| 1. |
- Gurung, Rejina, et al.
(författare)
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Scaling Up Safer Birth Bundle Through Quality Improvement in Nepal (SUSTAIN) - a stepped wedge cluster randomized controlled trial in public hospitals
- 2019
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Ingår i: Implementation Science. - : BMC. - 1748-5908. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Each year, 2.2 million intrapartum-related deaths (intrapartum stillbirths and first day neonatal deaths) occur worldwide with 99% of them taking place in low- and middle-income countries. Despite the accelerated increase in the proportion of deliveries taking place in health facilities in these settings, the stillborn and neonatal mortality rates have not reduced proportionately. Poor quality of care in health facilities is attributed to two-thirds of these deaths. Improving quality of care during the intrapartum period needs investments in evidence-based interventions. We aim to evaluate the quality improvement packageScaling Up Safer Bundle Through Quality Improvement in Nepal (SUSTAIN)on intrapartum care and intrapartum-related mortality in public hospitals of Nepal.Methods: We will conduct a stepped wedge cluster randomized controlled trial in eight public hospitals with each having least 3000 deliveries a year. Each hospital will represent a cluster with an intervention transition period of 2months in each. With a level of significance of 95%, the statistical power of 90% and an intra-cluster correlation of 0.00015, a study period of 19months should detect at least a 15% change in intrapartum-related mortality. Quality improvement training, mentoring, systematic feedback, and a continuous improvement cycle will be instituted based on bottleneck analyses in each hospital. All concerned health workers will be trained on standard basic neonatal resuscitation and essential newborn care. Portable fetal heart monitors (Moyo (R)) and neonatal heart rate monitors (Neobeat (R)) will be introduced in the hospitals to identify fetal distress during labor and to improve neonatal resuscitation. Independent research teams will collect data in each hospital on intervention inputs, processes, and outcomes by reviewing records and carrying out observations and interviews. The dose-response effect will be evaluated through process evaluations.Discussion: With the global momentum to improve quality of intrapartum care, better understanding of QI package within a health facility context is important. The proposed package is based on experiences from a similar previous scale-up trial carried out in Nepal. The proposed evaluation will provide evidence on QI package and technology for implementation and scale up in similar settings.
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| 2. |
- Gurung, Rejina, et al.
(författare)
-
Scaling Up Safer Birth Bundle Through Quality Improvement in Nepal (SUSTAIN)-a stepped wedge cluster randomized controlled trial in public hospitals.
- 2019
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Ingår i: Implementation science : IS. - : Springer Science and Business Media LLC. - 1748-5908. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Each year, 2.2 million intrapartum-related deaths (intrapartum stillbirths and first day neonatal deaths) occur worldwide with 99% of them taking place in low- and middle-income countries. Despite the accelerated increase in the proportion of deliveries taking place in health facilities in these settings, the stillborn and neonatal mortality rates have not reduced proportionately. Poor quality of care in health facilities is attributed to two-thirds of these deaths. Improving quality of care during the intrapartum period needs investments in evidence-based interventions. We aim to evaluate the quality improvement package-Scaling Up Safer Bundle Through Quality Improvement in Nepal (SUSTAIN)-on intrapartum care and intrapartum-related mortality in public hospitals of Nepal.We will conduct a stepped wedge cluster randomized controlled trial in eight public hospitals with each having least 3000 deliveries a year. Each hospital will represent a cluster with an intervention transition period of 2 months in each. With a level of significance of 95%, the statistical power of 90% and an intra-cluster correlation of 0.00015, a study period of 19 months should detect at least a 15% change in intrapartum-related mortality. Quality improvement training, mentoring, systematic feedback, and a continuous improvement cycle will be instituted based on bottleneck analyses in each hospital. All concerned health workers will be trained on standard basic neonatal resuscitation and essential newborn care. Portable fetal heart monitors (Moyo®) and neonatal heart rate monitors (Neobeat®) will be introduced in the hospitals to identify fetal distress during labor and to improve neonatal resuscitation. Independent research teams will collect data in each hospital on intervention inputs, processes, and outcomes by reviewing records and carrying out observations and interviews. The dose-response effect will be evaluated through process evaluations.With the global momentum to improve quality of intrapartum care, better understanding of QI package within a health facility context is important. The proposed package is based on experiences from a similar previous scale-up trial carried out in Nepal. The proposed evaluation will provide evidence on QI package and technology for implementation and scale up in similar settings.ISRCTN16741720 . Registered on 2 March 2019.
