Clinical Series

The relationship between academe and industry is explored in this collection of papers. Important questions are raised about biotechnology and research, biotechnology and new companies arising from academia, and industry-sponsored clinical research.

A three-part Series assesses the global public-health toll and policy implications of drug addiction. The first paper summarises data for the prevalence and consequences of problem use of amphetamines, cannabis, cocaine, and opioids. In high-income countries, illicit drug use contributes less to the burden of disease than tobacco, but a substantial proportion of that burden is due to alcohol. Intelligent policy responses to drug problems need better prevalence data for different types of illicit drug use and the harms that their use causes globally. This need is especially urgent in high-income countries with substantial rates of illicit drug use and in low-income and middle-income countries close to illicit drug production areas. The second paper reviews existing drug policies and highlights the need for greater reliance on scientific evidence-based policy making. The final paper examines the value of international drug conventions in protecting public health.

ADHD is one of the most controversial areas in psychiatry. Questions and disputes abound. What are the underlying causes, and how might research inform new and better treatments? Is it possible for ADHD to prevail into adulthood—or even be diagnosed for the first time at that stage—and if so, what are the best management strategies? A new Series from The Lancet Psychiatry addresses these important questions.

Many young people today are living with HIV/AIDS or depression—the leading causes of disease burden for adolescents worldwide. However, hazardous alcohol use now accounts for 86% of the 8·6 million substance related deaths of 15–29–year-olds globally. The Lancet Series on Adolescent Health brings together experts from the Institute of Child Health, London, UK, Kings College London, UK, and the Royal Childrens Hospital, Melbourne, Australia, to highlight the gaps in health services to adolescents and to draw up an action plan for improved health services for this population worldwide.

In 2007, The Lancet published its first adolescent health series, which highlighted particular areas of attention, such as sexual and reproductive health, mental health, and substance misuse. Today's 1.8 billion adolescents are more exposed to harmful alcohol consumption, sexually transmitted diseases, and other risks than in the past, and face other new challenges such as social media. The Lancet's second Series on Adolescent Health, launched to coincide with the 45th Session of the United Nations Commission on Population and Development, argues that it is now time to put the young person, not the specific issue, centre stage. Four papers analyse the role of adolescence as a foundation for future health, the social determinants of adolescent health, the potential of the worldwide application of prevention science, and the current availability of data on 25 suggested core indicators in all countries.

Given the advent of new immunotherapy treatments in recent years, there comes with it great enthusiasm about combining different treatment modalities to enhance the effect of immunomodulatory agents. Of these, radiotherapy emerges as a particularly promising candidate that can mediate robust immunostimulatory effects for systemic tumour control. However, optimal radioimmunotherapy regimens are still under investigation, both in terms of optimal radiotherapy dose, fractionation, target sites, timing, target organs, and toxicity. In this Series, five papers discuss key advances in radioimmunotherapy treatment for cancer: Sana Karam (University of Colorado, Denver, CO, USA) and colleagues discuss radioimmunotherapy approaches for head and neck cancer; Fernanda Herrera (University of Lausanne, Lausanne, Switzerland) and colleagues explore radioimmunotherapy treatments for ovarian cancer; Sean Pitroda (University of Chicago, Chicago, IL, USA) and colleagues for oligometastatic disease; Martin Pomper (Johns Hopkins University, Baltimore, USA) and colleagues explore enhancing CAR-T cell therapy through cellular imaging and radiotherapy; and Guido Kroemer (INSERM, Paris, France) and colleagues discuss enhancing therapeutic responses to radioimmunotherapy treatment whilst minimising toxicity.

As the burden of cancer continues to increase, a major concern in high-income countries is how to sustain affordable health care to cope with these rising patient numbers and with the increasing costs of service provision. In September, 2011, The Lancet Oncology published a Commission outlining the challenges of delivering affordable cancer care in high-income countries. Here, we re-visit the topic 3 years on, and ask what, if any, progress has been made. This Series of three papers identifies the key drivers of health-care cost in high-income countries, offers debate and recommendation for their reduction, and pragmatically discusses what changes can be implemented across health-care systems in order to deliver affordable, efficient cancer care in the years of increased burden to come.

