| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Streatfield, P. Kim, et al.
(författare)
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Malaria mortality in Africa and Asia : evidence from INDEPTH health and demographic surveillance system sites
- 2014
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Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 7, s. 25369-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Malaria continues to be a major cause of infectious disease mortality in tropical regions. However, deaths from malaria are most often not individually documented, and as a result overall understanding of malaria epidemiology is inadequate. INDEPTH Network members maintain population surveillance in Health and Demographic Surveillance System sites across Africa and Asia, in which individual deaths are followed up with verbal autopsies.OBJECTIVE: To present patterns of malaria mortality determined by verbal autopsy from INDEPTH sites across Africa and Asia, comparing these findings with other relevant information on malaria in the same regions.DESIGN: From a database covering 111,910 deaths over 12,204,043 person-years in 22 sites, in which verbal autopsy data were handled according to the WHO 2012 standard and processed using the InterVA-4 model, over 6,000 deaths were attributed to malaria. The overall period covered was 1992-2012, but two-thirds of the observations related to 2006-2012. These deaths were analysed by site, time period, age group and sex to investigate epidemiological differences in malaria mortality.RESULTS: Rates of malaria mortality varied by 1:10,000 across the sites, with generally low rates in Asia (one site recording no malaria deaths over 0.5 million person-years) and some of the highest rates in West Africa (Nouna, Burkina Faso: 2.47 per 1,000 person-years). Childhood malaria mortality rates were strongly correlated with Malaria Atlas Project estimates of Plasmodium falciparum parasite rates for the same locations. Adult malaria mortality rates, while lower than corresponding childhood rates, were strongly correlated with childhood rates at the site level.CONCLUSIONS: The wide variations observed in malaria mortality, which were nevertheless consistent with various other estimates, suggest that population-based registration of deaths using verbal autopsy is a useful approach to understanding the details of malaria epidemiology.
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| 3. |
- Bedford, Lynn, et al.
(författare)
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Depletion of 26S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies
- 2008
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 28:33, s. 8189-98
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Tidskriftsartikel (refereegranskat)abstract
- Ubiquitin-positive intraneuronal inclusions are a consistent feature of the major human neurodegenerative diseases, suggesting that dysfunction of the ubiquitin proteasome system is central to disease etiology. Research using inhibitors of the 20S proteasome to model Parkinson's disease is controversial. We report for the first time that specifically 26S proteasomal dysfunction is sufficient to trigger neurodegenerative disease. Here, we describe novel conditional genetic mouse models using the Cre/loxP system to spatially restrict inactivation of Psmc1 (Rpt2/S4) to neurons of either the substantia nigra or forebrain (e.g., cortex, hippocampus, and striatum). PSMC1 is an essential subunit of the 26S proteasome and Psmc1 conditional knock-out mice display 26S proteasome depletion in targeted neurons, in which the 20S proteasome is not affected. Impairment of specifically ubiquitin-mediated protein degradation caused intraneuronal Lewy-like inclusions and extensive neurodegeneration in the nigrostriatal pathway and forebrain regions. Ubiquitin and alpha-synuclein neuropathology was evident, similar to human Lewy bodies, but interestingly, inclusion bodies contained mitochondria. We support this observation by demonstrating mitochondria in an early form of Lewy body (pale body) from Parkinson's disease patients. The results directly confirm that 26S dysfunction in neurons is involved in the pathology of neurodegenerative disease. The model demonstrates that 26S proteasomes are necessary for normal neuronal homeostasis and that 20S proteasome activity is insufficient for neuronal survival. Finally, we are providing the first reproducible genetic platform for identifying new therapeutic targets to slow or prevent neurodegeneration.
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| 4. |
- Bird, J., et al.
(författare)
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A matter of life and death : practical and ethical constraints in the development of a mobile verbal autopsy tool
- 2013
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Ingår i: CHI '13 Proceedings of the SIGCHI Conference on Human Factors in Computing SystemsPages 1489-1498. - New York, NY, USA : ACM. - 9781450318990 ; , s. 1489-1498
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Konferensbidrag (refereegranskat)abstract
- Verbal autopsy (VA) involves interviewing relatives of the deceased to identify the probable cause of death and is typically used in settings where there is no official system for recording deaths or their causes. Following the interview, physician assessment to determine probable cause can take several years to complete. The World Health Organization (WHO) recognizes that there is a pressing need for a mobile device that combines direct data capture and analysis if this technique is to become part of routine health surveillance. We conducted a field test in rural South Africa to evaluate a mobile system that we designed to meet WHO requirements (namely, simplicity, feasibility, adaptability to local contexts, cost-effectiveness and program relevance). If desired, this system can provide immediate feedback to respondents about the probable cause of death at the end of a VA interview. We assessed the ethical implications of this technological development by interviewing all the stakeholders in the VA process (respondents, fieldworkers, physicians, population scientists, data managers and community engagement managers) and highlight the issues that this community needs to debate and resolve.