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| 3. |
- Desai, Nikita, et al.
(författare)
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Performance of four computer-coded verbal autopsy methods for cause of death assignment compared with physician coding on 24,000 deaths in low- and middle-income countries
- 2014
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 12:1, s. 20-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Physician-coded verbal autopsy (PCVA) is the most widely used method to determine causes of death (CODs) in countries where medical certification of death is uncommon. Computer-coded verbal autopsy (CCVA) methods have been proposed as a faster and cheaper alternative to PCVA, though they have not been widely compared to PCVA or to each other.METHODS: We compared the performance of open-source random forest, open-source tariff method, InterVA-4, and the King-Lu method to PCVA on five datasets comprising over 24,000 verbal autopsies from low- and middle-income countries. Metrics to assess performance were positive predictive value and partial chance-corrected concordance at the individual level, and cause-specific mortality fraction accuracy and cause-specific mortality fraction error at the population level.RESULTS: The positive predictive value for the most probable COD predicted by the four CCVA methods averaged about 43% to 44% across the datasets. The average positive predictive value improved for the top three most probable CODs, with greater improvements for open-source random forest (69%) and open-source tariff method (68%) than for InterVA-4 (62%). The average partial chance-corrected concordance for the most probable COD predicted by the open-source random forest, open-source tariff method and InterVA-4 were 41%, 40% and 41%, respectively, with better results for the top three most probable CODs. Performance generally improved with larger datasets. At the population level, the King-Lu method had the highest average cause-specific mortality fraction accuracy across all five datasets (91%), followed by InterVA-4 (72% across three datasets), open-source random forest (71%) and open-source tariff method (54%).CONCLUSIONS: On an individual level, no single method was able to replicate the physician assignment of COD more than about half the time. At the population level, the King-Lu method was the best method to estimate cause-specific mortality fractions, though it does not assign individual CODs. Future testing should focus on combining different computer-coded verbal autopsy tools, paired with PCVA strengths. This includes using open-source tools applied to larger and varied datasets (especially those including a random sample of deaths drawn from the population), so as to establish the performance for age- and sex-specific CODs.
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| 4. |
- Forouzanfar, Mohammad H, et al.
(författare)
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Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
- 2015
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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| 5. |
- Ghosal, Suman, et al.
(författare)
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Immune signature of pheochromocytoma and paraganglioma in context of neuroendocrine neoplasms associated with prognosis
- 2023
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Ingår i: Endocrine. - : Springer Nature. - 1355-008X .- 1559-0100. ; 79:1, s. 171-179
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo understand prognostic immune cell infiltration signatures in neuroendocrine neoplasms (NENs), particularly pheochromocytoma and paraganglioma (PCPG), we analyzed tumor transcriptomic data from The Cancer Genome Atlas (TCGA) and other published tumor transcriptomic data of NENs.MethodsWe used CIBERSORT to infer immune cell infiltrations from bulk tumor transcriptomic data from PCPGs, in comparison to gastroenteropancreatic neuroendocrine tumors (GEPNETs) and small cell lung carcinomas (SCLCs). PCPG immune signature was validated with NanoString immune panel in an independent cohort. Unsupervised clustering of the immune infiltration scores from CIBERSORT was used to find immune clusters. A prognostic immune score model for PCPGs and the other NENs were calculated as a linear combination of the estimated infiltration of activated CD8+/CD4+ T cells, activated NK cells, and M0 and M2 macrophages.ResultsIn PCPGs, we found five dominant immune clusters, associated with M2 macrophages, monocytes, activated NK cells, M0 macrophages and regulatory T cells, and CD8+/CD4+ T cells respectively. Non-metastatic tumors were associated with activated NK cells and metastatic tumors were associated with M0 macrophages and regulatory T cells. In GEPNETs and SCLCs, M0 macrophages and regulatory T cells were associated with unfavorable outcomes and features, such as metastasis and high-grade tumors. The prognostic immune score model for PCPGs and the NENs could predict non-aggressive and non-metastatic diseases. In PCPGs, the immune score was also an independent predictor of metastasis-free survival in a multivariate Cox regression analysis.ConclusionThe transcriptomic immune signature in PCPG correlates with clinical features like metastasis and prognosis.