Sub-Saharan Africa faces a major public-health challenge from non-communicable diseases. Although infectious diseases continue to afflict Africa, the proportion of the overall disease burden in sub-Saharan Africa attributable to cancer is rising, and the region is predicted to have a greater than 85% increase in cancer burden by 2030. This Series of seven papers focuses on cancer control in Africa, outlining the current situation, detailing barriers to care, and presenting ideas to advance cancer care and control in the region.

With the world’s population ageing rapidly and endocrine-related comorbidities a major impediment to good health in old age, understanding how the endocrine system ages is paramount to realising the dream of healthy ageing. Written by leading experts in the field, this four-paper Series in The Lancet Diabetes & Endocrinology focuses on recent developments and key issues in endocrine-system ageing and opportunities for therapeutic intervention. The first paper provides a broad overview of how age affects the different hypothalamic–pituitary axes governing hormone secretion and age-related changes in calcium and bone metabolism and glucose homoeostasis. The second paper reviews findings from the Testosterone Trials, highlighting benefits as well as possible cardiovascular concerns. The third paper on thyroid dysfunction—one of the most common disorders in older people—focuses on the physiological changes in thyroid function that occur with ageing and treatment considerations for clinical and subclinical thyroid dysfunction. The final paper discusses the role of the endocrine system in frailty and key areas for future translational research. Accompanying the Series, an Editorial examines the regulatory and therapeutic implications of the recent decision by the WHO to classify ageing as a disease, and authors from each Series paper discuss in a Podcast the key research issues in endocrine-system ageing and the implications for achieving the goal of healthy ageing.

Alcohol use disorders are a major cause of morbidity and mortality worldwide, and of immense importance to all mental health professionals. This new Series puts heavy drinking and alcohol use disorder in clinical and public health contexts, providing clinicians with a concise but comprehensive summary of current knowledge and future directions for research and care. Topics include screening, brief intervention, and referral for treatment; evidence-based behavioural interventions; medication-assisted treatment; and technology-based and population-level interventions. It also covers alcohol use disorder co-occurring with mental health disorders, summarising and exploring hypotheses as to why these conditions so frequently co-exist, and outlining various possible causal pathways.

Excessive alcohol consumption is one of the leading causes of liver disease and the seventh leading cause of premature death worldwide. Alcohol-related liver diseases is now the leading cause of liver transplantation in the USA. In light of this burden, this Series examines alcohol-related liver disease from a number of angles, including diagnosis and outpatient management, current and future treatments for alcoholic hepatitis, and the place of liver transplantation in therapeutic strategies.

"Your patient is ready, Sir!" William T Morton is reported to have said as his ether took effect on July 16, 1846. The 19th century experimenters with nitrous oxide, ether, and chloroform would marvel at what has happened to their specialty.

This Series examines the access and sustainable effectiveness of antimicrobials. The first two papers provide an insight into the mechanisms and drivers of antimicrobial resistance, its disease burden, and the potential effect of vaccines in restricting the need for antibiotics. The last three papers in the Series examine access and sustainability of antimicrobials at a more geographical level: reviewing access in low-income and middle-income countries; considering different policy domains and their effectiveness at national and regional levels to combat resistance; and identifying gaps in the current global effort to improve international collaboration and achieve key policy goals.

A three-part Series reviews the epidemiology, diagnosis, and treatment of Arthritis. The first paper focuses on osteoarthritis; two-thirds of women and around half of men aged 50 years or older have osteoarthritis of the hand. The ageing population and obesity epidemic could lead to targeted therapy aimed at phenotypically distinct subtypes of osteoarthritis. The second paper highlights spondyloarthritis, a group of several related but phenotypically distinct arthritic disorders. The final paper discusses juvenile idiopathic arthritis, a heterogeneous group of diseases characterised by arthritis of unknown origin, with onset before age 16 years.

