Only when I cough? Adults' disclosure of cystic fibrosis

Cystic fibrosis has traditionally been conceptualized as a fatal childhood disease. In contrast, survival age has been increasing steadily such that adults now routinely seek to gain employment and form close relationships, situations that might require telling others about the disease. Here, the author examines three situations of disclosure based on interviews with 31 adults with the disease. First, in a low-risk situation, for example a short period of social contact, a low level of intimacy exists between the adult with cystic fibrosis and another. Here the disease may be concealed easily with little risk of discovery. Second, in a medium-risk situation, the perceived reaction of the other begins to influence the decision to disclose, as the level of intimacy becomes higher. Last, in high-risk situations, such as employment, the consequences of disclosing or concealing CF are most severe. However, a multiplicity of factors, including perceived social support and disease progression, are seen to influence adults' decisions to disclose their disease

Inflammation targets specific organs for cancer in carriers of BRCA1/2 pathway mutations

Women who inherit a defective BRCA1 or BRCA2 gene have risks for breast/ovarian cancer that are so high and apparently so selective that many mutation carriers choose to have the most likely targets for cancer surgically removed. Recent research has focused on better methods of treating such seemingly unavoidable hereditary cancers. Prevention has received much less attention so a positive test result for a cancer gene leaves carriers with very limited options. 
In order to prevent BRCA1/2 related cancers, it may be important to understand why they seem to occur only in certain characteristic organs. Results here show that mutations in a pathway depending on BRCA1/2 gene products magnify cancer risks from chronic infection and inflammation, making them especially important in selecting the site where hereditary cancer develops. Controlling chronic infections and inflammation may be a helpful option to prevent or delay cancers in mutation carriers

Flipping the odds of drug development success through human genomics

Drug development depends on accurately identifying molecular targets that both play a causal role in a disease and are amenable to pharmacological action by small molecule drugs or bio-therapeutics, such as monoclonal antibodies. Errors in drug target specification contribute to the extremely high rates of drug development failure. Integrating knowledge of genes that encode druggable targets with those that influence susceptibility to common disease has the potential to radically improve the probability of drug development success

Health Care Costs and the Arc of Innovation

Health care costs continue their inexorable rise, threatening America’s long-term fiscal stability, competitiveness, and standard of living. Over the past half-century, efforts to rein in spending have uniformly failed. In this Article, we explain why, breaking with standard accounts of regulatory and market dysfunction. We point instead to the nexus of economics, mutual empathy, and social expectations that drives medical innovation and locks in low-value technologies. We show how law reflects and reinforces this nexus and how and why health-policy-makers avert their gaze. Next, we propose to circumvent these barriers instead of surmounting them. Rather than targeting today’s excessive spending, we seek to leverage available legal tools to bend the arc of innovation, away from marginally-beneficial technology and toward high-value advances. To this end, we set forth a novel, value-based approach to pricing and patent protection—one that departs sharply from current practice by rewarding innovators in proportion to the therapeutic benefits new tests and treatments yield. Using cancer therapy as an example, we explain how emerging information technology and large troves of electronic clinical data are opening the way to near-real-time assessment of efficacy. We then show how such assessment can power ongoing adjustment of pricing and patent terms. Finally, we offer a blueprint for how laws governing health care payment and intellectual property can be tailored to realize this value-focused vision. For the reasons we lay out, the transformation of incentives we urge will both slow clinical spending growth and greatly enhance the social value that this spending yields

The Cancer Transition in Japan since 1951

The overall trend of cancer mortality in Japan has been decreasing since the 1960s (age-standardized death rates for ages 30-69), though trends differ enormously among various forms of the disease. Cancer mortality was heavily influenced by Japanese postwar economic recovery, which led to improved living conditions and better control of infectious agents known to cause some common forms of cancer (stomach, cervical). However, Japanese wealth and development have also been associated with risky personal behaviors (smoking, drinking) and other conditions, leading to increases in cancers with no known or else very weak links to infection. This shift away from infectious and toward non-infectious causes of prevalent forms of cancers is called the "cancer transition," by analogy to Omran's "epidemiologic transition." We suggest that the cancer transition described here in the case of Japan must be a part of efforts to revise and update the epidemiologic transition, which should incorporate new knowledge about the role of infection in chronic disease morbidity and mortality.cancer, cancer transition, epidemiologic transition, health, health and development, infectious diseases, Japan, mortality, non-infectious disease

Ability of verbal autopsy data to detect deaths due to uncontrolled hyperglycaemia:testing existing methods and development and validation of a novel weighted score

