“Morning sickness has no cure,” The Independent reported. The newspaper said that a new review of 27 past trials found that none of the treatments examined were safe and effective.

The review behind this news, conducted by the Cochrane research organisation, investigated a range of treatments for nausea, retching and vomiting in early pregnancy. The review, which looked at research on both anti-sickness drugs and alternative treatments such as ginger and acupuncture, found that there was a lack of high-quality evidence to support their effectiveness or safety. It should be noted that the body of evidence was found to be inconclusive rather than proving that there is “no cure”, as The Independent claimed.

In short, there is presently little reliable evidence to help pregnant women or doctors choose treatments for nausea and vomiting in pregnancy. This review specifically excluded studies that looked at treatments for more severe morning sickness (hyperemesis gravidarum), which can cause dehydration, vitamin and mineral imbalances, weight loss and other complications. Any pregnant woman whose wellbeing is affected by nausea and vomiting should consult her doctor or midwife.

Where did the story come from?

This Cochrane review was carried out by researchers from Dublin City University, the University of Liverpool, Indiana University School of Medicine and Mid-Western Regional Maternity Hospital, Limerick. It was funded by the University of Liverpool, Ireland’s Health Research Board and the UK’s National Institute for Health Research. The study was published online by the Cochrane Collaboration.

The review was widely covered by the media. Metro’s headline that pills for morning sickness are “useless” and the Daily Mail’s message that “none of them work” are misleading. Rather than clearly disproving the effectiveness of morning sickness treatments, the review found that there was very little evidence as to whether or not they worked, making it difficult for researchers to draw conclusions either way.

What kind of research was this?

This was a systematic review of all the evidence so far on treatments for nausea and vomiting in early pregnancy. A systematic review is the best and most reliable form of evidence for assessing healthcare interventions. In the process, researchers carry out a thorough search of the literature addressing a specific question and then critically appraise all individual studies to identify relevant evidence. This review is an update of a Cochrane review previously published in 2003.

The researchers point out that nausea, retching and vomiting are common in early pregnancy and can have considerable physical and psychological effects. Concerns over how unborn children may be affected by pharmaceutical treatments have led to more interest in complementary and alternative treatments, including acupressure, homeopathic remedies and herbal remedies such as ginger. Alternative treatments are often recommended by health professionals because they are perceived as “natural” and, therefore, safe. However, non-drug treatments are less rigorously regulated and, as a consequence, their potential risks may be underestimated. Doctors sometimes prescribe anti-emetic (anti-sickness) drugs and certain antihistamines.

What did the research involve?

Researchers carried out a search on various databases for all randomised controlled trials of any intervention for nausea, vomiting and retching in early pregnancy. This was defined as up to 20 weeks’ gestation. They excluded trials of interventions for severe morning sickness (hyperemesis gravidarum), as well as partially randomised and “crossover” trials (where different groups swap treatments within the same trial).

The researchers then examined evidence on whether treatments had been found to reduce symptoms or stop them getting worse, as measured by various validated scales and questionnaires. They also looked for information on adverse outcomes (side effects) on both mother and unborn baby, including foetal death and abnormalities, low birth weight and preterm birth. They also assessed information about how treatments affected quality of life and any economic costs, including purchase of treatments and time off work needed.

After all the data were collected, the reviewers independently assessed the studies to decide if they were suitable to be included in the review. Using established criteria, the researchers assessed the included studies for their quality, in particular their risk of bias. Researchers also analysed the effects of treatments using validated methods.

What were the basic results?

The researchers identified 27 trials, involving 4,041 women, that met their inclusion criteria. The trials covered many different treatments, including acupressure, acupuncture, ginger, vitamin B6 and several anti-emetic drugs. Overall, they found there was a lack of high-quality evidence on the effectiveness of any of the interventions. Although some studies showed benefits, the effects were inconsistent and limited.

