Under-five mortality is still a major health issue in many developing countries like Tanzania. To achieve the Sustainable Development Goal target of ending preventable child deaths in Tanzania, a ...detailed understanding of the risk factors for under-five deaths is essential to guide targeted interventions. This study aimed to investigate trends and determinants of neonatal, post-neonatal, infant, child and under-five mortalities in Tanzania from 2004 to 2016.
The study used combined data from the 2004-2005, 2010 and 2015-2016 Tanzania Demographic and Health Surveys, with a sample of 25,951 singletons live births and 1585 under-five deaths. We calculated age-specific mortality rates, followed by an assessment of trends and determinants (community, socioeconomic, individual and health service) of neonatal, postneonatal, infant, child and under-five mortalities in Cox regression models. The models adjusted for potential confounders, clustering and sampling weights.
Between 2004 and 2016, we found that neonatal mortality rate remained unchanged, while postneonatal mortality and child mortality rates have halved in Tanzania. Infant mortality and under-five mortality rates have also declined. Mothers who gave births through caesarean section, younger mothers (< 20 years), mothers who perceived their babies to be small or very small and those with fourth or higher birth rank and a short preceding birth interval (≤2 years) reported higher risk of neonatal, postneonatal and infant mortalities.
Our study suggests that there was increased survival of children under-5 years in Tanzania driven by significant improvements in postneonatal, infant and child survival rates. However, there remains unfinished work in ending preventable child deaths in Tanzania.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Thoracic surgeries involving resection of lung tissue pose a risk of severe postoperative pulmonary complications, including acute respiratory distress syndrome (ARDS) and respiratory failure. Lung ...resections require one-lung ventilation (OLV) and, thus, are at higher risk of ventilator-induced lung injury (VILI) attributable to barotrauma and volutrauma in the one ventilated lung, as well as hypoxemia and reperfusion injury on the operated lung. Further, we also aimed to assess the differences in localized and systemic markers of tissue injury/inflammation in those who developed respiratory failure after lung surgery versus matched controls who did not develop respiratory failure. We aimed to assess the different inflammatory/injury marker patterns induced in the operated and ventilated lung and how this compared to the systemic circulating inflammatory/injury marker pattern. A case-control study nested within a prospective cohort study was performed. Patients with postoperative respiratory failure after lung surgery (
= 5) were matched with control patients (
= 6) who did not develop postoperative respiratory failure. Biospecimens (arterial plasma, bronchoalveolar lavage separately from ventilated and operated lungs) were obtained from patients undergoing lung surgery at two timepoints: (1) just prior to initiation of OLV and (2) after lung resection was completed and OLV stopped. Multiplex electrochemiluminescent immunoassays were performed for these biospecimen. We quantified 50 protein biomarkers of inflammation and tissue injury and identified significant differences between those who did and did not develop postoperative respiratory failure. The three biospecimen types also display unique biomarker patterns.
Multidrug resistance (MDR) is one of the key barriers in chemotherapy, leading to the generation of insensitive cancer cells towards administered therapy. Genetic and epigenetic alterations of the ...cells are the consequences of MDR, resulted in drug resistivity, which reflects in impaired delivery of cytotoxic agents to the cancer site. Nanotechnology-based nanocarriers have shown immense shreds of evidence in overcoming these problems, where these promising tools handle desired dosage load of hydrophobic chemotherapeutics to facilitate designing of safe, controlled and effective delivery to specifically at tumor microenvironment. Therefore, encapsulating drugs within the nano-architecture have shown to enhance solubility, bioavailability, drug targeting, where co-administered P-gp inhibitors have additionally combat against developed MDR. Moreover, recent advancement in the stimuli-sensitive delivery of nanocarriers facilitates a tumor-targeted release of the chemotherapeutics to reduce the associated toxicities of chemotherapeutic agents in normal cells. The present article is focused on MDR development strategies in the cancer cell and different nanocarrier-based approaches in circumventing this hurdle to establish an effective therapy against deadliest cancer disease.