Objectives: Verbal autopsy (VA) is a useful tool to ascertain cause of death where no other mechanisms exist. We aimed to assess the utility of VA data to ascertain deaths due to uncontrolled hyperglycaemia and to develop a weighted score (WS) to specifically identify cases. Cases were identified by a study or site physician with training in diabetes. These diagnoses were also compared with diagnoses produced by a standard computer algorithm (InterVA-4). Setting: This study was done using VA data from the Health and Demographic Survey sites in Agincourt in rural South Africa. Validation of the WS was done using VA data from Karonga in Malawi. Participants: All deaths from ages 1 to 49 years between 1992 and 2015 and between 2002 and 2016 from Agincourt and Karonga, respectively. There were 8699 relevant deaths in Agincourt and 1663 in Karonga. Results: Of the Agincourt deaths, there were 77 study physician classified cases and 58 computer algorithm classified cases. Agreement between study physician classified cases and computer algorithm classified cases was poor (Cohen’s kappa 0.14). Our WS produced a receiver operator curve with area under the curve of 0.952 (95% CI 0.920 to 0.985). However, positive predictive value (PPV) was below 50% when the WS was applied to the development set and the score was dominated by the necessity for a premortem diagnosis of diabetes. Independent validation showed the WS performed reasonably against site physician classified cases with sensitivity of 86%, specificity of 99%, PPV of 60% and negative predictive value of 99%. Conclusion: Our results suggest that widely used VA methodologies may be missing deaths due to uncontrolled hyperglycaemia. Our WS may offer improved ability to detect deaths due to uncontrolled hyperglycaemia in large populations studies where no other means exist

White Paper 4: Challenges In Biomedicine & Health

Publicado en Madrid, 231 p. ; 17 cm.A lesson that we have learned from the pandemia caused by coronavirus is that solutions in health require coordinated actions. Beside this and other emerging and re-emerging infectious diseases, millions of Europeans are suffering a plethora of disorders that are currently acquiring epidemic dimensions, including cancer, rare diseases, pain and food allergies, among others. New tools for prevention, diagnosis and treatment need to be urgently designed and implemented using new holistic and multidisciplinary approaches at three different levels (basic research, translational/clinical and public/social levels) and involving researchers, clinicians, industry and all stakeholders in the health system. The CSIC is excellently positioned to lead and coordinate these challenges in Biomedicine and Health.Peer reviewe

Is Cystic Fibrosis Genetic Medicine\u27s Canary?

In 1989 the gene that causes cystic fibrosis (CF) was identified in a search accompanied by intense anticipation that the gene, once discovered, would lead rapidly to gene therapy. Many hoped that the disease would effectively disappear. Those affected were going to inhale vectors packed with functioning genes, which would go immediately to work in the lungs. It was a bewitching image, repeatedly invoked in both scientific and popular texts. Gene therapy clinical trials were carried out with a range of strategies and occasionally success seemed close, but by 1996 the idea that gene therapy for CF would quickly provide a cure was being abandoned by the communities engaged with treatment and research. While conventional wisdom holds that the death of Jesse Gelsinger in an unrelated gene therapy trial in 1999 produced new skepticism about gene therapy for CF and suggests that CF may provide a particularly compelling case study of a failed genomic technology, perhaps even of a medical canary. The story of CF might be a find of warning to us that genetic medicine may create as many problems as it solves, and that moving forward constructively with these techniques and practices requires many kinds of right information, not just about biology, but also about values, priorities, market forces, uncertainty, and consumer choice

Environmental factors in the development of Alzheimer’s disease

This article delves into the profound significance of the early diagnosis of Alzheimer’s disease (AD), the leading cause of dementia worldwide. With no current cure for AD, early detection stands as a cornerstone in managing the disease. Early diagnosis not only enables symptomatic treatment to enhance the quality of life but also facilitates proactive planning, addressing health care and living arrangements for the future. Additionally, early diagnosis can promote participation in clinical trials, granting patients access to emerging treatments. An essential component to this early detection is a robust understanding of the disease\u27s causes. The paper examines the pathological indicators, such as beta-amyloid plaques and neurofibrillary tangles, while highlighting the multifaceted origins of AD encompassing genetics, environmental factors, inflammation, and potential links with other diseases. An in-depth discussion on the influence of the environment further illustrates the complex interplay between genetics and external factors. Toxic chemicals, lifestyle choices in western societies, and other environmental determinants are scrutinized for their potential role in AD onset. In summary, the piece underscores the importance of a holistic understanding of Alzheimer\u27s etiology, emphasizing that only through comprehensive knowledge can we aspire to identify, manage, and ultimately find a cure for this debilitating condition