While most influenza patients have a self-limited respiratory illness, 5–10% of hospitalized patients develop severe disease requiring ICU admission. The aim of this study was to identify ...influenza-specific factors associated with ICU admission and mortality. Furthermore, influenza-specific pulmonary bacterial, fungal and viral co-infections were investigated.
199 influenza patients, admitted to two academic hospitals in the Netherlands between 01-10-2015 and 01-04-2016 were investigated of which 45/199 were admitted to the ICU.
A history of Obstructive/Central Sleep Apnea Syndrome, myocardial infarction, dyspnea, influenza type A, BMI > 30, the development of renal failure and bacterial and fungal co-infections, were observed more frequently in patients who were admitted to the ICU, compared with patients at the normal ward. Co-infections were evident in 55.6% of ICU-admitted patients, compared with 20.1% of patients at the normal ward, mainly caused by Staphylococcus aureus, Streptococcus pneumoniae, and Aspergillus fumigatus. Non-survivors suffered from diabetes mellitus and (pre-existent) renal failure more often.
The current study indicates that a history of OSAS/CSAS, myocardial infarction and BMI > 30 might be related to ICU admission in influenza patients. Second, ICU patients develop more pulmonary co-infections. Last, (pre-existent) renal failure and diabetes mellitus are more often observed in non-survivors.
•A history of OSAS/CSAS, myocardial infarction and BMI > 30 are risk factors for ICU admission.•Non-survivors suffer more often from diabetes mellitus and (pre-existent) renal failure.•ICU patients develop renal failure and bacterial/fungal co-infections more often.
The effect of extended adjuvant aromatase inhibition in hormone receptor-positive breast cancer after sequential endocrine therapy of tamoxifen followed by an aromatase inhibitor for a 5-year ...treatment period still needs clarification. To address this issue, we began the DATA study to assess different durations of anastrozole therapy after tamoxifen.
DATA was a prospective, randomised, open-label, multicentre, phase 3 study done in 79 hospitals in the Netherlands. We randomly assigned postmenopausal women with hormone receptor-positive early breast cancer with no signs of disease recurrence after 2–3 years of adjuvant tamoxifen to either 3 or 6 years of anastrozole treatment (1 mg orally once a day) in a 1:1 ratio. We used TENALEA (Trans European Network for Clinical Trials Services) for the randomisation procedure. Stratification factors were nodal status, hormone receptor status, HER2 status, and tamoxifen treatment duration. The primary study endpoint of this analysis was disease-free survival starting beyond 3 years after randomisation (adapted disease-free survival). Here we report the final analysis from the DATA trial, which is registered with ClinicalTrials.gov, number NCT00301457.
Between June 28, 2006, and Aug 10, 2009, we screened 1912 patients of whom 955 were assigned to the 3-year group and 957 to the 6-year anastrozole treatment group. 1860 patients were eligible (931 in the 6-year group and 929 in the 3-year group) and 1660 were disease free 3 years after randomisation. The 5-year adapted disease-free survival was 83·1% (95% CI 80·0–86·3) in the 6-year group and 79·4% (76·1–82·8) in the 3-year group (hazard ratio HR 0·79 95% CI 0·62–1·02; p=0·066). Patients in the 6-year treatment group had more adverse events than those in the 3-year treatment group, including all-grade arthralgia or myalgia (478 58% of 827 in the 6-year treatment group vs 438 53% of 833 in the 3-year treatment group) and osteopenia or osteoporosis (173 21% vs 137 16%).
We cannot recommend the use of extended adjuvant aromatase inhibition after 5 years of sequential endocrine therapy in all postmenopausal women with hormone receptor-positive breast cancer.
AstraZeneca.
There is little evidence that supports the registered high dose of dexamethasone used around docetaxel. However, this high dose is associated with considerable side effects. This study evaluates the ...feasibility of reducing the prophylactic oral dosage of dexamethasone around docetaxel infusion.
