To assess satisfaction with the serum-free formulation of subcutaneous (sc) interferon (IFN) beta-1a among patients with relapsing multiple sclerosis (MS).
Patients with relapsing MS who had been ...receiving sc IFN beta-1a for at least 6 months, were transitioned to the new formulation, 44 mug three times weekly. Patients were randomized to preventative ibuprofen (400 mg 30-60 minutes prior to injection) or ibuprofen as needed (PRN) for 4 weeks. The primary endpoint was the 'flu-like' symptom (FLS) domain score of the validated Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ).
Of the 117 patients enrolled, 109 (93.2%) completed the study. Neither group's MSTCQ FLS score showed a clinically meaningful change from baseline to week 4: mean +/- SD changes were -1.1 +/- 4.4 in the preventative ibuprofen group and 0.8 +/- 3.6 in the ibuprofen PRN group. MSTCQ injection system satisfaction and global side-effect scores were unchanged; total and injection-site reaction scores improved moderately in both groups between baseline and week 4.
Results showed continued or increased levels of satisfaction with the new formulation of sc IFN beta-1a. FLS occurring with the new formulation were generally mild and seldom sufficiently bothersome to require ibuprofen treatment.
Phenylketonuria (PKU) is a rare inborn error of metabolism that affects the ability of patients to metabolise phenylalanine (Phe). Lifelong management of blood Phe levels is required in order to ...avoid the complications associated with PKU. This constitutes a severely protein restricted diet, and regular monitoring of Phe levels. Management of PKU may be costly and time-consuming for adult patients or caregivers of PKU-affected children. A cross-sectional study was performed with patients or their caregivers in the Netherlands to gain insight into the personal time burden and cost of living with PKU.
A systematic literature review was performed to identify all aspects of PKU management that may pose a financial or time burden on patients or caregivers. Findings were confirmed through interviews with PKU experts and feedback from patients and caregivers, and consolidated into a questionnaire that aimed to evaluate the impact of each of these factors. Early and continuously treated adult patients and caregivers from seven metabolic centres were recruited to complete the questionnaire online.
22 adult patients and 24 caregivers participated in the study. Managing a Phe-restricted diet represented an extra time burden of 1h and 24min for caregivers and 30min for adult patients per day. Caregivers reported a significantly higher time burden than adult patients. The median total out-of-pocket cost (OOPC) for patients was €604 annually, with 99% of expenditure on low-protein food products. Greater disease severity was significantly associated with increased OOPC and time burden for both adult patients and caregivers.
Management of PKU is associated with a considerable time burden for both caregivers of children with PKU and adult patients. Caregivers of PKU-affected children reported a significantly higher time burden than adult patients. The OOPC of caregivers and patients was mainly driven by the expenditure on low protein food.
•First study to investigate the time burden and cost of living with PKU.•46 PKU patients completed a web based questionnaire.•Management of PKU poses a considerable time burden on PKU patients.•Greater disease severity was associated with increased time burden and costs.
The presence of extreme horizontal branch (EHB) and blue hook stars in some Galactic globular clusters (GGCs) constitutes one of the remaining mysteries of stellar evolution. While several ...evolutionary scenarios have been proposed to explain the characteristics of this peculiar population of evolved stars, their observational verification has been limited by the availability of spectroscopic data for a statistically significant sample of such objects in any single GGC. We recently launched the SHOTGLAS project with the aim of providing a comprehensive picture of this intriguing stellar population in terms of spectroscopic properties for all readily accessible GGCs hosting an EHB. In this first paper, we focus on
ω
Cen, a peculiar, massive GGC that hosts multiple stellar populations. We use non-LTE model atmospheres to derive atmospheric parameters (
T
eff
, log
g
and
N
(He)/
N
(H)) and spectroscopic masses for 152 EHB stars in the cluster. This constitutes the largest spectroscopic sample of EHB stars ever analyzed in a GGC and represents ≈20% of the EHB population of
ω
Cen. We also search for close binaries among these stars based on radial velocity variations. Our results show that the EHB population of
ω
Cen is divided into three spectroscopic groups that are very distinct in the
T
eff
− helium abundance plane. The coolest sdB-type stars (
T
eff
≲ 30 000 K) have a hydrogen-rich atmosphere, populate the theoretical EHB region in the
T
eff
− log
g
plane, and form 26% of our sample. The hottest sdO-type stars (
T
eff
≳ 42 000 K) make up 10% of the sample, have a hydrogen-rich atmosphere and are thought to be in a post-EHB evolutionary phase. The majority of our sample is found at intermediate temperatures and consists of sdOB stars that have roughly solar or super-solar atmospheric helium abundances. It is these objects that constitute the blue hook at
V
> 18.5 mag in the
ω
Cen color-magnitude diagram. Interestingly, the helium-enriched sdOBs do not have a significant counterpart population in the Galactic field, indicating that their formation is dependent on the particular environment found in
ω
Cen and other select GGCs. Another major difference between the EHB stars in
ω
Cen and the field is the fraction of close binaries. From our radial velocity survey we identify two binary candidates, however no orbital solutions could be determined. We estimate an EHB close binary fraction of ≈5% in
ω
Cen. This low fraction is in line with findings for other GGCs, but in sharp contrast to the situation in the field, where around 50% of the sdB stars reside in close binaries. Finally, the mass distribution derived is very similar for all three spectroscopic groups, however the average mass (0.38
M
⊙
) is lower than that expected from stellar evolution theory. While this mass conundrum has previously been noted for EHB stars in
ω
Cen, it so far appears to be unique to that cluster.
Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate ...the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs).
We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature.
From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval UI 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece.
Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases.