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| 5. |
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| 6. |
- Byass, Peter, et al.
(författare)
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Comparing verbal autopsy cause of death findings as determined by physician coding and probabilistic modelling : a public health analysis of 54 000 deaths in Africa and Asia
- 2015
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Ingår i: Journal of Global Health. - 2047-2978 .- 2047-2986. ; 5:1, s. 65-73
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coverage of civil registration and vital statistics varies globally, with most deaths in Africa and Asia remaining either unregistered or registered without cause of death. One important constraint has been a lack of fit-for-purpose tools for registering deaths and assigning causes in situations where no doctor is involved. Verbal autopsy (interviewing care-givers and witnesses to deaths and interpreting their information into causes of death) is the only available solution. Automated interpretation of verbal autopsy data into cause of death information is essential for rapid, consistent and affordable processing.METHODS: Verbal autopsy archives covering 54 182 deaths from five African and Asian countries were sourced on the basis of their geographical, epidemiological and methodological diversity, with existing physician-coded causes of death attributed. These data were unified into the WHO 2012 verbal autopsy standard format, and processed using the InterVA-4 model. Cause-specific mortality fractions from InterVA-4 and physician codes were calculated for each of 60 WHO 2012 cause categories, by age group, sex and source. Results from the two approaches were assessed for concordance and ratios of fractions by cause category. As an alternative metric, the Wilcoxon matched-pairs signed ranks test with two one-sided tests for stochastic equivalence was used.FINDINGS: The overall concordance correlation coefficient between InterVA-4 and physician codes was 0.83 (95% CI 0.75 to 0.91) and this increased to 0.97 (95% CI 0.96 to 0.99) when HIV/AIDS and pulmonary TB deaths were combined into a single category. Over half (53%) of the cause category ratios between InterVA-4 and physician codes by source were not significantly different from unity at the 99% level, increasing to 62% by age group. Wilcoxon tests for stochastic equivalence also demonstrated equivalence.CONCLUSIONS: These findings show strong concordance between InterVA-4 and physician-coded findings over this large and diverse data set. Although these analyses cannot prove that either approach constitutes absolute truth, there was high public health equivalence between the findings. Given the urgent need for adequate cause of death data from settings where deaths currently pass unregistered, and since the WHO 2012 verbal autopsy standard and InterVA-4 tools represent relatively simple, cheap and available methods for determining cause of death on a large scale, they should be used as current tools of choice to fill gaps in cause of death data.
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| 7. |
- Byass, Peter, et al.
(författare)
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Using verbal autopsy to track epidemic dynamics : the case of HIV-related mortality in South Africa.
- 2011
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Ingår i: Population Health Metrics. - : BioMed Central (BMC). - 1478-7954. ; 9, s. 46-
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Tidskriftsartikel (refereegranskat)abstract
- Background Verbal autopsy (VA) has often been used for point estimates of cause-specific mortality, but seldom to characterize long-term changes in epidemic patterns. Monitoring emerging causes of death involves practitioners' developing perceptions of diseases and demands consistent methods and practices. Here we retrospectively analyze HIV-related mortality in South Africa, using physician and modeled interpretation.Methods Between 1992 and 2005, 94% of 6,153 deaths which occurred in the Agincourt subdistrict had VAs completed, and coded by two physicians and the InterVA model. The physician causes of death were consolidated into a single consensus underlying cause per case, with an additional physician arbitrating where different diagnoses persisted. HIV-related mortality rates and proportions of deaths coded as HIV-related by individual physicians, physician consensus, and the InterVA model were compared over time.Results Approximately 20% of deaths were HIV-related, ranging from early low levels to tenfold-higher later population rates (2.5 per 1,000 person-years). Rates were higher among children under 5 years and adults 20 to 64 years. Adult mortality shifted to older ages as the epidemic progressed, with a noticeable number of HIV-related deaths in the over-65 year age group latterly. Early InterVA results suggested slightly higher initial HIV-related mortality than physician consensus found. Overall, physician consensus and InterVA results characterized the epidemic very similarly. Individual physicians showed marked interobserver variation, with consensus findings generally reflecting slightly lower proportions of HIV-related deaths. Aggregated findings for first versus second physician did not differ appreciably.Conclusions VA effectively detected a very significant epidemic of HIV-related mortality. Using either physicians or InterVA gave closely comparable findings regarding the epidemic. The consistency between two physician coders per case (from a pool of 14) suggests that double coding may be unnecessary, although the consensus rate of HIV-related mortality was approximately 8% lower than by individual physicians. Consistency within and between individual physicians, individual perceptions of epidemic dynamics, and the inherent consistency of models are important considerations here. The ability of the InterVA model to track a more than tenfold increase in HIV-related mortality over time suggests that finely tuned "local" versions of models for VA interpretation are not necessary.