The review included the following findings:

• Acupuncture and acupressure showed no significant benefit to women in pregnancy. In six studies of acupressure and two of acupuncture, there were no significant differences in benefit between women taking these treatments and women in a control group. One study of acustimulation (mild electrical stimulation of acupuncture points) reported some improvement.
• There was some evidence for the effectiveness of auricular pressure (gentle pressure on the outer ear), but further research on this treatment is required.
• The use of ginger products may be helpful, but evidence of their effectiveness was limited and inconsistent.
• There was only limited evidence to support the use of drugs such as vitamin B6, anti-emetic drugs and antihistamines.
• Importantly, there was little information available on possible adverse outcomes and on psychological, social and economic outcomes. Some anti-emetic drugs were associated with drowsiness, while ginger was associated with heartburn in some people.
• The researchers did not find any trials of dietary or other lifestyle interventions.

Critical appraisal of the studies revealed that some had a high risk of bias, which would make results unreliable. Also, the researchers were unable to pool together findings from the studies to give an overall idea of effectiveness. This was because the studies differed in their methods, inclusions and ways of measuring symptoms. The researchers say that the methods used to carry out the studies were also of mixed quality.

How did the researchers interpret the results?

The researchers said that they found little strong evidence that non-drug treatments are effective in reducing symptoms of nausea and vomiting in early pregnancy. There was only limited evidence to support the use of vitamin B6, antihistamines and other anti-emetic drugs.

They concluded that there is little evidence to support any advice given to pregnant women about these interventions and that high-quality research on treatments for this condition is needed.

Conclusion

This well-conducted review found little evidence for the effectiveness of any treatments for nausea and vomiting in early pregnancy, in particular alternative treatments. Importantly, it also found little evidence about possible adverse effects of these treatments, many of which can be bought over the counter or are given by private practitioners.  Further good-quality research is needed before pregnant women can make informed choices about treatment for morning sickness or before health professionals can offer evidence-based advice to support them.

In summary, there is currently little reliable evidence on which women and health professionals can base their decisions about treatments for nausea and vomiting in pregnancy. It is important to note that morning sickness can be severe, and this review specifically excluded studies that looked at treatments for more severe morning sickness (hyperemesis gravidarum). This condition can be associated with dehydration, vitamin and mineral imbalance, weight loss and other complications.
Any pregnant woman who experiences nausea and vomiting that affects her wellbeing should consult her doctor.

Links To The Headlines

Morning sickness has no cure. The Independent, September 8 2010

Morning sickness 'cures' put to the test... and none of them work. Daily Mail, September 8 2010

Call for morning sickness action. BBC News, September 8 2010

Pills 'useless for sickness in pregnancy'. Metro, September 8 2010

Links To Science

Matthews A, Dowswell T, Haas DM. Interventions for nausea and vomiting in early pregnancy. The Cochrane Library, September 8 2010

“Vitamin B tablets could slow and even halt the devastating march of Alzheimer's disease,” The Daily Telegraph reported. According to the newspaper, large daily doses of vitamin B can halve the rate of brain shrinkage, a process that can precede Alzheimer’s disease and dementia.

This story is based on a well-conducted two-year trial, which compared vitamin B pills with inactive placebo pills in 271 elderly people with mild memory problems. The study found that those given vitamin B experienced brain shrinkage (atrophy) 30% slower than those given inactive tablets. However, slower brain shrinkage may not necessarily lead to any improvement in symptoms.

This research does not show that vitamin B can prevent Alzheimer’s disease or dementia because there is no evidence to confirm that slower brain shrinkage will lead to benefits for people with early dementia symptoms. Nevertheless, these results are promising and clearly warrant more research.

Where did the story come from?

The study was carried out by researchers from the University of Oxford, the Oxford Radcliffe Hospitals NHS Trust and the University of Oslo in Norway.

The study received funding from a number of sources, including the Charles Wolfson Charitable Trust, the Medical Research Council, the Alzheimer’s Research Trust and the National Institute for Health Research. It was published in PLoS One, the peer-reviewed journal of the Public Library of Science.

Newspapers generally covered the research in a balanced way, although the headlines are overly optimistic in proclaiming that vitamin B will delay or beat Alzheimer’s disease. A diagnosis of Alzheimer’s is based on specific, characteristic clinical features and the exclusion of other causes of cognitive impairment. However, this research only assessed an outcome of brain shrinkage, which is not necessarily the same thing. The functional effects of reducing brain shrinkage were not investigated and it is an extrapolation to conclude that B vitamins improved cognitive health or protected against Alzheimer’s disease.

