Projected health workforce requirements and shortage for addressing the disease burden in the WHO Africa Region, 2022-2030: a needs-based modelling study.

INTRODUCTION: An adequate health workforce (HWF) is essential to achieving the targets of the Sustainable Development Goals (SDG), including universal health coverage. However, weak HWF planning and constrained fiscal space for health, among other factors in the WHO Africa Region, has consistently resulted in underinvestment in HWF development, shortages of the HWF at the frontlines of service delivery and unemployment of qualified and trained health workers. This is further compounded by the ever-evolving disease burden and reduced access to essential health services along the continuum of health promotion, disease prevention, diagnostics, curative care, rehabilitation and palliative care. METHODS: A stock and flow model based on HWF stock in 2022, age structure, graduation and migration was conducted to project the available stock by 2030. To estimate the gap between the projected stock and the need, a population needs-based modelling was conducted to forecast the HWF needs by 2030. These estimations were conducted for all 47 countries in the WHO African Region. Combining the stock projection and needs-based estimation, the modelling framework included the stock of health workers, the population's need for health services, the need for health workers and gap analysis expressed as a needs-based shortage of health workers. RESULTS: The needs-based requirement for health workers in Africa was estimated to be 9.75 million in 2022, with an expected 21% increase to 11.8 million by 2030. The available health workers in 2022 covered 43% of the needs-based requirements and are anticipated to improve to 49% by 2030 if the current trajectory of training and education outputs is maintained. An increase of at least 40% in the stock of health workers between 2022 and 2030 is anticipated, but this increase would still leave a needs-based shortage of 6.1 million workers by 2030. Considering only the SDG 3.c.1 tracer occupations (medical doctors, nurses, midwives, pharmacists and dentists), the projected needs-based shortage is 5.3 million by 2030. In sensitivity analysis, the needs-based shortage is most amenable to the prevalence of diseases/risk factors and professional standards for service delivery CONCLUSIONS: The WHO African Region would need to more than double its 2022 HWF stock if the growing population's health needs are to be adequately addressed. The present analysis offers new prospects to better plan HWF efforts considering country-specific HWF structure, and the burden of disease.

COVID-19 Vaccination Acceptance and Hesitancy in Healthcare Workers and the General Population: A Systematic Review and Policy Recommendations.

INTRODUCTION: The COVID-19 pandemic challenged the scientific community to find and develop a vaccine to fight the disease. However, problems with achieving high vaccine coverage have emerged, even among high-risk groups such as healthcare workers (HCWs). OBJECTIVE: The objective of this study is to examine factors that influence HCW's and the general population's adherence to COVID-19 vaccination and national policies to vaccinate HCWs and other target groups. METHODS: This study implemented a systematic review. The eligibility criterion for inclusion was being a HCW, target population for COVID-19 vaccination, or general population. Vaccination was the target intervention, and the COVID-19 pandemic was the context. We selected publications published between 1 January 2020 and 31 March 2022. Qualitative synthesis used a meta-aggregation approach. RESULTS: Nineteen articles were included in the review, with study samples varying from 48 to 5708 participants. Most of the evidence came from cross-sectional and qualitative studies. The main findings were related to vaccine hesitancy rather than acceptance. Factors associated with HCW vaccine hesitancy included subjective feelings such as safety concerns, rapid vaccine development, and insufficient testing. Countries have adopted few public policies to address this problem, and the main concern is whether to enforce vaccination and the extent to which measures are legal. CONCLUSION: The quality of the evidence base remains weak. Skepticism, mistrust, and hesitancy toward vaccination are global issues that can jeopardize vaccination coverage.

Understanding COVID-19 Impacts on the Health Workforce: AI-Assisted Open-Source Media Content Analysis.