Eligible patients had a histologically confirmed diagnosis of prostate or breast cancer and had received at least three cycles of docetaxel as monotherapy or combination therapy. Prophylactic dexamethasone around docetaxel infusion was administered in a de-escalating order per cohort of patients. Primary endpoint was the occurrence of grade III/IV fluid retention and hypersensitivity reactions (HSRs).
Of the 46 enrolled patients, 39 were evaluable (prostate cancer (
= 25), breast cancer (
= 14). In patients with prostate cancer, the dosage of dexamethasone was reduced to a single dose of 4 mg; in patients with breast cancer, the dosage was reduced to a 3-day schedule of 4 mg-8 mg-4 mg once daily, after which no further reduction has been tested. None of the 39 patients developed grade III/IV fluid retention or HSR. One patient (2.6%) had a grade 1 HSR, and there were six patients (15.4%) with grade I or II edema. There were no differences in quality of life (QoL) between cohorts.
It seems that the prophylactic dose of dexamethasone around docetaxel infusion can be safely reduced with respect to the occurrence of grade III/IV HSRs or the fluid retention syndrome.
The treatment landscape has completely changed for advanced melanoma. We report survival outcomes and the differential impact of prognostic factors over time in daily clinical practice.
From a Dutch ...nationwide population-based registry, patients with advanced melanoma diagnosed from 2013 to 2017 were analysed (n = 3616). Because the proportional hazards assumption was violated, a multivariable Cox model restricted to the first 6 months and a multivariable landmark Cox model from 6 to 48 months were used to assess overall survival (OS) of cases without missing values. The 2017 cohort was excluded from this analysis because of the short follow-up time.
Median OS of the 2013 and 2016 cohort was 11.7 months (95% confidence interval CI: 10.4–13.5) and 17.7 months (95% CI: 14.9–19.8), respectively. Compared with the 2013 cohort, the 2016 cohort had superior survival in the Cox model from 0 to 6 months (hazard ratio HR = 0.55 95% CI: 0.43–0.72) and in the Cox model from 6 to 48 months (HR = 0.68 95% CI: 0.57–0.83). Elevated lactate dehydrogenase levels, distant metastases in ≥3 organ sites, brain and liver metastasis and Eastern Cooperative Oncology Group performance score of ≥1 had stronger association with inferior survival from 0 to 6 months than from 6 to 48 months. BRAF-mutated melanoma had superior survival in the first 6 months (HR = 0.50 95% CI: 0.42–0.59).
Prognosis for advanced melanoma in the Netherlands has improved from 2013 to 2016. Prognostic importance of most evaluated factors was higher in the first 6 months after diagnosis. BRAF-mutated melanoma was only associated with superior survival in the first 6 months.
•Overall survival of patients with advanced melanoma improved from 2013 to 2016.•Most prognostic factors had the highest impact on survival in the first 6 months.•Over one-third patients with advanced melanoma had brain metastases and/or Eastern Cooperative Oncology Group performance score of ≥2.•Treatment completely shifted to anti-PD-1, BRAFi plus MEKi and ipilimumab plus nivolumab.
Many recipients of lung transplants from brain-dead donors develop bronchiolitis obliterans, a manifestation of chronic rejection. It has been shown that brain death increases inflammatory mediators ...and accelerates acute rejection in kidney, liver, and heart transplants. In this study, the authors investigated the hypothesis that brain death increases inflammatory mediators in the donor lung and subsequently aggravates chronic rejection of the lungs after transplantation in rats.
Brain death was induced in F344 rats by inflation of a subdurally placed balloon catheter. After 6 hr, donor lungs were assessed for influx of leukocytes, expression of cell adhesion molecules, and cytokine mRNA expression. For assessment of the lung after transplantation, lungs from brain-dead F344 rats were transplanted into WKY rats. Lung function after transplantation was monitored by chest radiographs during an observation period of 100 days. At the end of this period, the lungs were histologically examined; also, cytokine mRNA expression was measured. Lungs from ventilated living donors and living donors served as controls.
