Globally, cancer is the second leading cause of death, with numbers greatly exceeding those for human immunodeficiency virus/acquired immunodeficiency syndrome, tuberculosis, and malaria combined. Limited access to timely diagnosis, to affordable, effective treatment, and to high‐quality care are just some of the factors that lead to disparities in cancer survival between countries and within countries. In this article, the authors consider various factors that prevent access to cancer medicines (particularly access to essential cancer medicines). Even if an essential cancer medicine is included on a national medicines list, cost might preclude its use, it might be prescribed or used inappropriately, weak infrastructure might prevent it being accessed by those who could benefit, or quality might not be guaranteed. Potential strategies to address the access problems are discussed, including universal health coverage for essential cancer medicines, fairer methods for pricing cancer medicines, reducing development costs, optimizing regulation, and improving reliability in the global supply chain. Optimizing schedules for cancer therapy could reduce not only costs, but also adverse events, and improve access. More and better biomarkers are required to target patients who are most likely to benefit from cancer medicines. The optimum use of cancer medicines depends on the effective delivery of several services allied to oncology (including laboratory, imaging, surgery, and radiotherapy). Investment is necessary in all aspects of cancer care, from these supportive services to technologies, and the training of health care workers and other staff.

In the Research Letter entitled “Change in Prevalence of Disabilities and Accommodation Practices Among US Medical Schools, 2016 vs 2019” published in the November 26, 2019, issue of JAMA,1 incorrect percent values were reported in the text and in Table 1. A sentence in the Results should have read: “Of the 64 schools that responded in both years, the total number of students reporting disabilities increased from 1142 (2.9%) in 2016 to 2028 (4.9%) in 2019 (difference, 1.9% [95% CI, 1.8%-2.3%]; relative increase, 69%) (Table 1).” In Table 1, the overall percent of students with disability in 2016 should have been reported as 2.9%, and in 2019, the overall percent should have been reported as 4.9%. Correction of these values does not affect the results, which remain as a 69% relative increase. This article was corrected online.

In the Editorial entitled “Statins for Primary Prevention: The Debate Is Intense, but the Data Are Weak”1 published in the November 15, 2016, issue of JAMA, incorrect data were reported in the text. In the first sentence of the second paragraph on the first page, the absolute benefit for use of statins should have been reported as 0.20%, rather than 0.43%, for cardiovascular mortality. This article was corrected online.

In the US Preventive Services Task Force Evidence Report entitled “Statins for Prevention of Cardiovascular Disease in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force” published in the November 15, 2016, issue of JAMA,1 incorrect data were reported. In the abstract Results, the data reported for cardiovascular mortality should have read “RR, 0.82 [95% CI, 0.71 to 0.94]; I2 = 0%; ARD, –0.20% [95% CI, –0.35% to –0.05%]; I2 = 11%.” In the second paragraph of the “Benefits of Statin Treatment” subsection in the text, the data reported for cardiovascular mortality should have read “RR, 0.82 [95% CI, 0.71 to 0.94]; I2 = 0%; ARD, –0.20% [95% CI, –0.35% to –0.05%]; I2 = 11%”; 2 paragraphs later, the sentence “For cardiovascular mortality, statistical heterogeneity was present (I2 = 54%), but the estimate was similar using the profile likelihood method (RR, 0.71 [95% CI, 0.55 to 0.88])” should have been deleted; and the text 2 paragraphs later should have read “Funnel plot asymmetry was not observed for outcomes reported in at least 10 trials, except for cardiovascular mortality (P = .049 for Egger test).” In the first paragraph of the Discussion, the data reported for cardiovascular mortality should have read “RR, 0.82 after 2-6 years [95% CI, 0.71 to 0.94]; I2 = 0%; ARD, –0.20% [95% CI, –0.35% to –0.05%],” and the NNT for cardiovascular death should have been reported as 500. In Table 3, “Key Question 1a” section, “Summary of Findings” column, the data reported for cardiovascular mortality should have read “RR, 0.82 [95% CI, 0.71-0.94]; I2 = 0%; ARD, –0.20%; NNT, 500.” Incorrect data also appeared in Figure 3 and the online supplement. This article was corrected online.

In the US Preventive Services Task Force (USPSTF) Recommendation Statement entitled “Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: US Preventive Services Task Force Recommendation Statement”1 published in the November 15, 2016, issue of JAMA, incorrect data were reported in the text. In the first paragraph of the “Statin Use in Adults Aged 40 to 75 Years” subsection and in the third paragraph of the “Benefits of Statin Use” subsection, the text “RR, 0.69 [95% CI, 0.54-0.88]” should have read “RR, 0.82 [95% CI, 0.71-0.94].” The certainty, magnitude of net benefit, and grades of the USPSTF recommendation remain the same. This article was corrected online.