BACKGROUND: To investigate the impacts of the COVID-19 pandemic on the health workforce, we aimed to develop a framework that synergizes natural language processing (NLP) techniques and human-generated analysis to reduce, organize, classify, and analyze a vast volume of publicly available news articles to complement scientific literature and support strategic policy dialogue, advocacy, and decision-making. OBJECTIVE: This study aimed to explore the possibility of systematically scanning intelligence from media that are usually not captured or best gathered through structured academic channels and inform on the impacts of the COVID-19 pandemic on the health workforce, contributing factors to the pervasiveness of the impacts, and policy responses, as depicted in publicly available news articles. Our focus was to investigate the impacts of the COVID-19 pandemic and, concurrently, assess the feasibility of gathering health workforce insights from open sources rapidly. METHODS: We conducted an NLP-assisted media content analysis of open-source news coverage on the COVID-19 pandemic published between January 2020 and June 2022. A data set of 3,299,158 English news articles on the COVID-19 pandemic was extracted from the World Health Organization Epidemic Intelligence through Open Sources (EIOS) system. The data preparation phase included developing rules-based classification, fine-tuning an NLP summarization model, and further data processing. Following relevancy evaluation, a deductive-inductive approach was used for the analysis of the summarizations. This included data extraction, inductive coding, and theme grouping. RESULTS: After processing and classifying the initial data set comprising 3,299,158 news articles and reports, a data set of 5131 articles with 3,007,693 words was devised. The NLP summarization model allowed for a reduction in the length of each article resulting in 496,209 words that facilitated agile analysis performed by humans. Media content analysis yielded results in 3 sections: areas of COVID-19 impacts and their pervasiveness, contributing factors to COVID-19-related impacts, and responses to the impacts. The results suggest that insufficient remuneration and compensation packages have been key disruptors for the health workforce during the COVID-19 pandemic, leading to industrial actions and mental health burdens. Shortages of personal protective equipment and occupational risks have increased infection and death risks, particularly at the pandemic's onset. Workload and staff shortages became a growing disruption as the pandemic progressed. CONCLUSIONS: This study demonstrates the capacity of artificial intelligence-assisted media content analysis applied to open-source news articles and reports concerning the health workforce. Adequate remuneration packages and personal protective equipment supplies should be prioritized as preventive measures to reduce the initial impact of future pandemics on the health workforce. Interventions aimed at lessening the emotional toll and workload need to be formulated as a part of reactive measures, enhancing the efficiency and maintainability of health delivery during a pandemic.

Impacts for health and care workers of Covid-19 and other public health emergencies of international concern: living systematic review, meta-analysis and policy recommendations.

BACKGROUND: Health and care workers (HCW) faced the double burden of the SARS-CoV-2 pandemic: as members of a society affected by a public health emergency and as HWC who experienced fear of becoming infected and of infecting others, stigma, violence, increased workloads, changes in scope of practice, among others. To understand the short and long-term impacts in terms of the COVID-19 pandemic and other public health emergencies of international concern (PHEICs) on HCW and relevant interventions to address them, we designed and conducted a living systematic review (LSR). METHODS: We reviewed literature retrieved from MEDLINE-PubMed, Embase, SCOPUS, LILACS, the World Health Organization COVID-19 database, the ClinicalTrials.org and the ILO database, published from January 2000 until December 2021. We included quantitative observational studies, experimental studies, quasi-experimental, mixed methods or qualitative studies; addressing mental, physical health and well-being and quality of life. The review targeted HCW; and interventions and exposures, implemented during the COVID-19 pandemic or other PHEICs. To assess the risk of bias of included studies, we used the Johanna Briggs Institute (JBI) Critical Appraisal Tools. Data were qualitatively synthetized using meta-aggregation and meta-analysis was performed to estimate pooled prevalence of some of the outcomes. RESULTS: The 1013 studies included in the review were mainly quantitative research, cross-sectional, with medium risk of bias/quality, addressing at least one of the following: mental health issue, violence, physical health and well-being, and quality of life. Additionally, interventions to address short- and long-term impact of PHEICs on HCW included in the review, although scarce, were mainly behavioral and individual oriented, aimed at improving mental health through the development of individual interventions. A lack of interventions addressing organizational or systemic bottlenecks was noted. DISCUSSION: PHEICs impacted the mental and physical health of HCW with the greatest toll on mental health. The impact PHEICs are intricate and complex. The review revealed the consequences for health and care service delivery, with increased unplanned absenteeism, service disruption and occupation turnover that subvert the capacity to answer to the PHEICs, specifically challenging the resilience of health systems.