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| 8. |
- 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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| 9. |
- Gomez-Olive, F. Xavier, et al.
(författare)
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Social conditions and disability related to the mortality of older people in rural South Africa
- 2014
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 43:5, s. 1531-1541
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Tidskriftsartikel (refereegranskat)abstract
- Background: South Africa is experiencing a health and social transition including an ageing population and an HIV epidemic. We report mortality experience of an older rural South African population.Methods: Individual survey data and longer-term demographic data were used to describe factors associated with mortality. Individuals aged 50 years and over (n = 4085) answered a health and quality of life questionnaire in 2006 and were followed for 3 years thereafter. Additional vital events and socio-demographic data were extracted from the Agincourt Health and Demographic Surveillance System from 1993 to 2010, to provide longer-term trends in mortality. Cox regression analysis was used to determine factors related to survival.Results: In 10 967 person-years of follow-up between August 2006 and August 2009, 377 deaths occurred. Women had lower mortality {hazard ratio [HR] 0.35 [95% confidence interval (CI) 0.28-0.45]}. Higher mortality was associated with being single [HR 1.48 (95% CI 1.16-1.88)], having lower household assets score [HR 1.79 (95% CI 1.28-2.51)], reporting greater disability [HR 2.40 (95% CI 1.68-3.42)] and poorer quality of life [HR 1.59 (95% CI 1.09-2.31)]. There was higher mortality in those aged under 69 as compared with those 70 to 79 years old. Census data and cause specific regression models confirmed that this was due to deaths from HIV/TB in the younger age group.Conclusions: Mortality due to HIV/TB is increasing in men, and to some extent women, aged over 50. Policy makers and practitioners should consider the needs of this growing and often overlooked group.
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| 10. |
- Joubert, Jané, et al.
(författare)
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Record-linkage comparison of verbal autopsy and routine civil registration death certification in rural north-east South Africa : 2006-09
- 2014
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 43:6, s. 1945-1958
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Tidskriftsartikel (refereegranskat)abstract
- Background: South African civil registration (CR) provides a key data source for local health decision making, and informs the levels and causes of mortality in data-lacking sub-Saharan African countries. We linked mortality data from CR and the Agincourt Health and Socio-demographic Surveillance System (Agincourt HDSS) to examine the quality of rural CR data. Methods: Deterministic and probabilistic techniques were used to link death data from 2006 to 2009. Causes of death were aggregated into the WHO Mortality Tabulation List 1 and a locally relevant short list of 15 causes. The matching rate was compared with informant-reported death registration. Using the VA diagnoses as reference, misclassification patterns, sensitivity, positive predictive values and cause-specific mortality fractions (CSMFs) were calculated for the short list. Results: A matching rate of 61% [95% confidence interval (CI): 59.2 to 62.3] was attained, lower than the informant-reported registration rate of 85% (CI: 83.4 to 85.8). For the 2264 matched cases, cause agreement was 15% (kappa 0.1083, CI: 0.0995 to 0.1171) for the WHO list, and 23% (kappa 0.1631, CI: 0.1511 to 0.1751) for the short list. CSMFs were significantly different for all but four (tuberculosis, cerebrovascular disease, other heart disease, and ill-defined natural) of the 15 causes evaluated. Conclusion: Despite data limitations, it is feasible to link official CR and HDSS verbal autopsy data. Data linkage proved a promising method to provide empirical evidence about the quality and utility of rural CR mortality data. Agreement of individual causes of death was low but, at the population level, careful interpretation of the CR data can assist health prioritization and planning.
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| 11. |
- Kabudula, Chodziwadziwa W., et al.
