| 1. |
- Darby, S, et al.
(författare)
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Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death : meta-analysis of individual patient data for 10,801 women in 17 randomised trials
- 2011
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 378:9804, s. 16-1707
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk.METHODS: We undertook a meta-analysis of individual patient data for 10,801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease.FINDINGS: Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35·0% to 19·3% (absolute reduction 15·7%, 95% CI 13·7-17·7, 2p<0·00001) and reduced the 15-year risk of breast cancer death from 25·2% to 21·4% (absolute reduction 3·8%, 1·6-6·0, 2p=0·00005). In women with pN0 disease (n=7287), radiotherapy reduced these risks from 31·0% to 15·6% (absolute recurrence reduction 15·4%, 13·2-17·6, 2p<0·00001) and from 20·5% to 17·2% (absolute mortality reduction 3·3%, 0·8-5·8, 2p=0·005), respectively. In these women with pN0 disease, the absolute recurrence reduction varied according to age, grade, oestrogen-receptor status, tamoxifen use, and extent of surgery, and these characteristics were used to predict large (≥20%), intermediate (10-19%), or lower (<10%) absolute reductions in the 10-year recurrence risk. Absolute reductions in 15-year risk of breast cancer death in these three prediction categories were 7·8% (95% CI 3·1-12·5), 1·1% (-2·0 to 4·2), and 0·1% (-7·5 to 7·7) respectively (trend in absolute mortality reduction 2p=0·03). In the few women with pN+ disease (n=1050), radiotherapy reduced the 10-year recurrence risk from 63·7% to 42·5% (absolute reduction 21·2%, 95% CI 14·5-27·9, 2p<0·00001) and the 15-year risk of breast cancer death from 51·3% to 42·8% (absolute reduction 8·5%, 1·8-15·2, 2p=0·01). Overall, about one breast cancer death was avoided by year 15 for every four recurrences avoided by year 10, and the mortality reduction did not differ significantly from this overall relationship in any of the three prediction categories for pN0 disease or for pN+ disease.INTERPRETATION: After breast-conserving surgery, radiotherapy to the conserved breast halves the rate at which the disease recurs and reduces the breast cancer death rate by about a sixth. These proportional benefits vary little between different groups of women. By contrast, the absolute benefits from radiotherapy vary substantially according to the characteristics of the patient and they can be predicted at the time when treatment decisions need to be made.FUNDING: Cancer Research UK, British Heart Foundation, and UK Medical Research Council.
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| 2. |
- Clarke, M, et al.
(författare)
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Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer : patient-level meta-analysis of randomised trials
- 2008
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Ingår i: The Lancet. - 0140-6736. ; 371:9606, s. 29-40
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: The long-term effects of adjuvant polychemotherapy regimens in oestrogen-receptor-poor (ER-poor) breast cancer, and the extent to which these effects are modified by age or tamoxifen use, can be assessed by an updated meta-analysis of individual patient data from randomised trials.METHODS: Collaborative meta-analyses of individual patient data for about 6000 women with ER-poor breast cancer in 46 trials of polychemotherapy versus not (non-taxane-based polychemotherapy, typically about six cycles; trial start dates 1975-96, median 1984) and about 14 000 women with ER-poor breast cancer in 50 trials of tamoxifen versus not (some trials in the presence and some in the absence of polychemotherapy; trial start dates 1972-93, median 1982).FINDINGS: In women with ER-poor breast cancer, polychemotherapy significantly reduced recurrence, breast cancer mortality, and death from any cause, in those younger than 50 years and those aged 50-69 years at entry into trials of polychemotherapy versus not. In those aged younger than 50 years (1907 women, 15% node-positive), the 10-year risks were: recurrence 33% versus 45% (ratio of 10-year risks 0.73, 2p<0.00001), breast cancer mortality 24% versus 32% (ratio 0.73, 2p=0.0002), and death from any cause 25% versus 33% (ratio 0.75, 2p=0.0003). In women aged 50-69 years (3965 women, 58% node-positive), the 10-year risks were: recurrence 42% versus 52% (ratio 0.82, 2p<0.00001), breast cancer mortality 36% versus 42% (ratio 0.86, 2p=0.0004), and death from any cause 39% versus 45% (ratio 0.87, 2p=0.0009). Few were aged 70 years or older. Tamoxifen had little effect on recurrence or death in women who were classified in these trials as having ER-poor disease, and did not significantly modify the effects of polychemotherapy.INTERPRETATION: In women who had ER-poor breast cancer, and were either younger than 50 years or between 50 and 69 years, these older adjuvant polychemotherapy regimens were safe (ie, had little effect on mortality from causes other than breast cancer) and produced substantial and definite reductions in the 10-year risks of recurrence and death. Current and future chemotherapy regimens could well yield larger proportional reductions in breast cancer mortality.
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| 3. |
- Seidler, Anna Lene, et al.
(författare)
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Deferred cord clamping, cord milking, and immediate cord clamping at preterm birth: a systematic review and individual participant data meta-analysis.