LIFETIME AMBIENT ULTRAVIOLET RADIATION EXPOSURE AND INCIDENCE OF AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the link between lifelong exposure to ultraviolet radiation (UVR) and the development of age-related macular degeneration (AMD). METHODS: The Alienor study is a prospective population-based cohort involving 963 residents of Bordeaux, France, older than 73 years. A subset of 614 participants for advanced AMD and 422 participants for early AMD were included in the analysis. The participants' residential history combined with UVR estimates from the EuroSun satellite were used to estimate the amount of ambient UVR they have been exposed to over their lifetime. Age-related macular degeneration was classified from retinal fundus photographs and spectral domain optical coherence tomography at 2 to 3 years intervals over the 2006 to 2017 period. Associations between cumulative exposure to ultraviolet A, ultraviolet B, and total (total UV) and the incidence of early and advanced AMD were estimated using multivariate Cox models. RESULTS: Intermediate quartiles of total UV, ultraviolet A, and ultraviolet B exposures were associated with a higher risk for incident early AMD (Hazard Ratio [HR] =2.01 [95% confidence interval [CI] = 1.27-3.13], HR = 2.20 [95% CI = 1.38-3.50], HR = 1.79 [95% CI = 1.13-2.80], respectively) as compared with the lower quartile. However, this risk did not further increase in the highest quartiles of exposure. None of the three types of UVR exposure was significantly associated with incident advanced AMD. CONCLUSION: Despite an increased risk with intermediate compared with low UVR exposure, our study cannot confirm a dose-response relationship of UVR exposure with early AMD onset.

The global inequity in COVID-19 vaccination coverage among health and care workers.

BACKGROUND: Health and care workers (HCWs) are at the forefront of COVID-19 response, at high risk of infection, and as a result they are a priority group for COVID-19 vaccination. This paper presents the global patterns in COVID-19 vaccination coverage among HCWs in 2021, how HCWs were prioritized, and identifies factors associated with the early vaccination coverage. METHODS: Using monthly data reported to the World Health Organization, the percentages of partially and fully vaccinated HCWs were computed. The rates of vaccination of HCWs for the first and second half of 2021 were compared in a stratified analysis using several factors. A multivariate analysis was used to investigate the independent associations of these factors with the percentage of HCWs fully vaccinated. RESULTS: Based on data from 139 Member States, as of end of 2021, 82% HCWs were reported as fully vaccinated with important variations by income groups: 33% for low income countries, 83% for lower-middle income countries, 79% for upper-middle income countries and 88% for high income countries. Overall 76% of countries did not achieve 70% vaccination coverage of their HCWs in the first half of 2021, and 38% of countries by end of 2021. Compared with the general population, the rate of HCWs full vaccination was 3.5 times higher, in particular for low income countries (RR = 5.9). Stratified analysis showed that beyond income group, the availability of vaccine doses was a critical factor of HCWs vaccination coverage with medians of 59.1% and 88.6% coverage in the first and second half of 2021, respectively for countries with enough doses to cover 70% of their population, compared with 0.8% and 47.5% coverage, respectively for countries with doses to cover 40% of their population. The multivariate analysis confirmed this observation with a 35.9% overall difference (95%CI 15.1%; 56.9%) between these two groups. CONCLUSION: Despite being considered a priority group, more than a third of countries did not achieve 70% vaccination coverage of their HCWs at the end of 2021. Large inequities were observed with low income countries lagging behind. Additional efforts should be dedicated to ensure full protection of HCWs through vaccination.

The global health workforce stock and distribution in 2020 and 2030: a threat to equity and 'universal' health coverage?

OBJECTIVE: The 2016 Global Strategy on Human Resources for Health: Workforce 2030 projected a global shortage of 18 million health workers by 2030. This article provides an assessment of the health workforce stock in 2020 and presents a revised estimate of the projected shortage by 2030. METHODS: Latest data reported through WHO's National Health Workforce Accounts (NHWA) were extracted to assess health workforce stock for 2020. Using a stock and flow model, projections were computed for the year 2030. The global health workforce shortage estimation was revised. RESULTS: In 2020, the global workforce stock was 29.1 million nurses, 12.7 million medical doctors, 3.7 million pharmacists, 2.5 million dentists, 2.2 million midwives and 14.9 million additional occupations, tallying to 65.1 million health workers. It was not equitably distributed with a 6.5-fold difference in density between high-income and low-income countries. The projected health workforce size by 2030 is 84 million health workers. This represents an average growth of 29% from 2020 to 2030 which is faster than the population growth rate (9.7%). This reassessment presents a revised global health workforce shortage of 15 million health workers in 2020 decreasing to 10 million health workers by 2030 (a 33% decrease globally). WHO African and Eastern Mediterranean regions' shortages are projected to decrease by only 7% and 15%, respectively. CONCLUSIONS: The latest NHWA data show progress in the increasing size of the health workforce globally as more jobs are and will continue to be created in the health economy. It however masks considerable inequities, particularly in WHO African and Eastern Mediterranean regions, and alarmingly among the 47 countries on the WHO Support and Safeguards List. Progress should be acknowledged with caution considering the immeasurable impact of COVID-19 pandemic on health workers globally.