What kind of research was this?

Brain atrophy, which describes the loss of neurones and their connections, can be caused by a number of diseases. Some degree of atrophy and subsequent brain shrinkage is common with old age, even in people who are cognitively healthy. However, this brain shrinkage is accelerated in people with mild cognitive impairment and even faster in those who ultimately progress from mild cognitive impairment to Alzheimer’s disease. A range of factors has been implicated in affecting the rate of brain atrophy, one of which is high levels of an amino acid in the blood called homocysteine (tHcy). Studies have shown that raised levels of tHcy increase the risk of Alzheimer’s disease.

In this randomised controlled trial, the researchers investigated the role of vitamin B in regulating levels of tHcy. They specifically wanted to test whether lowering tHcy through giving high doses of vitamin B for two years could reduce the rate of brain atrophy in people with pre-existing mild cognitive impairment.

What did the research involve?

Volunteers aged 70 years and over with concerns about their memory were recruited in the Oxford area, through radio and newspaper advertisements, between April 2004 and November 2006. It was specified that volunteers should have a diagnosis of mild cognitive impairment, defined using specific  criteria. These included a concern about memory that did not interfere with activities of daily living and pre-specified scores on some cognitive scales assessing word recall and fluency. The study excluded people with a diagnosis of dementia, who were taking anti-dementia drugs or who had active cancer. People taking folic acid and vitamin B6 or B12 above certain doses were also excluded.

Every six months, the volunteers were randomly assigned to receive either high-dose oral vitamin B tablets (0.8 mg folic acid, 0.5 mg vitamin B12 and 20 mg vitamin B6) or placebo pills during the two-year period. The participants, their partners and all staff directly involved in the study were unaware which pills were being received. The ‘double blind’ nature of the study was important as it eliminated potential biases associated with the patients’ or researchers’ knowledge of which treatment was being received. MRI scans were performed at the start of the study and again after two years. The researchers used these to calculate the rate of brain atrophy each year.

A total of 271 people were randomly assigned a treatment, although five did not start the study. A similar proportion from each treatment group dropped out along the course of the study. The researchers measured adherence to the study treatments by counting returned tablets. For the main analysis of brain shrinkage, the researchers used data on 168 people (85 receiving active treatment and 83 receiving placebo) who had completed an MRI at both the start and a follow-up. The analyses took into account a variety of factors that may be linked to brain atrophy or use of vitamin B, which the researchers had tested and found to be important. These factors were age, blood pressure, initial brain volume and concentration of tHcy at the start of the study.

What were the basic results?

Treatment with vitamin B tablets had notable effects on the levels of tHcy in the blood, reducing it by 22.5%. Levels of tHcy increased by 7.7% in the placebo group. Overall, treatment with B vitamins for a period of 24 months led to a reduction in the rate of brain atrophy. After the age of the participants was taken into account, the rate of shrinkage in people receiving the vitamins was 30% less than in the placebo group (0.76% shrinkage and 1.08% shrinkage respectively). The effect was greater in people who were more compliant with taking their medication and in those who started with the highest levels of tHcy. The researchers also found that, overall, the safety of vitamins was good with no adverse events.

How did the researchers interpret the results?

The researchers concluded that they have shown that a “simple and safe treatment” can slow down the accelerated rate of brain atrophy in people with mild cognitive impairment.

Conclusion

This is an important but early study in establishing the effects of vitamin B on the stages of brain atrophy that precede Alzheimer’s disease. It assessed the effects of the vitamin on the rate of brain shrinkage, a process that has been linked to old age, mild cognitive impairment and Alzheimer’s disease in other studies. Although other studies have found that the rate of brain atrophy is linked to cognitive decline, this particular study did not assess whether the participants’ brain changes translated into changes of cognitive ability or memory.

