Pre-hospital care is emergency medical care given to patients before arrival in hospital after activation of emergency medical services. It traditionally incorporated a breadth of care from bystander resuscitation to statutory emergency medical services treatment and transfer. New concepts of care including community paramedicine, novel roles such as emergency care practitioners, and physician delivered pre-hospital emergency medicine are re-defining the scope of pre-hospital care. For severely ill or injured patients, acting quickly in the pre-hospital period is crucial with decisions and interventions greatly affecting outcomes. The transfer of skills and procedures from hospital care to pre-hospital medicine enables early advanced care across a range of disciplines. The variety of possible pathologies, challenges of environmental factors, and hazardous situations requires management that is tailored to the patient's clinical need and setting. Pre-hospital clinicians should be generalists with a broad understanding of medical, surgical, and trauma pathologies, who will often work from locally developed standard operating procedures, but who are able to revert to core principles. Pre-hospital emergency medicine consists of not only clinical care, but also logistics, rescue competencies, and scene management skills (especially in major incidents, which have their own set of management principles). Traditionally, research into the hyper-acute phase (the first hour) of disease has been difficult, largely because physicians are rarely present and issues of consent, transport expediency, and resourcing of research. However, the pre-hospital phase is acknowledged as a crucial period, when irreversible pathology and secondary injury to neuronal and cardiac tissue can be prevented. The development of pre-hospital emergency medicine into a sub-specialty in its own right should bring focus to this period of care.

Extreme, expedition, and wilderness medicine are modern and rapidly evolving specialties that address the spirit of adventure and exploration. The relevance of and interest in these specialties are changing rapidly to match the underlying activities, which include global exploration, adventure travel, and military deployments. Extreme, expedition, and wilderness medicine share themes of providing best available medical care in the outdoors, especially in austere or remote settings. Early clinical and logistics decision making can often have important effects on subsequent outcomes. There are lessons to be learned from out-of-hospital care, military medicine, humanitarian medicine, and disaster medicine that can inform in-hospital medicine, and vice-versa. The future of extreme, expedition, and wilderness medicine will be defined by both recipients and practitioners, and empirical observations will be transformed by evidence-based practice.

The benefits of blood pressure lowering treatment for prevention of cardiovascular disease are well established. However, the extent to which these effects differ by baseline blood pressure, presence of comorbidities, or drug class is less clear. We therefore performed a systematic review and meta-analysis to clarify these differences.

Tissue deposition of protein fibrils causes a group of rare diseases called systemic amyloidoses. This Seminar focuses on changes in their epidemiology, the current approach to diagnosis, and advances in treatment. Systemic light chain (AL) amyloidosis is the most common of these conditions, but wild-type transthyretin cardiac amyloidosis (ATTRwt) is increasingly being diagnosed. Typing of amyloid fibrils, a critical determinant of therapy, has improved with the wide availability of laser capture and mass spectrometry from fixed histological tissue sections. Specific and accurate evaluation of cardiac amyloidosis is now possible using cardiac magnetic resonance imaging and cardiac repurposing of bone scintigraphy tracers. Survival in AL amyloidosis has improved markedly as novel chemotherapy agents have become available, but challenges remain in advanced disease. Early diagnosis, a key to better outcomes, still remains elusive. Broadening the amyloid-specific therapeutic landscape to include RNA inhibitors, fibril formation stabilisers and inhibitors, and immunotherapeutic targeting of amyloid deposits holds promise to transform outcomes in systemic amyloidoses.

Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone.

Malignant pleural mesothelioma is an aggressive cancer with poor prognosis, linked to occupational asbestos exposure. Vascular endothelial growth factor is a key mitogen for malignant pleural mesothelioma cells, therefore targeting of vascular endothelial growth factor might prove effective. We aimed to assess the effect on survival of bevacizumab when added to the present standard of care, cisplatin plus pemetrexed, as first-line treatment of advanced malignant pleural mesothelioma.

Despite recent advances in the treatment of advanced non-small-cell lung cancer, there remains a need for effective treatments for progressive disease. We assessed the efficacy of pembrolizumab for patients with previously treated, PD-L1-positive, advanced non-small-cell lung cancer.

Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality.

Effective systemic therapies for patients with advanced, progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce. We aimed to assess the efficacy and safety of everolimus compared with placebo in this patient population.

Successive Governments of India have promised to transform India's unsatisfactory health-care system, culminating in the present government's promise to expand health assurance for all. Despite substantial improvements in some health indicators in the past decade, India contributes disproportionately to the global burden of disease, with health indicators that compare unfavourably with other middle-income countries and India's regional neighbours. Large health disparities between states, between rural and urban populations, and across social classes persist. A large proportion of the population is impoverished because of high out-of-pocket health-care expenditures and suffers the adverse consequences of poor quality of care. Here we make the case not only for more resources but for a radically new architecture for India's health-care system. India needs to adopt an integrated national health-care system built around a strong public primary care system with a clearly articulated supportive role for the private and indigenous sectors. This system must address acute as well as chronic health-care needs, offer choice of care that is rational, accessible, and of good quality, support cashless service at point of delivery, and ensure accountability through governance by a robust regulatory framework. In the process, several major challenges will need to be confronted, most notably the very low levels of public expenditure; the poor regulation, rapid commercialisation of and corruption in health care; and the fragmentation of governance of health care. Most importantly, assuring universal health coverage will require the explicit acknowledgment, by government and civil society, of health care as a public good on par with education. Only a radical restructuring of the health-care system that promotes health equity and eliminates impoverishment due to out-of-pocket expenditures will assure health for all Indians by 2022--a fitting way to mark the 75th year of India's independence.

The NSABP B-35 trial compared 5 years of treatment with anastrozole versus tamoxifen for reducing subsequent occurrence of breast cancer in postmenopausal patients with ductal carcinoma in situ. This report assesses the effect of these drugs on quality of life and symptoms.

Ductal carcinoma in situ is currently managed with excision, radiotherapy, and adjuvant hormone therapy, usually tamoxifen. We postulated that an aromatase inhibitor would be safer and more effective. We therefore undertook this trial to compare anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy.

Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS.

Poor health can cause unhappiness and poor health increases mortality. Previous reports of reduced mortality associated with happiness could be due to the increased mortality of people who are unhappy because of their poor health. Also, unhappiness might be associated with lifestyle factors that can affect mortality. We aimed to establish whether, after allowing for the poor health and lifestyle of people who are unhappy, any robust evidence remains that happiness or related subjective measures of wellbeing directly reduce mortality.

Isavuconazole is a novel triazole with broad-spectrum antifungal activity. The SECURE trial assessed efficacy and safety of isavuconazole versus voriconazole in patients with invasive mould disease.

Whether rises in life expectancy are increases in good-quality years is of profound importance worldwide, with population ageing. We investigate how various health expectancies have changed in England between 1991 and 2011, with identical study design and methods in each decade.

Uptake in the national colorectal cancer screening programme in England varies by socioeconomic status. We assessed four interventions aimed at reducing this gradient, with the intention of improving the health benefits of screening.

Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma.

For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions.

Maternal overweight and obesity are risk factors for stillbirth and infant mortality. Whether temporal changes in maternal weight affect these risks is not clear. We aimed to assess whether change of BMI between first and second pregnancies affects risks of stillbirth and infant mortality in the second-born offspring.