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| 6. |
- Jha, Abhishek, et al.
(författare)
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High-Specific-Activity-131I-MIBG versus 177Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma
- 2021
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Ingår i: Clinical Cancer Research. - : American Association For Cancer Research (AACR). - 1078-0432 .- 1557-3265. ; 27:11, s. 2989-2995
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Tidskriftsartikel (refereegranskat)abstract
- Targeted radionuclide therapies (TRT) using 131I-metaiodobenzylguanidine (131I-MIBG) and peptide receptor radionuclide therapy (177Lu or 90Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-131I-MIBG therapy was approved by the FDA and both 177Lu-DOTATATE and 131I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.
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| 7. |
- Jha, Abhishek Kumar Rajesh, et al.
(författare)
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Comparison of Methods for Calculating Indirect Upstream Carbon Emissions from Information and Communication Technology Manufacturing
- 2023
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Ingår i: WSEAS Transactions on Environment and Development. - 1790-5079 .- 2224-3496. ; 19, s. 1045-1057
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Tidskriftsartikel (refereegranskat)abstract
- The use of Information Communication technology (ICT) is rapidly increasing in an age ofdigitalization. Measurement of carbon dioxide equivalent (CO2e) emissions from ICT is crucial for reducingthem. Most ICT organizations focus on Scope 1 and 2 emissions as they have greater control over them, commonly ignoring Scope 3 emissions. Scope 3 Category 1 (S3C1) emissions occur throughout the rawmaterial acquisition and manufacturing stages of an ICT product's life cycle accounting for a large portion ofthe sector's overall CO2e emissions and energy consumption. By not reporting Scope 3 emissions, companieslose the ability to reduce their overall CO2e corporate emissions. Although Category 1 and 11 under Scope 3account for 85% of ICT's worldwide CO2e emissions, the methodologies for calculating S3C1 emissions in ICTare understudied. This study focuses on these emissions in the framework of Sustainable Development Goals 9,12, and 13. Product life cycle assessment (PLCA) and Spend-based methods have been used to analyze S3C1emissions in the ICT sector with two case examples of laptop computers and smartphones. The ExcelManagement Life Cycle Assessment (EMLCA) tool has been used for the S3C1 emissions estimation. PLCAand Spend-based methods are compared on their ability to calculate CO2e emissions. It is concluded that theSpend-based is faster than PLCA for predicting ICT emissions with modest uncertainty for smartphone andlaptop components. Furthermore, this work explores the advantages and downsides of both methods.
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| 8. |
- Kassebaum, Nicholas J., et al.
(författare)
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Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
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Tidskriftsartikel (refereegranskat)abstract
- Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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| 9. |
- KC, Ashish, 1982-, et al.