•MDR phenomenon accounts for significant treatment failure of conventional chemotherapeutics•Nanocarrier holds the potential to deliver chemotherapeutics within the MDR cancer microenvironment for improved efficacy•Nanotechnologies have made considerable contributions towards the reduction of associated toxic effects of chemotherapeutics•Nanocarrier have progressed to clinical trials for a better tomorrow to overcome MDR cancer
Metabolic alterations in malignant cells play a vital role in tumor initiation, proliferation, and metastasis. Biofluids from patients with non–small cell lung cancer (NSCLC) harbor metabolic ...biomarkers with potential clinical applications. In this study, we assessed the changes in the metabolic profile of patients with early-stage NSCLC using mass spectrometry and nuclear magnetic resonance spectroscopy before and after surgical resection. A single cohort of 35 patients provided a total of 29 and 32 pairs of urine and serum samples, respectively, pre-and post-surgery. We identified a profile of 48 metabolites that were significantly different pre- and post-surgery: 17 in urine and 31 in serum. A higher proportion of metabolites were upregulated than downregulated post-surgery (p < 0.01); however, the median fold change (FC) was higher for downregulated than upregulated metabolites (p < 0.05). Purines/pyrimidines and proteins had a larger dysregulation than other classes of metabolites (p < 0.05 for each class). Several of the dysregulated metabolites have been previously associated with cancer, including leucyl proline, asymmetric dimethylarginine, isopentenyladenine, fumaric acid (all downregulated post-surgery), as well as N6-methyladenosine and several deoxycholic acid moieties, which were upregulated post-surgery. This study establishes metabolomic analysis of biofluids as a path to non-invasive diagnostics, screening, and monitoring in NSCLC.
Every year, close to two million people world-wide are diagnosed with and die of lung cancer. Most patients present with advanced-stage cancer with limited curative options and poor prognosis. ...Diagnosis of lung cancer at an early stage provides the best chance for a cure. Low- dose CT screening of the chest in the high-risk population is the current standard of care for early detection of lung cancer. However, CT screening is invasive due to radiation exposure and carries the risk of unnecessary biopsies in non-cancerous tumors. In this pilot study, we present metabolic alterations observed in sputum and breath condensate of the
same
population of early- stage non-small cell lung cancer (NSCLC) patients cancer before and after surgical resection (SR), which could serve as noninvasive diagnostic tool. Exhaled breath condensate (EBC) (n=35) and sputum (n=15) were collected from early-stage non-small cell lung cancer (NSCLC) patients before and after SR. Median number of days for EBC and sputum collection before and after SR were 7 and 42; and 7 and 36 respectively Nuclear magnetic resonance (NMR) and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) were used to analyze the metabolic profile of the collected samples. A total of 26 metabolites with significant alteration post SR were identified, of which 14 (54%) were lipids and 12 constituted nine different chemical metabolite classes. Eighteen metabolites (69%) were significantly upregulated and 8 (31%) were downregulated. Median fold change for all the up- and downregulated metabolites (LC-QTOF-MS) were 10 and 8, respectively. Median fold change (MFC) in concentration of all the up- and downregulated metabolites (NMR) were 0.04 and 0.27, respectively. Furthermore, glucose (median fold change, 0.01, p=0.037), adenosine monophosphate (13 log fold, p=0.0037) and N1, N12- diacetylspermine (8 log fold p=0.011) sputum levels were significantly increased post-SR. These identified sputa and EBC indices of altered metabolism could serve as basis for further exploration of biomarkers for early detection of lung cancer, treatment response, and targets for drug discovery. Validation of these promising results by larger clinical studies is warranted.