The 2016 review1 for the US Preventive Services Task Force on statins for prevention of cardiovascular disease in adults had errors in the analysis of statins vs placebo and cardiovascular mortality. For the JUPITER trial, we interpreted “MI, stroke or cardiovascular death” as reported in the main trial publication2 as “myocardial death, stroke death, or cardiovascular death,” when it meant “nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death.” Therefore, the analysis erroneously included nonfatal myocardial infarction and stroke events (83/8901 vs 157/8901 in the rosuvastatin vs placebo groups, respectively) in the analysis of cardiovascular mortality (Figure 3, panel B in the evidence review). The US Food and Drug Administration (FDA) review of atorvastatin reported 29 vs 37 cardiovascular mortality events in the rosuvastatin vs placebo groups, respectively, in JUPITER.3 However, a subsequent publication from 2 of the original JUPITER authors4 reported numbers of confirmed cardiovascular deaths of 35 vs 43 (not including 16 vs 25 cases of sudden death) in the rosuvastatin vs placebo groups. For the ASTRONOMER trial, data for cardiovascular deaths were transposed from another trial (2/103 vs 12/79 for statins vs placebo); the correct data are 2/134 vs 5/135.5

In Reply We agree with Dr Auger and colleagues that there are several effects of gastric bypass surgery that may influence the risk of birth defects, including positive effects from weight loss and improved glucose control, as well as negative effects such as nutrient deficiencies and increased risk of substance abuse.1 With our study design, matching controls and gastric bypass surgery–exposed women on presurgery data regarding BMI, diabetes, and substance abuse, we attempted to answer the research question of whether gastric bypass surgery (vs no surgery) influences the risk of offspring birth defects.2 It aimed to inform women with severe obesity, prior to surgical intervention, about the risk or benefit for postsurgery pregnancy and childbirth. Hence, we estimated the net effect from both positive and negative consequences of treatment.

To the Editor In a Research Letter, Dr Neovius and colleagues investigated the association between gastric bypass surgery and risk of birth defects in offspring.1 The authors found that bariatric surgery was protective against birth defects. Although the data set was large, the results are somewhat challenging to interpret because of the choice of comparison group. The authors identified 2921 pregnant women with previous gastric bypass surgery and a comparison group of pregnant women with no history of bypass surgery. Women were matched on several risk factors for birth defects, including weight and diabetes. However, the authors matched the presurgery body mass index (BMI) for exposed women with the BMI at the time of pregnancy for controls. Similarly, women who had diabetes before surgery were matched with controls who had diabetes during pregnancy. Because women were less obese and had better glucose control after gastric bypass surgery, the authors compared women who lost weight after surgery with women who were more obese and had diabetes. Obesity and diabetes are both risk factors for birth defects;2 thus, it is expected that women who lose weight after bariatric surgery will have a lower risk of birth defects. The results confirm that weight loss is an effective tool to reduce the risk of birth defects but do not answer the question of whether women with gastric bypass procedures have an elevated risk of birth defects relative to women with similar weight.

In Reply We agree with Dr Rehberg and colleagues that our study demonstrated that selepressin had a number of advantageous physiologic effects on blood pressure, urine output, and other features associated with septic shock.1 In this way, as the authors suggest, it appears that selepressin shares a set of properties similar to that of other agents used for cardiovascular support in septic shock, including the recently approved angiotensin II.2 In contrast to the study on which angiotensin II was approved, we chose a primary outcome designed to determine whether care with selepressin improved downstream patient-centered outcomes, and, at least in this setting, we were unable to demonstrate any such improvement. That said, we were reassured that there was no obvious sign that care with selepressin was associated with more adverse events than care with norepinephrine alone. Rehberg and colleagues note there are limited data suggesting that any vasopressor improves downstream patient-centered outcomes compared with any other and therefore imply that if selepressin appears to work as well as other vasopressors, surely it should be added to the armamentarium of vasopressors for the care of septic shock, or at least be available for further evaluation. This line of reasoning represents one side of an old argument, namely, is there value in providing clinicians with a larger number of agents with clinically similar effects? Rehberg and colleagues, at least in this instance, seem to think so, and either way, we agree this is an important question to consider.

To the Editor Compared with placebo, the nonadrenergic vasopressor angiotensin II was shown to increase mean arterial pressure after 3 hours in patients with vasodilatory shock in the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial (primary end point).1 In addition, angiotensin II also reached the secondary goal of a greater reduction in the cardiovascular Sequential Organ Failure Assessment (SOFA) score after 48 hours vs placebo. As a consequence, research with angiotensin II continued and it was approved by the US Food and Drug Administration.

To the Editor In a propensity score–matched cohort of 578 patients from 4 observational cohort studies, Dr Kuramatsu and colleagues showed that evacuation of medium-sized intracerebellar hematomas (approximate volume, 20 cm3) was not associated with better functional outcome.1 Assessing treatment effectiveness in observational data is challenging because treatment decisions are based on patient characteristics that also are typically predictive of outcome, causing confounding by indication. Although the authors addressed this potential bias with propensity scores, we would like to emphasize the possibility of residual confounding.

