Updates from the European Association Clinical Pharmacology & Therapeutics

@HealthMed The EACPT is planning two major events in the Summer of 2013. 

Professors David Webb and Simon Maxwell are organizing an EACPT Summer School for young researchers to be held in their home city, Edinburgh, 6 - 8 July, 2013. The programme includes keynote talks by invited expert speakers, workshops, poster presentations, free communications and social events. 

And August 28 - 31, 2103, the 11th EACPT Congress takes place in Geneva, hosted by the Swiss Society for Clinical Pharmacology and Toxicology. Over 900 participants are expected to attend including health professionals, scientists, policy makers, biotechnology and pharmaceutical professionals and others with an interest in basic and clinical pharmacology, pharmacotherapy, drug discovery and development, regulatory affairs and related areas.

11th EACPT Congress website 

11th EACPT Congress updates

EACPT Summer School details

Painkillers and hearing loss in women?

@HealthMed Researchers from Boston in the USA have reported that pain-killer use increases risk of hearing loss in women. Sounds worrying but worth looking at what the study involved and asking the obvious questions: are the findings credible and can they be generalised beyond the population in the report?

This was a prospective observational study of around 62,000 women in the US Nurses Study, the overwhelming majority of whom were of Caucasian origin. Information was collected on use of three types of painkiller - ibuprofen, acetaminophen (paracetamol in the UK), and aspirin. Nurses were following for 22 years on average.

What did they find? The rate of reported hearing loss from all causes was high at one in six over the entire population in the study. For those using painkillers, there was no link with hearing change with occasional use (once or less per week) or with aspirin whatever the reported frequency if use. For ibuprofen or acetaminophen (paracetamol), regular use for 2 days a week or more was linked to increased risk of hearing loss. The highest relative reported increase in risk was 1in 4 (24%) excess hearing loss linked to use of ibuprofen on at least 6 days a week. The authors state they are unaware of the specific mechanisms linking hearing loss to these medicines in their study.

What potential weaknesses are there in the study?
These include:
-   Noise exposure is an important cause of hearing loss; and of headaches, an obvious reason to be taking painkillers. There was no information available on noise exposure as a confounding cause of hearing loss. The authors acknowledge that is an important flaw in their study.
- Hearing loss was self-reported and severity of hearing loss not measured.
- No information was given on the dose of pain-killers used.
- Taking painkillers regularly from 2 days a week to every day suggests underlying medical problems which may themselves have had an impact on hearing. Co-morbidity accounting for the pain-killer use was not clear.
- Oddly there was no consistent increase in risk of reported hearing loss with increasing numbers of days a week of painkiller use: similar hearing loss reported with paracetamol 6 or more days a week, as for 2 days a week but more hearing loss when taken taken 4 or 5 days a week
- In this study aspirin was not associated with hearing loss but would be expected to be based on previous studies, including studies in men. This raises questions about the accuracy of data collection.

Are the findings generalisable to people outside the study group?
- These were mainly Caucasian origin women who were nurses working in the USA. It is unclear whether similar findings would have occurred in other occupational groups, ethnic groups or other countries. However there are biochemical mechanisms by which all these drugs, including aspirin, could affect the hearing system. Therefore it would be premature to suggest that aspirin would be a safe alternative painkiller with regard to hearing.

Further research is needed to explore whether these findings are due to painkillers or co-incidental, and if confirmed, to find out who is at particular risk. For the present, any risk appears relatively low and linked in this study only to women taking selected painkillers (ibuprofen or paracetamol) for several days each week over long periods. Any long-term use of pain-killers should be discussed with a medical advisor or pharmacist. People who have unexplained hearing loss and are currently on these medicines at least 2 days a week for long periods should seek advice from their medical advisor, pharmacist or hearing consultant.

Anti-depressants, benzodiazepines, newer sleeping medicines and risk of motor accidents?

@HealthMed: The following comments were in response to a new paper linking use of anti-depressants, benzodiazepines and newer sleeping medicines to increased risk of motor vehicle accidents.

These comments were part of the briefing on this paper from the Science Media Centre.