Despite advances in the diagnosis and management of asthma, this heterogeneous disease still poses an unacceptable health and economic burden globally. The prevalence of asthma is increasing in many regions, and inadequate treatment can lead to substantial disease morbidity and mortality. Steps to ensure that existing therapeutic approaches are available to people living with asthma would go some way to addressing the burden, but a pressing need exists for new approaches to reduce the risk of developing asthma, influence its natural history, reduce its severity, and realise the potential of precision medicine. A Series of three papers in The Lancet and The Lancet Respiratory Medicine considers the promise of novel strategies to drive down the global burden of asthma. Erika von Mutius and Hermelijn Smits discuss risk and protective factors for asthma and the prospect of developing strategies for primary prevention. Mariëlle W Pijnenburg and Louise Fleming provide an overview of the management of severe asthma in children, discussing the promise of treatment options tailored to the needs of individual patients. And Gerard Koppelman and colleagues review advances in our understanding of the genetics of asthma and consider how genomics studies could guide the identification of new drug targets.

Atrial fibrillation affects 33 million individuals worldwide,and increases the risk of stroke, heart failure, and death; it also impairs quality of life. The goals of care in atrial fibrillation include the prevention of stroke, control of the ventricular rate, and minimisation of symptoms to improve quality of life.

Despite impressive efforts to unravel the causes and pathogenic mechanisms of autism spectrum disorders (ASD), major breakthroughs with clear therapeutic implications are still lacking. In the first of four Series papers in The Lancet Neurology, Daniel Geschwind and Matthew State consider how genetic findings might contribute to understanding of pathophysiology and to clinical management. Next, Christine Ecker and colleagues discuss the clinical relevance of neuroimaging findings in autism, looking at brain structure and function across the lifespan. John Constantino and Tony Charman consider how knowledge of causation and symptom structure might contribute to a “revolution” in ASD diagnosis. And in our final Series paper, Meng-Chuan Lai and colleagues propose a framework for evidence-based care and support across the lifespan, and consider what the future might hold as we reap the benefits of translational research.

Autoimmune rheumatic diseases, including rheumatoid arthritis, scleroderma, and systemic vasculitides, are debilitating, painful conditions that are rare but cause substantial morbidity and mortality in patients, and disproportionately affect women. In The Lancet, we publish a Clinical Series of three papers on these diseases. The Series points to many promising avenues and developments in detection and management of these diseases, which, if seized by clinicians and researchers, should accelerate this reduction further. Indeed, as Goldblatt and O'Neill write: "Rheumatology is entering an exciting time."

Bacterial meningitis is a devastating disease that is associated with substantial mortality and morbidity. Major causative bacteria are Streptococcus pneumoniae and Neisseria meningitis, with case-fatality rates of 30% and 7% in higher-income countries. In resource-poor settings, fatality rates can be as high as 50%. Neurological sequelae, including hearing loss, developmental disorders, and neuropsychological impairment are reported to occur in up to half of survivors of bacterial meningitis. Although routine vaccination against the three most common causative bacteria had considerable impact on the occurrence of bacterial meningitis, there are an estimated 1·2 million cases each year worldwide resulting in 180,000 deaths among children aged 1–59 months in 2010.

The obesity epidemic is a worldwide public health problem; around one third of the global population are overweight or obese. Excess adiposity has direct physiological consequences, including impaired mobility, sleep apnoea, increased bone load, and psychological distress. However, it is the cardiometabolic consequences of obesity - such as type 2 diabetes, cardiovascular and renal disease, and retinopathy - that constitute the major burden of the disease. Although diet and lifestyle interventions have been shown to be effective in trials, they have been less successful at a population level. The most effective treatment for obesity is bariatric surgery, which might also have effects beyond merely reducing excess weight. In this Series of articles from The Lancet Diabetes & Endocrinology, the effects of bariatric surgery on end-organ health are discussed, with detailed information about the mechanisms behind the physiological changes that occur after bariatric surgery presented. Additionally, the safety of such surgery is touched upon and the pathophysiology of bone loss, a major adverse consequence of bariatric surgery, is explored in detail. The Series concludes with a review of existing guidelines governing the use of bariatric surgery and calls for changes to recommendations on the basis of the latest evidence.