(författare)
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Evaluation of record linkage of mortality data between a health and demographic surveillance system and national civil registration system in South Africa
- 2014
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Ingår i: Population Health Metrics. - : Springer Science and Business Media LLC. - 1478-7954. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Health and Demographic Surveillance Systems (HDSS) collect independent mortality data that could be used for assessing the quality of mortality data in national civil registration (CR) systems in low- and middle-income countries. However, the use of HDSS data for such purposes depends on the quality of record linkage between the two data sources. We describe and evaluate the quality of record linkage between HDSS and CR mortality data in South Africa with HDSS data from Agincourt HDSS. Methods: We applied deterministic and probabilistic record linkage approaches to mortality records from 2006 to 2009 from the Agincourt HDSS and those in the CR system. Quality of the matches generated by the probabilistic approach was evaluated using sensitivity and positive predictive value (PPV) calculated from a subset of records that were linked using national identity number. Matched and unmatched records from the Agincourt HDSS were compared to identify characteristics associated with successful matching. In addition, the distribution of background characteristics in all deaths that occurred in 2009 and those linked to CR records was compared to assess systematic bias in the resulting record-linked dataset in the latest time period. Results: Deterministic and probabilistic record linkage approaches combined linked a total of 2264 out of 3726 (60.8%) mortality records from the Agincourt HDSS to those in the CR system. Probabilistic approaches independently linked 1969 (87.0%) of the linked records. In a subset of 708 records that were linked using national identity number, the probabilistic approaches yielded sensitivity of 90.0% and PPV of 98.5%. Records belonging to more vulnerable people, including poorer persons, young children, and non-South Africans were less likely to be matched. Nevertheless, distribution of most background characteristics was similar between all Agincourt HDSS deaths and those matched to CR records in the latest time period. Conclusion: This study shows that record linkage of mortality data from HDSS and CR systems is possible and can be useful in South Africa. The study identifies predictors for death registration and data items and registration system characteristics that could be improved to achieve more optimal future matching possibilities.
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| 12. |
- Kabudula, Chodziwadziwa W, et al.
(författare)
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Two decades of mortality change in rural northeast South Africa
- 2014
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Ingår i: Global Health Action. - : CoAction Publishing. - 1654-9716 .- 1654-9880. ; 7, s. 25596-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The MRC/Wits University Agincourt research centre, part of the INDEPTH Network, has documented mortality in a defined population in the rural northeast of South Africa for 20 years (1992-2011) using long-term health and socio-demographic surveillance. Detail on the unfolding, at times unpredicted, mortality pattern has been published. This experience is reviewed here and updated using more recent data.OBJECTIVE: To present a review and summary of mortality patterns across all age-sex groups in the Agincourt sub-district population for the period 1992-2011 as a comprehensive basis for public health action.DESIGN: Vital events in the Agincourt population have been updated in annual surveys undertaken since 1992. All deaths have been rigorously recorded and followed by verbal autopsy interviews. Responses to questions from these interviews have been processed retrospectively using the WHO 2012 verbal autopsy standard and the InterVA-4 model for assigning causes of death in a standardised manner.RESULTS: Between 1992 and 2011, a total of 12,209 deaths were registered over 1,436,195 person-years of follow-up, giving a crude mortality rate of 8.5 per 1,000 person-years. During the 20-year period, the population experienced a major HIV epidemic, which resulted in more than doubling of overall mortality for an extended period. Recent years show signs of declining mortality, but levels remain above the 1992 baseline recorded using the surveillance system.CONCLUSIONS: The Agincourt population has experienced a major mortality shock over the past two decades from which it will take time to recover. The basic epidemic patterns are consistent with generalised mortality patterns observed in South Africa as a whole, but the detailed individual surveillance behind these analyses allows finer-grained analyses of specific causes, age-related risks, and trends over time. These demonstrate the complex, somewhat unpredicted course of mortality transition over the years since the dawn of South Africa's democratic era in 1994.
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| 13. |
- Kahn, Kathleen, et al.
(författare)
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Profile : Agincourt Health and Socio-demographic Surveillance System
- 2012
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:4, s. 988-1001
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Tidskriftsartikel (refereegranskat)abstract
- The Agincourt health and socio-demographic surveillance system (HDSS), located in rural northeast South Africa close to the Mozambique border, was established in 1992 to support district health systems development led by the post-apartheid ministry of health. The HDSS (90 000 people), based on an annual update of resident status and vital events, now supports multiple investigations into the causes and consequences of complex health, population and social transitions. Observational work includes cohorts focusing on different stages along the life course, evaluation of national policy at population, household and individual levels and examination of household responses to shocks and stresses and the resulting pathways influencing health and well-being. Trials target children and adolescents, including promoting psycho-social well-being, preventing HIV transmission and reducing metabolic disease risk. Efforts to enhance the research platform include using automated measurement techniques to estimate cause of death by verbal autopsy, full 'reconciliation' of in- and out-migrations, follow-up of migrants departing the study area, recording of extra-household social connections and linkage of individual HDSS records with those from sub-district clinics. Fostering effective collaborations (including INDEPTH multi-centre work in adult health and ageing and migration and urbanization), ensuring cross-site compatibility of common variables and optimizing public access to HDSS data are priorities.
