Summary Background In 2008, 2·45 million people were diagnosed with cancer and 1·23 million died because of cancer in the 27 countries of the European Union (EU). We aimed to estimate the economic ...burden of cancer in the EU. Methods In a population-based cost analysis, we evaluated the cost of all cancers and also those associated with breast, colorectal, lung, and prostate cancers. We obtained country-specific aggregate data for morbidity, mortality, and health-care resource use from international and national sources. We estimated health-care costs from expenditure on care in the primary, outpatient, emergency, and inpatient settings, and also drugs. Additionally, we estimated the costs of unpaid care provided by relatives or friends of patients (ie, informal care), lost earnings after premature death, and costs associated with individuals who temporarily or permanently left employment because of illness. Findings Cancer cost the EU €126 billion in 2009, with health care accounting for €51·0 billion (40%). Across the EU, the health-care costs of cancer were equivalent to €102 per citizen, but varied substantially from €16 per person in Bulgaria to €184 per person in Luxembourg. Productivity losses because of early death cost €42·6 billion and lost working days €9·43 billion. Informal care cost €23·2 billion. Lung cancer had the highest economic cost (€18·8 billion, 15% of overall cancer costs), followed by breast cancer (€15·0 billion, 12%), colorectal cancer (€13·1 billion, 10%), and prostate cancer (€8·43 billion, 7%). Interpretation Our results show wide differences between countries, the reasons for which need further investigation. These data contribute to public health and policy intelligence, which is required to deliver affordable cancer care systems and inform effective public research funds allocation. Funding Pfizer.
Background Melioidosis therapy is divided into an intravenous intensive phase and an oral eradication phase. The Darwin melioidosis treatment guideline has evolved over two decades, with over 1150 ...consecutive patients with culture-confirmed melioidosis managed under the Darwin Prospective Melioidosis Study. The current guideline, published in 2015, has been associated with low rates of recrudescence, relapse and mortality, and together with the treatment trials in Thailand, forms the basis for consensus global guidelines. We aimed to reassess the Darwin guideline and determine if any adjustments to the recommendations better reflect current practice in melioidosis therapy at Royal Darwin Hospital. Methodology/Principal findings This retrospective cohort study reviews the characteristics, admission duration, duration of intravenous antibiotics, recrudescence, recurrence and mortality in all patients presenting with first episode culture-confirmed melioidosis in the tropical north of Australia's Northern Territory from 1.sup.st October 2012 until 1.sup.st January 2017. 234 patients were available for analysis. 16 (6.8%) died during the intensive phase treatment and 6 (2.6%) did not have complete treatment at Royal Darwin Hospital, leaving 212 patients for analysis. Six (2.8%) patients had recrudescence during therapy and 10 (4.7%) had recurrent melioidosis (relapse or new infection) after completion of therapy. Persisting osteomyelitis requiring surgery was an important reason for recrudescence as was unrecognized osteomyelitis for relapse. For patients presenting with an antibiotic duration determining focus of pneumonia, durations of intravenous antibiotics were often prolonged beyond the current 2-week minimum treatment recommendation. Prolongation of therapy in pneumonia mostly occurred in patients presenting with multi-lobar disease or with concurrent blood culture positivity. Conclusions/Significance The 2015 Darwin melioidosis guideline is working well with low rates of recrudescence, relapse and mortality. Based on the practice of the treating clinicians, the 2020 revision of the guideline has been adjusted to include a duration of a minimum of 3 weeks of intravenous antibiotics for those with concurrent bacteraemia and pneumonia involving only a single lobe and those with bilateral and unilateral multi-lobar pneumonias who do not have bacteraemia. We also extend to a minimum of 4 weeks intravenous therapy for those with concurrent bacteraemia and bilateral or unilateral multi-lobar pneumonia.