Many approaches are available for breast cancer screening and profiling, and this Lancet Series on Breast Cancer focuses on the evidence behind the differing approaches. The first Series article examines the sensitivity of MRI for screening of patients with known or suspected genetic mutation results. Implications for surgical treatment selection, long-term outcomes, recurrence rates, and chemotherapy response are assessed. The second paper in the Series discusses the development of a molecular classification system and prognostic multigene classifiers for breast cancer. Breast cancer is now perceived as a heterogeneous group of diseases characterised by distinct molecular aberrations, and this article examines results of gene expression profiling studies, and focuses on the conceptual effect and potential clinical use of the molecular classification of breast cancer.

The introduction of targeted therapies has profoundly changed the course of some subtypes of breast cancer—but many challenges remain. The Lancet’s 2016 Series on breast cancer discusses the most recent advances in the three most common breast cancer subtypes. The first pair of papers focus on the treatment of advanced oestrogen-receptor-positive and HER2-positive breast cancers, while the third describes how an improved understanding of molecular alterations in the heterogeneous and hard-to-treat triple-negative breast cancer may lead to more refined and more effective therapy.

The prevalence of bronchiectasis is increasing worldwide, yet treatment options remain limited and clinical management is challenging. This three-paper Series gives a comprehensive overview of the latest clinical developments and research in both adult and paediatric bronchiectasis.

Is bullying part of a 'normal' childhood? Or is it a damaging behaviour that health professionals can and should try to prevent? This Series looks at the nature and mental health consequences of bullying, and highlights ways in which clinicians and researchers might address the problem.

Part of a surgery themed issue dated Oct 1, 2016, a three-part clinical Series explores the latest knowledge and treatment for severe burns. Major burns provoke a profound stress response, which is unrivalled in terms of its magnitude and duration. Evidence suggests that the pathophysiological stress response to severe burn trauma persists for several years after injury. Thus, there is a pressing need for novel strategies that mitigate this response and restore normal metabolic function in patients with burns, detailed in the first Series paper.

The cancer burden in Africa is projected to become a leading cause of morbidity and mortality as a result of growing and aging populations and decreasing mortality from infectious diseases. In light of these changes, Africa’s healthcare systems face huge challenges in effective cancer control in the future. In this Series of papers in The Lancet Oncology, Joe Harford discusses social, geopolitical and cultural barriers to overcome for effective cancer control for the continent, while Saskia Mostert and others discuss the issue of corruption within Africa’s healthcare sector. Sara Stulac and others proposes guiding principles for building capacity for oncology programs in sub-Saharan Africa using Rwanda as a country-specific example, and Elvira Singh and others discuss the challenges in establishing population-based cancer registries in middle-income countries, using their experience in South Africa as an example.

In this five-part Series on cancer disparities in indigenous populations in Polynesia, Australia, North America, and Africa in The Lancet Oncology, the Series authors highlight the scarcity of cancer burden data for Indigenous peoples and the unique genetic, environmental, and lifestyle factors that influence this burden. Gabi U Dachs and colleagues and Joan Cunningham and colleagues report risk factors that differ between ethnicities and disparities in measures of health in Australia, New Zealand, Hawaii, and other Pacific islands. Jeppe T Friborg and colleagues summarise the current knowledge on cancer epidemiology in Inuit populations. D Max Parkin and colleagues highlight areas where better surveillance and monitoring are needed to improve cancer control in Africa and Freddy Sitas and colleagues assess cancer risk factors and their importance in Africa.

The Cancer in Peru Series is a detailed examination of the cancer burden and control measures taken in Peru.

First along the cancer development pathway is the stage before diagnosis: how to prevent the genesis of cancer. This Series of papers in The Lancet Oncology investigates five aspects of this difficult-to-study concept: how lifestyle changes, including physical activity and diet affect cancer prevention; the different preventive measures taken at both the pharmacologic and governmental level; strategies to prevent anthracycline-based cardiotoxicity; and the role of big data in the future of personalised cancer prevention. The Series also includes a comment on how to best conceptualise precision prevention.

This Series of five papers in The Lancet Oncology explores cancer survivorship programmes in US healthcare systems.

Almost two decades after The Lancet's groundbreaking Arrhythmia Octet in 1993, cardiac electrophysiology has developed as a subspecialty so successfully that "specialist cardiology units are now likely to have almost as many electricians as plumbers", according to Andrew Grace, who orchestrated the current Series.