(författare)
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Effect of a scaled-up neonatal resuscitation quality improvement package on intrapartum-related mortality in Nepal : A stepped-wedge cluster randomized controlled trial
- 2019
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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 16:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Improving quality of intrapartum care will reduce intrapartum stillbirth and neonatal mortality, especially in resource-poor settings. Basic neonatal resuscitation can reduce intrapartum stillbirth and early neonatal mortality, if delivered in a high-quality health system, but there is a dearth of evidence on how to scale up such evidence-based interventions. We evaluated the scaling up of a quality improvement (QI) package for neonatal resuscitation on intrapartum-related mortality (intrapartum stillbirth and first day mortality) at hospitals in Nepal. Methods and findings We conducted a stepped-wedge cluster randomized controlled trial in 12 hospitals over a period of 18 months from April 14, 2017, to October 17, 2018. The hospitals were assigned to one of four wedges through random allocation. The QI package was implemented in a stepped-wedge manner with a delay of three months for each step. The QI package included improving hospital leadership on intrapartum care, building health workers' competency on neonatal resuscitation, and continuous facilitated QI processes in clinical units. An independent data collection system was set up at each hospital to gather data on mortality through patient case note review and demographic characteristics of women using semi-structured exit interviews. The generalized linear mixed model (GLMM) and multivariate logistic regression were used for analyses. During this study period, a total of 89,014 women-infant pairs were enrolled. The mean age of the mother in the study period was 24.0 +/- 4.3 years, with 54.9% from disadvantaged ethnic groups and 4.0% of them illiterate. Of the total birth cohort, 54.4% were boys, 16.7% had gestational age less than 37 weeks, and 17.1% had birth weight less than 2,500 grams. The incidence of intrapartum-related mortality was 11.0 per 1,000 births during the control period and 8.0 per 1,000 births during the intervention period (adjusted odds ratio [aOR], 0.79; 95% CI, 0.69-0.92; p = 0.002; intra-cluster correlation coefficient [ICC], 0.0286). The incidence of early neonatal mortality was 12.7 per 1,000 live births during the control period and 10.1 per 1,000 live births during the intervention period (aOR, 0.89; 95% CI, 0.78-1.02; p = 0.09; ICC, 0.1538). The use of bag-and-mask ventilation for babies with low Apgar score (<7 at 1 minute) increased from 3.2% in the control period to 4.0% in the intervention period (aOR, 1.52; 95% CI, 1.32-1.77, p = 0.003). There were two major limitations to the study; although a large sample of women-infant pairs were enrolled in the study, the clustering reduced the power of the study. Secondly, the study was not sufficiently powered to detect reduction in early neonatal mortality with the number of clusters provided. Conclusion These results suggest scaled-up implementation of a QI package for neonatal resuscitation can reduce intrapartum-related mortality and improve clinical care. The QI intervention package is likely to be effective in similar settings. More implementation research is required to assess the sustainability of QI interventions and quality of care.
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| 10. |
- KC, Ashish, 1982, et al.
(författare)
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Effect of a scaled-up neonatal resuscitation quality improvement package on intrapartum-related mortality in Nepal: A stepped-wedge cluster randomized controlled trial.