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| 14. |
- Kong, Stefanie, et al.
(författare)
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Birthweight: EN-BIRTH multi-country validation study.
- 2021
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Ingår i: BMC pregnancy and childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 21:Suppl 1
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Tidskriftsartikel (refereegranskat)abstract
- Accurate birthweight is critical to inform clinical care at the individual level and tracking progress towards national/global targets at the population level. Low birthweight (LBW) < 2500 g affects over 20.5 million newborns annually. However, data are lacking and may be affected by heaping. This paper evaluates birthweight measurement within the Every Newborn Birth Indicators Research Tracking in Hospitals (EN-BIRTH) study.The EN-BIRTH study took place in five hospitals in Bangladesh, Nepal and Tanzania (2017-2018). Clinical observers collected time-stamped data (gold standard) for weighing at birth. We compared accuracy for two data sources: routine hospital registers and women's report at exit interview survey. We calculated absolute differences and individual-level validation metrics. We analysed birthweight coverage and quality gaps including timing and heaping. Qualitative data explored barriers and enablers for routine register data recording.Among 23,471 observed births, 98.8% were weighed. Exit interview survey-reported weighing coverage was 94.3% (90.2-97.3%), sensitivity 95.0% (91.3-97.8%). Register-reported coverage was 96.6% (93.2-98.9%), sensitivity 97.1% (94.3-99%). Routine registers were complete (> 98% for four hospitals) and legible > 99.9%. Weighing of stillbirths varied by hospital, ranging from 12.5-89.0%. Observed LBW rate was 15.6%; survey-reported rate 14.3% (8.9-20.9%), sensitivity 82.9% (75.1-89.4%), specificity 96.1% (93.5-98.5%); register-recorded rate 14.9%, sensitivity 90.8% (85.9-94.8%), specificity 98.5% (98-99.0%). In surveys, "don't know" responses for birthweight measured were 4.7%, and 2.9% for knowing the actual weight. 95.9% of observed babies were weighed within 1 h of birth, only 14.7% with a digital scale. Weight heaping indices were around two-fold lower using digital scales compared to analogue. Observed heaping was almost 5% higher for births during the night than day. Survey-report further increased observed birthweight heaping, especially for LBW babies. Enablers to register birthweight measurement in qualitative interviews included digital scale availability and adequate staffing.Hospital registers captured birthweight and LBW prevalence more accurately than women's survey report. Even in large hospitals, digital scales were not always available and stillborn babies not always weighed. Birthweight data are being captured in hospitals and investment is required to further improve data quality, researching of data flow in routine systems and use of data at every level.
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| 15. |
- Madhavan, Sangeetha, et al.
(författare)
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Kinship in Practice : Spatial Distribution of Children's Kin Networks
- 2014
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Ingår i: Journal of Southern African Studies. - : Informa UK Limited. - 0305-7070 .- 1465-3893. ; 40:2, s. 401-418
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Tidskriftsartikel (refereegranskat)abstract
- The examination of co-residential household arrangements has been a mainstay in demographic analysis, based on the assumption that those with whom one lives are the most important influences in one's life. In contrast, we know far less about the spaces not shared but none the less crucially important in the lives of children. In this analysis, we bring together detailed ethnographic data on kin connectivity with geographical information system (GIS) data in a rural area of South Africa, in order to: 1) describe the spatial distribution of kin from a child's perspective, with special attention paid to the role of circular migrants who constitute a critical point of spatial dispersion; 2) examine how type of kinship (maternal vs paternal) and 3) socio-economic status intersect with spatial distribution. Our analysis uses a three-category typology of kin spatial arrangement that reflects employment constraints, patterns of union formation and norms of kin obligation. Specifically, we find that 1) the high-density rural node with extensive dispersion is associated with economic and union stability and access to maternal and paternal kin; whereas 2) the rural node with limited dispersion faces greater economic vulnerability and often operates in the absence of formal unions; and 3) the rural node with minimal dispersion offers the least amount of economic security and is almost always dominated by single mothers reliant on maternal kin.
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| 16. |
- Mee, Harry, et al.
