Around the world, different models of paediatric palliative care have responded to the unique needs of children with life shortening conditions. However, research confirming their utility and impact ...is still lacking. This study compared patient-related outcomes and healthcare expenditures between those who received home-based paediatric palliative care and standard care. The quality of life and caregiver burden for patients receiving home-based paediatric palliative care were also tracked over the first year of enrolment to evaluate the service's longitudinal impact.
A structured impact and cost evaluation of Singapore-based HCA Hospice Care's Star PALS (Paediatric Advance Life Support) programme was conducted over a three-year period, employing both retrospective and prospective designs with two patient groups.
Compared to the control group (n = 67), patients receiving home-based paediatric palliative care (n = 71) spent more time at home than in hospital in the last year of life by 52 days (OR = 52.30, 95% CI: 25.44-79.17) with at least two fewer hospital admissions (OR = 2.46, 95% CI: 0.43-4.48); and were five times more likely to have an advance care plan formulated (OR = 5.51, 95% CI: 1.55-19.67). Medical costs incurred by this group were also considerably lower (by up to 87%). Moreover, both patients' quality of life (in terms of pain and emotion), and caregiver burden showed improvement within the first year of enrolment into the programme.
Our findings suggest that home-based paediatric palliative care brings improved resource utilization and cost-savings for both patients and healthcare providers. More importantly, the lives of patients and their caregivers have improved, with terminally ill children and their caregivers being able to spend more quality time at home at the final stretch of the disease.
The benefits of a community paediatric palliative care programme have been validated. Study findings can become key drivers when engaging service commissioners or even policy makers in appropriate settings.
INTRODUCTIONSARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused ...over 100 000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium- and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection.DEVELOPMENTWe systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system.CONCLUSIONSSARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.
The Javalambre-Physics of the Accelerating Universe Astrophysical Survey (J-PAS) will scan thousands of square degrees of the northern sky with a unique set of 56 filters using the dedicated 2.55 m ...Javalambre Survey Telescope (JST) at the Javalambre Astrophysical Observatory. Prior to the installation of the main camera (4.2 deg
2
field-of-view with 1.2 Gpixels), the JST was equipped with the JPAS-Pathfinder, a one CCD camera with a 0.3 deg
2
field-of-view and plate scale of 0.23 arcsec pixel
−1
. To demonstrate the scientific potential of J-PAS, the JPAS-Pathfinder camera was used to perform miniJPAS, a ∼1 deg
2
survey of the AEGIS field (along the Extended Groth Strip). The field was observed with the 56 J-PAS filters, which include 54 narrow band (
FWHM
∼ 145 Å) and two broader filters extending to the UV and the near-infrared, complemented by the
u
,
g
,
r
,
i
SDSS broad band filters. In this miniJPAS survey overview paper, we present the miniJPAS data set (images and catalogs), as we highlight key aspects and applications of these unique spectro-photometric data and describe how to access the public data products. The data parameters reach depths of mag
AB
≃ 22−23.5 in the 54 narrow band filters and up to 24 in the broader filters (5
σ
in a 3″ aperture). The miniJPAS primary catalog contains more than 64 000 sources detected in the
r
band and with matched photometry in all other bands. This catalog is 99% complete at
r
= 23.6 (
r
= 22.7) mag for point-like (extended) sources. We show that our photometric redshifts have an accuracy better than 1% for all sources up to
r
= 22.5, and a precision of ≤0.3% for a subset consisting of about half of the sample. On this basis, we outline several scientific applications of our data, including the study of spatially-resolved stellar populations of nearby galaxies, the analysis of the large scale structure up to
z
∼ 0.9, and the detection of large numbers of clusters and groups. Sub-percent redshift precision can also be reached for quasars, allowing for the study of the large-scale structure to be pushed to
z
> 2. The miniJPAS survey demonstrates the capability of the J-PAS filter system to accurately characterize a broad variety of sources and paves the way for the upcoming arrival of J-PAS, which will multiply this data by three orders of magnitude.