To coincide with the European Society of Cardiology Congress 2013, taking place in Amsterdam August 31—September 4, a special issue of The Lancet showcases the great strides that have been made in the care of patients with cardiovascular disease.

Ahead of the the ACC's 63^rd Annual Scientific Session a special issue of The Lancet focuses on cardiovascular disease. One of the many highlights from the issue is an Article that shows that the chance of surviving a hospital stay for a ruptured abdominal aortic aneurysm (rAAA) is significantly higher in the US than in England. Researchers compared survival patients admitted to hospital with rAAA in England and the US between 2005 and 2010. Findings show that just 58% of English patients were offered surgery compared with 80% of US patients, and that endovascular aneurysm repair was more than twice as common in the US.

Catatonia has been known to medicine for almost 150 years, but it is currently little discussed by mental health clinicians and researchers, and poorly understood. The first paper in this Series from The Lancet Psychiatry examines evidence regarding the structural and neural mechanisms underlying catatonia, outlines current treatment options, and maps a path for future research. The second paper examines the links between the cutting-edge science of neuroimmunology and catatonia, and explores the evidence that implicates glutamatergic hypofunction in its development. Finally, a Comment addresses the need to refine definitions of, and diagnostic criteria for, catatonia, in order to develop new treatments for this neglected condition.

Reductions in child mortality in high-income settings have been substantial over recent decades, although variations remain between and within countries. A three-part Series outlines the epidemiology of child mortality and a standardised approach to child death reviews in high-income countries. The Series authors delineate patterns of child mortality at different ages into five broad categories (perinatal causes, congenital abnormalities, acquired natural causes, external causes, and unexplained deaths), and describe contributory factors across four broad domains—biological and psychological factors, the physical environment, the social environment, and service delivery. In a Comment, the conclusions of these three reports are reviewed, and practical recommendations on strategies are proposed in three key areas: perinatal causes, notably preterm birth; acquired natural causes, such as sepsis or acute respiratory problems; and external causes, including road traffic fatalities.

The Lancet Series on Childhood Pneumonia and Diarrhoea, led by Aga Khan University, Pakistan, provides evidence for integrated control efforts for childhood pneumonia and diarrhoea. The first paper assesses the global burden of these two illnesses, comparing and contrasting them, and includes new estimates of severe disease and updated mortality estimates for 2011. Findings from the second paper show that a set of highly cost-effective interventions can prevent most diarrhoea deaths and nearly two thirds of pneumonia deaths by 2025, if delivered at scale. Furthermore, the paper estimates what the cost of scale up will be. The third paper presents the results of consultations with several hundred frontline workers in high-burden countries and explores the barriers and enablers they face in dealing with these two diseases and potential ways forward. The final paper represents a call to action and discusses the global and country-level remedies needed to eliminate preventable deaths from these illnesses by 2025.

Diabetes has become a major public health crisis in China, with an annual projected cost of 360 billion RMB (almost 60 billion USD) by 2030. Recent health system reforms have resulted in remarkable successes in other areas of medicine in China, but efforts to address diabetes and other non-communicable diseases lag behind. In addition to affecting the growing elderly population, type 2 diabetes increasingly affects young people, with the combined effect being enormous tolls on productivity and health-care systems. This Series in The Lancet Diabetes & Endocrinology examines the unique aspects of the diabetes epidemic in China and outlines potential public health strategies—such as targeted screening, improved prevention and access to care, and community support—that could help to manage diabetes in China as the health system continues to evolve.

Cough is a reflex action of the respiratory tract that is used to clear the upper airways. Chronic cough lasting for more than 8 weeks is common in the community. The causes include cigarette smoking, exposure to cigarette smoke, and exposure to environmental pollution, especially particulates.

The reduction of chronic disease is not a Millennium Development Goal (MDG). While the political fashions have embraced some diseases—HIV/AIDS, malaria, and tuberculosis, in particular—many other common conditions remain marginal to the mainstream of global action on health. Chronic diseases are among these neglected conditions.

Chronic diseases, principally cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes, are leading causes of death and disability but are grossly neglected on the global-health agenda.