(författare)
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Standardizing Cranioplasty Outcomes Following Stroke or Traumatic Brain Injury : Protocol for the Development of a Core Outcome Set
- 2023
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Ingår i: JMIR Research Protocols. - : JMIR Publications Inc.. - 1929-0748. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Core outcome sets (COSs) are important and necessary as they help standardize reporting in research studies. Cranioplasty following traumatic brain injury (TBI) or stroke is becoming increasingly common, leading to an ever-growing clinical and research interest, especially regarding the optimal material, cost-effectiveness, and timing of cranioplasty concerning neurological recovery and complications. Consequently, heterogeneous reporting of outcomes from such diverse studies has led to limited meta-analysis ability and an ongoing risk of outcome reporting bias. This study aims to define a standardized COS for reporting in all future TBI and stroke cranioplasty studies. Objective: This study has four aims: (1) undertake a systematic review to collate the most current outcome measures used within the cranioplasty literature; (2) undertake a qualitative study to understand better the views of clinicians, patients' relatives, and allied health professionals regarding clinical outcomes following cranioplasty; (3) undertake a Delphi survey as part of the process of gaining consensus for the COS; and (4) finalize consensus through a consensus meeting resulting in the COS. Methods: An international steering committee has been formed to guide the development of the COS. In addition, recommendations from other clinical initiatives such as COMET (Core Outcomes and Effectiveness Trials) and OMERACT (Outcome Measures in Rheumatology) have been adhered to. Phase 1 is data collection through a systematic review and qualitative study. Phase 2 is the COS development through a Delphi survey and consensus meetings with consensus definitions decided and agreed upon before the Delphi survey begins to avoid bias. Results: Phase 1 started at the end of 2019, following ethical approval in December 2019, and the project completion date is planned for the end of 2022 or beginning of 2023. Conclusions: This study should result in a consensus on a COS for cranioplasty, following TBI or stroke, to help standardize outcome reporting for future studies, which can be applied to future research and clinical services, help align future studies, build an increased understanding of cranioplasty and its impact on a patient’s function and recovery, and help standardize the evidence base.
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| 17. |
- Mee, Paul, et al.
(författare)
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Changing use of traditional healthcare amongst those dying of HIV related disease and TB in rural South Africa from 2003 - 2011 : a retrospective cohort study
- 2014
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Ingår i: BMC Complementary and Alternative Medicine. - : BioMed Central (BMC). - 1472-6882. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In 2011 there were 5.5 million HIV infected people in South Africa and 71% of those requiring antiretroviral therapy (ART) received it. The effective integration of traditional medical practitioners and biomedical providers in HIV prevention and care has been demonstrated. However concerns remain that the use of traditional treatments for HIV-related disease may lead to pharmacokinetic interactions between herbal remedies and ART drugs and delay ART initiation. Here we analyse the changing prevalence and determinants of traditional healthcare use amongst those dying of HIV-related disease, pulmonary tuberculosis and other causes in a rural South African community between 2003 and 2011. ART was made available in this area in the latter part of this period.METHODS: Data was collected during household visits and verbal autopsy interviews. InterVA-4 was used to assign causes of death. Spatial analyses of the distribution of traditional healthcare use were performed. Logistic regression models were developed to test associations of determinants with traditional healthcare use.RESULTS: There were 5929 deaths in the study population of which 47.7% were caused by HIV-related disease or pulmonary tuberculosis (HIV/AIDS and TB). Traditional healthcare use declined for all deaths, with higher levels throughout for those dying of HIV/AIDS and TB than for those dying of other causes. In 2003-2005, sole use of biomedical treatment was reported for 18.2% of HIV/AIDS and TB deaths and 27.2% of other deaths, by 2008-2011 the figures were 49.9% and 45.3% respectively. In bivariate analyses, higher traditional healthcare use was associated with Mozambican origin, lower education levels, death in 2003-2005 compared to the later time periods, longer illness duration and moderate increases in prior household mortality. In the multivariate model only country of origin, time period and illness duration remained associated.CONCLUSIONS: There were large decreases in reported traditional healthcare use and increases in the sole use of biomedical treatment amongst those dying of HIV/AIDS and TB. No associations between socio-economic position, age or gender and the likelihood of traditional healthcare use were seen. Further qualitative and quantitative studies are needed to assess whether these figures reflect trends in healthcare use amongst the entire population and the reasons for the temporal changes identified.
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| 18. |
- Mee, Paul, et al.
