12 research outputs found
Selective Hybrid EDFA/Raman Amplifier Placement to Avoid Lightpath Degradation in (C+L) Networks
No full textWe investigate optimized placement of hybrid EDFA/Raman amplifiers in (C+L) networks to avoid lightpath degradation due to ISRS. We numerically compare eight strategies for amplifier deployment showing that an optimized placement of Raman amplification can lead to 40% fewer amplifiers compared to baseline deployment practices
On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites
No full textBackground & Aims: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy. Methods: Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regression. Patients whose on-treatment serum albumin remained below normal were compared with a subset of patients from the control arm matched by principal score. Results: Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. Second-order polynomial regression revealed that survival improved in parallel with increased 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dl intervals) in the range 2.5–4.5 g/dl discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dl. Compared to untreated patients, survival even improved in patients whose on-treatment serum albumin remained below normal. Conclusion: Baseline serum albumin per se should not guide the decision to start albumin therapy. Conversely, 1-month on-treatment serum albumin levels are strongly associated with outcomes and could guide the use of albumin – 4.0 g/dl being the target threshold. However, even patients whose serum albumin remains below normal benefit from long-term albumin administration. Lay summary: The ANSWER study has shown that long-term albumin administration improves survival and prevents the occurrence of major complications in patients with cirrhosis and ascites. This study shows that the achievement of these beneficial effects is related to a significant increase in serum albumin concentration. Even though the best results follow the achievement of a serum albumin concentration of 4 g/dl, a survival benefit is also achieved in patients who fail to normalise serum albumin
Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial.
No full textBackground Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with
decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis
(ANSWER) study was designed to clarify this issue.
Methods We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic
and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who
were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard
medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months.
The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in
patients included in the modified intention-to-treat and per-protocol populations. This study is registered with
EudraCT, number 2008–000625–19, and ClinicalTrials.gov, number NCT01288794.
Findings From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the
modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT
group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier
estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40–0·95]).
46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3–4 non-liver related
adverse events.
Interpretation In this trial, long-term HA administration prolongs overall survival and might act as a disease
modifying treatment in patients with decompensated cirrhosis.
Funding Italian Medicine Agency.
Copyright © 2018 Elsevier Ltd. All rights reserved
Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy
No full textObjective: To investigate the outcome in children perinatally infected with HIV-1 whose mothers received zidovudine (ZDV) monotherapy in pregnancy.
Design: Observational retrospective study of a prospectively recruited cohort.
Setting: Italian Register for HIV Infection in Children.
Patients: A group of 216 children perinatally infected with HIV-1, born in 1992-1997 and derived prospectively from birth: 38 children had mothers receiving ZDV monotherapy and for 178 children the mothers received no antiretroviral treatment during pregnancy.
Main outcome measures: The estimated probability of developing severe disease or severe immune suppression, survival probability [95% confidence interval (CI)] within 3 years, and the hazard ratio (95% CI), adjusted for year of birth, maternal clinical condition at delivery, birthweight and treatments (Pneumocystis carinii pneumonia chemoprophylaxis and/or antiretroviral therapy before the onset of severe disease, severe immune suppression or death) were compared.
Results: Comparison of HIV-1-infected children whose mothers were treated with ZDV with children whose mothers were not treated showed that the former group had a higher probability of developing severe disease [57.3% (95% CI 40.9-74.3) versus 37.2% (95% CI 30.0-45.4); log-rank test 7.83, P = 0.005; adjusted hazard ratio 1.8 (95% CI 1.1-3.1)] or severe immune suppression [53.9% (95% CI 36.3-73.5) versus 37.5% (95% CI 30.0-46.2); log-rank test 5.58, P = 0.018; adjusted hazard ratio 2.4, (95% CI: 1.3-4.3)] and a lower survival [72.2% (95% CI 50.4-85.7) versus 81.0% (95% CI 73.7-86.5); log-rank test 4.23, P = 0.039; adjusted hazard ratio of death 1.9 (95% CI 1.1-3.6)].