Background Metabolomics is a potential means for biofluid-based lung cancer detection. We conducted a non-targeted, data-driven assessment of plasma from early-stage non-small cell lung cancer ...(ES-NSCLC) cases versus cancer-free controls (CFC) to explore and identify the classes of metabolites for further targeted metabolomics biomarker development. Methods Plasma from 250 ES-NSCLC cases and 250 CFCs underwent ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) in positive and negative electrospray ionization (ESI) modes. Molecular feature extraction, formula generation, and find-by-ion tools annotated metabolic entities. Analysis was restricted to endogenous metabolites present in greater than or equal to 80% of samples. Unsupervised hierarchical cluster analysis identified clusters of metabolites. The metabolites with the strongest correlation with the principal component of each cluster were included in logistic regression modeling to assess discriminatory performance with and without adjustment for clinical covariates. Results A total of 1900 UHPLC-QTOF-MS assessments identified 1667 and 2032 endogenous metabolites in the ESI-positive and ESI-negative modes, respectively. After data filtration, 676 metabolites remained, and 12 clusters of metabolites were identified from each ESI mode. Multivariable logistic regression using the representative metabolite from each cluster revealed effective classification of cases from controls with overall diagnostic accuracy of 91% (ESI positive) and 94% (ESI negative). Metabolites of interest identified for further targeted analysis include the following: 1b, 3a, 12a-trihydroxy-5b-cholanoic acid, pyridoxamine 5'-phosphate, sphinganine 1-phosphate, gamma-CEHC, 20-carboxy-leukotriene B4, isodesmosine, and 18-hydroxycortisol. Conclusions Plasma-based metabolomic detection of early-stage NSCLC appears feasible. Further metabolomics studies targeting phospholipid, steroid, and fatty acid metabolism are warranted to further develop noninvasive metabolomics-based detection of early-stage NSCLC. Keywords: Early-stage non-small cell lung cancer, Plasma metabolomics, Early detection, Non-targeted metabolomics
Endobronchial electromagnetic transponder beacons (EMT) provide real-time, precise positional data of moving lung tumors. We report results of a phase 1/2, prospective, single-arm cohort study ...evaluating the treatment planning effects of EMT-guided SABR for moving lung tumors.
Eligible patients were adults, Eastern Cooperative Oncology Group 0 to 2, with T1-T2N0 non-small cell lung cancer or pulmonary metastasis ≤4 cm with motion amplitude ≥5 mm. Three EMTs were endobronchially implanted using navigational bronchoscopy. Four-dimensional free-breathing computed tomography simulation scans were obtained, and end-exhalation phases were used to define the gating window internal target volume. A 3-mm expansion of gating window internal target volume defined the planning target volume (PTV). EMT-guided, respiratory-gated (RG) SABR was delivered (54 Gy/3 fractions or 48 Gy/4 fractions) using volumetric modulated arc therapy. For each RG-SABR plan, a 10-phase image-guided SABR plan was generated for dosimetric comparison. PTV/organ-at-risk (OAR) metrics were tabulated and analyzed using the Wilcoxon signed-rank pair test. Treatment outcomes were evaluated using RECIST (Response Evaluation Criteria in Solid Tumours; version 1.1).
Of 41 patients screened, 17 were enrolled and 2 withdrew from the study. Median age was 73 years, with 7 women. Sixty percent had T1/T2 non-small cell lung cancer and 40% had M1 disease. Median tumor diameter was 1.9 cm with 73% of targets located peripherally. Mean respiratory tumor motion was 1.25 cm (range, 0.53-4.04 cm). Thirteen tumors were treated with EMT-guided SABR and 47% of patients received 48 Gy in 4 fractions while 53% received 54 Gy in 3 fractions. RG-SABR yielded an average PTV reduction of 46.9% (P < .005). Lung V5, V10, V20, and mean lung dose had mean relative reductions of 11.3%, 20.3%, 31.1%, and 20.3%, respectively (P < .005). Dose to OARs was significantly reduced (P < .05) except for spinal cord. At 6 months, mean radiographic tumor volume reduction was 53.5% (P < .005).