(författare)
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Determinants of the risk of dying of HIV/AIDS in a rural South African community over the period of the decentralised roll-out of antiretroviral therapy : a longitudinal study
- 2014
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Ingår i: Global Health Action. - : Taylor & Francis. - 1654-9716 .- 1654-9880. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Antiretroviral treatment (ART) has significantly reduced HIV mortality in South Africa. The benefits have not been experienced by all groups. Here we investigate the factors associated with these inequities.DESIGN: This study was located in a rural South African setting and used data collected from 2007 to 2010, the period when decentralised ART became available. Approximately one-third of the population were of Mozambican origin. There was a pattern of repeated circular migration between urban areas and this community. Survival analysis models were developed to identify demographic, socioeconomic, and spatial risk factors for HIV mortality.RESULTS: Among the study population of 105,149 individuals, there were 2,890 deaths. The HIV/TB mortality rate decreased by 27% between 2007-2008 and 2009-2010. For other causes of death, the reduction was 10%. Bivariate analysis found that the HIV/TB mortality risk was lower for: those living within 5 km of the Bhubezi Community Health Centre; women; young adults; in-migrants with a longer period of residence; permanent residents; and members of households owning motorised transport, holding higher socioeconomic positions, and with higher levels of education. Multivariate modelling showed, in addition, that those with South Africa as their country of origin had an increased risk of HIV/TB mortality compared to those with Mozambican origins. For males, those of South African origin, and recent in-migrants, the risk of death associated with HIV/TB was significantly greater than that due to other causes.CONCLUSIONS: In this community, a combination of factors was associated with an increased risk of dying of HIV/TB over the period of the roll-out of ART. There is evidence for the presence of barriers to successful treatment for particular sub-groups in the population, which must be addressed if the recent improvements in population-level mortality are to be maintained.
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| 19. |
- Mee, Paul, et al.
(författare)
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Evidence for localised HIV related micro-epidemics associated with the decentralised provision of antiretroviral treatment in rural South Africa : a spatio-temporal analysis of changing mortality patterns (2007-2010)
- 2014
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Ingår i: Journal of Global Health. - : Edinburgh University Global Health Society. - 2047-2978 .- 2047-2986. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In this study we analysed the spatial and temporal changes in patterns of mortality over a period when antiretroviral therapy (ART) was rolled out in a rural region of north-eastern South Africa. Previous studies have identified localised concentrated HIV related sub-epidemics and recommended that micro-level analyses be carried out in order to direct focused interventions.METHODS: Data from an ongoing health and socio-demographic surveillance study was used in the analysis. The follow-up was divided into two periods, 2007-2008 and 2009-2010, representing the times immediately before and after the effects on mortality of the decentralised ART provision from a newly established local health centre would be expected to be evident. The study population at the start of the analysis was approximately 73 000 individuals. Data were aggregated by village and also using a 2 × 2 km grid. We identified villages, grid squares and regions in the site where mortality rates within each time period or rate ratios between the periods differed significantly from the overall trends. We used clustering techniques to identify cause-specific mortality hotspots.FINDINGS: Comparing the two periods, there was a 30% decrease in age and gender standardised adult HIV-related and TB (HIV/TB) mortality with no change in mortality due to other causes. There was considerable spatial heterogeneity in the mortality patterns. Areas separated by 2 to 4 km with very different epidemic trajectories were identified. There was evidence that the impact of ART in reducing HIV/TB mortality was greatest in communities with higher mortality rates in the earlier period.CONCLUSIONS: This study shows the value of conducting high resolution spatial analyses in order to understand how local micro-epidemics contribute to changes seen over a wider area. Such analyses can support targeted interventions.
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| 20. |
- Mee, Paul, et al.
(författare)
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The development of a localised HIV epidemic and the associated excess mortality burden in a rural area of South Africa
- 2016
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Ingår i: Global Health, Epidemiology and Genomics. - : Hindawi Limited. - 2054-4200. ; 1:e7
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Tidskriftsartikel (refereegranskat)abstract
- The human immunodeficiency virus (HIV) epidemic in South Africa rapidly developed into a major pandemic. Here we analyse the development of the epidemic in a rural area of the country. The data used were collected between 1992 and 2013 in a longitudinal population survey, the Agincourt Health and Demographic Surveillance Study, in the northeast of the country. Throughout the period of study mortality rates were similar in all villages, suggesting that there were multiple index cases evenly spread geographically. These were likely to have been returning migrant workers. For those aged below 39 years the HIV mortality rate was higher for women, above this age it was higher for men. This indicates the protective effect of greater access to HIV testing and treatment among older women. The recent convergence of mortality rates for Mozambicans and South Africans indicates that the former refugee population are being assimilated into the host community. More than 60% of the deaths occurring in this community between 1992 and 2013 could be attributed directly or indirectly to HIV. Recently there has been an increasing level of non-HIV mortality which has important implications for local healthcare provision. This study demonstrates how evidence from longitudinal analyses can support healthcare planning.