In a paper published in the British Journal of Clinical Pharmacology, Tsai and colleagues from Taiwan have reported a ~40-70% relative increase in risk of non-fatal driving accidents in Taiwan linked to prescription of a wide range of anti-depressants, benzodiazepines and newer Z-drug sleeping medicines. In their study, around 5200 people who had had motor accidents were compared with around 31,000 people with no history of accidents. The medicines appeared possibly linked to from 1 in 20, to 1 in 70 accidents, depending on the drug type. Obvious questions for pharmacologists, health professionals and the public are whether these findings are credible, and if so, generalisable to other parts of the world.

This Taiwan report was based on a case-control study – more open to bias than randomized trials. Although the researchers matched controls for age, gender and year of the accidents, they were unable to rule out differences in patterns of driving or in alcohol intake between the groups. Alcohol amplifies any impairment in concentration resulting from effects of drugs that act on the brain; and ethnic Taiwanese are commonly are intolerant of alcohol, due to genetic lack of the enzyme needed to break down alcohol.

It is also possible that the increased accident risk resulted from effects of underlying psychological or psychiatric disorders for which the drugs were prescribed e.g. through poorer concentration or indirectly through additional effects of sleep disturbance caused by the conditions under treatment, independent of the drugs. In addition the researchers noted that those who had accidents also had a higher burden of a range of non-psychiatric diseases, also recognized as increasing risk of accidents.

What do these results mean for populations in other countries? Several of the drugs implicated in Taiwan are not commonly used in other countries and there are several sources of bias indicating need for caution in interpreting the study. However other studies have stressed the need for caution when driving when using these types drugs. When these drugs are prescribed, patients should seek advice about risks of driving from their physician or pharmacist. In any event, patients on these drugs should avoid any alcohol when driving.

More information: Chia-Ming Chang and colleagues. Psychotropic Drugs and Risk of Motor Vehicle Accidents: a Population-based Case-Control Study; British Journal of Clinical Pharmacology; DOI: 10.1111/j.1365-2125.2012.04410.x

Prevalence of alcohol and other drugs in fatally injured drivers. Joanne E. Brady, Guohua Li.  Addiction. Published online August 20, 2012

Waistline and increased risk of premature death: what's so new?

@HealthMed The latest European Society of Cardiology Congress in Munich coincided with the last days of a Gallery of the Modern exhibition of caricatures by Munich satirist Karl Arnold:  amongst them a striking 1922 image of a stylish corpulent man said for 20 years not to have been able to see his feet. Then a social observation, it is of course now well recognized that the frankly obese are at high risk of diabetes, heart disease, stroke and other medical conditions.

At first sight surprising, that there should have been major interest from scientists and the press in new US research presented at the 2012 heart Congress linking a larger waistline to premature death; and not just from a beer belly, but for anyone with a body shape with above normal waist to hip circumference.  What’s so unusual? Surely everyone knows that being overweight increases risk of serious medical problems.

What did these American researchers do? They looked at the strength of the link between different measures of obesity and risk of early death. In the research, lead by Professor  Francisco Lopez-Jimenez from the Mayo Clinic, almost 13,000 American men and women were studied for around 14 years, within a cohort study: the Third National Health and Nutrition Examination Survey (NHANESIII). There were around 2500 deaths of which around 1100 were from cardiovascular causes. The researchers measured body-mass index (BMI), a general measure of fatness, and waist-to-hip ratio (WHR), a measure of central obesity. This meant they were able to include people not currently considered obese based on BMI, but who had a relatively large belly, as well as those overweight both based on BMI and abdominal girth. The surprising finding of the study was that, compared to subjects with normal BMI and WHR, the group with normal BMI but relatively high central fat not only had a high death rate (2.8 times for cardiovascular disease and 2.1 times for all causes), but their risk of premature death was much higher than participants who were obese based on BMI (1.4 times normal cardiovascular risk).

It is already well established that abdominal fat is particularly deadly in relation to risk of heart disease. This new NHANESIII research in addition reported that increasing waist-hip ratio is linked to earlier death from all causes, not just for heart disease. It also provided objective data of the graded increase in risk as abdominal fat and waist-hip ratio increases.

What messages to take from this study? Obvious questions include whether it is reliable and if so generalizable from US to European and other international populations. As a prospective observational study, the results are open to bias – i.e. factors co-incidentally present in the larger waisted people may have been responsible e.g. the type of diet causing the central overweight rather than distribution of the fat itself.

