mortality – AQuAS Blog

Sleep apnea: towards precision medicine

18 Jan

Obstructive sleep apnea is a chronic disorder characterised by recurrent episodes of a blockage of the upper airways during sleep which affects between 5% and 14% of adults from 30 to 70 years of age, mainly men. In addition, sleep apnea leads to a reduction of the intake of oxygen (hypoxia) during sleep. In order to counteract this lack of oxygen, the brain reacts by forcing a short awakening known as arousal which reactivates the muscles in the upper airway and allows air to pass through (reoxygenation).

These cycles of hypoxia-reoxygenation produce stress to the circulatory system and leads to an increase in the risk of cardiovascular, hypertensive, metabolic, cerebrovascular, or neoplastic diseases, and lastly, a risk of death. At the same time, the arousals prevent a person from having a good night’s rest, produce the feeling of tiredness and an excessive desire to sleep during the day, which is associated with an increase in road accident rates and a decrease in life quality.

A standardised approach in the treatment of sleep apnoea exists: the use of continuous positive airway pressure (CPAP) during the night in order to keep the upper airways open which helps the person rest.

However, treatment with CPAP shows contradictory results. On the one hand, it has been demonstrated that the use of a CPAP for at least 4h per night increases quality of life and reduces blood pressure among population groups with high blood pressure. In contrast, it has not been demonstrated that the use of CPAP reduces the risk of major cardiovascular events or deaths. Therefore, sleep apnea is a heterogeneous disorder and the use of CPAP is not equally effective with all patients. Which patients can benefit most from the treatment? Should all patients be treated in the same way?

We believe it is important to look for patients with sleep apnea profiles that can benefit from a treatment with CPAP. The creation of the PADRIS programme (Public Data Analysis for Health Research and Innovation Programme in Catalonia), whose aim it is to make related health data available to the scientific community to drive research, innovation and assessment in health, has given us the opportunity to be able to analyse all subjects with sleep apnea treated with CPAP in Catalonia. We are talking about 71,217 people, approximately 1% of the general population who were attended by the public health system in Catalonia (primary care, hospital care, social health and/or pharmacy) in the period 2012-2013.

To establish these profiles (that is, groups of patients having similarities with each other but at the same time very different from the remainder) the most frequent comorbidities of patients with sleep apnea have been taken into consideration as well as the clinically relevant comorbidities. Six different profiles of patients were identified among patients with sleep apnea and treated with CPAP in Catalonia.

Despite defining these six different patient profiles, we can safely say that the population of Catalonia receiving CPAP is divided into two large basic groups: on the one hand, old age patients, with a high mortality rate and a frequent use of resources, and on the other, patients with fewer comorbidities, a low mortality rate and an infrequent use of resources. You can read it in an article in Plos ONE.

Do both groups need to be treated in the same way? It seems not. In the group with fewer comorbidities, a low mortality rate and an infrequent use of resources, it seems that sleep apnea is the most important determinant in the prognosis of these patients and there is evidence that this would be the group that could most benefit from treatment with CPAP. In contrast, it seems that in the other group sleep apnoea is at a secondary level, given that the predominant diseases are more serious.

The study has allowed us to assess the association between treatment with CPAP and mortality; that is, whether more people die who are being treated with CPAP or whether more people die having the same comorbidities but without sleep apnea.

To be able to achieve this objective, for each patient treated with CPAP we looked for three people with similar characteristics but without sleep apnea. What we observed was surprising, namely that despite presenting a greater number of comorbidities, treatment with CPAP is associated with a decrease in mortality rate at a population level (Am J Crit Care Med 2018).

We now need to continue working to find out what occurs in each of the patient profiles. Having access to this volume of data helps us to make an estimate of the groups of patients with sleep apnoea that will benefit more with CPAP treatment and this means that we are getting closer and closer to precision medicine.

Diseases do not exist, ill people do

Post written by Ferran Barbé, Hospital Institut de Recerca Biomèdica de Lleida.

Saving lives, reducing vehicles in cities

23 Jun

Air pollution is a major public health concern, perhaps one of the most serious problems facing large developed cities. The evidence of the negative effects on health are growing day by day, with contributions from internationally renowned scientific groups such as the Centre for Research in Environmental Epidemiology (CREAL) which estimates that there are 3,500 premature deaths each year in the Barcelona area resulting from air pollution. Pollution not only affects patients suffering from respiratory diseases, but is also a cause of cancer and cardiovascular conditions when nitrogen oxides and smaller particles are capable of passing through the bronchi and enter the bloodstream. Recently, CREAL also discovered cognitive development impairment in children in schools in close proximity to highly contaminated streets.

Many European cities have done their homework focusing on one of the major causes of pollution: vehicle traffic, above all diesel engines which are the primary agent responsible for nitrogen oxide emissions reaching unacceptable levels, as revealed by the Volkswagen scandal. One of the most effective initiatives in this area is the delimitation of Low Emissions Zone (LEZ) in city centres, which restricts the access of the most pollutant vehicles to entering these areas in conjunction with improvements in public transport and promotion of sustainable mobility. These policies enjoy greater scientific consensus and have been implemented by more than 200 cities in 12 European countries, including Berlin and London.

None of the cities which have implemented measures restricting traffic wish to backtrack on these improvements, much in the same way as what we have experienced with the ban on smoking in public places. In fact, the story has a lot in common with the smoking ban if we consider for example that in Barcelona, only 15% of inner-city displacements use private vehicles. This means that most of the city’s inhabitants are passive smokers subject to emissions produced by others. Experts in mobility explain that traffic tends to adapt its behaviour. The greater the limitations in circulation, the less traffic there is and, inversely, when circulation is made easier and more channels are made available, the heavier traffic becomes to the point of collapsing entirely. Another advantage of reducing cars in cities, apart from the positive effects on health, is the greater occupation of public space by pedestrians and cyclists with the added benefit of an improvement in quality of life.