Inequal distribution of nursing personnel: a subnational analysis of the distribution of nurses across 58 countries.

BACKGROUND: Nursing personnel are critical for enabling access to health service in primary health care. However, the State of the World's Nursing 2020 report showed important inequalities in nurse availability between countries. METHODS: The purpose of this study/analysis was to describe the differences in nurse-to-population density in 58 countries from six regional areas and the relationship between differences in access to nurses and other indicators of health equity. RESULTS: All countries and income groups showed subnational inequalities in the distribution of nursing personnel with Gini coefficients ranging from 1 to 39. The latter indicated situation such as 13% of the population having access to 45% of nurses in a country. The average max-to-min ratio was on average of 11-fold. In our sample, the African region had the highest level of subnational inequalities with the average Gini coefficient of 19.6. The European Region had the lowest level of within-country inequalities with the average Gini coefficient being 5.6. A multivariate analysis showed a clustering of countries in three groups: (1) high Gini coefficients comprised mainly African countries; (2) moderate Gini coefficients comprised mainly South-East Asian, Central and South American countries; (3) low Gini coefficients comprised mainly Western countries, Japan, and Korea. The analysis also showed that inequality in distribution of nurses was correlated with other indices of health and inequality such as the Human Development Index, maternal mortality, and life expectancy. CONCLUSIONS: This study showed that there is a high level of geographic inequality in the distribution of nurses at subnational level. Inequalities in nursing distribution are multifactorial, to improve access to nurses, policies should be bundled, tailored to the local context and tackle the various root causes for inequalities.

Estimating the health workforce requirements and costing to reach 70% COVID-19 vaccination coverage by mid-2022: a modelling study and global estimates.

OBJECTIVES: The implementation of COVID-19 vaccination globally poses unprecedented stress to health systems particularly for countries with persisting health workforce shortages prior the pandemic. The present paper estimates the workforce requirement to reach 70% COVID-19 vaccination coverage in all countries by mid-2022 using service target-based estimation. METHODS: Health workforce data from National Health Workforce Accounts and vaccination coverage reported to WHO as of January 2022 were used. Workload parameters were used to estimate the number of health workers needed with a service target-based approach, the gap and the scale-up required partially accounting for countries' challenges, as well as the associated costs in human resources. RESULTS: As of 1 January 2022, only 34 countries achieved 70% COVID-19 vaccination coverage and 61 countries covered less than a quarter of their population. This analysis showed that 1 831 000 health workers working full time would be needed to reach a global coverage of 70% COVID-19 vaccination by mid-2022. To avoid severe disruptions to health system, 744 000 additional health workers should be added to domestic resources mostly (77%) in low-income countries. In a sensitivity analysis, allowing for vaccination over 12 months instead of 6 months would decrease the scale-up to 476 000 health workers. The costing for the employment of these 744 000 additional health workers is estimated to be US$2.5 billion. In addition to such a massive scale-up, it is estimated that 29 countries would have needed to redeploy more than 20% of their domestic workforce, placing them at serious risk of not achieving the mid-year target. CONCLUSION: Reaching 70% global coverage with COVID-19 vaccination by mid-2022 requires extraordinary efforts not before witnessed in the history of immunisation programmes. COVID-19 vaccination programmes should receive rapid and sustainable investment in health workforce.

Increasing access to health workers in rural and remote areas: what do stakeholders' value and find feasible and acceptable?

BACKGROUND: The primary aim of this study is to assess stakeholders' views of the acceptability and feasibility of policy options and outcome indicators presented in the 2010 World Health Organization (WHO) global policy recommendations on increasing access to health workers in remote and rural areas through improved retention. METHODS: A survey on the acceptability, feasibility of recruitment and retention policy options, and the importance of their outcome indicators was developed. It followed a cross-sectional approach targeting health workers in rural and remote settings as well as policy- and decision-makers involved in the development of recruitment and retention policies for such areas. Respondents were asked their perception of the importance of the policy outcomes of interest, as well as the acceptability and feasibility of the 2010 WHO guidelines' policy options using a 9-point Likert scale. RESULTS: In total, 336 participants completed the survey. Almost a third worked in government; most participants worked in community settings and were involved in the administration and management of rural health workers. Almost all 19 outcomes of interests assessed were valued as important or critical. For the 16 guideline policy options, most were perceived to be "definitely acceptable" and "definitely feasible", although the policy options were generally considered to be more acceptable than feasible. CONCLUSION: The findings of this study provide insight into the revision and update of the 2010 WHO guideline on increasing access to health workers in remote and rural areas. Stakeholders' views of the acceptability, feasibility of policy options and the importance of outcomes of interest are important for the development of relevant and effective policies to improve access to health workers in rural and remote areas.