However the authors reported that their findings were similar after adjusting for other well-known risk factors for premature heart disease and death, such age, male gender, ethnicity, socio-economic factors, smoking, hypertension, and diabetes.  Furthermore, this new report from Munich supported the previous systematic review by the authors noting similar findings in patients with coronary artery disease: i.e. central obesity a much stronger link  than BMI to premature death.

Reasons for the observed health risks are thought to include major regional differences in types chemicals secreted by fat from different parts of the body. Unlike fat padding in other part of the body, abdominal (or visceral fat) makes chemicals that promote resistance to insulin, increasing risk of diabetes, an important risk factor for heart disease. This fat also makes inflammatory chemicals that can accelerate damage to arteries, leading to atheroma (deposits of fat and abnormal cells – from the Greek for ‘porridge lump’) in the arterial walls. This both reduces blood flow to vital organs, and increases the likelihood of a clot forming to cause critical narrowing or complete blockage of an artery, a major cause of heart attack and stroke. There is also  evidence that in contrast there may also be a protective metabolic profile associated with the presence of lower body fat.

These findings add to increasing concern about health risks from central overweight and stress the importance of preventive measures, even if BMI is within the normal range. Health professionals need to make the public aware of these risks and explain what preventive measures may help. The good news is that losing excess central weight is practical through a healthy, lower calorie diet, combined with regular aerobic exercise, reduces major risk factors for heart disease: reduces cholesterol, decreases blood pressure and reduces risk of diabetes, and lowers risk of heart and other serious diseases. Other reasons for benefits may include better metabolic profile from the increase in muscle mass with exercise, and the improved tissue nutrition resulting from generation of more micro-vessels.

Calculate your waist-hip ratio.

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Health risks in the Sierra Nevada?

@HealthMed Every year millions of people visit beautiful Yosemite and Lake Tahoe in the Sierra Nevada of the Western USA. The individual risk of contracting a serious infection is low, however there are several rare but important public health risks. These range from minor nuisance from irritating bites by ‘no-see-ums’ to a range of serious infections.

Yosemite National Park

While visiting there in mid-August, there were reports in the US press of 2 deaths from hantavirus infection, attributed to contact in the Yosemite National Park area with deer-mice as the carrier. There are also notices posted at other beauty spots in the Sierra Nevada not to handle small animals; ground squirrels and other small mammals were reported to harbour plague; ‘no-see-ums’ to be vectors for West Nile virus infection (around half those affected developing an encephalitis syndrome); and ticks to carry risk of acquiring Lyme disease or the protozoal infection, babesiosis. The Centers for Disease Control in Atlanta report that these infections are rare, however urgent treatment for infected individuals may be needed, with public health measures important.

In practice, in mid-August, whether or not due to insect spray provided by a friendly bed and breakfast host, there was little insect activity evident - but that's the nature of 'no-see-ums'. There were plenty of small mammals keen to share visitors’ food – including grey squirrels to golden-manteled ground squirrels and marmots.

And why the lag in international media coverage until the end of August? The regional California press appear to have begun to cover the hantavirus story around 16^th August. The BBC and other UK media began reporting the news from 28^th August, in part perhaps because US public health authorities had begun to alert Yosemite visitors potentially at risk, typically those who had used tents and tent-cabins into which culprit rodents may have entered.

What is hantavirus? It is one of a family of viruses. Hantavirus infection can affect the skin, lungs, kidneys and other organs. Since the first recognized major outbreak, affecting several thousand US soldiers in the 1950s during the Korean War in the Hanta River region of South Korea, the virus has been detected in many parts of the world, from elsewhere in SE Asia to Scandinavia, mainland Europe and the USA. The type of small rodent carrier varies with geography. Clinical illness appears be rare, with however potentially severe illness in those who are affected, and a high mortality rate, treatment based on supportive measures.

Syndromes caused by hantaviruses differ across geographical regions. Typically old world hantaviruses affect predominantly the skin and kidneys, causing a ‘haemorrhagic renal syndrome’. New World viruses typified by the ‘Sin Nombre Virus’ first described in 1993 usually cause a serious pulmonary syndrome, with around 1-6 weeks incubation period.