 2004, J CROSS CULT PSYCHOL, V35, P50, DOI 10.1177-0022022103260380; Smith PB, 2003, SAGE HDB SOCIAL PSYC, P43; Torres C. V., 2008, ARIZONA J HISPANIC C, V12, P41; Torres CV, 2006, FAMILIES ACROSS CULTURES: A 30-NATION PSYCHOLOGICAL STUDY, P259, DOI 10.1017-CBO9780511489822.012; TRIANDIS HC, 1984, J PERS SOC PSYCHOL, V47, P1363, DOI 10.1037--0022-3514.47.6.1363; Tseng Wen-Shing, 2006, Transcult Psychiatry, V43, P554, DOI 10.1177-1363461506070781; Vinagre Brasil H., 1991, INT STUDIES MANAGEME, V21, P38; Xin KR, 1996, ACAD MANAGE J, V39, P1641, DOI 10.2307-257072; Yahiaoui D, 2006, ROUT GLOB HUM RESOUR, P233; Yamaguchi S, 2006, INT CUL PSY, P163, DOI 10.1007-0-387-28662-4_798
Urinary porphyrin excretion in hepatitis C infection
No full textA high prevalence of hepatitis C virus infection in porphyria cutanea tarda in some populations suggests a close link between viral hepatitis and alteration of porphyrin metabolism. Moreover, there is evidence of a role of porphyrinopathies in hepatocarcinogenesis. The aim of our study was to obtain data on the prevalence and patterns of heme metabolism alterations in patients with chronic hepatitis C virus infection. Urinary porphyrin excretion was prospectively studied in 100 consecutive outpatients with chronic hepatitis C infection without signs of photosensitivity, using an ion-pair high performance liquid chromatography method. Increased total porphyrin excretion was found in 41 patients, with predominant excretion of coproporphyrins (whole study group: mean 146 mu g/g creatinine, interquartile range 76-186; normal <150), in 10 patients excretion exceeded 300 mu g/g creatinine. In the majority of all patients studied (75/100) an increased ratio of the relatively hydrophobic coproporphyrin isomer I to isomer III was found. In just one case, urinary porphyrin pattern characteristic for chronic hepatic porphyria was present (uroporphyrin > coproporphyrin, heptacarboxyporphyrin III increased) but the total porphyrin excretion was only slightly elevated in this case. In the whole group, total urinary porphyrin excretion correlated well with serum bilirubin and was inversely correlated with albumin and thrombin time. In conclusion, secondary coproporphyrinuria occurs frequently in heptatitis C infection, whereas in Germany, preclinical porphyria cutanea tarda seems to be rare in these patients
Canon Barnett and the first thirty years of Toynbee Hall
No full textPhDThis thesis is a study of the changing role which Toynbee
Hall, the first university settlement, played in East London between
1884 and 1914. The first chapter presents a brief biography of
Sainiel Augustus Barnett, the founder and first warden of the
settlement, and analyzes his social thought in relation to the
beliefs which were current in Britain during the period. The
second chapter discusses the founding of the settlement, its organization, structure and the aims which underlay its early work. The
third chapter, concentrating on three residents, C.R. Ashbee, .H.
Beveridge and T. Edmund Harvey, shows the way in which subsequent
settlement workers reformulated these aims In accordance with their
own social and economic views. The subsequent chapters discuss the
accomplishments of the settlement in various fields. The fourth
shows that Toynbee Hall's educational program, which was largely an
attempt to work out Matthew Arnold's theory of culture, left little
impact on the life of East London. The fifth chapter discusses the
settlement residents' ineffectual attempts to establish contact with
working men's organizations. The final chapter seeks to demonstrate
that In the field of philanthropy the residents were far more successful than in any other sphere in adapting the settlement to changing
social thought
IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic Hepatitis C virus infection in a European cohort: A cross-sectional study
No full textBackground
To date, drug response genes have not proved as useful in clinical practice as was anticipated at the start of the genomic era. An exception is in the treatment of chronic hepatitis C virus (HCV) genotype 1 infection with pegylated interferon-alpha and ribavirin (PegIFN/R). Viral clearance is achieved in 40%–50% of patients. Interleukin 28B (IL28B) genotype predicts treatment-induced and spontaneous clearance. To improve the predictive value of this genotype, we studied the combined effect of variants of IL28B with human leukocyte antigen C (HLA-C), and its ligands the killer immunoglobulin-like receptors (KIR), which have previously been implicated in HCV viral control.