This was a well-conducted, albeit small, study. It was a randomised controlled trial, which is the most appropriate way to assess the effects of a new treatment. No study is perfect, though, and the researchers highlighted some shortcomings:

• The treatment was a combination of three B vitamins, so the researchers cannot determine whether these have different effects individually.
• The study was not set up to assess the effects of treatment on cognition, but only on the rate of change in brain measurements.

This study will pave the way for future research into the use of vitamin B to prevent Alzheimer’s disease. Based on the evidence gathered so far, it is too early to claim that vitamin B can prevent clinical disease, but these results are promising. More research will undoubtedly follow.

Links To The Headlines

Vitamin B is revolutionary new weapon against Alzheimer's Disease. The Daily Telegraph, September 9 2010

Vitamin B 'puts off Alzheimer's'. BBC News, September 9 2010

Vitamin B 'cocktail' to beat Alzheimer's. The Sun, September 9 2010

Vitamin B 'may slow' dementia. Daily Mirror, September 9 2010

Vitamin B claim on Alzheimer's. Financial Times, September 9 2010

Daily vitamin pill could reduce dementia's effects by up to 50 per cent. The Independent, September 9 2010

Links To Science

David Smith A, Smith SM, de Jager CA et al. Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. PLoS ONE 5(9): e12244

Cholesterol-lowering statin drugs may also reduce the risk of developing rheumatoid arthritis by over 40%, the Daily Mail reported.

The news is based on a large Israeli study, which looked at how the regularity of patients’ use of statins related to their chances of developing the painful joint problem. It found that the most infrequent users of statins had around double the risk of rheumatoid arthritis as those taking the most statins. The research was well conducted and generally well reported, but its design has some limitations. An important shortcoming is its failure to take into account some medical and lifestyle factors that could have influenced its results. Controlled trials are now necessary to establish whether statins do reduce the risk of arthritis.

People who have not been recommended or prescribed statins should not take them to attempt to prevent rheumatoid arthritis. Equally, people who have been prescribed or recommended statins by their GP should take their medication as instructed to lower cholesterol.

Where did the story come from?

The study was carried out by researchers from Tel Aviv University and other medical and academic centres in Israel. The authors report that no funding was required for the study, which was published in PLoS Medicine, the peer-reviewed medical journal of the Public Library of Science.

There are some potentially misleading points in the news articles. Firstly, the Daily Mirror’s claim that people taking the drugs had a “42% reduced risk of the disease, compared with those not taking the drugs” is incorrect. All the people in this study took statins for at least part of the study period, and there was no analysis of the effects of not taking the drugs.

Some news sources also suggested that the study sample included 1.8 million participants, which is incorrect. The research only looked at a subset of that total, who had taken statins and had other necessary data available for analysis. The study analysed data on 211,627 people in the rheumatoid arthritis calculations and 193,770 in the osteoarthritis calculations.

What kind of research was this?

This was a retrospective cohort study of people who were taking statins. The study followed them up for about five years on average to determine the rate of new cases of rheumatoid arthritis and osteoarthritis in relation to the participants’ levels of statin use.

What did the research involve?

The researchers recruited adults aged over 18 who registered with a particular Israeli health insurance organisation between 1995 and 1998. Those recruited to the study had been prescribed at least one statin (simvastatin, fluvastatin, pravastatin, cerivastatin or lovastatin) for the first time between January 1998 and July 2007. This cohort population, which was identified through the health insurer’s database, was followed up until one of the following outcomes: a diagnosis of rheumatoid arthritis or osteoarthritis, death, leaving the insurance organisation or the end of the study in December 2007. People with rheumatoid arthritis, osteoarthritis or rheumatic fever at the start of the study were excluded.

For each participant, the researchers calculated the “proportion of days covered”, a measure of the amount of time they had spent taking statins during the study period. They grouped the participants into the following proportions of statin coverage: <20%, 20-39%, 40-59%, 60-79% and ≥80% of the study period. They compared each category with the people who used statins for less than 20% of the time (considered to be “non-adherent patients”) to see whether greater statin use was associated with a different incidence of rheumatoid arthritis or osteoarthritis.