Stakeholders' perceptions of policy options to support the integration of community health workers in health systems.

BACKGROUND: Community health workers (CHWs) are an important component of the health workforce in many countries. The World Health Organization (WHO) has developed a guideline to support the integration of CHWs into health systems. This study assesses stakeholders' valuation of outcomes of interest, acceptability and feasibility of policy options considered for the CHW guideline development. METHODS: A cross-sectional mixed methods (quantitative and qualitative) study targeting stakeholders involved directly or indirectly in country implementation of CHW programmes was conducted in 2017. Data was collected from 96 stakeholders from five WHO regions using an online questionnaire. A Likert scale (1 to 9) was used to grade participants' assessments of the outcomes of interest, and the acceptability and feasibility of policy options were considered. RESULTS: All outcomes of interest were considered by at least 90% of participants as 'important' or 'critical'. Most critical outcomes were 'improved quality of CHW health services' and 'increased health service coverage' (91.5% and 86.2% participants judging them as 'critical' respectively). Out of 40 policy options, 35 were considered as 'definitely acceptable' and 36 'definitely feasible' by most participants. The least acceptable option (37% of participants rating 'definitely not acceptable') was the selection of candidates based on age. The least feasible option (29% of participants rating 'definitely not feasible') was the selection of CHWs with a minimum of secondary education. CONCLUSION: Outcomes of interest and policy options proposed were rated highly by most stakeholders. This finding helps to reinforce their usefulness in meeting the expectations of the CHW guideline end-users to properly integrate CHWs into health systems.

Collagen Prolyl Hydroxylases Are Bifunctional Growth Regulators in Melanoma.

Appropriate post-translational processing of collagen requires prolyl hydroxylation, catalyzed by collagen prolyl 3-hydroxylase and collagen prolyl 4-hydroxylase, and is essential for normal cell function. Here we have investigated the expression, transcriptional regulation, and function of the collagen prolyl 3-hydroxylase and collagen prolyl 4-hydroxylase families in melanoma. We show that the collagen prolyl 3-hydroxylase family exemplified by Leprel1 and Leprel2 is subject to methylation-dependent transcriptional silencing in primary and metastatic melanoma consistent with a tumor suppressor function. In contrast, although there is transcriptional silencing of P4HA3 in a subset of melanomas, the collagen prolyl 4-hydroxylase family members P4HA1, P4HA2, and P4HA3 are often overexpressed in melanoma, expression being prognostic of worse clinical outcomes. Consistent with tumor suppressor function, ectopic expression of Leprel1 and Leprel2 inhibits melanoma proliferation, whereas P4HA2 and P4HA3 increase proliferation, and particularly invasiveness, of melanoma cells. Pharmacological inhibition with multiple selective collagen prolyl 4-hydroxylase inhibitors reduces proliferation and inhibits invasiveness of melanoma cells. Together, our data identify the collagen prolyl 3-hydroxylase and collagen prolyl 4-hydroxylase families as potentially important regulators of melanoma growth and invasiveness and suggest that selective inhibition of collagen prolyl 4-hydroxylase is an attractive strategy to reduce the invasive properties of melanoma cells.

National cancer control plans: a global analysis.

There is increasing global recognition that national cancer plans are crucial to effectively address the cancer burden and to prioritise and coordinate programmes. We did a global analysis of available national cancer-related health plans using a standardised assessment questionnaire to assess their inclusion of elements that characterise an effective cancer plan and, thereby, improve understanding of the strengths and limitations of existing plans. The results show progress in the development of cancer plans, as well as in the inclusion of stakeholders in plan development, but little evidence of their implementation. Areas of continued unmet need include setting of realistic priorities, specification of programmes for cancer management, allocation of appropriate budgets, monitoring and evaluation of plan implementation, promotion of research, and strengthening of information systems. We found that countries with a non-communicable disease (NCD) plan but no national cancer control plan (NCCP) were less likely than countries with an NCCP and NCP plan or an NCCP only to have comprehensive, coherent, or consistent plans. As countries move towards universal health coverage, greater emphasis is needed on developing NCCPs that are evidence based, financed, and implemented to ensure translation into action.