For all these reasons, courageous decisions are needed from governments, as they were when it came to the application of the smoking ban legislation. In order to promote these initiatives and help raising awareness about the problem of pollution, last year the Platform for Air Quality in Catalonia was set up, which includes neighbourhood associations, environmentalists, public transport activists and advocates for the use of bicycles, as well as citizen groups and professionals from the areas of health, the environment and mobility. One of these groups is the Catalan Association for Science Communication, which understands that scientific journalism should serve the community if it is to be responsible and play a leading role in a society where everyone is potentially a means of communication.

It is also vital for the authorities to understand that they must collaborate with the public and experts in disseminating and using information. Applications to measure contamination levels should not be limited only to warning us when European legal standards have been exceeded, but must in addition take into account the limits recommended by the WHO, the only secure parameters in terms of safeguarding health. This, together with the different data and models utilised, result in the fact that the services and applications which provide information on pollution in the Catalan region do not agree 100% in their forecasts: Aire.cat, Caliope, Plumbe, Real Time Air Quality Index… The most serious feature is that despite all these resources, people do not quite understand when, where and why it is dangerous to walk, play sports or simply breathe.

Thus, the platform calls for free and open access to all the data: pollution measurements and positioning, traffic, weather, models… so that one can create one’s own applications, extract the know-how and create services that the public feel are useful. With the data available, journalists can also provide reports of public interest such as this interactive map of the UK drawn up by The Guardian that shows the boroughs with the most deaths from particulate air pollution.

Post written by Cristina Ribas (@cristinaribas), Catalan Association for Science Communication and Platform for Air Quality.

The Great Escape

21 Jan

Joan MV Pons, Head of Evaluation AQuAS — Joan MV Pons

A few days ago, Anna Garcia-Altés in a previous post referred to the Nobel Prize in Economics, which Alfred Nobel never granted – that was awarded in 2015 to Angus Deaton and his work on inequality. This is not the subject that I wish to talk about today but another that also features in the recent book from this Nobel proze winner which is titled “The Great Escape” (The Great Escape). Yes, just like the movie, set in a German camp for prisoners of war starring Steve McQueen and recalling a real fact of World War II. Unlike reality, the book predicts a better ending. For Deaton, the greatest escape in human history was in overcoming poverty and ageing.

For centuries, those who did not die at a young age could face years of misery. Beginning in period called the Enlightenment, with its scientific revolution and subsequent later industrial revolution, some people in certain countries began to escape this meagre fate.

Meanwhile, germ theories founded in the late nineteenth century surpassed the paradigm of the miasma theory in explaining contagious diseases. The key was and still is scientific knowledge and its dissemination. This point in history marks the extraordinary increase in life expectancy, initially for the better-off and then for the rest of the population.

This higher life expectancy, manifested especially in the developed countries, is largely due to the remarkable reduction in infant mortality and, more recently, to the epidemiological transition to chronic non-contagious diseases, the improvement in life expectancy in adulthood (increased life expectancy ≥ 50 years from 1950), but without a substantial improvement in longevity. Deaton shows us all this with data and graphics.

To illustrate it, Deaton mentions the progress in combating smallpox with a vaccination of smallpox (initially using matter from infected people and later the much safer vaccine Edward Jenner introduced in 1799). The public health measures introduced in the last few hundred years, including sanitation, water supply, nutrition and better hygiene, have led to a significant reduction in infant mortality.

Here, it was due to not only the knowledge but also the determination of the authorities in improving the conditions of the population. The improvement in life expectancy in adulthood is explained largely by reducing cardiovascular mortality through diagnostic and therapeutic advances in this field.

As mentioned before, we witnessed not only increased life expectancy but also a significant increase in the world population, an authentic explosion starting in the second half of the twentieth century. Malthusian alarms re-emerged but they were fortunately overcome by improvements in agricultural productivity, without excluding initiatives – for better or worse – for controlling the birth rate in developing countries; again, examples of scientific knowledge and its dissemination.

Deaton is very critical about the operating methods in which help flows from developed countries to developing countries. From the times of imperialism and colonization where (natural) resources were moved from poor countries to rich ones (Nineteenth century) and since the end of World War II we’ve also seen a flow of resources from developed countries to developing countries.

This external help, whether from governmental or NGO sources and despite the illusion that might it create if it continues as usual, may end up doing more harm than good. There’s no shortage of examples in the book of wasted resources by governments and corrupt politicians, granting donations or grants to countries (government to government) without these ever reaching the people. Not to mention situations where these grants are part of the geopolitics of the former colonies or contemporary powers.

Contrary to what an engineered hydraulic vision (communicating vessels) may show, we must invest in projects and programs that promote conditions for economic development to make external aid unnecessary, as is the reality in Africa, where paradoxically, the more external help yields the least growth in GDP per capita.

Health aid, without underestimating its achievements (vaccination campaigns, infrastructure construction, drugs against HIV / AIDS, mosquito nets), continues to be in most cases, vertical health programs with a very specific focus. This contrasts with the horizontal programs aimed at strengthening local health care systems, especially a good network of primary and community care.

Often foreign aid and the development of local capacity are not aligned; on the contrary, often one damages the other. Rich countries’ subsidies to their agriculture – consider the famous European PAC – is detrimental to farmers in poor countries where most of the workforce still works the land. There are more effective ways to help.

(It notes that another Nobel laureate in economics, Robert Fogel (1926-2013), had already written about the great escape in “The Escape from Hunger and Premature Death, 1700-2100” (2004), Deaton and had revised appointment. Thank Anna Garcia-Altés to call me about this)