European Centre for Disease Prevention and Control.
Outcomes remain poor for refractory severe aplastic anemia (SAA) patients. Alternative donor transplantation may be considered, but results from previous studies are not encouraging. We conducted a ...prospective nationwide phase 2 study to assess unrelated cord blood (CB) transplantation (CBT) efficacy and safety in refractory SAA patients (Aplastic Anemia and Cord Blood Transplantation protocol). To demonstrate a significant difference in 1-year survival from 20% (null hypothesis) to 50% (alternative hypothesis), we needed to include 25 transplanted patients and therefore included 26 (median age, 16 years). Eligibility criteria required 1 or 2 unrelated CB units, containing separately or together >4 × 107 frozen nucleated cells (NCs) per kilogram of recipient body weight. Conditioning regimen comprised fludarabine (FLU), cyclophosphamide (CY), antithymocyte globulin (ATG), and 2-Gy total body irradiation (TBI). With a median follow-up of 38.8 months, engraftment occurred in 23 patients (88%); cumulative incidences of grade II-IV acute and chronic graft-versus-host disease were 45.8% and 36%, respectively. Twenty-three patients were alive at 1 year, with an 88.5% overall survival (OS) rate, differing significantly from the expected 20% (P < .0001; 84% OS at 2 years). CBT with units containing ≥4 × 107 frozen NCs per kilogram is therefore a valuable curative option for young adults with refractory SAA and no available matched unrelated donors. This trial was registered at www.clinicaltrials.gov as #NCT01343953.
•CBT after FLU-CY-ATG-2-Gy TBI with at least 4 × 107 frozen NCs per kilogram leads to satisfactory OS in refractory SAA.•CBT is a valuable curative option in young patients with refractory idiopathic SAA and no available matched unrelated donors.
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Hepatitis E virus (HEV) genotype 3 is the most common genotype linked to HEV infections in Europe and America. Three major clades (HEV-3.1, HEV-3.2, and HEV-3.3) have been identified but the overlaps ...between intra-subtype and inter-subtype p-distances make subtype classification inconsistent. Reference sequences have been proposed to facilitate communication between researchers and new putative subtypes have been identified recently. We have used the full or near full-length HEV-3 genome sequences available in the Genbank database (April 2020;
= 503) and distance analyses of clades HEV-3.1 and HEV-3.2 to determine a p-distance cut-off (0.093 nt substitutions/site) in order to define subtypes. This could help to harmonize HEV-3 genotyping, facilitate molecular epidemiology studies and investigations of the biological and clinical differences between HEV-3 subtypes.
Background
Admission of an infant to a neonatal intensive care unit (NICU) is often a stressful experience for parents and can be associated with feelings of inadequacy to fulfil the desirable ...parental role. The values, opportunities, integration, control, and evaluation (VOICE) programme was developed to engage parents in care, to decrease stress, and to increase empowerment.
Aim
To explore the experiences of parents regarding involvement in the VOICE programme during admission of their infant to the NICU.
Design
The VOICE programme includes at least five personal structured meetings between parents, nurses, and other health care professionals throughout the pathway from birth, NICU, and follow up. A qualitative design was adopted using semi‐structured interviews. Interviews with 13 parents of 11 infants born at <27 weeks' gestational age were conducted: nine mothers and two couples of father and mother. Thematic analysis was deployed.
Results
The findings have been described in one overarching theme: “parental empowerment.” Parents felt strengthened and were empowered in the development of their role as primary caretaker by the VOICE programme. The parental empowerment theme emerged from four related interpretive themes that were derived: (a) involvement in care, (b) personalized information and communication, (c) transition to a parental role, and (d) emotional support.
Conclusion
The VOICE programme can be a structured approach used to implement family support in a NICU to empower parents to become a partner in the care of their infant and feel confident.
Relevance to clinical practice
This study encourages health care professionals to provide parental support through a structured intervention programme, which contributes to the empowerment of parents in the NICU and encouraged them to participate in care and decision‐making.
Due to increased rates of secondary solid organ cancer in patients with severe aplastic anemia who received an irradiation-based conditioning regimen, we decided some years ago to use the combination ...of cyclophosphamide and antithymocyte globulin. We report the long-term follow up of patients who underwent hematopoietic stem cell transplantation from an HLA-matched sibling donor after this conditioning regimen.
We analyzed 61 consecutive patients transplanted from June 1991 to February 2010, following conditioning with cyclophosphamide (200 mg/kg) and antithymocyte globulin (2.5 mg/kg/day × 5 days).
Median age was 21 years (range 4-43); 41 of the 61 patients were adults. Median duration of the disease before hematopoietic stem cell transplantation was 93 days. All but 2 patients received bone marrow as the source of stem cells and all but 2 engrafted. Cumulative incidence of acute grade II-IV graft-versus-host disease was 23% (95%CI 13-34) and 18 developed chronic graft-versus-host disease (cumulative incidence 32% at 72 months, 95% CI 20-46). In multivariate analysis, a higher number of infused CD3 cells was associated with an increased risk of developing chronic graft-versus-host disease (P = 0.017). With a median follow up of 73 months (range 8-233), the estimated 6-year overall survival was 87% (95% CI 78-97). At 72 months, the cumulative incidence of avascular necrosis was 21% and 12 patients presented with endocrine dysfunction (cumulative incidence of 19%). Only one patient developed a secondary malignancy (Hodgkin's lymphoma) during follow up.
Cyclophosphamide and antithymocyte globulin is an effective conditioning regimen for patients with severe aplastic anemia and is associated with low treatment-related mortality. Long-term complications include avascular necrosis and endocrine dysfunction.
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