Incretin-Based Therapies and the Short-term Risk of Pancreatic Cancer: Results From Two Retrospective Cohort Studies.

OBJECTIVE: Concerns have been raised about a possible increased risk of pancreatic cancer associated with incretin-based therapies. We examined the risk of pancreatic cancer among patients with diabetes prescribed incretin drugs. RESEARCH DESIGN AND METHODS: With the use of public health insurance databases of Belgium and the Lombardy Region, Italy, we created two retrospective cohorts that included adult patients who were first prescribed an incretin drug or another noninsulin antidiabetic drug (NIAD) from 1 July 2008 to 31 December 2013 in Belgium and from 1 January 2008 to 31 December 2012 in the Lombardy Region. The risk of pancreatic cancer was evaluated by multivariate-adjusted Cox models that included time-dependent variables. Adjusted hazard ratios (aHRs) from Belgium and Italy were pooled by using fixed-effects meta-analyses. RESULTS: The cohorts included 525,733 patients with diabetes treated with NIADs and 33,292 with incretin drugs. Results in both cohorts were similar. Eighty-five and 1,589 subjects who developed pancreatic cancer were registered among the incretin and NIAD new users, respectively, which represented an aHR of pancreatic cancer of 2.14 (95% CI 1.71-2.67) among those prescribed an incretin compared with an NIAD. The aHR with a drug use lag exposure of 6 months was 1.69 (1.24-2.32). The aHR decreased from 3.35 (2.32-4.84) in the first 3 months after the first incretin prescription to 2.12 (1.22-3.66) in months 3-5.9, 1.95 (1.20-3.16) in months 6-11.9, and 1.69 (1.12-2.55) after 12 months. Among those prescribed an NIAD, pancreatic cancer occurred mostly within the year after the first prescription. The risk of pancreatic cancer among patients subsequently prescribed insulin was 6.89 (6.05-7.85). CONCLUSIONS: The recent prescription of incretin therapy is associated with an increased risk of pancreatic cancer. The reason for such an increase is likely the consequence of an occult pancreatic cancer that provokes or aggravates diabetes. Studies are warranted for assessing the risk of pancreatic cancer associated with long-term use of incretin drugs.

Mammography screening: A major issue in medicine.