Methods and Findings
We genotyped chronic hepatitis C (CHC) genotype 1 patients with PegIFN/R treatment-induced clearance (n = 417) and treatment failure (n = 493), and 234 individuals with spontaneous clearance, for HLA-C C1 versus C2, presence of inhibitory and activating KIR genes, and two IL28B SNPs, rs8099917 and rs12979860. All individuals were Europeans or of European descent. IL28B SNP rs8099917 “G” was associated with absence of treatment-induced clearance (odds ratio [OR] 2.19, p = 1.27×10−8, 1.67–2.88) and absence of spontaneous clearance (OR 3.83, p = 1.71×10−14, 2.67–5.48) of HCV, as was rs12979860, with slightly lower ORs. The HLA-C C2C2 genotype was also over-represented in patients who failed treatment (OR 1.52, p = 0.024, 1.05–2.20), but was not associated with spontaneous clearance. Prediction of treatment failure improved from 66% with IL28B to 80% using both genes in this cohort (OR 3.78, p = 8.83×10−6, 2.03–7.04). There was evidence that KIR2DL3 and KIR2DS2 carriage also altered HCV treatment response in combination with HLA-C and IL28B.
Conclusions
Genotyping for IL28B, HLA-C, and KIR genes improves prediction of HCV treatment response. These findings support a role for natural killer (NK) cell activation in PegIFN/R treatment-induced clearance, partially mediated by IL28B
Probiotics and prebiotics for severe acute malnutrition (PRONUT study): a double-blind efficacy randomised controlled trial in Malawi.
No full textBACKGROUND: Severe acute malnutrition affects 13 million children worldwide and causes 1-2 million deaths every year. Our aim was to assess the clinical and nutritional efficacy of a probiotic and prebiotic functional food for the treatment of severe acute malnutrition in a HIV-prevalent setting. METHODS: We recruited 795 Malawian children (age range 5 to 168 months [median 22, IQR 15 to 32]) from July 12, 2006, to March 7, 2007, into a double-blind, randomised, placebo-controlled efficacy trial. For generalisability, all admissions for severe acute malnutrition treatment were eligible for recruitment. After stabilisation with milk feeds, children were randomly assigned to ready-to-use therapeutic food either with (n=399) or without (n=396) Synbiotic2000 Forte. Average prescribed Synbiotic dose was 10(10) colony-forming units or more of lactic acid bacteria per day for the duration of treatment (median 33 days). Primary outcome was nutritional cure (weight-for-height >80% of National Center for Health Statistics median on two consecutive outpatient visits). Secondary outcomes included death, weight gain, time to cure, and prevalence of clinical symptoms (diarrhoea, fever, and respiratory problems). Analysis was on an intention-to-treat basis. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN19364765. FINDINGS: Nutritional cure was similar in both Synbiotic and control groups (53.9% [215 of 399] and 51.3% [203 of 396]; p=0.40). Secondary outcomes were also similar between groups. HIV seropositivity was associated with worse outcomes overall, but did not modify or confound the negative results. Subgroup analyses showed possible trends towards reduced outpatient mortality in the Synbiotic group (p=0.06). INTERPRETATION: In Malawi, Synbiotic2000 Forte did not improve severe acute malnutrition outcomes. The observation of reduced outpatient mortality might be caused by bias, confounding, or chance, but is biologically plausible, has potential for public health impact, and should be explored in future studies. FUNDING: Department for International Development (DfID)
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