Summary Every year, more than 2 million women worldwide are diagnosed with breast or cervical cancer, yet where a woman lives, her socioeconomic status, and agency largely determines whether she will ...develop one of these cancers and will ultimately survive. In regions with scarce resources, fragile or fragmented health systems, cancer contributes to the cycle of poverty. Proven and cost-effective interventions are available for both these common cancers, yet for so many women access to these is beyond reach. These inequities highlight the urgent need in low-income and middle-income countries for sustainable investments in the entire continuum of cancer control, from prevention to palliative care, and in the development of high-quality population-based cancer registries. In this first paper of the Series on health, equity, and women’s cancers, we describe the burden of breast and cervical cancer, with an emphasis on global and regional trends in incidence, mortality, and survival, and the consequences, especially in socioeconomically disadvantaged women in different settings.
Over the past century, many of the world's major rivers have been modified for the purposes of flood mitigation, power generation and commercial navigation. Engineering modifications to the ...Mississippi River system have altered the river's sediment levels and channel morphology, but the influence of these modifications on flood hazard is debated. Detecting and attributing changes in river discharge is challenging because instrumental streamflow records are often too short to evaluate the range of natural hydrological variability before the establishment of flood mitigation infrastructure. Here we show that multi-decadal trends of flood hazard on the lower Mississippi River are strongly modulated by dynamical modes of climate variability, particularly the El Niño-Southern Oscillation and the Atlantic Multidecadal Oscillation, but that the artificial channelization (confinement to a straightened channel) has greatly amplified flood magnitudes over the past century. Our results, based on a multi-proxy reconstruction of flood frequency and magnitude spanning the past 500 years, reveal that the magnitude of the 100-year flood (a flood with a 1 per cent chance of being exceeded in any year) has increased by 20 per cent over those five centuries, with about 75 per cent of this increase attributed to river engineering. We conclude that the interaction of human alterations to the Mississippi River system with dynamical modes of climate variability has elevated the current flood hazard to levels that are unprecedented within the past five centuries.
Summary Background The global economic crisis has been associated with increased unemployment and reduced public-sector expenditure on health care (PEH). We estimated the effects of changes in ...unemployment and PEH on cancer mortality, and identified how universal health coverage (UHC) affected these relationships. Methods For this longitudinal analysis, we obtained data from the World Bank and WHO (1990–2010). We aggregated mortality data for breast cancer in women, prostate cancer in men, and colorectal cancers in men and women, which are associated with survival rates that exceed 50%, into a treatable cancer class. We likewise aggregated data for lung and pancreatic cancers, which have 5 year survival rates of less than 10%, into an untreatable cancer class. We used multivariable regression analysis, controlling for country-specific demographics and infrastructure, with time-lag analyses and robustness checks to investigate the relationship between unemployment, PEH, and cancer mortality, with and without UHC. We used trend analysis to project mortality rates, on the basis of trends before the sharp unemployment rise that occurred in many countries from 2008 to 2010, and compared them with observed rates. Results Data were available for 75 countries, representing 2·106 billion people, for the unemployment analysis and for 79 countries, representing 2·156 billion people, for the PEH analysis. Unemployment rises were significantly associated with an increase in all-cancer mortality and all specific cancers except lung cancer in women. By contrast, untreatable cancer mortality was not significantly linked with changes in unemployment. Lag analyses showed significant associations remained 5 years after unemployment increases for the treatable cancer class. Rerunning analyses, while accounting for UHC status, removed the significant associations. All-cancer, treatable cancer, and specific cancer mortalities significantly decreased as PEH increased. Time-series analysis provided an estimate of more than 40 000 excess deaths due to a subset of treatable cancers from 2008 to 2010, on the basis of 2000–07 trends. Most of these deaths were in non-UHC countries. Interpretation Unemployment increases are associated with rises in cancer mortality; UHC seems to protect against this effect. PEH increases are associated with reduced cancer mortality. Access to health care could underlie these associations. We estimate that the 2008–10 economic crisis was associated with about 260 000 excess cancer-related deaths in the Organisation for Economic Co-operation and Development alone. Funding None.
To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways.
Systematic review and meta-analysis.
Published studies in ...Medline from 1 January 2000 to 10 April 2020.
Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models.
The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings.
Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.