Conclusions: This epidemiological observation could stimulate virologic studies to elucidate whether this rapid progression depends on in utero infection or transmission of resistant virus. Findings may suggest a need to hasten HIV-1 diagnosis in infants of ZDV-treated mothers and undertake an aggressive antiretroviral therapy in those found to be infected
Long-term albumin improves the outcomes of patients with decompensated cirrhosis and diabetes mellitus: Post hoc analysis of the ANSWER trial
No full textType-2 diabetes mellitus is a frequent comorbidity of cirrhosis independently associated with cirrhosis-related complications and mortality. This post hoc analysis of the ANSWER trial database assessed the effects of long-term human albumin (HA) administration on top of the standard medical treatment (SMT) on the clinical outcomes of a subgroup of 85 outpatients with liver cirrhosis, uncomplicated ascites and insulin-treated diabetes mellitus type 2 (ITDM). Compared to patients in the SMT arm, the SMT + HA group showed a better overall survival (86% vs. 57%, p =.016) and lower incidence rates of paracenteses, overt hepatic encephalopathy, bacterial infections, renal dysfunction and electrolyte disorders. Hospital admissions did not differ between the two arms, but the number of days spent in hospital was lower in the SMT + HA group. In conclusion, in a subgroup of ITDM outpatients with decompensated cirrhosis and ascites, long-term HA administration was associated with better survival and a lower incidence of cirrhosis-related complications
Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial
No full textBackground Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue.Methods We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (>= 200 mg/day) and furosemide (>= 25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008-000625-19, and ClinicalTrials. gov, number NCT01288794.Findings From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0.028), resulting in a 38% reduction in the mortality hazard ratio (0.62 [95% CI 0.40-0.95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3-4 non-liver related adverse events.Interpretation In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. (C) 2018 Elsevier Ltd. All rights reserved
LOW PREVALENCE OF SELECTIVE IgA DEFICIENCY IN INFECTED CHILDREN BORN TO HIV-SEROPOSITIVE MOTHERS: AN IN VIVO MODEL FOR SPECULATION ON SELECTIVE IgA DEFICIENCY PATHOGENESIS
No full textAnecdotal reports of restored immunoglobulin production in individuals with common variable immunodeficiency after acquiring HIV infection suggest that perturbation of the immune system occurring during HIV infection may force some underlying functional defects. These findings raise intriguing questions about the pathogenesis of common variable immunodeficiency. No study has investigated the possible influence of HIV infection on the development: of selective IgA deficiency, a primary immunologic defect genetically related to common variable immunodeficiency. IgA serum levels were evaluated in a large cohort of children born to HIV-infected mothers from 1985 to 2006. To avoid differences possibly due to different follow-up durations we considered only infected and noninfected children aged over 4 years at last-follow-up. The study included 1,157 non-infected children and 964 infected children, aged >= 4 years at last-follow-up and with availability of two or more serum IgA determinations over six months of age. No child displayed immunoglobulin values compatible with diagnosis of common variable immunodeficiency. However, 0/964 infected children vs. 5/1157 noninfected children had selective IgA deficiency (P=0.048). It may be speculated that several immunological alterations, occurring simultaneously in perinatal HIV infection, surpass the functional defect exhibited in some children with selective IgA deficiency. Our data may shed light on the pathogenesis of selective IgA deficiency
Discordance between CD4 cell count and CD4 cell percentage : implications for when to start antiretroviral therapy in HIV-1 infected children
No full textAntiretroviral therapy (ART) guidelines for HIV-1-infected children specify both absolute CD4 cell count and CD4 percentage thresholds at which consideration should be given to initiating ART. This leads to clinical dilemma when one marker is below the threshold, whereas the other is above
Five-year follow-up of children with perinatal HIV-1 infection receiving early highly active antiretroviral therapy
No full textBackground: Early highly active antiretroviral therapy ( HAART), started within the first months of age, has been proven to be the optimal strategy to prevent immunological and clinical deterioration in perinatally HIV-infected children. Nevertheless, data about long-term follow-up of early treated children are lacking.
Methods: We report data from 40 perinatally HIV-infected-children receiving early HAART, with a median follow-up period of 5.96 years (interquartile range [IQR]: 4.21-7.62). Children were enrolled at birth in the Italian Register for HIV Infection in Children. Comparison with 91 infected children born in the same period, followed-up from birth, and receiving deferred treatment was also provided.
Results: Nineteen children (47.5%) were still receiving their first HAART regimen at last follow-up. In the remaining children the first regimen was discontinued, after a median period of 3.77 years (IQR: 1.71-5.71) because of viral failure (8 cases), liver toxicity (1 case), structured therapy interruption (3 cases), or simplification/switch to a PI-sparing regimen (9 cases). Thirty-nine (97.5%) children showed CD4(+) T-lymphocyte values>25%, and undetectable viral load was reached in 31 (77.5%) children at last visit. Early treated children displayed significantly lower viral load than not-early treated children, until 6 years of age, and higher median CD4(+) T-lymphocyte percentages until 4 years of age. Twenty-seven (29.7%) not-early treated vs. 0/40 early treated children were in clinical category C at last follow-up (P < 0.0001).
Conclusion: Our findings suggest that clinical, virologic and immunological advantages from early-HAART are long-lasting. Recommendations indicating the long-term management of early treated children are needed
‘Dyvers kyndes of religion in sondry partes of the Ilande’: the geography of pastoral care in thirteenth-century England
No full textThe Church was not the only progenitor and disseminator of ideas in medieval England, but it was the most pervasive. Relations between the ecclesiastical and lay realms are well documented at high social levels but become progressively obscure as one descends to the influence of the Church at large on society at large (and vice versa). The twelfth century was a time of great energy and renewal in the leadership and scholarship of the Church; comparable religious energy and renewal can be seen in late-medieval lay culture. The momentum was passed on in the thirteenth century, and pastoral care was the means of its transfer.
The historical sources in this field tend to be either prescriptive, such as treatises on how to hear confessions, or descriptive, such as bishops’ registers. Prescription and description have generally been addressed separately. Likewise, the parish clergy and the friars are seldom studied together. These families of primary sources and secondary literature are brought together here to produce a more fully-rounded picture of pastoral care and church life.
The Church was an inherently local institution, shaped by geography, personalities, social structures, and countless ad hoc solutions to local problems. Few studies of medieval English ecclesiastical history have fully accepted the considerable implications of this for pastoral care; close attention to local variation is a governing methodology of this thesis, which concludes with a series of local case studies of pastoral care in several dioceses, demonstrating not only the divergences between them but also the variations within them
