Children and adolescents dying from complex chronic conditions require paediatric palliative care. One aim of palliative care is to enable a home death if desired and well supported. However, there ...is little data to inform care, particularly from countries without paediatric palliative care, which constitute the majority worldwide.
This is an epidemiological study analysing death certificate data of decedents aged between 0 and 17 years in Portugal, a developed Western European country without recognised provision of paediatric palliative care, from 1987 to 2011. We analysed death certificate data on cause and place of death; the main outcome measure was home death. Complex chronic conditions included cancer, cardiovascular, neuromuscular, congenital/genetic, respiratory, metabolic, gastro-intestinal, renal, and haematology/immunodeficiency conditions. Multivariate analysis determined factors associated with home death in these conditions.
Annual deaths decreased from 3268 to 572. Of 38,870 deaths, 10,571 were caused by complex chronic conditions, their overall proportion increasing from 23.7% to 33.4% (22.4% to 45.4% above age 1-year). For these children, median age of death increased from 0.5 to 4.32-years; 19.4% of deaths occurred at home, declining from 35.6% to 11.5%; factors associated with home death were year of death (adjusted odds ratio 0.89, 95% confidence interval 0.89-0.90), age of death (6-10 year-olds 21.46, 16.42-28.04, reference neonates), semester of death (October-March 1.18, 1.05-1.32, reference April-September), and cause of death (neuromuscular diseases 1.59, 1.37-1.84, reference cancer), with wide regional variation.
This first trend analysis of paediatric deaths in Portugal (an European country without paediatric palliative care) shows that palliative care needs are increasing. Children are surviving longer and, in contrast with countries where paediatric palliative care is thriving, there is a long-term trend of dying in hospital instead of at home. Age, diagnosis, season and region are associated with home death, and should be considered when planning services to support families choosing this option. Priorities should address needs of the youngest children, those with cancer, neuromuscular and cardiovascular conditions, as well as inequities related to place of residence.
VEXAS syndrome is a recently described autoinflammatory syndrome caused by the somatic acquisition of UBA1 mutations in myeloid precursors and is frequently associated with hematologic malignancies, ...chiefly myelodysplastic syndromes. Disease presentation can mimic several rheumatologic disorders, delaying the diagnosis. We describe a case of atypical presentation resembling late-onset axial spondylarthritis, later progressing to a systemic inflammatory syndrome with chondritis, cutaneous vasculitis, and transfusion-dependent anemia, requiring high doses of steroids. Ruxolitinib was used as the first steroid-sparing strategy without response. However, azacitidine showed activity in controlling both inflammation and the mutant clone. This case raises the question of whether azacitidine’s anti-inflammatory effects are dependent on or independent of clonal control. We discuss the potential relevance of molecular remission in VEXAS syndrome and highlight the importance of a multidisciplinary team for the care of such complex patients.
•Age-adjusted breast cancer incidence rates increased in all regions and at all ages.•Southern Portugal presented the highest age-adjusted rate.•Northern Portugal presented the fastest rate of ...increase.•Women under age 45 years have expressed higher EAPCs than women age 45+ years.•Forecasts have shown that Northern rates might soon surpass Southern rates.
Female breast cancer incidence rates have been increasing in Portugal for years. We, therefore, conducted the first nationwide breast cancer study to assess regional differences.
Cases were obtained from population-based cancer registries covering the country’s Mainland (South, North, Centre), as well as the two Autonomous Regions (Azores and Madeira), for the time-period 1998 through 2011. Analyses were restricted to ages 30–84 years and stratified by region. We used the age-period-cohort (APC) framework to complement standard descriptive techniques and to forecast future trends. Estimable APC parameters included net drift, longitudinal age-specific incidence rate curves, and fitted age-specific incidence rate ratios.
There were 71 545 breast cancer cases diagnosed in Portugal at ages 30–84 years from 1998 to 2011. The South presented the highest age-standardized rate (155.8/100 000), while the North presented the fastest rate of increase (3.6%/year). Age-specific statistical interactions were observed between regions. Younger women in the North revealed a decreased risk of developing breast cancer compared to women from the same age group in the South and Centre, while that risk was reversed in older women (p < 0.05). We estimate that from 2014 onwards, the North might rank first among all regions.
The variant patterns observed could be due to a combination of different screening practices and/or exposure to risk factors across regions. Disease heterogeneity among younger and older women may also explain part of the differences in age-specific rates. These results justify continued monitoring of breast cancer incidence by region.
The Instituto Angolano de Controlo do Cancer (IACC) Cancer Registry in Luanda, Angola is the most ancient and organized hospital-based cancer registry in Angola and provides data on cancer cases ...treated in several hospital facilities in Luanda.
Newly-diagnosed cancer cases (2012-2016) of IACC were collected. A total of 6638 malignant neoplasms were recorded. After excluding duplicates, missing data and non-melanoma skin cancers cases, a final number of 5609 cancer cases was considered valid for analysis.
