Introduction: Stereotactic MR-guided Adaptive RadioTherapy (SMART) is a novel process to treat pancreatic tumors. We present an update of the data from our prospective registry of SMART for ...pancreatic tumors. Materials and methods: After the establishment of the SMART indication in a multidisciplinary board, we included all patients treated for pancreatic tumors. Primary endpoints were acute and late toxicities. Secondary endpoints were survival outcomes (local control, overall survival, distant metastasis free survival) and dosimetric advantages of adaptive process on targets volumes and OAR. Results: We included seventy consecutive patients in our cohort between October 2019 and April 2022. The prescribed dose was 50 Gy in 5 consecutive fractions. No severe acute SMART related toxicity was noted. Acute and late Grade ≤ 2 gastro intestinal were low. Daily adaptation significantly improved PTV and GTV coverage as well as OAR sparing. With a median follow-up of 10.8 months since SMART completion, the median OS, 6-months OS, and 1-year OS were 20.9 months, 86.7% (95% CI: (75−93%), and 68.6% (95% CI: (53−80%), respectively, from SMART completion. Local control at 6 months, 1 year, and 2 years were, respectively, 96.8 % (95% CI: 88−99%), 86.5 (95% CI: 68−95%), and 80.7% (95% CI: 59−92%). There was no grade > 2 late toxicities. Locally Advanced Pancreatic Cancers (LAPC) and Borderline Resectable Pancreatic Cancers (BRPC) patients (52 patients) had a median OS, 6-months OS, and 1-year OS from SMART completion of 15.2 months, 84.4% (95% CI: (70−92%)), and 60.5% (95% CI: (42−75%)), respectively. The median OS, 1-year OS, and 2-year OS from initiation of induction chemotherapy were 22.3 months, 91% (95% CI: (78−97%)), and 45.8% (95% CI: (27−63%)), respectively. Twenty patients underwent surgical resection (38.7 % of patients with initially LAPC) with negative margins (R0). Conclusion: To our knowledge, this is the largest series of SMART for pancreatic tumors. The treatment was well tolerated with only low-grade toxicities. Long-term OS and LC rates were achieved. SMART achieved high secondary resection rates in LAPC patients.
Although several health and development indicators have improved significantly in Cambodia, inadequate breastfeeding and inappropriate complementary feeding practices leave many children at high risk ...of malnutrition during the early stages of life. In 2014, the prevalence of wasting and stunting among Cambodian children under 5 were 10% and 32%, respectively. Thus, a strong focus on improving feeding practices within the first 1000 days window to reduce child malnutrition prevalence in Cambodia is needed. This cross-sectional study assessed the current feeding practices among of women of reproductive age, pregnant women, lactating women and children less than 24 months living in six districts from Phnom Penh and two rural provinces in the North East of Cambodia. The nutritional status of pregnant women was poor, with 21.4% having a Middle Upper arm circumference below 23 cm. While breastfeeding was predominant within the first 6 months of age in every district, feeding practices of pregnant women and children were a concern, as >70% of the children were not meeting the minimum acceptable diet, and most of the women did not improve their diet during pregnancy. Inadequate nutrition during the first 1000 days is highly prevalent in Cambodia. A comprehensive national Mother, Infant and Young Child Nutrition strategy needs to be developed and operationalized to improve feeding practices of Cambodian women and children.
The adverse outcomes of malnutrition on the development of a child are well acknowledged as are the broad variety of contextual factors that may impact child nutritional status. Adequate nutrient ...intake and the adoption of appropriate water, sanitation and hygiene measures are largely documented for their positive influence on health. Improved sanitation and protection from human feces can significantly lower the incidence of diarrhea and environmental enteropathy. However, the impact of excessive exposure to animal feces on child health is less well documented.
This study tests the hypothesis that there is a positive association between exposure to animal feces, morbidity and anthropometric outcomes in children under 5 years of age, in Cambodia. It aims to improve insights that can contribute to discerning high-impact policies that promote children can develop to their full potential.
Data for this study was drawn from the third follow-up round of the MyHealth project cohort study that is conducted in six districts of three Cambodian provinces (Phnom Penh, Kratie and Ratanak Kiri). The analysis included a sample of 639 children under 5 years of age.