After 6 hr of brain death, influx of polymorphonuclear cells and macrophages and expression of vascular cell adhesion molecule-1 in the donor lungs was increased. After transplantation at postoperative day 100, the lung function was significantly decreased compared with allografts from living donors. In the lung allografts from brain-dead donors, histologic symptoms of chronic rejection were obvious, including severe intimal hyperplasia but without bronchiolitis obliterans. Interleukin-2 mRNA was significantly increased in allografts from brain-dead donors compared with living donors.
This study shows that brain death induces an inflammatory response in the donor lung and subsequently aggravates chronic rejection after transplantation. This may explain the clinical difference in long-term function between lungs from cadaveric donors and living donors.
A benchmark control problem was developed for a special session of the IFAC Workshop on Engine and Powertrain Control, Simulation and Modeling (E-COSM 12), held in Rueil-Malmaison, France, in October ...2012. The online energy management of a plug-in hybrid-electric vehicle was to be developed by the benchmark participants. The simulator, provided by the benchmark organizers, implements a model of the GM Voltec powertrain. Each solution was evaluated according to several metrics, comprising of energy and fuel economy on two driving profiles unknown to the participants, acceleration and braking performance, computational performance. The nine solutions received are analyzed in terms of the control technique adopted (heuristic rule-based energy management vs. equivalent consumption minimization strategies, ECMS), battery discharge strategy (charge depleting–charge sustaining vs. blended mode), ECMS implementation (vector-based vs. map-based), ways to improve the implementation and improve the computational performance. The solution having achieved the best combined score is compared with a global optimal solution calculated offline using the Pontryagin's minimum principle-derived optimization tool HOT.
Objectives
To investigate the role of specialised genitourinary multidisciplinary team meetings (MDTMs) in decision‐making and identify factors that influence the probability of receiving a treatment ...plan with curative intent for patients with muscle invasive bladder cancer (MIBC).
Patients and methods
Data relating to patients with cT2‐4aN0/X‐1 M0 urothelial cell carcinoma, diagnosed between November 2017 and October 2019, were selected from the nationwide, population‐based Netherlands Cancer Registry (‘BlaZIB study’). Curative treatment options were defined as radical cystectomy (RC) with or without neoadjuvant chemotherapy, chemoradiation or brachytherapy. Multilevel logistic regression analyses were used to examine the association between MDTM factors and curative treatment advice and how this advice was followed.
Results
Of the 2321 patients, 2048 (88.2%) were discussed in a genitourinary MDTM. Advanced age (>80 years) and poorer World Health Organization performance status (score 1–2 vs 0) were associated with no discussion (P < 0.001). Being discussed was associated with undergoing treatment with curative intent (odds ratio OR 3.0, 95% confidence interval CI 1.9–4.9), as was the involvement of a RC hospital (OR 1.70, 95% CI 1.09–2.65). Involvement of an academic centre was associated with higher rates of bladder‐sparing treatment (OR 2.05, 95% CI 1.31–3.21). Patient preference was the main reason for non‐adherence to treatment advice.
Conclusions
For patients with MIBC, the probability of being discussed in a MDTM was associated with age, performance status and receiving treatment with curative intent, especially if a representative of a RC hospital was present. Future studies should focus on the impact of MDTM advice on survival data.