From 5609 new cases, 2059 were males and 3550 females. Of all cases, 9.7% was in children below the age of 15 years. Most of the cases were residents from the Luanda district. The five most common cancers for all periods were breast (21.4%), cervix (16.8%), prostate (7.1%), non-Hodgkin lymphoma (4.5%) and Kaposi sarcoma (4.3%). For men, 19.3% of the cancers were prostate, 7.5% Kaposi sarcoma and 7.5% non-Hodgkin lymphoma. Cancers of the breast and cervix together accounted 60% of all cancers in females. Comparison of our data onto the 5 most frequent tumours, by sex, according to GLOBOCAN 2018 estimations for Angola, highlights the potential deviation from reality that estimates may have and reinforces the urgent need to build a truly population-based cancer registry in Luanda.
To accomplish that task, it is mandatory to implement a more rigorous quality control program at the hospital-based cancer registry at IACC and to optimize the network of health institutions that actively working on and contributing to the cancer registry, in Luanda.
On the assumption that most infants with disseminated neuroblastoma without MYCN amplification (MYCNA) have a favorable prognosis, two concomitant prospective trials were started in which ...chemotherapy was limited to patients presenting life- or organ-threatening symptoms or overt metastases to skeleton, lung, or CNS. Surgery was to be performed only in the absence of surgical risk factors.
One hundred seventy infants with disseminated neuroblastoma without MYCNA, diagnosed between June 1999 and June 2004 in nine European countries were eligible for either of the two studies. Trial 99.2 included all stage 4S infants and those with stage 4 with a primary tumor infiltrating across the midline or positive skeletal scintigraphy who were to be observed in absence of symptoms. Trial 99.3 included infants with overt metastases to the skeleton, lung, and CNS to be treated with a minimum of four chemotherapy courses.
The 125 infants treated on trial 99.2 had a 2-year overall survival (OS) of 97.6% with no difference between asymptomatic and symptomatic patients (97.7% v 97.3%), patients without or with unresectable primary tumors (96.8% v 100%), and patients without or with positive skeletal scintigraphy without radiologic abnormalities (97.2% v 100%). The 45 infants treated on trial 99.3 had a 2-year OS of 95.6%. No patients died of surgery- or chemotherapy-related complications.
Infants with disseminated disease without MYCNA have excellent survival with minimal or no treatment. Asymptomatic infants with an unresectable primary tumor or positive skeletal scintigraphy without radiologic abnormalities may undergo observation alone.
We investigated differences in net cancer survival (survival observed if the only possible cause of death was the cancer under study) estimated using new approaches for relative survival (RS) and ...cause-specific survival (CSS).
We used SEER data for patients diagnosed in 2000 to 2013, followed-up through December 31, 2014. For RS, we used new life tables accounting for geography and socio-economic status. For CSS, we used the SEER cause of death algorithm for attributing cancer-specific death. Estimates were compared by site, age, stage, race, and time since diagnosis.
Differences between 5-year RS and CSS were generally small. RS was always higher in screen-detectable cancers, for example, female breast (89.2% vs. 87.8%) and prostate (98.5% vs. 93.7%) cancers; differences increased with age or time since diagnosis. CSS was usually higher in the remaining cancer sites, particularly those related to specific risk factors, for example, cervix (70.9% vs. 68.3%) and liver (20.7% vs. 17.1%) cancers. For most cancer sites, the gap between estimates was smaller with more advanced stage.
RS is the preferred approach to report cancer survival from registry data because cause of death may be inaccurate, particularly for older patients and long-term survivors as comorbidities increase challenges in determining cause of death. However, CSS proved to be more reliable in patients diagnosed with localized disease or cancers related to specific risk factors as general population life tables may not capture other causes of mortality.
Different approaches for net survival estimation should be considered depending on cancer under study.
Early death (ED) is still the major obstacle to cure in acute promyelocytic leukemia (APL). Most studies focus on 30-day ED; however, little is known on predictors of death before starting APL ...treatment (very early death — VED) and on predictors of 7-day ED, the period with most deaths due to thrombohemorrhagic diathesis. We hypothesized whether the severity of the coagulopathy of APL could predict VED and 7-day ED. We also aimed to evaluate other characteristics associated with these outcomes. We undertook a retrospective, single-center observational study including newly diagnosed APL patients admitted to our institution between January 2000 and November 2022. Baseline demographical, clinical, and laboratorial data were collected. Statistical analysis was performed using Stata. One hundred four patients were included. The VED rate was 4.8%. A DIC Score ≥ 7 (
p
= 0.045), serum creatinine > 1.5 mg/dL (
p
< 0.001%), a DIC Score ≥ 6 within 24 h (
p
= 0.009), and mechanical ventilation (
p
< 0.001) were associated with VED. The 7-day ED rate was 12.5%. High-risk (
p
= 0.007) and hypogranular APL (
p
= 0.029), DIC Score at diagnosis (
p
= 0.047), DIC Score ≥ 7 (
p
= 0.043), DIC Score ≥ 6 within 24 h (
p
= 0.025), PT prolongation > 6 s (
p
= 0.002), and creatinine > 1.5 mg/dL (
p
= 0.004) were associated with 7-day ED. However, only elevated creatinine emerged as an independent predictor of 7-day ED (OR 21.4;
p
= 0.008). Our study shows that in patients with APL, an elevated creatinine at diagnosis strongly predicts for 7-day ED. A DIC Score ≥ 7 and a Score that remains ≥ 6 within 24 h and a serum creatinine > 1.5 mg/dL significantly associated with VED.