Contributions to Medical and Biological Research. Dedicated to Sir William Osler, Bart., M.D., F.R.S., in honor of his seventieth birthday, July 12, 1919, by his pupils and co-workers. Two volumes. Pp. 1268. Paul B. Hoeber, New York. Edition limited to 1,600 copies. In these two large octavo volumes have been collected essays by some of the numerous pupils and co-workers of the late Sir William Osler. They are issued as a tribute to him on his seventieth birthday. The 142 essays are contributed by 151 writers, including 106 American, 33 English, 10 Canadian and 2 Scotch physicians; they are scientific, historical and literary…. In general, it may be said that the articles on historical, educational and social subjects distinctly surpass in literary quality and general interest those of a scientific or clinical nature. This is perhaps accounted for by the very nature of things, since the research worker or clinician could not produce a special study for this purpose, but must needs report work already done and use something already published, or, perhaps, rewrite for this purpose. The first volume opens with a frontispiece—a steel engraving of Sir William Osler—an excellent likeness. Following is a beautiful poem by Sir Clifford Allbutt. In an editorial note the committee states the purpose and method of preparation of these volumes…. Mr. Acland, in the first article, describes the Oxford University Museum. The article is well illustrated with especially fine half-tone photographs of the museum, and is a most interesting account of the relation to this museum of some of the predecessors of Sir William Osler in the chair of medicine at Oxford. It is brought out that John Ruskin was in part responsible for the designing of this structure. The second essay is a timely discussion of graduate study in London by Professor Adami, who is well adapted to the task, through his Canadian experience, his experience in the world war, and his intimate knowledge of conditions in America. Following two historical essays are some personal reminiscences of Sir William Osler by Dr. Crozier describing the early life of the great teacher.

for PeterYou sail into the garageon your bike, report onthe miles wheeled in the woods,on the serpent that crossed your path,a turtle bobbing its head amid pudd

A recentstudy suggested that Borna disease virus 1 (BoDV-1), which is carried by wild shrews in Germany, Austria, Switzerland, and Liechtenstein, could be a more common cause of severe or fatal encephalitis among people in endemic areas than previously realized. Although BoDV-1 is known to cause fatal neurologic disease in horses and sheep, recent case reports of severe or fatal encephalitis in people with BoDV-1 infection raised concerns that the virus is a threat to humans. In the latest study, researchers tested for BoDV-1 RNA and antibodies to the virus in brain tissue samples from 56 patients who died of suspected viral encephalitis between 1999 and 2019. The researchers identified another 6 human BoDV-1 cases and other laboratories identified 2 more. Viral RNA sequencing found that each person had a unique strain, suggesting that they were infected independently of each other, likely from a local wild animal reservoir. “Our findings indicate that Borna disease virus infection has to be considered a severe and potentially lethal human disease transmitted from a wildlife reservoir,” senior author Barbara Schmidt, MD, professor at the Institute of Clinical Microbiology and Hygiene at Regensburg University Hospital, said in a press release. “It’s not a newly emerging disease, but one that appears to have occurred unnoticed in humans for at least decades and may have caused other unexplained cases of encephalitis in regions where the virus is endemic in the host shrew populations.”

Poor infection control practices led to an unprecedented HIV outbreak among hundreds of children in Pakistan, according to a recent study. The outbreak in Pakistan’s Sindh province was detected in April 2019. A government task force’s investigation discovered that private and public health facilities reused needles and transfused blood products that weren’t screened for infection. In the aftermath, 3 blood banks and 300 clinics were closed. A free HIV screening and counseling camp also was established at Tehsil Hospital in the town of Ratodero. The study authors analyzed data from more than 31 000 people who were tested there. Overall, 3% of those screened tested HIV positive. Children were disproportionately affected: 82% of the infections were detected among those younger than 16 years and 79% were in children aged 5 years or younger. Among children whose mothers were tested, only 11% had mothers with HIV infection. Of the 453 children whose potential exposure history was available, 89% had received multiple injections primarily for diarrheal illnesses and respiratory tract infections. In addition, 9% had undergone a blood transfusion.

A recent drug safety communication alerted health professionals and the public about a potential increased risk of cancer associated with the weight management medication lorcaserin. The FDA has advised clinicians to consider whether the drug’s benefits outweigh its potential risks when deciding to prescribe or continue prescribing it. Lorcaserin, a satiety promoter marketed as Belviq or Belviq XR, was approved in 2012 for use with a reduced-calorie diet and increased physical activity to help adults with obesity or overweight lose weight if they have weight-related medical problems. The FDA required the drug’s manufacturer, Eisai Inc, of Woodcliff Lake, New Jersey, to conduct a postmarketing trial to evaluate the risk of heart-related problems when taking lorcaserin. The 5-year randomized controlled trial, which included about 12 000 participants, showed that more patients who took lorcaserin were diagnosed with cancer than those who received a placebo. “[T]he cause of the cancer is uncertain, and we cannot conclude that lorcaserin contributes to the cancer risk,” agency officials wrote in the safety communication. “However, we wanted to make the public aware of this potential risk. We are continuing to evaluate the clinical trial results and will communicate our final conclusions and recommendations when we have completed our review.”