The researchers adjusted their analysis model to account for the influence of a number of other factors, including age, gender, socioeconomic level, nationality, marital status, other health conditions, use of health services, LDL cholesterol levels and how effective the statin therapy had been (in terms of how well it lowered LDL cholesterol levels). The analysis only included people who had taken statins and for whom information on the potential confounders was available. This left 211,627 people for inclusion in the rheumatoid arthritis analysis and 193,770 people in the osteoarthritis analysis.

The researchers compared the risk of onset of rheumatoid arthritis and osteoarthritis across the different levels of statin use during the follow-up period. Patients were followed up for an average of about five years.

What were the basic results?

During the follow-up period, there were 2,578 cases of rheumatoid arthritis across the 211,627 people in this analysis. There were 17,878 cases of osteoarthritis in the 193,770 people included for this analysis. As expected, the type of arthritis that occurred differed across the age groups, with new cases of osteoarthritis peaking in women aged 65 to 74.

After adjusting for the influence of health and lifestyle factors, the study found that those taking statins for 80% or more of the time were almost half as likely (0.58 times) to develop rheumatoid arthritis as people taking statins for less than 20% of the study time (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.52 to 0.65).

In a separate analysis, it seems that the reduction in risk of rheumatoid arthritis was associated with the effectiveness of the statin treatment. Patients with the greatest reduction in cholesterol levels showed a greater reduction in rheumatoid arthritis risk than those with less effective anti-cholesterol treatments. Also, the effects seemed more pronounced in younger age groups.

A reduced risk of osteoarthritis was also associated with greater statin use, but not to the same degree as with rheumatoid arthritis (HR 0.85, 95% CI 0.81 to 0.88).

How did the researchers interpret the results?

The researchers concluded that their study demonstrates a link between persistence with statin therapy and a reduced risk of developing rheumatoid arthritis.

Conclusion

This large cohort study has established a link between longer use of statins and a reduced risk of rheumatoid arthritis and osteoarthritis. It should be noted that the study compared the incidence of rheumatoid arthritis in people taking different amounts of statins, but did not assess arthritis risk in people who did not use statins. Therefore, this study cannot tell us whether taking the drugs is better at preventing rheumatoid arthritis than taking no statins at all.

The study’s design had a number of potential limitations:

• It is not clear whether the study took into account all possible confounding factors (those linked to the exposure and outcome).
• One important potential confounder is the cholesterol-lowering action of statin drugs. Lower rates of rheumatoid arthritis were associated with greater reductions in cholesterol levels, but the study does not show whether any potential arthritis-preventing effect might be due to the properties of the statin drugs or the lower cholesterol levels.
• The researchers also note that the “proportion of days covered with statins” may be a surrogate for other unmeasured variables, such as higher quality of care or more aggressive treatment strategies.
• Mild muscle pains are one of the frequent side effects of statins, which the researchers say are documented in 5% to 10% of outpatients on statins. If the pain of early rheumatoid arthritis was mistaken for this side effect and made people stop their statin therapy, this could account for some of the association seen.
• Another important problem is a bias called “healthy adherer effect”. This describes the fact that people who adhere to treatments, even placebos, have better outcomes. To investigate this, the researchers assessed the incidence of osteoarthritis in a similar sample to the rheumatoid arthritis group. They found a small but significant reduction in risk of this condition too. However, they say that because this was small compared to the reduction in rheumatoid arthritis risk, the finding supports the notion that most of the reduction in rheumatoid arthritis risk is due to a real biological effect.

The researchers call for further study in this area, saying that “larger, systematic, controlled, prospective studies with high efficacy statins, particularly in younger adults who are at increased risk for rheumatoid arthritis” are needed to confirm their findings. The most appropriate way to test a drug for a new use is with randomised controlled trials.

Links To The Headlines

Patients on statins to lower cholesterol 'at less risk of arthritis' study finds. Daily Mail, September 8 2010

Cholesterol drugs help in arthritis. Daily Mirror, September 8 2010

Statins may cut arthritis risk, study suggests. BBC News, September 8 2010

Links To Science

Chodick G, Amital H, Shalem Y et al. Persistence with Statins and Onset of Rheumatoid Arthritis: A Population-Based Cohort Study. PLoS Medicine 7(9)

“People with mental illness are no more likely to commit violent crimes than ordinary members of the public,” reported The Independent. “Substance abuse is the chief cause of violent crime and increases the risk equally in people with and without mental illness,” it added.