EMT-guided RG-SABR significantly reduced PTVs of moving lung tumors compared with image-guided SABR. EMT-guided RG-SABR should be considered for tumors with large respiratory motion amplitudes or those located in close proximity to OARs.
AbstractBackgroundLung cancer is a major cause of global morbidity and mortality. Current low dose CT screening is invasive and its role remains contentious. There are no known biomarkers to monitor ...treatment response, detect disease recurrence and patient selection for adjuvant treatment after curative surgical resection. Hence there is an urgent need to explore non-conventional and noninvasive tools to develop novel biomarkers to improve the outcome of this lethal cancer. MethodsThis is an ongoing exploratory and translational study involving collection of bio fluids from 50 patients with early stage non-small cell lung cancer before and after surgical resection. The primary Objective is to identify cancer specific metabolome in body fluids - sputum, exhaled breath condensate, blood and urine of the patients with early stage non-small. cell lung cancer (NSCLC) using Magnetic Resonance Spectroscopy (MRS) and Mass Spectroscopy (MS). ConclusionThe trajectory of change in metabolic profile of body fluids before and after surgical resection may have potential clinical applications in lung cancer screening, as biomarkers for disease recurrence and exploration of novel targets for therapeutic intervention.
The unequal distribution of academic and professional outcomes between different minority groups is a pervasive issue in many fields, including surgery. The implications of differential attainment ...remain significant, not only for the individuals affected but also for the wider health care system. An inclusive health care system is crucial in meeting the needs of an increasingly diverse patient population, thereby leading to better outcomes. One barrier to diversifying the workforce is the differential attainment in educational outcomes between Black and Minority Ethnic (BME) and White medical students and doctors in the United Kingdom. BME trainees are known to have lower performance rates in medical examinations, including undergraduate and postgraduate exams, Annual Review of Competence Progression, as well as training and consultant job applications. Studies have shown that BME candidates have a higher likelihood of failing both parts of the Membership of the Royal Colleges of Surgeons exams and are 10% less likely to be considered suitable for core surgical training. Several contributing factors have been identified; however, there has been limited evidence investigating surgical training experiences and their relationship to differential attainment. To understand the nature of differential attainment in surgery and to develop effective strategies to address it, it is essential to examine the underlying causes and contributing factors. The Variation in Experiences and Attainment in Surgery Between Ethnicities of UK Medical Students and Doctors (ATTAIN) study aims to describe and compare the factors and outcomes of attainment between different ethnicities of doctors and medical students.
The primary aim will be to compare the effect of experiences and perceptions of surgical education of students and doctors of different ethnicities.
This protocol describes a nationwide cross-sectional study of medical students and nonconsultant grade doctors in the United Kingdom. Participants will complete a web-based questionnaire collecting data on experiences and perceptions of surgical placements as well as self-reported academic attainment data. A comprehensive data collection strategy will be used to collect a representative sample of the population. A set of surrogate markers relevant to surgical training will be used to establish a primary outcome to determine variations in attainment. Regression analyses will be used to identify potential causes for the variation in attainment.
Data collected between February 2022 and September 2022 yielded 1603 respondents. Data analysis is yet to be competed. The protocol was approved by the University College London Research Ethics Committee on September 16, 2021 (ethics approval reference 19071/004). The findings will be disseminated through peer-reviewed publications and conference presentations.
Drawing upon the conclusions of this study, we aim to make recommendations on educational policy reforms. Additionally, the creation of a large, comprehensive data set can be used for further research.
DERR1-10.2196/40545.
With the ever increasing number of geriatric surgical patients, there is a need to develop efficient processes that address all of the potential issues faced by patients during the perioperative ...period. This article explores the physiological changes in elderly surgical patients and the outcomes achieved after major abdominal surgery. Perioperative management strategies for elderly surgical patients in line with the practices of the Geriatric Surgical Team of Alexandra Health, Singapore, are also presented. A coordinated transdisciplinary approach best tackles the complexities encountered in these patients.
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