- 2019
-
Ingår i: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 16:9
-
Tidskriftsartikel (refereegranskat)abstract
- Improving quality of intrapartum care will reduce intrapartum stillbirth and neonatal mortality, especially in resource-poor settings. Basic neonatal resuscitation can reduce intrapartum stillbirth and early neonatal mortality, if delivered in a high-quality health system, but there is a dearth of evidence on how to scale up such evidence-based interventions. We evaluated the scaling up of a quality improvement (QI) package for neonatal resuscitation on intrapartum-related mortality (intrapartum stillbirth and first day mortality) at hospitals in Nepal.We conducted a stepped-wedge cluster randomized controlled trial in 12 hospitals over a period of 18 months from April 14, 2017, to October 17, 2018. The hospitals were assigned to one of four wedges through random allocation. The QI package was implemented in a stepped-wedge manner with a delay of three months for each step. The QI package included improving hospital leadership on intrapartum care, building health workers' competency on neonatal resuscitation, and continuous facilitated QI processes in clinical units. An independent data collection system was set up at each hospital to gather data on mortality through patient case note review and demographic characteristics of women using semi-structured exit interviews. The generalized linear mixed model (GLMM) and multivariate logistic regression were used for analyses. During this study period, a total of 89,014 women-infant pairs were enrolled. The mean age of the mother in the study period was 24.0 ± 4.3 years, with 54.9% from disadvantaged ethnic groups and 4.0% of them illiterate. Of the total birth cohort, 54.4% were boys, 16.7% had gestational age less than 37 weeks, and 17.1% had birth weight less than 2,500 grams. The incidence of intrapartum-related mortality was 11.0 per 1,000 births during the control period and 8.0 per 1,000 births during the intervention period (adjusted odds ratio [aOR], 0.79; 95% CI, 0.69-0.92; p = 0.002; intra-cluster correlation coefficient [ICC], 0.0286). The incidence of early neonatal mortality was 12.7 per 1,000 live births during the control period and 10.1 per 1,000 live births during the intervention period (aOR, 0.89; 95% CI, 0.78-1.02; p = 0.09; ICC, 0.1538). The use of bag-and-mask ventilation for babies with low Apgar score (<7 at 1 minute) increased from 3.2% in the control period to 4.0% in the intervention period (aOR, 1.52; 95% CI, 1.32-1.77, p = 0.003). There were two major limitations to the study; although a large sample of women-infant pairs were enrolled in the study, the clustering reduced the power of the study. Secondly, the study was not sufficiently powered to detect reduction in early neonatal mortality with the number of clusters provided.These results suggest scaled-up implementation of a QI package for neonatal resuscitation can reduce intrapartum-related mortality and improve clinical care. The QI intervention package is likely to be effective in similar settings. More implementation research is required to assess the sustainability of QI interventions and quality of care.ISRCTN30829654.
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| 11. |
- KC, Ashish, 1982, et al.
(författare)
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Trends for Neonatal Deaths in Nepal (2001-2016) to Project Progress Towards the SDG Target in 2030, and Risk Factor Analyses to Focus Action.
- 2020
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Ingår i: Maternal and child health journal. - : Springer Science and Business Media LLC. - 1573-6628 .- 1092-7875. ; 24:Suppl 1, s. 5-14
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Tidskriftsartikel (refereegranskat)abstract
- Nepal has made considerable progress on improving child survival during the Millennium Development Goal period, however, further progress will require accelerated reduction in neonatal mortality. Neonatal survival is one of the priorities for Sustainable Development Goals 2030. This paper examines the trends, equity gaps and factors associated with neonatal mortality between 2001 and 2016 to assess the likelihood of Every Newborn Action Plan (ENAP) target being reached in Nepal by 2030.This study used data from the 2001, 2006, 2011 and 2016 Nepal Demographic and Health Surveys. We examined neonatal mortality rate (NMR) across the socioeconomic strata and the annual rate of reduction (ARR) between 2001 and 2016. We assessed association of socio-demographic, maternal, obstetric and neonatal factors associated with neonatal mortality. Based on the ARR among the wealth quintile between 2001 and 2016, we made projection of NMR to achieve the ENAP target. Using the Lorenz curve, we calculated the inequity distribution among the wealth quintiles between 2001 and 2016.In NDHS of 2001, 2006, 2011 and 2016, a total of 8400, 8600, 13,485 and 13,089 women were interviewed respectively. There were significant disparities between wealth quintiles that widened over the 15 years. The ARR for NMR declined with an average of 4.0% between 2001 and 2016. Multivariate analysis of the 2016 data showed that women who had not been vaccinated against tetanus had the highest risk of neonatal mortality (adjusted odds ratio [AOR] 3.38; 95% confidence interval [CI] 1.20-9.55), followed by women who had no education (AOR 1.87; 95% CI 1.62-2.16). Further factors significantly associated with neonatal mortality were the mother giving birth before the age of 20 (AOR 1.76; CI 95% 1.17-2.59), household air pollution (AOR 1.37; CI 95% 1.59-1.62), belonging to a poorest quintile (AOR 1.37; CI 95% 1.21-1.54), residing in a rural area (AOR 1.28; CI 95% 1.13-1.44), and having no toilet at home (AOR 1.21; CI 95% 1.06-1.40). If the trend of neonatal mortality rate of 2016 continues, it is projected that the poorest family will reach the ENAP target in 2067.Although neonatal mortality is declining in Nepal, if the current trend continues it will take another 50 years for families in the poorest group to attain the 2030 ENAP target. There are different factors associated with neonatal mortality, reducing the disparities for maternal and neonatal care will reduce mortality among the poorest families.