A key FDA official told members of Congress last month that the agency supports the development of new drugs that contain cannabis or are derived from the plant. Speaking before the House Committee on Energy and Commerce, Douglas Throckmorton, MD, deputy director for regulatory programs at the FDA’s Center for Drug Evaluation and Research, said investigators interested in conducting cannabis research that could lead to a drug approval need to first submit an investigational new drug (IND) application. Even though cannabis is among Schedule I substances considered to have a high potential for abuse and no accepted medical value, Throckmorton said these substances can be evaluated in clinical trials as long as sponsors submit an IND and register with the Drug Enforcement Administration.

Two well-established first-line cognitive-behavioral psychotherapies for posttraumatic stress disorder (PTSD), prolonged exposure therapy (PE) and cognitive processing therapy (CPT), are used in the US Department of Veterans Affairs (VA) and US Department of Defense (DoD) based chiefly on good outcomes in randomized clinical trials (RCTs) with civilians. PE and CPT are manualized (ie, protocolized in a session-by-session manner) trauma-focused therapies that are based on processing the emotional and cognitive aspects of the traumatic event. Consequently, these treatments are emotionally demanding for patients because PTSD is characterized by a strong motivation to avoid talking about the trauma and rekindling negative emotions associated with it. The prominence of PE and CPT in treating individuals with military-related PTSD has been increasingly challenged in recent years because RCTs of veterans and military personnel have yielded mixed results, with patients often not obtaining clinically meaningful symptom improvement. These findings have led to questions about the extent to which these therapies should be prioritized and how military-related PTSD is best conceptualized, namely as a disorder that can be reliably managed by brief (approximately 12 session) monotherapies or as a highly complex and multiform condition requiring more individualized and comprehensive intervention.

A risk-based prevention strategy is the most widely accepted approach to guide clinician-patient decision-making for prevention of coronary artery disease (CAD). According to this approach, the intensity of prevention efforts is matched to the estimated risk of the individual.1 American College of Cardiology/American Heart Association guidelines currently recommend pooled cohort equations for initial risk assessment, which integrate age, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking status, and treatment for hypertension and diabetes to provide race- and sex-specific estimates of a broadly relevant end point of atherosclerotic cardiovascular risk (myocardial infarction, death from coronary heart disease, and fatal or nonfatal stroke).2 While risk assessment for CAD is known to be an imprecise estimate,3 no other tests of cardiovascular risk are uniformly agreed to enhance risk stratification. Thus, the search for additional and better risk markers continues to be a focus of cardiovascular research.4,5

Among critically ill patients in the intensive care unit (ICU), complications are frequent, including stress ulcers in the upper gastrointestinal tract. To help prevent the development of ulcers, antagonism of gastric acid (with antacids historically) or inhibition of the production of acid (with histamine-2 receptor blockers more recently) were implemented as part of routine critical care. The introduction of proton pump inhibitors, with data demonstrating improved ulcer prevention and recovery compared with histamine-2 receptor blockers in non–critically ill patients, led many physicians who provide care for critically ill patients to incorporate proton pump inhibitors for routine stress ulcer prophylaxis.1 However, the lack of randomized clinical trials (RCTs) that directly compared histamine-2 receptor blockers with proton pump inhibitors for stress ulcer prophylaxis in critically ill patients, combined with decreasing incidence of significant gastrointestinal bleeding in these patients and emerging evidence of an association between proton pump inhibitor use and adverse events, including Clostridioides difficile (Clostridium difficile) infection,2 cognitive decline,3 and nosocomial pneumonia,4 made the optimal choice of routine stress ulcer prophylaxis less clear.

My parents tell me that I began questioning my faith at a young age. As one story goes, when I was 4 years old, a pet fish at my preschool died. My father heard me crying in my room later that night. When he entered to ask me what was wrong, I replied, “What's the point of living if we are all going to die?” My father, a medical oncologist, thought for a moment. Then he responded quietly, “That’s not a very unique question.” According to my parents, I digested this information for a few seconds, then lay down and fell into a satisfied sleep. Growing up in a secular Jewish household, my family’s connection with faith was less about God or prayer and more about togetherness, comfort, food, and shared history. As a child, spirituality was also inextricably linked with music: my 2 grandfathers singing Yiddish duets; my own small voice joining in harmony to the swell of a congregation. The lesson that I interred from an early age was that connection with the divine was predicated not on a system of rites or rules but rather on a feeling: being part of something bigger than myself. This feeling—at times confusing, but also comforting—is not dissimilar to the feeling that drew me into the field of medicine. For the past 40 years, my father has dedicated his career to caring for patients with advanced cancer. On a near daily basis, he bears witness to catastrophic physical, psychological, and spiritual suffering, with a quiet equipoise and resilience that I both admire and envy. When I ask my father about his faith, he typically deflects with wry humor: “Why worry about the unknowable when our atoms will inevitably intermingle with stardust?” But even as a child, I noticed how my father created and found opportunities for meaning-making within the mundane. Each patient; each thoughtful, intentional treatment decision; each gentle interaction with grieving families on a Saturday night via his personal cell phone—across my childhood, these are the moments that I learned to appreciate as sacred.