- 2023
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Ingår i: Lancet (London, England). - 1474-547X. ; 402:10418, s. 2209-2222
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Forskningsöversikt (refereegranskat)abstract
- Umbilical cord clamping strategies at preterm birth have the potential to affect important health outcomes. The aim of this study was to compare the effectiveness of deferred cord clamping, umbilical cord milking, and immediate cord clamping in reducing neonatal mortality and morbidity at preterm birth.We conducted a systematic review and individual participant data meta-analysis. We searched medical databases and trial registries (from database inception until Feb 24, 2022; updated June 6, 2023) for randomised controlled trials comparing deferred (also known as delayed) cord clamping, cord milking, and immediate cord clamping for preterm births (<37 weeks' gestation). Quasi-randomised or cluster-randomised trials were excluded. Authors of eligible studies were invited to join the iCOMP collaboration and share individual participant data. All data were checked, harmonised, re-coded, and assessed for risk of bias following prespecified criteria. The primary outcome was death before hospital discharge. We performed intention-to-treat one-stage individual participant data meta-analyses accounting for heterogeneity to examine treatment effects overall and in prespecified subgroup analyses. Certainty of evidence was assessed with Grading of Recommendations Assessment, Development, and Evaluation. This study is registered with PROSPERO, CRD42019136640.We identified 2369 records, of which 48 randomised trials provided individual participant data and were eligible for our primary analysis. We included individual participant data on 6367 infants (3303 [55%] male, 2667 [45%] female, two intersex, and 395 missing data). Deferred cord clamping, compared with immediate cord clamping, reduced death before discharge (odds ratio [OR] 0·68 [95% CI 0·51-0·91], high-certainty evidence, 20 studies, n=3260, 232 deaths). For umbilical cord milking compared with immediate cord clamping, no clear evidence was found of a difference in death before discharge (OR 0·73 [0·44-1·20], low certainty, 18 studies, n=1561, 74 deaths). Similarly, for umbilical cord milking compared with deferred cord clamping, no clear evidence was found of a difference in death before discharge (0·95 [0·59-1·53], low certainty, 12 studies, n=1303, 93 deaths). We found no evidence of subgroup differences for the primary outcome, including by gestational age, type of delivery, multiple birth, study year, and perinatal mortality.This study provides high-certainty evidence that deferred cord clamping, compared with immediate cord clamping, reduces death before discharge in preterm infants. This effect appears to be consistent across several participant-level and trial-level subgroups. These results will inform international treatment recommendations.Australian National Health and Medical Research Council.
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| 4. |
- Seidler, Anna Lene, et al.
(författare)
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Short, medium, and long deferral of umbilical cord clamping compared with umbilical cord milking and immediate clamping at preterm birth: a systematic review and network meta-analysis with individual participant data.
- 2023
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Ingår i: Lancet (London, England). - 1474-547X. ; 402:10418, s. 2223-2234
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Forskningsöversikt (refereegranskat)abstract
- Deferred (also known as delayed) cord clamping can improve survival of infants born preterm (before 37 weeks of gestation), but the optimal duration of deferral remains unclear. We conducted a systematic review and individual participant data network meta-analysis with the aim of comparing the effectiveness of umbilical cord clamping strategies with different timings of clamping or with cord milking for preterm infants.We searched medical databases and trial registries from inception until Feb 24, 2022 (updated June 6, 2023) for randomised controlled trials comparing cord clamping strategies for preterm infants. Individual participant data were harmonised and assessed for risk of bias and quality. Interventions were grouped into immediate clamping, short deferral (≥15 s to <45 s), medium deferral (≥45 s to <120 s), long deferral (≥120 s), and intact cord milking. The primary outcome was death before hospital discharge. We calculated one-stage, intention-to-treat Bayesian random-effects individual participant data network meta-analysis. This study was registered with PROSPERO, CRD42019136640.We included individual participant data from 47 trials with 6094 participants. Of all interventions, long deferral reduced death before discharge the most (compared with immediate clamping; odds ratio 0·31 [95% credibility interval] 0·11-0·80; moderate certainty). The risk of bias was low for 10 (33%) of 30 trials, 14 (47%) had some concerns, and 6 (20%) were rated as having a high risk of bias. Heterogeneity was low, with no indication of inconsistency.This study found that long deferral of clamping leads to reduced odds of death before discharge in preterm infants. In infants assessed as requiring immediate resuscitation, this finding might only be generalisable if there are provisions for such care with the cord intact. These results are based on thoroughly cleaned and checked individual participant data and can inform future guidelines and practice.Australian National Health and Medical Research Council.
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| 5. |
- Micah, Angela E., et al.
(författare)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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Forskningsöversikt (refereegranskat)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 6. |
- Carvalho, Andre F., et al.