Summary 23% of the total global burden of disease is attributable to disorders in people aged 60 years and older. Although the proportion of the burden arising from older people (≥60 years) is ...highest in high-income regions, disability-adjusted life years (DALYs) per head are 40% higher in low-income and middle-income regions, accounted for by the increased burden per head of population arising from cardiovascular diseases, and sensory, respiratory, and infectious disorders. The leading contributors to disease burden in older people are cardiovascular diseases (30·3% of the total burden in people aged 60 years and older), malignant neoplasms (15·1%), chronic respiratory diseases (9·5%), musculoskeletal diseases (7·5%), and neurological and mental disorders (6·6%). A substantial and increased proportion of morbidity and mortality due to chronic disease occurs in older people. Primary prevention in adults aged younger than 60 years will improve health in successive cohorts of older people, but much of the potential to reduce disease burden will come from more effective primary, secondary, and tertiary prevention targeting older people. Obstacles include misplaced global health priorities, ageism, the poor preparedness of health systems to deliver age-appropriate care for chronic diseases, and the complexity of integrating care for complex multimorbidities. Although population ageing is driving the worldwide epidemic of chronic diseases, substantial untapped potential exists to modify the relation between chronological age and health. This objective is especially important for the most age-dependent disorders (ie, dementia, stroke, chronic obstructive pulmonary disease, and vision impairment), for which the burden of disease arises more from disability than from mortality, and for which long-term care costs outweigh health expenditure. The societal cost of these disorders is enormous.
Exposure to Plasmodium falciparum is associated with circulating "atypical" memory B cells (atMBCs), which appear similar to dysfunctional B cells found in HIV-infected individuals. Functional ...analysis of atMBCs has been limited, with one report suggesting these cells are not dysfunctional but produce protective antibodies. To better understand the function of malaria-associated atMBCs, we performed global transcriptome analysis of these cells, obtained from individuals living in an area of high malaria endemicity in Uganda. Comparison of gene expression data suggested down-modulation of B cell receptor signaling and apoptosis in atMBCs compared to classical MBCs. Additionally, in contrast to previous reports, we found upregulation of Fc receptor-like 5 (FCRL5), but not FCRL4, on atMBCs. Atypical MBCs were poor spontaneous producers of antibody ex vivo, and higher surface expression of FCRL5 defined a distinct subset of atMBCs compromised in its ability to produce antibody upon stimulation. Moreover, higher levels of P. falciparum exposure were associated with increased frequencies of FCRL5+ atMBCs. Together, our findings suggest that FCLR5+ identifies a functionally distinct, and perhaps dysfunctional, subset of MBCs in individuals exposed to P. falciparum.
ObjectivesTo estimate the impact of the COVID-19 pandemic on cancer care services and overall (direct and indirect) excess deaths in people with cancer.MethodsWe employed near real-time weekly data ...on cancer care to determine the adverse effect of the pandemic on cancer services. We also used these data, together with national death registrations until June 2020 to model deaths, in excess of background (pre-COVID-19) mortality, in people with cancer. Background mortality risks for 24 cancers with and without COVID-19-relevant comorbidities were obtained from population-based primary care cohort (Clinical Practice Research Datalink) on 3 862 012 adults in England.ResultsDeclines in urgent referrals (median=−70.4%) and chemotherapy attendances (median=−41.5%) to a nadir (lowest point) in the pandemic were observed. By 31 May, these declines have only partially recovered; urgent referrals (median=−44.5%) and chemotherapy attendances (median=−31.2%). There were short-term excess death registrations for cancer (without COVID-19), with peak relative risk (RR) of 1.17 at week ending on 3 April. The peak RR for all-cause deaths was 2.1 from week ending on 17 April. Based on these findings and recent literature, we modelled 40% and 80% of cancer patients being affected by the pandemic in the long-term. At 40% affected, we estimated 1-year total (direct and indirect) excess deaths in people with cancer as between 7165 and 17 910, using RRs of 1.2 and 1.5, respectively, where 78% of excess deaths occured in patients with ≥1 comorbidity.ConclusionsDramatic reductions were detected in the demand for, and supply of, cancer services which have not fully recovered with lockdown easing. These may contribute, over a 1-year time horizon, to substantial excess mortality among people with cancer and multimorbidity. It is urgent to understand how the recovery of general practitioner, oncology and other hospital services might best mitigate these long-term excess mortality risks.
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