Summary Background High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patients with high-risk neuroblastoma; however, which regimen has the greatest patient ...benefit has not been established. We aimed to assess event-free survival after high-dose chemotherapy with busulfan and melphalan compared with carboplatin, etoposide, and melphalan. Methods We did an international, randomised, multi-arm, open-label, phase 3 cooperative group clinical trial of patients with high-risk neuroblastoma at 128 institutions in 18 countries that included an open-label randomised arm in which high-dose chemotherapy regimens were compared. Patients (age 1–20 years) with neuroblastoma were eligible to be randomly assigned if they had completed a multidrug induction regimen (cisplatin, carboplatin, cyclophosphamide, vincristine, and etoposide with or without topotecan, vincristine, and doxorubicin) and achieved an adequate disease response. Patients were randomly assigned (1:1) to busulfan and melphalan or to carboplatin, etoposide, and melphalan by minimisation, balancing age at diagnosis, stage, MYCN amplification, and national cooperative clinical group between groups. The busulfan and melphalan regimen comprised oral busulfan (150 mg/m2 given on 4 days consecutively in four equal doses); after Nov 8, 2007, intravenous busulfan was given (0·8–1·2 mg/kg per dose for 16 doses according to patient weight). After 24 h, an intravenous melphalan dose (140 mg/m2 ) was given. Doses of busulfan and melphalan were modified according to bodyweight. The carboplatin, etoposide, and melphalan regimen consisted of carboplatin continuous infusion of area under the plasma concentration–time curve 4·1 mg/mL per min per day for 4 days, etoposide continuous infusion of 338 mg/m2 per day for 4 days, and melphalan 70 mg/m2 per day for 3 days, with doses for all three drugs modified according to bodyweight and glomerular filtration rate. Stem-cell rescue was given after the last dose of high-dose chemotherapy, at least 24 h after melphalan in patients who received busulfan and melphalan and at least 72 h after carboplatin etoposide, and melphalan. All patients received subsequent local radiotherapy to the primary tumour site followed by maintenance therapy. The primary endpoint was 3-year event-free survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT01704716 , and EudraCT, number 2006-001489-17. Findings Between June 24, 2002, and Oct 8, 2010, 1347 patients were enrolled and 676 were eligible for random allocation, 598 (88%) of whom were randomly assigned: 296 to busulfan and melphalan and 302 to carboplatin, etoposide, and melphalan. Median follow-up was 7·2 years (IQR 5·3–9·2). At 3 years, 146 of 296 patients in the busulfan and melphalan group and 188 of 302 in the carboplatin, etoposide, and melphalan group had an event; 3-year event-free survival was 50% (95% CI 45–56) versus 38% (32–43; p=0·0005). Nine patients in the busulfan and melphalan group and 11 in the carboplatin, etoposide, and melphalan group had died without relapse by 5 years. Severe life-threatening toxicities occurred in 13 (4%) patients who received busulfan and melphalan and 29 (10%) who received carboplatin, etoposide, and melphalan. The most frequent grade 3–4 adverse events were general condition (74 26% of 281 in the busulfan and melphalan group vs 103 38% of 270 in the carboplatin, etoposide, and melphalan group), infection (55 19% of 283 vs 74 27% of 271), and stomatitis (138 49% of 284 vs 162 59% of 273); 60 (22%) of 267 patients in the busulfan and melphalan group had Bearman grades 1–3 veno-occlusive disease versus 21 (9%) of 239 in the carboplatin, etoposide, and melphalan group. Interpretation Busulfan and melphalan improved event-free survival in children with high-risk neuroblastoma with an adequate response to induction treatment and caused fewer severe adverse events than did carboplatin, etoposide, and melphalan. Busulfan and melphalan should thus be considered standard high-dose chemotherapy and ongoing randomised studies will continue to aim to optimise treatment for high-risk neuroblastoma. Funding European Commission 5th Framework Grant and the St Anna Kinderkrebsforschung.
Fernando Pessoa writes The Mad Fiddler according to the three principles of Sensationism he delineates in a letter to an unnamed British editor: Sensation, Suggestion, and Construction. This article ...examines the aesthetic reach of Pessoa’s threefold process to understand how the poet’s early work in English conceptualizes the abstract feelings and expressions that would eventually allow his heteronyms “to feel everything in all possible ways.” Analyzing the collection through each of these parameters reveals the breadth of Pessoa’s aspirations for sensationism as a literary movement. Grounded in new traditions within French symbolism and conceptualized in the English language, both The Mad Fiddler and Sensationism depart from the perceived insularity of Portuguese expression to affirm a more expansive artistic philosophy.
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