Oxygen therapy is one of the most ubiquitously applied therapies in modern medicine. Clinicians usually react rapidly to declining oxygen saturations. Although this response is appropriate in the setting of hypoxia, there are many circumstances in which excess oxygen is indiscriminately administered for extended periods. Medicine has recently experienced a shift from “more is better” to “less is more” as more has been learned about the ability of the human body to adapt to extreme physiological conditions and about the inappropriate use of various therapies. Examples include hemoglobin thresholds and carbon dioxide levels. Attention in recent years has focused on the potential harms associated with excess oxygen therapy. Oxygen toxicity was first recognized clinically in an outbreak of retinal hyperplasia in premature infants leading to childhood blindness in the 1940s. Reports of oxygen pneumonitis were first described in the 1970s when autopsy findings demonstrated lung injury across patients who were exposed to concentrations of oxygen greater than 0.60 for at least 3 days of mechanical ventilation. In critical care, an early focus on harms of hyperoxia was attenuated after recognition of ventilator–associated lung injury, which shifted the cause from hyperoxia to injurious ventilation.

Transparency in science is a laudable goal. By describing with sufficient clarity, detail, and completeness the methods they use, and by making available the raw data that underlie their analyses, scientists can help ensure the reproducibility of their results and thus increase the trustworthiness of their findings and conclusions. At the same time, transparency is not in and of itself a definitive standard for the usefulness of science in policy making. A proposed rule at the Environmental Protection Agency (EPA), “Strengthening Transparency in Regulatory Science,”1 goes too far in barring from pivotal consideration in regulations any scientific study that does not have all data and analytic models made publicly available, unless special dispensations are granted. In particular, epidemiological and clinical studies that are designed to protect the confidentiality of personal health information may be highly germane to establishing environmental standards yet ethically barred from making all data publicly available. Other studies may rely on proprietary information, and their main findings may have been replicated in independent, proprietary studies, yet under the proposed rule, such studies similarly could not be relied on as a basis for regulation. The proposed rule provoked hundreds of thousands of comments and also was the subject of a recent congressional hearing.2 While sometimes falling short in its use of science,3 the EPA has traditionally strived to base regulations on the best available scientific evidence. For example, in 1997 the EPA adopted new air pollution regulations based mainly on 2 large epidemiological studies. The Harvard Six Cities study had begun in the 1970s to monitor the health of more than 8000 adults and children in 6 cities over 15 years while simultaneously tracking levels of air pollution, mainly related to burning of fossil fuels to generate electricity. Published in December 1993, the study found a strong gradient of mortality associated with increasing levels of airborne small particulates (diameter <2.5 μm).4 A second, independent study by the American Cancer Society followed 500 000 people in 154 cities for 8 years and reached similar conclusions in 1995.5

Clinical trial end points are outcome measures used to assess the efficacy and safety of an intervention. The selection of end points is based on their perceived clinical importance and accuracy of measurement. If correctly defined and collected, these outcome variables enable the translation of clinical trial data into evidence-based recommendations. Yet as technology changes and clinical practices evolve, emerging clinical events that are unrelated to the study intervention may be missed when conventional end points are used.

Ambient intelligence in hospitals is an emerging form of technology characterized by a constant awareness of activity in designated physical spaces and of the use of that awareness to assist health care workers such as physicians and nurses in delivering quality care. Recently, advances in artificial intelligence (AI) and, in particular, computer vision, the domain of AI focused on machine interpretation of visual data, have propelled broad classes of ambient intelligence applications based on continuous video capture. One important goal is for computer vision-driven ambient intelligence to serve as a constant and fatigue-free observer at the patient bedside, monitoring for deviations from intended bedside practices, such as reliable hand hygiene and central line insertions.1 While early studies took place in single patient rooms,2 more recent work has demonstrated ambient intelligence systems that can detect patient mobilization activities across 7 rooms in an ICU ward3 and detect hand hygiene activity across 2 wards in 2 hospitals.4 As computer vision–driven ambient intelligence accelerates toward a future when its capabilities will most likely be widely adopted in hospitals, it also raises new ethical and legal questions. Although some of these concerns are familiar from other health surveillance technologies, what is distinct about ambient intelligence is that the technology not only captures video data as many surveillance systems do but does so by targeting the physical spaces where sensitive patient care activities take place, and furthermore interprets the video such that the behaviors of patients, health care workers, and visitors may be constantly analyzed. This Viewpoint focuses on 3 specific concerns: (1) privacy and reidentification risk, (2) consent, and (3) liability.

Listen to the JAMA Editor’s Audio Summary for an overview and discussion of the important articles appearing in this week’s issue of JAMA. Click the multimedia icon above for the audio link.