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| 12. |
- Korhonen, Emilia A., et al.
(författare)
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Lymphangiogenesis requires Ang2/Tie/PI3K signaling for VEGFR3 cell-surface expression
- 2022
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Ingår i: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 132:15
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor C (VEGF-C) induces lymphangiogenesis via VEGF receptor 3 (VEGFR3), which is encoded by the most frequently mutated gene in human primary lymphedema. Angiopoietins (Angs) and their Tie receptors regulate lymphatic vessel development, and mutations of the ANGPT2 gene were recently found in human primary lymphedema. However, the mechanistic basis of Ang2 activity in lymphangiogenesis is not fully understood. Here, we used gene deletion, blocking Abs, transgene induction, and gene transfer to study how Ang2, its Tie2 receptor, and Tie1 regulate lymphatic vessels. We discovered that VEGF-C???induced Ang2 secretion from lymphatic endothelial cells (LECs) was involved in full Akt activation downstream of phosphoinositide 3 kinase (PI3K). Neonatal deletion of genes encoding the Tie receptors or Ang2 in LECs, or administration of an Ang2-blocking Ab decreased VEGFR3 presentation on LECs and inhibited lymphangiogenesis. A similar effect was observed in LECs upon deletion of the PI3K catalytic p110?? subunit or with small -molecule inhibition of a constitutively active PI3K located downstream of Ang2. Deletion of Tie receptors or blockade of Ang2 decreased VEGF-C???induced lymphangiogenesis also in adult mice. Our results reveal an important crosstalk between the VEGF-C and Ang signaling pathways and suggest new avenues for therapeutic manipulation of lymphangiogenesis by targeting Ang2/Tie/PI3K signaling.
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| 13. |
- Leitao, Jordana, et al.
(författare)
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Comparison of physician-certified verbal autopsy with computer-coded verbal autopsy for cause of death assignment in hospitalized patients in low- and middle-income countries : systematic review
- 2014
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 12:1, s. 22-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Computer-coded verbal autopsy (CCVA) methods to assign causes of death (CODs) for medically unattended deaths have been proposed as an alternative to physician-certified verbal autopsy (PCVA). We conducted a systematic review of 19 published comparison studies (from 684 evaluated), most of which used hospital-based deaths as the reference standard. We assessed the performance of PCVA and five CCVA methods: Random Forest, Tariff, InterVA, King-Lu, and Simplified Symptom Pattern.METHODS: The reviewed studies assessed methods' performance through various metrics: sensitivity, specificity, and chance-corrected concordance for coding individual deaths, and cause-specific mortality fraction (CSMF) error and CSMF accuracy at the population level. These results were summarized into means, medians, and ranges.RESULTS: The 19 studies ranged from 200 to 50,000 deaths per study (total over 116,000 deaths). Sensitivity of PCVA versus hospital-assigned COD varied widely by cause, but showed consistently high specificity. PCVA and CCVA methods had an overall chance-corrected concordance of about 50% or lower, across all ages and CODs. At the population level, the relative CSMF error between PCVA and hospital-based deaths indicated good performance for most CODs. Random Forest had the best CSMF accuracy performance, followed closely by PCVA and the other CCVA methods, but with lower values for InterVA-3.CONCLUSIONS: There is no single best-performing coding method for verbal autopsies across various studies and metrics. There is little current justification for CCVA to replace PCVA, particularly as physician diagnosis remains the worldwide standard for clinical diagnosis on live patients. Further assessments and large accessible datasets on which to train and test combinations of methods are required, particularly for rural deaths without medical attention.