Breast cancer mortality is declining in most high-income countries. The role of mammography screening in these declines is much debated. Screening impacts cancer mortality through decreasing the incidence of number of advanced cancers with poor prognosis, while therapies and patient management impact cancer mortality through decreasing the fatality of cancers. The effectiveness of cancer screening is the ability of a screening method to curb the incidence of advanced cancers in populations. Methods for evaluating cancer screening effectiveness are based on the monitoring of age-adjusted incidence rates of advanced cancers that should decrease after the introduction of screening. Likewise, cancer-specific mortality rates should decline more rapidly in areas with screening than in areas without or with lower levels of screening but where patient management is similar. These two criteria have provided evidence that screening for colorectal and cervical cancer contributes to decreasing the mortality associated with these two cancers. In contrast, screening for neuroblastoma in children was discontinued in the early 2000s because these two criteria were not met. In addition, overdiagnosis - i.e. the detection of non-progressing occult neuroblastoma that would not have been life-threatening during the subject's lifetime - is a major undesirable consequence of screening. Accumulating epidemiological data show that in populations where mammography screening has been widespread for a long time, there has been no or only a modest decline in the incidence of advanced cancers, including that of de novo metastatic (stage IV) cancers at diagnosis. Moreover, breast cancer mortality reductions are similar in areas with early introduction and high penetration of screening and in areas with late introduction and low penetration of screening. Overdiagnosis is commonplace, representing 20% or more of all breast cancers among women invited to screening and 30-50% of screen-detected cancers. Overdiagnosis leads to overtreatment and inflicts considerable physical, psychological and economic harm on many women. Overdiagnosis has also exerted considerable disruptive effects on the interpretation of clinical outcomes expressed in percentages (instead of rates) or as overall survival (instead of mortality rates or stage-specific survival). Rates of radical mastectomies have not decreased following the introduction of screening and keep rising in some countries (e.g. the United States of America (USA)). Hence, the epidemiological picture of mammography screening closely resembles that of screening for neuroblastoma. Reappraisals of Swedish mammography trials demonstrate that the design and statistical analysis of these trials were different from those of all trials on screening for cancers other than breast cancer. We found compelling indications that these trials overestimated reductions in breast cancer mortality associated with screening, in part because of the statistical analyses themselves, in part because of improved therapies and underreporting of breast cancer as the underlying cause of death in screening groups. In this regard, Swedish trials should publish the stage-specific breast cancer mortality rates for the screening and control groups separately. Results of the Greater New York Health Insurance Plan trial are biased because of the underreporting of breast cancer cases and deaths that occurred in women who did not participate in screening. After 17 years of follow-up, the United Kingdom (UK) Age Trial showed no benefit from mammography screening starting at age 39-41. Until around 2005, most proponents of breast screening backed the monitoring of changes in advanced cancer incidence and comparative studies on breast cancer mortality for the evaluation of breast screening effectiveness. However, in an attempt to mitigate the contradictions between results of mammography trials and population data, breast-screening proponents have elected to change the criteria for the evaluation of cancer screening effectiveness, giving precedence to incidence-based mortality (IBM) and case-control studies. But practically all IBM studies on mammography screening have a strong ecological component in their design. The two IBM studies done in Norway that meet all methodological requirements do not document significant reductions in breast cancer mortality associated with mammography screening. Because of their propensity to exaggerate the health benefits of screening, case-control studies may demonstrate that mammography screening could reduce the risk of death from diseases other than breast cancer. Numerous statistical model approaches have been conducted for estimating the contributions of screening and of patient management to reductions in breast cancer mortality. Unverified assumptions are needed for running these models. For instance, many models assume that if screening had not occurred, the majority of screen-detected asymptomatic cancers would have progressed to symptomatic advanced cancers. This assumption is not grounded in evidence because a large proportion of screen-detected breast cancers represent overdiagnosis and hence non-progressing tumours. The accumulation of population data in well-screened populations diminishes the relevance of model approaches. The comparison of the performance of different screening modalities - e.g. mammography, digital mammography, ultrasonography, magnetic resonance imaging (MRI), three-dimensional tomosynthesis (TDT) - concentrates on detection rates, which is the ability of a technique to detect more cancers than other techniques. However, a greater detection rate tells little about the capacity to prevent interval and advanced cancers and could just reflect additional overdiagnosis. Studies based on the incidence of advanced cancers and on the evaluation of overdiagnosis should be conducted before marketing new breast-imaging technologies. Women at high risk of breast cancer (i.e. 30% lifetime risk and more), such as women with BRCA1/2 mutations, require a close breast surveillance. MRI is the preferred imaging method until more radical risk-reduction options are eventually adopted. For women with an intermediate risk of breast cancer (i.e. 10-29% lifetime risk), including women with extremely dense breast at mammography, there is no evidence that more frequent mammography screening or screening with other modalities actually reduces the risk of breast cancer death. A plethora of epidemiological data shows that, since 1985, progress in the management of breast cancer patients has led to marked reductions in stage-specific breast cancer mortality, even for patients with disseminated disease (i.e. stage IV cancer) at diagnosis. In contrast, the epidemiological data point to a marginal contribution of mammography screening in the decline in breast cancer mortality. Moreover, the more effective the treatments, the less favourable are the harm-benefit balance of screening mammography. New, effective methods for breast screening are needed, as well as research on risk-based screening strategies.

Effectiveness of and overdiagnosis from mammography screening in the Netherlands: population based study.

Objective To analyse stage specific incidence of breast cancer in the Netherlands where women have been invited to biennial mammography screening since 1989 (ages 50-69) and 1997 (ages 70-75), and to assess changes in breast cancer mortality and quantified overdiagnosis.Design Population based study.Setting Mammography screening programme, the Netherlands.Participants Dutch women of all ages, 1989 to 2012.Main outcome measures Stage specific age adjusted incidence of breast cancer from 1989 to 2012. The extra numbers of in situ and stage 1 breast tumours associated with screening were estimated by comparing rates in women aged 50-74 with those in age groups not invited to screening. Overdiagnosis was estimated after subtraction of the lead time cancers. Breast cancer mortality reductions and overdiagnosis during 2010-12 were computed without (scenario 1) and with (scenario 2) a cohort effect on mortality secular trends.Results The incidence of stage 2-4 breast cancers in women aged 50 or more was 168 per 100 000 in 1989 and 166 per 100 000 in 2012. Screening would be associated with a 5% mortality reduction in scenario 1 and with no influence on mortality in scenario 2. In both scenarios, improved treatments would be associated with 28% reductions in mortality. Overdiagnosis has steadily increased over time with the extension of screening to women aged 70-75 and with the introduction of digital mammography. After deduction of clinical lead time cancers, 33% of cancers found in women invited to screening in 2010-12 and 59% of screen detected cancers would be overdiagnosed.Conclusions The Dutch mammography screening programme seems to have little impact on the burden of advanced breast cancers, which suggests a marginal effect on breast cancer mortality. About half of screen detected breast cancers would represent overdiagnosis.

Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials.

Randomised trials reported up to Dec 31, 2012, did not confirm that vitamin D supplementation could protect from non-skeletal health conditions affecting adults, as was expected on the basis of data from observational studies. To examine whether the more recently published meta-analyses and trials would change past conclusions, we systematically reviewed meta-analyses of vitamin D supplementation and non-skeletal disorders published between Jan 1, 2013, and May 31, 2017, that included study participants of all ages, including pregnant women. We also searched for randomised trials not included in meta-analyses. We identified 87 meta-analyses, of which 52 were excluded because they contained less recent literature or were of suboptimal quality. We retrieved 202 articles on trials that were not included in meta-analyses. Recent meta-analyses reinforce the finding that 10-20 µg per day of vitamin D can reduce all-cause mortality and cancer mortality in middle-aged and older people. Although vitamin D doses were greater than those assessed in the past, we found no new evidence that supplementation could have an effect on most non-skeletal conditions, including cardiovascular disease, adiposity, glucose metabolism, mood disorders, muscular function, tuberculosis, and colorectal adenomas, or on maternal and perinatal conditions. New data on cancer outcomes were scarce. The compilation of results from 83 trials showed that vitamin D supplementation had no significant effect on biomarkers of systemic inflammation. The main new finding highlighted by this systematic review is that vitamin D supplementation might help to prevent common upper respiratory tract infections and asthma exacerbations. There remains little evidence to suggest that vitamin D supplementation has an effect on most conditions, including chronic inflammation, despite use of increased doses of vitamin D, strengthening the hypothesis that low vitamin D status is a consequence of ill health, rather than its cause. We further hypothesise that vitamin D supplementation could exert immunomodulatory effects that strengthen resistance to acute infections, which would reduce the risk of death in debilitated individuals. We identified many meta-analyses of suboptimal quality, which is of concern. Future systematic reviews on vitamin D should be based on data sharing so that data for participants with the same outcomes measured in the same way can be pooled to generate stronger evidence.

Meta-analysis of occupational exposures in the rubber manufacturing industry and risk of cancer.

Background: Occupational exposures in the rubber manufacturing industry showed an increased risk of cancer and have been classified as a group 1 carcinogen, largely from studies on workers employed before 1950s. Cancer sites considered as causally associated are bladder, lung and stomach, and leukaemia. Recent studies did not report an increased risk of cancer. Methods: A meta-analysis was conducted on observational studies published until April 2016 on occupational exposures in the rubber manufacturing industry and risk of cancer. Case-control and cohort studies were included. Random effect models were used. Heterogeneity and publication bias were evaluated. Stratified analyses were conducted on study characteristics. Results: The literature search identified 46 cohorts and 59 case-control studies. An increased risk was found for bladder cancer [standardised incidence ratio (SRR) = 1.36; 95% confidence interval (CI) 1.18, 1.57], leukaemia (SRR = 1.29; 95% CI 1.11, 1.52), lymphatic and haematopoietic system (SRR = 1.16; 95% CI 1.02, 1.31) and larynx cancer (SRR = 1.46; 95% CI 1.10, 1.94). For lung cancer, a borderline statistically significant increased risk was identified (SRR = 1.08; 95% CI 0.99, 1.17). No association was found for stomach cancer (SRR = 1.06; 95% CI 0.95, 1.17). In stratified analyses, risks of cancer were not increased for workers employed after 1960 for bladder cancer (SRR = 1.06; 95% CI 0.66, 1.71), lung cancer (SRR = 0.94; 95% CI 0.68, 1.29) or leukaemia (SRR = 0.92; 95% CI 0.62, 1.36). Conclusions: Risk of bladder cancer, lung cancer, leukaemia and larynx cancer were increased among workers in rubber industry. Evidence of elevated risks was no longer seen for bladder cancer, lung cancer or leukemia among workers first employed after 1960.