The presence of livestock and more particularly, pigs near the main household dwelling was found a risk factor associated with
infection (23%).
infection was found to be a protective factor for acute diarrhea, yet, associated with stunting in the univariate model.
Preventive measures that protect from extensive exposure to animal feces may be most effective to prevent infection with
and consequent stunting, thereby improving the potential for a healthy development in young Cambodian children. The results support the need for cross-sector policy measures that reinforce comprehensive early childhood interventions towards improving nutritional status as part of a wider set of child welfare and development measures.
Reduction of neonatal and under-five mortality rates remains a primary target in the achievement of universal health goals, as evident in renewed investments of Sustainable Development Goals. Various ...studies attribute declines in mortality to the combined effects of improvements in health care practices and changes in socio-economic factors. Since the early nineties, Cambodia has managed to evolve from a country devastated by war to a nation soon to enter the group of middle income countries. Cambodia's development efforts are reflected in some remarkable health outcomes such as a significant decline in child mortality rates and the early achievement of related Millennium Development Goals. An achievement acknowledged through the inclusion of Cambodia as one of the ten fast-track countries in the Partnership for Maternal, Newborn and Child Health. This study aims to highlight findings from the field so to provide evidence for future programming and policy efforts. It will be argued that to foster further advances in health, Cambodia will need to keep neonatal survival and health high on the agenda and tackle exacerbating inequities that arise from a pluralistic health system with considerable regional differences and socio-economic disparities.
Data was drawn from Demographic Health Surveys (2000, 2005, 2010, 2014). Information on a series of demographic and socio-economic household characteristics and on child anthropometry, feeding practices and child health were collected from nationally representative samples. To reach the required sample size, live-births that occurred over the past 10 years before the date of the interview were included. Demographic variables included: gender of the child, living area (urban or rural; four ecological regions (constructed by merging provinces and the capital), mother's age at birth (<20, 20-35, 35+), birth interval (long, short) and birth order (1st, 2-3, 4-6, 7+). Socio-economic variables included: mother education level (none, primary, secondary+) and household wealth (asset-based index). Data on antenatal care, tetanus injection and skilled assistance at birth were used for the mother's last child. Between 2000 and 2014, Cambodia achieved a considerable reduction in neonatal mortality (46% reduction rate). By 2014, gender inequities became almost non-existent (for all measures of equality); inequity related to mother's education decreased for all time periods; improvements were observed for differences in neonatal mortality by preceding birth interval; and a reduction in neonatal mortality rates could be noted among all the regional subgroups. Inequities increased between mothers who had limited antenatal care and those who received more than four antenatal care visits. In most scale indicators, the Slope Index of Inequality and Relative Index of Inequality estimates for all four rounds of the survey suggest inequity exacerbated in deprived communities. Also, wealth and residence (urban/rural divide) continued to be major determinants in neonatal mortality rates and related inequity trends.
Analysis highlighted some of the complex patterns and determinants of neonatal mortality, in Cambodia. There has been a considerable decline in neonatal mortality which echoes global trends. Our analysis reveals that despite these advances, additional socio-economic and demographic characteristics considerably affected neonatal mortality rates and its inequities. There continue to be pockets of vulnerable groups that are lagging behind. This analysis highlights the determinants along the urban-rural and rich-poor divides in neonatal mortality inequities and how these affect access to and utilization of quality basic health services. This calls for future policy and programming efforts to be deliberate in their equity approach. Quality improvements in health services and targeted interventions for specific socio-economic groups will be required to further accelerate progress in reducing neonatal mortality and address Cambodia's pressing unfinished agenda in health.