The story is based on research that looked at the risk of people with bipolar disorder committing violent crimes such as assault and robbery, compared with the general population. It found that, although bipolar disorder was associated with a higher risk of violent crime, the increase in risk was largely due to drug and alcohol abuse.

This large, well-designed study found that the increased risk of violent crime in people with bipolar disorder was largely associated with substance abuse and not with the disorder per se. There was no significantly increased risk of violent crime in individuals with bipolar disorder who had no history of substance abuse when compared with the rest of the population. These findings may help to contradict assumptions that associate bipolar disorder with violence. They should also be considered during the risk assessment and treatment of individuals with bipolar disorder who misuse alcohol and illegal drugs.

Where did the story come from?

The study was carried out by researchers from Karolinska Institutet, Stockholm, and Oxford University. The study was published in the peer-reviewed medical journal Archives of General Psychiatry. It was funded by the Swedish Medical Research Council and the Swedish Council for Working Life and Social Research.

Media coverage of the study was generally fair and responsible, emphasising that people with bipolar disorder were no more likely to commit violent crimes than other members of the population, unless they also abused drugs or alcohol. The Financial Times’s headline, “Call to improve psychiatric help” emphasised the need for improved provision of specialised drug and alcohol services for those with mental illness. The Independent’s reporting that the study was of the “mentally ill” was misleading, since the study only looked at bipolar disorder.

What kind of research was this?

This was a population-based, longitudinal cohort study that compared the risk of violent crime in people with bipolar disorder with the risk in the general population and also with siblings unaffected by the disorder. The researchers also carried out a systematic review and meta-analysis which included previous research in this area.

The researchers point out that various adverse health outcomes have been associated with bipolar disorder, including suicide, homelessness and repeat offending. But the evidence for any association between bipolar disorder and violent crime is less clear. Their aim, they say, was to quantify any possible risk of violent crime associated with bipolar disorder, and to adjust for other factors such as social class and income, early environment and genetics, and to examine the effect of substance abuse.

What did the research involve?

The researchers compared the rate of violent crime in 3,743 individuals diagnosed with bipolar disorder who were cared for in Swedish hospitals between 1973 and 2004 with that of 37,429 individuals in the general population. They also compared rates of violent crime in people with bipolar disorder with their unaffected siblings.

To identify these groups the researchers used national population-based registries in Sweden: the Hospital Discharge Registry (HDR), the National Crime Register, the national census from 1970 and 1990 and the Multi-Generation Register.

To be included in the study, patients had to have been discharged from hospital with a diagnosis of bipolar disorder according to internationally accepted definitions, on at least two separate occasions between 1973 and 2004, and had to be at least 15 years old at the start of the study. The researchers also extracted data for each of these patients about diagnoses of alcohol and drug abuse or dependence.

Researchers also identified two comparison groups of individuals who had never been hospitalised with bipolar disorder during the study period. The first was a random sample of approximately 10 individuals in the general population who were matched on birth year and sex for each individual with bipolar disorder. The second was made up of 4,059 siblings of a subgroup of 2,570 individuals with bipolar disorder. Both comparison groups included people who may have had a history of substance abuse.

Researchers also retrieved data on all convictions for violent crime from 1973 to 2004 for all individuals aged 15 (the age of criminal responsibility in Sweden) and older. Definition of violent crime included homicide, assault, robbery and rape.

They also took into account sociodemographic factors such as income, marital and immigrant status.

Using validated statistical methods the researchers used this information to identify any association between violent crime and bipolar disorder, compared with the two control groups. Only violent crime after the second diagnosis of bipolar disorder was included.

They also carried out a systematic review and meta-analysis, with searches for studies in this area between 1970 and 2009.

What were the results?