Summary Background Problems associated with lifelong antiretroviral therapy, such as need for strict adherence, drug-related toxic effects, difficulties with treatment schedules, and cost, mean that ...simplification strategies should be sought. We aimed to explore the efficacy and safety of dual treatment with atazanavir–ritonavir plus lamivudine as an option to switch to from standard combination antiretroviral therapy in patients with an HIV-1 infection who are virologically suppressed. Methods In this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years and older with chronic HIV-1 infection and no previous treatment failure or resistance, and with HIV-1 RNA of less than 50 copies per mL for at least 6 months, negative hepatitis B virus surface antigen, and good general health, from 30 hospitals in Spain. Exclusion criteria were switch in antiretroviral therapy during the previous 4 months, previous virological failure, pregnancy or breastfeeding, Gilbert's syndrome, use of contraindicated drugs, grade 4 laboratory abnormalities, and previous intolerance to any of the study drugs. We randomly assigned patients (1:1; stratified by active hepatitis C virus infection and previous treatment; computer-generated random number sequence) to dual treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus lamivudine (300 mg once daily) or triple treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus two nucleos(t)ide reverse transcriptase inhibitors at the discretion of the investigators. The primary endpoint was virological response, defined as HIV-1 RNA of less than 50 copies per mL at week 48, in the per-protocol population, with a non-inferiority margin of 12%. We included patients who received at least one dose of the study drug in the safety analysis. This study is registered at ClinicalTrials.gov , number NCT01307488. Findings Between Sept 29, 2011, and May 2, 2013, we randomly assigned 286 patients (143 50% to each group). At week 48 in the per-protocol population, 112 (84%) of 133 patients had virological response in the dual-treatment group versus 105 (78%) of 135 in the triple-treatment group (difference 6% 95% CI −5 to 16%), showing non-inferiority at the prespecified level. 14 (5%) patients developed severe adverse events (dual treatment six 4%; triple treatment eight 6%), none of which we deemed related to the study drug. Grade 3–4 adverse events were similar between groups (dual treatment 77 55% of 140; triple treatment 78 55% of 141). Treatment discontinuations were less frequent in the dual-treatment group (three 2%) than in the triple-treatment group (ten 7%; p=0·047). Interpretation In our trial, dual treatment was effective, safe, and non-inferior to triple treatment in patients with an HIV-1 infection who are virologically suppressed who switch antiretroviral therapy because of toxic effects, intolerance, or simplification. This combination has the potential to suppress some of the long-term toxic effects associated with nucleos(t)ide reverse transcriptase inhibitors, preserve future treatment options, and reduce the cost of antiretroviral therapy. Funding Bristol Myers-Squibb and Fundación SEIMC-GESIDA.
We evaluated whether maintenance therapy with atazanavir/ritonavir plus lamivudine (ATV/r + 3TC) was non-inferior to ATV/r plus two nucleosides (ATV/r + 2NUCs) at 96 weeks of follow-up.
SALT is a ...multicentre, open-label, non-inferiority clinical trial in HIV-1-infected virologically suppressed patients. Hepatitis B virus surface antigen-negative subjects with no previous treatment failure/resistance mutations and HIV-1-RNA <50 copies/mL for ≥6 months were randomized (1 : 1) to ATV/r + 3TC or ATV/r + 2NUCs. The primary endpoint was HIV-1-RNA <50 copies/mL in the PP population. Non-inferiority was demonstrated if the lower bound of the 95% CI for the difference was not below -12%.
Some 286 patients were analysed. At week 96, 74.4% had HIV-1-RNA <50 copies/mL in the ATV/r + 3TC arm versus 73.9% in the ATV/r + 2NUCs arm (95% CI for the difference, -9.9%-11.0%). In both groups, similar values were observed for patients with confirmed virological failure in ATV/r + 3TC versus ATV/r + 2NUCs (9 versus 5), death (1 versus 0), discontinuation due to ART-related toxicity (7 versus 11), withdrawal from the study (7 versus 9) and loss to follow-up (6 versus 6). One patient taking ATV/r + 2NUCs developed resistance mutations (M184V and L63P). Similar values were obtained for change in mean CD4 count 19 versus 18 cells/mm
(95% CI for the difference, -49.3-50.7), grade 3-4 adverse events (70.7% versus 70.2%) and changes in the global deficit score, -0.3 (95% CI, -0.5 to -0.1) for ATV/r + 3TC, versus -0.2 (95% CI, -0.4 to -0.1) for ATV/r + 2NUCs.
The long-term results of switching to ATV/r + 3TC show that this strategy is effective, safe and non-inferior to ATV + 2NUCs in virologically suppressed HIV-infected patients.
Isolated limb perfusion (ILP) is a method for treating unresectable lesions of limbs in patients with melanoma or sarcoma by using high doses of tumor necrosis factor alpha and melphalan. These high ...doses can result in high systemic toxicity if there is a drug leak from the isolated circulation of the limb to the systemic. This makes it imperative to monitor the leakage rate (F%) during the infusion, currently performed with radiotracers. The objective of this work was to develop a leakage monitoring protocol as accurate as possible to ensure safe ILP. MATERIAL AND METHODWe built a phantom with 3compartments (body, limb and precordial area) and a high sensitivity collimator fitted to a portable gammacamera. We simulate ILP with scheduled leaks every 10minutes from 1% to 9% (theorical F%). We mesured F(%) using 2equation: one is the proposed in the literature and another corrected by decay of the radioisotope. We test the optimal radiopharmaceutical doses to minimize the detector dead time error and compare F(%) mesured by both equations regarding the theoretical F(%). The leakage monitoring protocol was used in 17 ILP of 16 patients and an analysis of the recorded data was performed. RESULTSWe found significant differences between F(%) mesured using the first equation and theoretical F(%), obtaining results very adjusted to the theorical after applying the decay correction. CONCLUSIONSThe decay correction of the radioisotope is a simple manner to carry out the procedure more safely, reducing the error in the calculation of F(%).