CONTEXT Understanding the risk of human immunodeficiency virus (HIV) transmission
through breastfeeding is essential for advising HIV-infected mothers and formulating
public health policy ...recommendations. OBJECTIVE To measure the frequency, timing, and risk factors of HIV transmission
through breast milk. DESIGN Prospective cohort study conducted between 1994 and 1997, with follow-up
of infants through 24 months of age. SETTING Postnatal clinic of tertiary care hospital, Blantyre, Malawi. PARTICIPANTS A total of 672 infants (HIV-negative at birth) born to HIV-infected
women who had not received antiretroviral drugs during or after pregnancy. MAIN OUTCOME MEASURE Incidence of HIV in breastfed infants by age and maternal and infant
risk factors for HIV transmission, using proportional hazard models to derive
risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS Forty-seven children became HIV-infected while breastfeeding but none
after breastfeeding had stopped. The cumulative infection rate while breastfeeding,
from month 1 to the end of months 5, 11, 17, and 23, was 3.5%, 7.0%, 8.9%,
and 10.3%, respectively. Incidence per month was 0.7% during age 1 to 5 months,
0.6% during age 6 to 11 months, and 0.3% during age 12 to 17 months (P=.01 for trend). The only factors significantly associated
with low risk of postnatal HIV transmission in a multivariate model were high
maternal parity (RR, 0.23; 95% CI, 0.09-0.56) and older maternal age (RR,
0.44; 95% CI, 0.23-0.84). CONCLUSIONS Our data suggest that the risk of HIV infection is highest in the early
months of breastfeeding, which should be considered in formulating breastfeeding
policy recommendations.
The development of new catalyst materials for energy-efficient chemical synthesis is critical as over 80% of industrial processes rely on catalysts, with many of the most energy-intensive processes ...specifically using heterogeneous catalysis. Catalytic performance is a complex interplay of phenomena involving temperature, pressure, gas composition, surface composition, and structure over multiple length and time scales. In response to this complexity, the integrated approach to heterogeneous dilute alloy catalysis reviewed here brings together materials synthesis, mechanistic surface chemistry, reaction kinetics, in situ and operando characterization, and theoretical calculations in a coordinated effort to develop design principles to predict and improve catalytic selectivity. Dilute alloy catalystsin which isolated atoms or small ensembles of the minority metal on the host metal lead to enhanced reactivity while retaining selectivityare particularly promising as selective catalysts. Several dilute alloy materials using Au, Ag, and Cu as the majority host element, including more recently introduced support-free nanoporous metals and oxide-supported nanoparticle “raspberry colloid templated (RCT)” materials, are reviewed for selective oxidation and hydrogenation reactions. Progress in understanding how such dilute alloy catalysts can be used to enhance selectivity of key synthetic reactions is reviewed, including quantitative scaling from model studies to catalytic conditions. The dynamic evolution of catalyst structure and composition studied in surface science and catalytic conditions and their relationship to catalytic function are also discussed, followed by advanced characterization and theoretical modeling that have been developed to determine the distribution of minority metal atoms at or near the surface. The integrated approach demonstrates the success of bridging the divide between fundamental knowledge and design of catalytic processes in complex catalytic systems, which can accelerate the development of new and efficient catalytic processes.
Purpose
In the phase II DIRECT study a fasting mimicking diet (FMD) improved the clinical response to neoadjuvant chemotherapy as compared to a regular diet. Quality of Life (QoL) and illness ...perceptions regarding the possible side effects of chemotherapy and the FMD were secondary outcomes of the trial.
Methods
131 patients with HER2-negative stage II/III breast cancer were recruited, of whom 129 were randomly assigned (1:1) to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and the day of neoadjuvant chemotherapy. The European Organisation for Research and Treatment of Cancer (EORTC) questionnaires EORTC-QLQ-C30 and EORTC-QLQ-BR23; the Brief Illness Perception Questionnaire (BIPQ) and the Distress Thermometer were used to assess these outcomes at baseline, halfway chemotherapy, before the last cycle of chemotherapy and 6 months after surgery.
Results
Overall QoL and distress scores declined during treatment in both arms and returned to baseline values 6 months after surgery. However, patients’ perceptions differed slightly over time. In particular, patients receiving the FMD were less concerned and had better understanding of the possible adverse effects of their treatment in comparison with patients on a regular diet. Per-protocol analyses yielded better emotional, physical, role, cognitive and social functioning scores as well as lower fatigue, nausea and insomnia symptom scores for patients adherent to the FMD in comparison with non-adherent patients and patients on their regular diet.
Conclusions
FMD as an adjunct to neoadjuvant chemotherapy appears to improve certain QoL and illness perception domains in patients with HER2-negative breast cancer.
Trialregister
ClinicalTrials.gov Identifier: NCT02126449.
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