Government’s public enthusiasm looks premature given the lack of available data The UK government recently announced an “innovative and ground-breaking collaboration” with the drug company Novartis to launch a clinical trial of inclisiran, a new cholesterol lowering drug.1 In addition, health officials said that they would provide the “cutting edge new cholesterol treatment” to patients once it was approved by regulators and the National Institute for Health and Care Excellence.2 They also stated that early results suggest that if 300 000 patients are treated each year, 55 000 heart attacks and strokes could be prevented and 30 000 lives saved over 10 years.1 This collaboration comes in the context of increasing uncertainty about the use of statins,3 and the newer PCSK9 inhibitors, which are expensive,2 and may not have lived up to expectations in terms of reductions in cardiovascular deaths or all-cause mortality.4 Inclisiran is not yet approved by any regulatory body worldwide, and there is currently no reliable publicly available evidence on its effect on cardiovascular disease or long term safety and cost effectiveness. Inclisiran is …

From April NHS services in England will be able to bar non-emergency patients or visitors who inflict discriminatory or harassing behaviour on staff.1 Previously, individual NHS organisations could refuse services to patients only if they were aggressive or violent. The news comes as results of the NHS staff survey in England show that more than a quarter of members of staff (28.5%) said they had experienced harassment, bullying, or abuse from patients, relatives, or members of the public. The 2019 survey was completed by 569 000 NHS employees (excluding those working in primary care) across 300 separate organisations in England. It found that overall almost one in seven staff members (14.9%) had experienced physical violence. While 16.4% of ethnic minority staff said that …

The US Equal Employment Opportunity Commission (EEOC) is suing Yale New Haven Hospital over its policy of requiring doctors aged over 70 to undergo a neuropsychological screening evaluation and basic ophthalmologic examination. Because such tests are demanded only of older doctors, the EEOC argues in its lawsuit,1 Yale’s “late career practitioner policy” breaches the Age Discrimination in Employment Act. The commission also contends that the policy contravenes the Americans with Disabilities Act, which prohibits subjecting employees to medical examinations that are not job …

The Royal College of Pathologists has barred its president elect, Peter Furness, from taking office after a disciplinary panel convened by the college upheld allegations of misconduct against him. Furness, 64, who was due to take over as president in November, is a consultant histopathologist at Leicester Royal Infirmary and honorary professor of renal pathology at Leicester University. He ran for the presidency and was elected on a platform that argued that “the college should cut back to its core function of defining and maintaining quality.” He had previously served as president from 2008 to 2011. It was only when he left office after the first term “that I realised how excessively our …

It’s quite different, not least because this war might actually be winnable. New research1 has shown that in Chile—a nation beset by obesity—sales of sugary drinks dropped by nearly a quarter in two years after the country introduced a “uniquely comprehensive” set of tough new obesity prevention policies in 2016. It banned schools from selling all foods and drinks containing …

Falling trainee numbers mean that addiction psychiatry could be wiped out in the next 10 years unless urgent measures are taken, the Royal College of Psychiatrists has warned. A report on the state of training in addiction psychiatry,1 published by the college, revealed that the number of higher training posts across England had …

Objectives To identify and summarise existing indices for measuring multimorbidity beyond disease counts, to establish which indices include mental health comorbidities or outcomes, and to develop recommendations based on applicability, performance, and usage. Design Systematic review. Data sources Seven medical research databases (Medline, Web of Science Core Collection, Cochrane Library, Embase, PsycINFO, Scopus, and CINAHL Plus) from inception to October 2018 and bibliographies and citations of relevant papers. Searches were limited to English language publications. Eligibility criteria for study selection Original articles describing a new multimorbidity index including more information than disease counts and not focusing on comorbidity associated with one specific disease. Studies were of adults based in the community or at population level. Results Among 7128 search results, 5560 unique titles were identified. After screening against eligibility criteria the review finally included 35 papers. As index components, 25 indices used conditions (weighted or in combination with other parameters), five used diagnostic categories, four used drug use, and one used physiological measures. Predicted outcomes included mortality (18 indices), healthcare use or costs (13), hospital admission (13), and health related quality of life (7). 29 indices considered some aspect of mental health, with most including it as a comorbidity. 12 indices are recommended for use. Conclusions 35 multimorbidity indices are available, with differing components and outcomes. Researchers and clinicians should examine existing indices for suitability before creating new ones. Systematic review registration PROSPERO CRD42017074211.

I slept dreadfully that night. I fought with my pillow and perched on the narrow corner ledge of my mattress, almost falling to the floor despite the adequate space next to me. The next day I found myself trying to cheat my circadian rhythm with a double espresso in my favourite cafe, contemplating a trip to the gym to short circuit my tiredness. The previous night I had arrived home from work after midnight, when the children were dreaming, the dog was snoring, and even the lampposts had been extinguished. But my turmoil was completely insignificant when …