Malnutrition remains a serious health problem in Cambodia with over 10% of children less than five years of age suffering from acute malnutrition. In addition to the presence of nutritional edema, ...two indicators are recommended by the World Health Organization for the diagnosis of acute malnutrition: weight-for-height Z-scores (WHZ; with acute malnutrition defined as WHZ < −2 Z-score) and mid-upper arm circumference (MUAC, with acute malnutrition defined as MUAC < 12.5 cm). Earlier, we showed that WHZ and MUAC identified different subgroups of children with acute malnutrition. To explore factors associated with both indicators of acute malnutrition, we analyzed baseline data from a longitudinal study in three provinces in Cambodia: Phnom Penh (capital, urban environment), Kratie (rural province), and Ratanakiri (hilly, rural province). Data was available for 4381 children below 30 months of age. Malnutrition rates were higher in the two rural provinces than in the capital. Although both MUAC and WHZ showed gender bias, with MUAC identifying more girls, and WHZ identifying more boys with acute malnutrition, the gender effect was strongest for MUAC. The gender bias of MUAC diminished with older age, but remained significant up to 30 months of age. Only using both MUAC and WHZ as indicators resulted in gender neutral identification of acute malnutrition. WHZ alone always identified more children with acute malnutrition than MUAC alone. In Phnom Penh, MUAC alone identified only 11% with acute malnutrition in addition to WHZ. To conclude, both MUAC and WHZ showed gender bias in this cohort of Cambodian children. In Cambodia, implementation of a MUAC-only or a WHZ-only program for the identification of acute malnutrition would be unethical as it will lead to many children remaining undiagnosed.
Background
More than 10% of HER2-positive metastatic breast cancer (mBC) will develop Central Nervous System (CNS) metastases as first and isolated site of relapse on trastuzumab and pertuzumab ...first-line therapy. However, few clinical data are available to guide the best strategy in this setting.
Methods
Patients experiencing isolated CNS progression on trastuzumab and pertuzumab first-line therapy were retrospectively identified from the French Epidemiological Strategy and Medical Economics (ESME) real-life database between 2008 and 2016.
Results
Among 995 patients treated with first-line trastuzumab and pertuzumab for HER2-positive mBC, 132 patients (13%) experienced isolated CNS progression with a median time of 12 months after mBC diagnosis. Twelves patients did not receive any treatment and were excluded from the analysis. Among the 120 patients considered, 76 (63%) received CNS-directed local therapy, 73 (60%) continued trastuzumab and pertuzumab, whereas 47 (39%) started another systemic treatment.
After a median follow-up of 21 months, there was no difference in progression-free survival for patient who continued trastuzumab–pertuzumab or switched to another systemic treatment. In multivariate analysis, trastuzumab–pertuzumab continuation was associated with longer OS (HR 0,28 IC 95%: 0,14–0,54
p
< 0,001). mOS was not reached (95% 37.6-NE) and was 23.2 months (95% CI 15.5–53.6) in patients who continued trastuzumab and pertuzumab therapy and in patients who switched for another systemic therapy, respectively.
Conclusion
In this real-life cohort, trastuzumab–pertuzumab continuation after local treatment for isolated CNS progression did not negatively impact PFS and OS. Prospective trials and assessment of new strategies are warranted in this specific situation.
Palbociclib is a good candidate for therapeutic drug monitoring (TDM) due to its narrow therapeutic range and frequency of toxicities, particularly high-grade neutropenia. In this prospective, ...bicentric clinical trial, we evaluated the palbociclib exposure−toxicity relationship and determined the relevant sources of palbociclib pharmacokinetic variability, including drug−drug interactions (DDI). We followed 58 patients (mean age: 62.9 years) for 1 year. The geometric median of palbociclib plasma trough concentration (Ctrough) was 74.1 ng/mL. Neutropenia occurred in 70.7% of patients (high grade in 67.2% of patients). High-grade neutropenia occurrence during the first two palbociclib cycles was higher in patients with lower neutrophil count at initiation (p = 0.002). Palbociclib plasma Ctrough was correlated with high-grade neutropenia occurrence during the first two cycles (p = 0.024, OR 5.51). Co-treatment with agents that may interfere with palbociclib PK significantly influenced palbociclib Ctrough (p < 0.05). CYP3A4/P-glycoprotein inhibitors increased by 25% palbociclib Ctrough (p = 0.035), while antacids reduced it by 20% (p = 0.036). However, DDI did not have any significant effect on high-grade neutropenia occurrence (p > 0.05). This study confirms the major role of TDM to manage palbociclib safe use from the first week of treatment, particularly the significant incidence of hematological toxicity. Moreover, this first dedicated prospective study confirmed the importance of characterizing co-treatments to limit the DDI risk with oral-targeted therapies.