In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified ...exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data.
PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis.
At date cut-off of 24 March 2017, median follow-up was 31 months (range 23–41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 95% confidence interval (CI): 0.57, 0.77. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ≥50%. For TPS ≥50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ≥1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ≥50%, PFS HRs were similar across archival 0.63 (95% CI: 0.45, 0.89) and newly collected samples 0.53 (95% CI: 0.38, 0.72). In patients with TPS ≥1%, PFS HRs were similar across archival 0.82 (95% CI: 0.66, 1.02) and newly collected samples 0.83 (95% CI: 0.68, 1.02).
Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples.
ClinicalTrials.gov: NCT01905657.
Background
Acute kidney injury (AKI) is frequent in Coronavirus Infection Disease 2019 (COVID-19) patients. Factors associated with AKI in COVID-19 intensive care unit (ICU) patients and their ...outcomes have not been previously explored.
Methods
Prospective observational study of COVID-19 patients admitted to the ICUs of the Hospital Clínic of Barcelona (Spain), from March 25th to April 21st, 2020, who developed AKI stage 2 or higher (AKIN classification). The primary goal was to describe the characteristics of moderate-severe AKI of COVID-19 patients in an ICU context. As a secondary goal, we aimed to find independent predictors of AKI progression, Renal Replacement Therapy (RRT) requirement and mortality among these patients.
Results
During the study period, 52 out of 237 ICU patients, developed AKIN stage 2 or higher and were included in the study. A Sequential Organ Failure Assessment (SOFA) score at AKI diagnosis of 8 or higher was associated with RRT, OR 5.2, p 0.032. At the time of AKI diagnosis, patients had a worse liver profile and higher inflammation markers than at admission. Fifty per cent of the patients presented AKI progression from AKIN 2 to 3 and 28.85% required RRT. The use of corticosteroids in 69.2% of patients was associated with a reduced requirement of RRT, OR 0.13 (CI 95% 0.02–0.89), p 0.037. AKI was associated with high mortality (50%) and a longer hospital stay, median 35 vs 18 days (p 0.024).
Conclusions
The prevalence of moderate/severe AKI in COVID-19 patients admitted to the ICU is high and has a strong correlation with mortality and length of hospital stay.
Concerns have been voiced over the capacity of deintensification strategies to preserve neurocognitive function and prevent neurocognitive impairment.
We present the 96 week results of a ...neurocognitive substudy nested within the SALT clinical trial: a randomized, open-label, non-inferiority trial that compares whether atazanavir/ritonavir + lamivudine is non-inferior to atazanavir/ritonavir + two NRTIs in HIV-suppressed patients on stable triple therapy. A global deficit score (GDS) for five neurocognitive tasks was used to assess neurocognitive function. Changes in neurocognitive function (GDS value) were determined at weeks 48 and 96. The effect of atazanavir/ritonavir + lamivudine, adjusted for significant confounders, on the change in neurocognitive function was determined using analysis of covariance (ANCOVA) at week 96.
The per-protocol analysis included 92 participants (47 atazanavir/ritonavir + lamivudine and 45 atazanavir/ritonavir + two NRTIs). All baseline characteristics were comparable in both groups. At weeks 48 and 96, changes in GDS week 48, atazanavir/ritonavir + lamivudine -0.3 (95% CI -0.5 to -0.1) versus atazanavir/ritonavir + two NRTIs -0.2 (95% CI -0.4 to 0.0), P = 0.39; week 96, atazanavir/ritonavir + lamivudine -0.3 (95% CI -0.5 to -0.1) versus atazanavir/ritonavir + two NRTIs -0.2 (95% CI -0.4 to -0.1); P = 0.471 were similar. This absence of differences was also observed in all cognitive tasks. Atazanavir/ritonavir + lamivudine did not impact the change in neurocognitive function at week 96; the adjusted effect of atazanavir/ritonavir + lamivudine on GDS change, considering atazanavir/ritonavir + two NRTIs as a reference, was 0.01 (95% CI -0.18 to 0.21) (P = 0.90).
Neurocognitive function remained stable after 96 weeks, both in the atazanavir/ritonavir + lamivudine and in the atazanavir/ritonavir + two NRTIs arms, provided HIV remained suppressed.
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