In this issue of JAMA, Lee and colleagues1 examine the association between Physician Orders for Life-Sustaining Treatment (POLST), which involve portable medical orders that document treatment limitations for out-of-hospital emergency care and for limiting overtreatment at the end of life. The authors studied adults with chronic life-limiting illnesses who were hospitalized within the last 6 months of life and who had completed a POLST before their last inpatient admission. Among 1818 patients enrolled, 656 (36%) had POLST orders for “full treatment” and 1162 had orders for either “limited additional interventions” (761 [42%]) or “comfort measures only” (401 [22%]). Among the combined latter 2 groups, 472 (41%) were admitted to the intensive care unit (ICU), 436 (38%) received POLST-discordant intensive care, and 204 (18%) received POLST-discordant life-sustaining treatments, defined as mechanical ventilation, vasoactive infusions, new renal replacement therapy, or cardiopulmonary resuscitation. Patients with cancer or dementia were less likely to receive POLST-discordant intensive care, whereas patients hospitalized for traumatic injuries were more likely to receive POLST-discordant intensive care. These results are sobering. The authors conclude that patients with treatment-limiting POLSTs hospitalized near the end of life often receive care that seems inconsistent with their preferences. However, certain aspects of the study design may have contributed to overestimation of the number of patients at the end of life who received care not consistent with their wishes. The investigators only included patients with POLSTs who were hospitalized within 6 months of their death, such that those who died without being hospitalized were not included, even though their care may have been aligned with their preferences. In addition, patients with serious illness who were hospitalized, received POLST-concordant care, but did not die within 6 months were also not included. Advance care planning for treatment near the end of life involves several challenges. The Patient Self-Determination Act was enacted by Congress in 1990 to address the concern that patients were receiving care at the end of their lives that was not consistent with their wishes. Today, patients have a variety of options to facilitate advance care planning, including the ability to create POLST forms to limit the use of life-sustaining treatments in the out-of-hospital setting. POLST documents, living wills, and other types of instructional advanced care planning all share at least 3 common challenges because they depend on predictions made at a single point in time to determine what will happen at a future time.

As patient data are increasingly captured digitally, the opportunities to deploy artificial intelligence (AI), especially machine learning, are increasing rapidly. Machine learning is automated learning by computers using tools such as artificial neural networks to search data iteratively for optimal solutions.1 Typical applications include searching for novel patterns (eg, latent cancer subtypes2), making a diagnosis or outcome prediction (eg, diabetic retinopathy3), and optimizing treatment decisions (eg, fluid and vasopressor titration for septic shock4). Although many express excitement regarding the promise of AI, others express concern about adverse consequences, such as loss of physician and patient autonomy or unintended bias, and still others claim that the entire endeavor is largely hype, with virtually no data that actual patient outcomes have improved.5,6 One issue complicating this debate is that the classic measure of clinical benefit, the randomized clinical trial (RCT), is rare in this field, if not entirely absent. For example, the US Food and Drug Administration recently approved AI-enabled decision support tools (also called software as medical devices or SaMDs) for diagnosis of diabetic retinopathy on digital fundoscopy and early warning of stroke on computed tomography scans.7,8 In neither instance was approval based on any RCT evidence that the information provided by the SaMD improved care. Of course, diagnostic tools entered clinical practice for decades without the requirement for RCT data. However, these tools were traditionally framed as providing data, leaving judgment to physicians. In contrast, AI can provide data and judgment, thus altering clinician actions much more substantially.9 Against this backdrop, in this issue of JAMA, the report by Wijnberge et al10 of a clinical trial of an AI-derived clinical decision support tool provides important insight into the way RCTs might inform the debate on AI in health care. The study, somewhat ironically entitled the Hypotension Prediction During Surgery (HYPE) trial, randomized 68 patients who were undergoing elective noncardiac surgery to intraoperative management guided by an AI-based early warning system (intervention group) or standard care (control group). The primary objective was to test whether the intervention reduced the depth and duration of intraoperative hypotension (calculated as a time-weighted average). Both groups were managed with continuous radial artery pressure monitoring. In the intervention group, the arterial pressure was monitored by a SaMD that used 23 waveform variables, extracted continuously, to provide an updated prediction every 20 seconds of the likelihood of intraoperative hypotension (defined as mean arterial pressure <65 mm Hg) in the subsequent 15 minutes. The device issued an alarm when the risk exceeded 85% and encouraged the anesthesiologist to take preemptive action. The device displayed the risk score and a read-out of key variables (eg, stroke volume) used by the algorithm. The investigators also educated the anesthesiologists about the features of the device and provided a protocol to aid interpretation together with training on suggested actions to take (eg, intravenous fluid bolus or infusion of vasoactive agent) when the algorithm generated an alarm. In the control group, arterial wave data still flowed to the AI algorithm to allow it to run in silent mode, but only routine pulse and blood pressure data were displayed, as per standard care.