Hepatitis B is a leading cause of morbidity and mortality worldwide. In view of the World Health Organization 2030 targets, effective screening of chronic infection is crucial. We have assessed the ...prevalence and risk factors of hepatitis B surface antigen in adults presenting for screening.
Free-of-charge and anonymous services for simultaneous hepatitis B, hepatitis C, human immunodeficiency virus and syphilis screening and counseling were provided in four facilities in northern Thailand. Analyses were performed separately in clients born before integration into the 1992 hepatitis B vaccine Thailand's Expanded Program on Immunization and in clients born afterwards.
Between October 2015 and August 2020, hepatitis B surface antigen prevalence was 7.2 % (185/2578) in clients born before 1992 (95 % confidence interval CI = 6.2%-8.2 %). In the multivariable analysis, characteristics independently associated with a higher risk of infection were being born male (adjusted odds ratio aOR = 1.49, 95 % CI = 1.10-2.01) and being part of a hill tribe (aOR = 1.65, 95 % CI = 1.01-2.70). Forty-two percent were unaware of their infection. In clients born in 1992 or afterwards, prevalence was 1.5 % (43/2933) (95 % CI = 1.1%-2.0 %) and characteristics independently associated with a higher risk were being born between 1992 and 1995 (aOR = 1.90, 95 % CI = 1.00-3.61), being born male (aOR = 2.60, 95 % CI = 1.34-5.07), being part of a hill tribe (aOR = 5.09, 95 % CI = 2.52-10.26) and having ever injected drugs (aOR = 4.33, 95 % CI = 1.23-15.24).
Risk factor-based screening would miss many chronic hepatitis cases. Screening all adults once in their lifetime may be beneficial until the second generation of immunized infants have reached adult age.
In this paper, we present integrated lead-free energy converters based on a suitable MEMS fabrication process with an embedded layer of LiNbO3. The fabrication technology has been developed to ...realize micromachined self-generating transducers to convert kinetic energy into electrical energy. The process proposed presents several interesting features with the possibility of realizing smaller scale devices, integrated systems, miniaturized mechanical and electromechanical sensors, and transducers with an active layer used as the main conversion element. When the system is fabricated in the typical cantilever configuration, it can produce a peak-to-peak open-circuit output voltage of 0.208 V, due to flexural deformation, and a power density of 1.9 nW·mm−3·g−2 at resonance, with values of acceleration and frequency of 2.4 g and 4096 Hz, respectively. The electromechanical transduction capability is exploited for sensing and power generation/energy harvesting applications. Theoretical considerations, simulations, numerical analyses, and experiments are presented to show the proposed LiNbO3-based MEMS fabrication process suitability. This paper presents substantial contributions to the state-of-the-art, proposing an integral solution regarding the design, modelling, simulation, realization, and characterization of a novel transducer.
The study assessed the trends of nutritional status of children under age five in Cambodia over four DHS surveys from 2000 to 2014 and the contribution of socioeconomic and demographic factors to its ...changes. Undernutrition was a public health problem in all surveys. Despite consistent improvement over the years, stunting still affected 32.5% of children in 2014. Wasting prevalence did not improve since 2005 and affected 9.6% of children under five in 2014. Low wealth and mother education; and rural residence contributed to undernutrition. In 2014; wealth status was the main socioeconomic factor associated with undernutrition and the nutritional status of children was strongly related to that of their mothers. Anemia prevalence was high and after a decrease between 2000 and 2005 remained at 45%. The prevalence of overweight was less than 10% and did not change over the years despite an increasing trend in the richest households of urban areas. Persistent inequalities in child undernutrition call for action, giving priority to the most vulnerable households to ensure availability and access to nutrient-rich foods for women and children through nutrition-sensitive and nutrition-specific programs. The recent increase of overweight in the richest populations must also be considered in Cambodian health policies.
PDF