(författare)
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Alcohol use disorders
- 2019
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Ingår i: The Lancet. - : ELSEVIER SCIENCE INC. - 0140-6736 .- 1474-547X. ; 394:10200, s. 781-792
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Forskningsöversikt (refereegranskat)abstract
- Alcohol use disorders consist of disorders characterised by compulsive heavy alcohol use and loss of control over alcohol intake. Alcohol use disorders are some of the most prevalent mental disorders globally, especially in high-income and upper-middle-income countries; and are associated with high mortality and burden of disease, mainly due to medical consequences, such as liver cirrhosis or injury. Despite their high prevalence, alcohol use disorders are undertreated partly because of the high stigma associated with them, but also because of insufficient systematic screening in primary health care, although effective and cost-effective psychosocial and pharmacological interventions do exist. Primary health care should be responsible for most treatment, with routine screening for alcohol use, and the provision of a staggered treatment response, from brief advice to pharmacological treatment. Clinical interventions for these disorders should be embedded in a supportive environment, which can be bolstered by the creation of alcohol control policies aimed at reducing the overall level of consumption.
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| 7. |
- Clemens, John D., et al.
(författare)
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Cholera
- 2017
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 390, s. 1539-1549
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Forskningsöversikt (refereegranskat)abstract
- © 2017 Elsevier Ltd Cholera is an acute, watery diarrhoeal disease caused by Vibrio cholerae of the O1 or O139 serogroups. In the past two centuries, cholera has emerged and spread from the Ganges Delta six times and from Indonesia once to cause global pandemics. Rational approaches to the case management of cholera with oral and intravenous rehydration therapy have reduced the case fatality of cholera from more than 50% to much less than 1%. Despite improvements in water quality, sanitation, and hygiene, as well as in the clinical treatment of cholera, the disease is still estimated to cause about 100 000 deaths every year. Most deaths occur in cholera-endemic settings, and virtually all deaths occur in developing countries. Contemporary understanding of immune protection against cholera, which results from local intestinal immunity, has yielded safe and protective orally administered cholera vaccines that are now globally stockpiled for use in the control of both epidemic and endemic cholera.
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| 8. |
- Danaei, Goodarz, et al.
(författare)
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Iran in transition
- 2019
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 393:10184, s. 1984-2005
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Forskningsöversikt (refereegranskat)abstract
- Being the second-largest country in the Middle East, Iran has a long history of civilisation during which several dynasties have been overthrown and established and health-related structures have been reorganised. Iran has had the replacement of traditional practices with modern medical treatments, emergence of multiple pioneer scientists and physicians with great contributions to the advancement of science, environmental and ecological changes in addition to large-scale natural disasters, epidemics of multiple communicable diseases, and the shift towards non-communicable diseases in recent decades. Given the lessons learnt from political instabilities in the past centuries and the approaches undertaken to overcome health challenges at the time, Iran has emerged as it is today. Iran is now a country with a population exceeding 80 million, mainly inhabiting urban regions, and has an increasing burden of non-communicable diseases, including cardiovascular diseases, hypertension, diabetes, malignancies, mental disorders, substance abuse, and road injuries.
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| 9. |
- Ghoreschi, Kamran, et al.
(författare)
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Therapeutics targeting the IL-23 and IL-17 pathway in psoriasis
- 2021
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Ingår i: The Lancet. - : ELSEVIER SCIENCE INC. - 0140-6736 .- 1474-547X. ; 397:10275, s. 754-766
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Forskningsöversikt (refereegranskat)abstract
- Psoriasis is a chronic inflammatory disease characterised by sharply demarcated erythematous and scaly skin lesions accompanied by systemic manifestations. Classified by WHO as one of the most serious non-infectious diseases, psoriasis affects 2-3% of the global population. Mechanistically, psoriatic lesions result from hyperproliferation and disturbed differentiation of epidermal keratinocytes that are provoked by immune mediators of the IL-23 and IL-17 pathway. Translational immunology has had impressive success in understanding and controlling psoriasis. Psoriasis is the first disease to have been successfully treated with therapeutics that directly block the action of the cytokines of this pathway; in fact, therapeutics that specifically target IL-23, IL-17, and IL-17RA are approved for clinical use and show excellent efficacy. Furthermore, inhibitors of IL-23 and IL-17 intracellular signalling, such as TYK2 or ROR gamma t, are in clinical development. Although therapies that target the IL-23 and IL-17 pathway also improve psoriatic arthritis symptoms, their effects on long-term disease modification and psoriasis-associated comorbidities still need to be explored.
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| 10. |
- Gilbert, Ruth, et al.
(författare)
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Child maltreatment : variation in trends and policies in six developed countries
- 2012
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9817, s. 758-772
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Forskningsöversikt (refereegranskat)abstract
- We explored trends in six developed countries in three types of indicators of child maltreatment for children younger than 11 years, since the inception of modern child protection systems in the 1970s. Despite several policy initiatives for child protection, we recorded no consistent evidence for a decrease in all types of indicators of child maltreatment. We noted falling rates of violent death in a few age and country groups, but these decreases coincided with reductions in admissions to hospital for maltreatment-related injury only in Sweden and Manitoba (Canada). One or more child protection agency indicators increased in five of six countries, particularly in infants, possibly as a result of early intervention policies. Comparisons of mean rates between countries showed five-fold to ten-fold differences in rates of agency indicators, but less than two-fold variation in violent deaths or maltreatment-related injury, apart from high rates of violent child death in the USA. These analyses draw attention to the need for robust research to establish whether the high and rising rates of agency contacts and out-of-home care in some settings are effectively reducing child maltreatment.
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