In acute respiratory distress syndrome (ARDS), the alveolar-capillary units are disrupted, with lung endothelial and epithelial injury resulting in exudative pulmonary edema containing inflammatory mediators, solutes, proteins, and leukocytes.1 Treating pulmonary endothelial injury in ARDS may improve patient outcomes. Interferon β-1a (IFN-β-1a), a type 1 IFN, is one such treatment that may improve pulmonary endothelial barrier function. In addition to its myriad immunologic effects, IFN-β-1a upregulates cluster of differentiation 73 (CD73) on pulmonary endothelial cells, thereby increasing extracellular adenosine concentrations, which acting via adenosine receptors improves pulmonary endothelial barrier function through junctional reorganization, cytoskeleton rearrangement, and further transcriptional upregulation of CD73.2-4 Based on these preclinical experimental observations, the clinical utility of IFN-β-1a for ARDS was previously tested by Bellingan and colleagues5 in an open-label, phase 1/2 dose-finding study in adult patients with ARDS, with 28-day mortality as the primary end point. In this nonrandomized study, IFN-β-1a was administered in escalating doses, with an optimum tolerated dose of 10 μg. Among the 37 patients who received IFN-β-1a, mortality was 8% compared with a higher mortality rate of 32.2% among 59 control patients (recruited contemporaneously but not randomized). This mortality difference, albeit in a nonrandomized sample, prompted the authors to design an efficacy trial. In this issue of JAMA, Ranieri and colleagues6 report the results of a clinical trial in which 301 adults admitted with moderate or severe ARDS based on the Berlin definition7 were randomized to receive intravenous IFN-β-1a (10 μg) or placebo once daily for 6 days. The trial enrolled patients from 74 intensive care units in 8 European countries between December 2015 and December 2017. A novel approach was used to confirm ARDS, with eligibility verified by 1 of the 2 clinicians (ie, medical monitors) and the requirement that the enrolling clinician match the patient’s chest radiograph against a panel of unlabeled chest radiographs to ensure that imaging was truly consistent with ARDS. The primary outcome, a composite end point of days alive and free of mechanical ventilation at day 28 (ventilator-free days), was analyzed using a modified intention-to-treat analysis consisting of all randomized patients who received at least 1 dose of the study drug (IFN-β-1a [n = 144] vs placebo [n = 152]). At baseline, the cohort was well-balanced across the 2 groups, with features typical of moderate to severe ARDS: pneumonia was the most common predisposing diagnosis (in approximately 67% overall) and use of ARDS-specific interventions such as prone position (in about 20%), neuromuscular blockade (in about 30%), and corticosteroids (in about 35%).

Claire Hope tells Francesca Robinson how setting up a hockey team for her hospital colleagues has helped them to rediscover the joys of team sports Claire Hope, a paediatric registrar at Musgrove Park Hospital, Taunton, feels that time for hobbies is often squeezed out by the pressures of a busy hospital job. “At medical school we play lots of sports but then we become doctors and suddenly we don’t have time for these activities anymore,” she says. “So we lose the hobbies that gave us the leadership skills and the ability to be team players that the medical schools recruited us for.” A hockey player since the age of 12, Hope played for her medical school but later found she was unable to combine the sport with her medical training. She has always been passionate about the game so when a friend suggested she made up a hospital team for a local, friendly mixed …

Haematology is a flexible specialty that offers the opportunity to develop special interests in a variety of clinical and laboratory areas. It is also possible to combine a clinical and academic career. A certificate of completion of training is awarded by the General Medical Council once a trainee successfully completes specialist training, has passed the Fellow of the Royal College of Pathologists examination, and is deemed competent by the specialist advisory committee. They will then be placed on the specialist register and allowed to apply for consultant posts. The Royal College of Pathologists 2017 census showed there were 1035 consultant haematologists across the UK. The 2018 workforce survey identified 76 consultants working in paediatric haematology with a further eight vacant consultant posts in that area Haematologists are responsible for the management of acute and chronic haematological conditions in NHS hospitals; in addition, they provide clinical oversight for haematology laboratory services and a liaison service which supports all other areas of the hospital and community medical services. Haematology consultant posts range from general hospital posts which cover all areas of haematology to more specialist posts in larger …

We know what to do, and the tobacco industry should be made to pay for it Smoking is on course to kill around one billion people in the 21st century1 and is the leading preventable cause of morbidity and mortality. The adult smoking rate in England is now 14.4%, down from 19.3% five years ago, but this still represents six million smokers.2 Smoking is an important driver of health inequality; more than 25% of routine and manual workers smoke, compared with 10% in the professional and managerial group. The UK government’s prevention green paper3 set out an ambition for England to be smoke free by 2030, defined in its 2017 tobacco control plan as a smoking rate below 5%. The equivalent target for Scotland is 2034. The UK has made important progress in tackling the tobacco epidemic4 through policies such as taxation to reduce the affordability of tobacco products and the introduction of standardised packaging and display bans,5 as well as by advancing smoke-free legislation, most recently a ban on smoking in cars with children …

In their recent article in The BMJ (“Is elimination of vertical transmission of HIV in high prevalence settings achievable?”)1 Goga and colleagues make several important points, including that more realistic targets are needed to maintain momentum to reduce vertical transmission of HIV in countries with high prevalence. They also make a constructive proposal to encourage countries to use “dashboards” to track key coverage and process indicators, particularly during the “pre-elimination period,” and to encourage continuous programme assessment and use of data for improvement. We are concerned, however, that they misrepresent the World Health Organization (WHO) and global partners’ elimination of mother-to-child transmission of HIV and syphilis (EMTCT) initiative.2 The authors include a box showing the criteria for elimination of vertical transmission of HIV from the …