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| 21. |
- Mee, Paul, 1966-
(författare)
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Who died, where, when and why? : an investigation of HIV-related mortality in rural South Africa
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundSouth Africa has experienced the most severe consequences of the HIV/AIDS pandemic. Every community has been affected in some way, many experiencing huge increases in mortality,particularly before antiretroviral therapies (ART) were readily available. However, the micro-level understanding of the HIV epidemic in South Africa is weak, because of a lack of detailed data for most of the population. This thesis is based on detailed individual follow-up in the Agincourt Health and Demographic Surveillance Site (HDSS) located in the Agincourt subdistrict of Mpumalanga Province and investigates micro-level determinants of HIV epidemiology and the impact of treatment provided.MethodsThe Agincourt HDSS has followed a geographically defined population since 1992,approximately the time when the HIV/AIDS epidemic first became apparent. This population based surveillance has included capturing details of all deaths, with cause of death determined by verbal autopsy, as well as the geographical location of individual households within the overall Agincourt area. Background information on the roll-out of ART over time was also recorded.ResultsA comparison immediately before and after the major roll-out of ART showed a substantial decrease in HIV-related mortality, greater in some local communities within the area than others. Individual determinants associated with a decreased risk of HIV/AIDS mortality included proximity to ART services, as well as being female, younger, and in higher socioeconomic and educational strata. There was a decrease in the use of traditional healthcare sources and an increase in the use of biomedical healthcare amongst those dying of HIV/AIDS between periods before and after the roll-out of ART.ConclusionsUnderstanding micro-level determinants of HIV/AIDS infection and mortality was very important in terms of characterising the overall epidemic in this community. This approach will enable public health interventions to be more effectively targeted towards those who need them most in the continuing evolution of the HIV/AIDS epidemic.
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| 22. |
- Paczkowska, Marta, et al.
(författare)
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Integrative pathway enrichment analysis of multivariate omics data
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.
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| 23. |
- Rosenberg, Molly, et al.
(författare)
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Relationship between Receipt of a Social Protection Grant for a Child and Second Pregnancy Rates among South African Women : A Cohort Study
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Social protection programs issuing cash grants to caregivers of young children may influence fertility. Grant-related income could foster economic independence and/or increase access to job prospects, education, and health services, resulting in lower pregnancy rates. In the other direction, these programs may motivate family expansion in order to receive larger grants. Here, we estimate the net effect of these countervailing mechanisms among rural South African women. Methods We constructed a retrospective cohort of 4845 women who first became eligible for the Child Support Grant with the birth of their first child between 1998 and 2008, with data originally collected by the Agincourt Health and Socio- Demographic Surveillance System in Mpumalanga province, South Africa. We fit Cox regression models to estimate the hazard of second pregnancy in women who reported grant receipt after birth of first child, relative to non- recipients. As a secondary analysis to explore the potential for grant loss to incentivize second pregnancy, we exploited a natural experiment created by a 2003 expansion of the program's age eligibility criterion from age seven to nine. We compared second pregnancy rates between (i) women with children age seven or eight in 2002 (recently aged out of grant eligibility) to (ii) women with children age seven or eight in 2003 (remained grant-eligible). Results The adjusted hazard ratio for the association between grant exposure and second pregnancy was 0.66 (95% CI: 0.58, 0.75). Women with first children who aged out of grant eligibility in 2002 had similar second pregnancy rates to women with first children who remained grant-eligible in 2003 [IRR (95% CI): 0.9 (0.5, 1.4)]. Conclusions Across both primary and secondary analyses, we found no evidence that the Child Support Grant incentivizes pregnancy. In harmony with South African population policy, receipt of the Child Support Grant may result in longer spacing between pregnancies.
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| 24. |
- Streatfield, P Kim, et al.
(författare)
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HIV/AIDS-related mortality in Africa and Asia : evidence from INDEPTH health and demographic surveillance system sites
- 2014
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Ingår i: Global Health Action. - : CoAction Publishing. - 1654-9716 .- 1654-9880. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data.OBJECTIVE: To present standardised comparisons of HIV/AIDS-related mortality at sites across Africa and Asia, including closely related causes of death such as pulmonary tuberculosis (PTB) and pneumonia.DESIGN: Deaths related to HIV/AIDS were extracted from individual demographic and VA data from 22 INDEPTH sites across Africa and Asia. VA data were standardised to WHO 2012 standard causes of death assigned using the InterVA-4 model. Between-site comparisons of mortality rates were standardised using the INDEPTH 2013 standard population.RESULTS: The dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over 12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates varied widely across Africa and Asia, with highest burdens in eastern and southern Africa, and lowest burdens in Asia. There was evidence of rapidly declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was also strongly related to PTB mortality. On a country basis, there were strong similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived from modelled estimates.CONCLUSIONS: Measuring HIV/AIDS-related mortality continues to be a challenging issue, all the more so as anti-retroviral treatment programmes alleviate mortality risks. The congruence between these results and other estimates adds plausibility to both approaches. These data, covering some of the highest mortality observed during the pandemic, will be an important baseline for understanding the future decline of HIV/AIDS.
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