In September 2011, the UN will hold its first High-level Meeting of the General Assembly on chronic non-communicable diseases. The Lancet's Series of papers is our contribution to preparations for the September meeting. These papers cover a range of diseases - cardiovascular, diabetes, cancer, and chronic obstructive respiratory diseases - and present strategies for substantial health gains, monitoring, and scaling up of interventions. We also highlight earlier Lancet Series and provide links through to all of the relevant content.

The Global Burden of Diseases investigators reported that 3·2 million people died worldwide from COPD in 2015, an increase of 11·6% compared with 1990. With risk factors such as smoking and household air pollution prevalent in many countries, there continues to be a large burden of disease globally. But not all COPD disease is the same. Researchers are increasingly interested in the tailoring of treatment to specific patient groups to improve outcome by deciphering different patient groups who might respond variably to treatments. Patient endotyping, where patients are separated by their treatment response or disease mechanism is an area of current interest and is discussed in this Series. Biological markers, such as blood eosinophils, are the focus of another paper, while the final paper focuses on palliative care and refractory breathlessness, a particularly troublesome symptom for patients. This Series provides the latest concepts with regards to the biology of disease and mechanistic pathways involved in disease development, with the aim to eventually help guide treatment and management of the patient.

Chronic Obstructive Pulmonary disease (COPD) is the fourth largest cause of mortality worldwide; according to new Lancet data, 1 in 4 adults over the age of 35 years will be diagnosed with COPD during their lifetime. Despite limited pharmacological developments in treatment over the past few decades, a Series assesses advances in COPD, including insights into immunology, future treatment strategies, the use of biomarkers, and important controversies such as the role of inhaled corticosteroids and antibiotics.

Cancer and cardiovascular disease are distressing diagnoses. When one is diagnosed and treated for cancer or cardiovascular disorders, depression, anxiety and other psychiatric conditions may develop. Cancer-Related Post Traumatic Stress Disorder (PTSD) and Cardiovascular-Related PTSD have also been documented with a growing evidence-based literature. New diagnostic PTSD criteria in the revised DSM-5 contain important changes compared to the previous DSM-IV-TR diagnostic criteria.

Fewer than half of new drugs have data on their comparative benefits and harms against existing treatment options at the time of regulatory approval in Europe and the US. Even when active comparator trials do exist, they might not produce meaningful data to inform decisions in clinical practice and health policy. This series of two reviews and a comment discusses the ethical implications of poor comparative effectiveness evidence, and the changes to the current approval systems that would be required to ensure that patients, clinicians and payers have timely access to the comparative data then need for decision making.

The UN's emergency relief coordinator on disaster reduction, Jan Egeland, is frustrated by the lack of attention given to natural disasters by the international community. For example, by comparison with the response to appeals over the complex emergency in Darfur, western Sudan, an appeal for money to tackle Africa's plague of locusts was a failure.

On Friday 2 May, 2014, The Lancet and The Lancet Respiratory Medicine published three new Reviews and an Editorial on asthma, ahead of 2014 World Asthma Day on May 6 and the American Thoracic Society's international conference (ATS 2014) in San Diego.

More than 25 years after the start of Drugs for the Heart, a new series of articles reviews the progress in cardiovascular therapy, with an emphasis on controversies in cardiology. Four articles encompass some of the most common diseases in the world that still tax cardiologists, let alone general physicians and general practitioners: stable coronary disease, hypertension, atrial fibrillation, and remodelling of the left ventricle.

This series includes three Reviews about intensive care medicine. The papers describe the evolution of the specialty, the demand for and ability to supply appropriate levels of care, and some of the commonly faced ethical dilemmas and challenges. These topics are apt in this period of economic constraint. Intensive care medicine consumes a considerable proportion of health-care resources and these costs will need to be justified. The appropriateness and effectiveness of the care provided will need to be improved to ensure that these resources are directed to patients most in need of them.

A large proportion of resources are consumed by the need for critical care services, also known as intensive care medicine. Close to 1% of the gross domestic product in the USA is now spent on such services, and patients with respiratory diseases make up a substantial proportion of critically ill cases.

The Lancet and The Lancet Respiratory Medicine have therefore published a Series of papers highlighting areas of current debate in critical care medicine. Topics include clinical challenges in mechanical ventilation, use of inhaled therapies in the ICU, and the prevention and care of the obese patient in the ICU.