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| 14. |
- Soliman, Ahmed Elmahdy, 1994, et al.
(författare)
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Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats.
- 2024
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Ingår i: Frontiers in cardiovascular medicine. - 2297-055X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Ischemic preconditioning (IPC), i.e., brief periods of ischemia, protect the heart from subsequent prolonged ischemic injury, and reduces infarction size. Myocardial stunning refers to transient loss of contractility in the heart after myocardial ischemia that recovers without permanent damage. The relationship between IPC and myocardial stunning remains incompletely understood. This study aimed primarily to examine the effects of IPC on the relationship between ischemia duration, stunning, and infarct size in an ischemia-reperfusion injury model. Secondarily, this study aimed to examine to which extent the phosphoproteomic changes induced by IPC relate to myocardial contractile function.Rats were subjected to different durations of left anterior descending artery (LAD) occlusion, with or without preceding IPC. Echocardiograms were acquired to assess cardiac contraction in the affected myocardial segment. Infarction size was evaluated using triphenyl tetrazolium chloride staining. Phosphoproteomic analysis was performed in heart tissue from preconditioned and non-preconditioned animals. In contrast to rats without IPC, reversible akinesia was observed in a majority of the rats that were subjected to IPC and subsequently exposed to ischemia of 13.5 or 15min of ischemia. Phosphoproteomic analysis revealed significant differential regulation of 786 phosphopeptides between IPC and non-IPC groups, with significant associations with the sarcomere, Z-disc, and actin binding.IPC induces changes in phosphosites of proteins involved in myocardial contraction; and both accentuates post-ischemic myocardial stunning and reduces infarct size.
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| 15. |
- Taïeb, David, et al.
(författare)
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Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants : an international expert Consensus statement
- 2024
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Ingår i: Nature Reviews Endocrinology. - : Springer Nature. - 1759-5029 .- 1759-5037. ; 20:3, s. 168-184
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Forskningsöversikt (refereegranskat)abstract
- Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.
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| 16. |
- Wang, Haidong, et al.
(författare)
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Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
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| 17. |
- Zulfaj, Ermir, 1993, et al.
(författare)
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Development of a small animal model replicating core characteristics of takotsubo syndrome in humans.
- 2024
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Ingår i: European heart journal open. - 2752-4191. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- Adequate animal models are necessary to understand human conditions, such as takotsubo syndrome (TS) characterized by the heart's transient regional wall motion abnormalities. This study aims to develop a reproducible, low-mortality TS model that closely mimics the human condition and addresses the limitations of existing models.We conducted six experiments using 309 Sprague Dawley rats, each approximately 300 g and aged 7-8 weeks. Initially, we replicated an established model using intraperitoneal isoprenaline injections. Subsequent experiments varied the doses and infusion durations of intravenous isoprenaline and assessed the effects of sex, strain, and breeder on the development of reversible akinetic segments. High-resolution echocardiography monitored the regional wall motion over 30 days to correlate with histological changes. Increasing the isoprenaline dose and the infusion time significantly enhanced akinesia (P < 0.01), resulting in pronounced apical ballooning observed in three-dimensional imaging. Akinesia peaked at 6 h post-infusion, with recovery observed at 24 h; most rats recovered from akinetic segments within 48-72 h. Optimizing the mode of administration, dose, and duration achieved a TS-like phenotype in 90% of cases, with a 16.7% mortality rate. Histological examinations confirmed that myocardial injury occurred, independent of apical ballooning.This study presents a refined TS model that reliably replicates the syndrome's key features, including morphological and electrocardiographic changes, demonstrating its transient nature with high fidelity and reduced mortality. The model's reproducibility, evidenced by consistent results across trials, suggests its potential for broader application pending further validation.
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