The researchers found that:

• In the individuals with bipolar disorder, 8.4% committed violent crime compared with 3.5% in the general population (adjusted OR [aOR] 2.3; 95% confidence interval [CI] 2.0 to 2.6) and 5.1% of unaffected siblings (aOR 1.1; 95% CI 0.7 to 1.6).
• In those with bipolar disorder, the risk of violent crime was mostly confined to patients with a history of substance abuse (aOR 6.4; 95% CI 5.1 to 8.1). Of the patients with bipolar disorder and severe substance abuse, 21.3% were convicted of violent crimes compared with 4.9% of those without substance abuse.
• Risk increase was minimal in patients with no history of substance abuse (aOR 1.3; 95% CI 1.0 to 1.5).
• There were no differences in violent crime rates by clinical subgroups (for example, manic versus depressive phases of the disorder, or psychotic versus non-psychotic).

The researchers’ systematic review identified eight previous studies in this area. A meta-analysis that included their own study found that the odds ratios for the risk of violent crime in individuals with bipolar disorder, ranged from 2 to 9.

How did the researchers interpret the results?

The researchers point out that while there is an increased risk of violent crime among individuals with bipolar disorder, most of the excess risk is associated with a history of substance abuse.

They also say that the increased risk of violent crime shown among the siblings of those with bipolar disorder weakens the relationship between a diagnosis of bipolar disorder and violent crime, and highlights the importance of genetic and early environmental factors.

Substance misuse is high in individuals with bipolar disorder, so substance abuse treatment in this group is likely to reduce the risk of violent crime.

Conclusion

This large well-conducted study has several strengths. Its size increases its statistical power and makes its conclusions more reliable. Its results are adjusted for possible confounders such as income. It also only included violent crime after diagnosis, which reduces the risk that hospital admission may have been triggered by a criminal conviction. The comparison population group was well matched for birth year and sex.

The authors note some limitations in its methods, which could mean the possibility that some individuals with bipolar disorder were missed and the effects of substance abuse may have been underestimated.

The study’s conclusion that bipolar disorder per se is not associated with violent crime is important, as is the strong association between bipolar disorder, substance misuse and violent crime. The findings suggest that there should be risk assessment for violent crime in patients with both bipolar and substance misuse and strengthens the case for improved treatment services for these people.

Links To The Headlines

Mentally ill not more violent, says study. The Independent, September 8 2010

Call to improve psychiatric help. Financial Times, September 8 2010

Bipolar 'not linked to violence'. BBC News, September 8 2010

Substance abuse, not mental illness, causes violent crime. The Guardian, September 8 2010

Links To Science

Fazel S, Lichtenstein P, Grann M et al. Bipolar Disorder and Violent Crime: New Evidence From Population-Based Longitudinal Studies and Systematic Review. Archives of General Psychiatry. 2010;67(9):931-938

“Men who work more than 45 hours a week are more than twice as likely to die from heart disease if they are unfit,” The Daily Telegraph has reported.

The news comes from a 30-year Danish study of 5,000 men, which looked at how their working hours and physical fitness related to their risk of dying of a heart attack. The research has a number of strengths, such as its unusually long length and its assessment of participants’ fitness and working hours at the start of the study, rather than estimating them during the past. Its limitations include the fact that the participants’ physical fitness and working hours were only measured once and may not have been representative of the men’s lives as a whole.

Further studies will be needed to confirm whether long working hours only affect risk of death from heart disease in the least fit individuals or if groups with higher levels of fitness are also affected. However, we already know that keeping physically fit reduces the risk of cardiovascular disease, and people should aim to stay physically active.

Where did the story come from?

The study was carried out by researchers from Denmark’s National Research Centre for the Working Environment and other Danish research centres. No sources of funding for the study were reported. The study was published in the peer-reviewed medical journal Heart.

Both The Daily Telegraph and The Guardian reported the story in a balanced way.

What kind of research was this?

This prospective cohort study looked at whether men who are less physically fit are at greater risk of death from cardiovascular causes as a result of working long hours. The researchers reported that long working hours are an established risk factor for cardiovascular disease. However, it is not known whether the long-term effect of working long hours differs depending on how physically fit a person is. The researchers say that physical fitness may be able to counteract some of the effects of long working hours.

This study used an appropriate design for investigating the relationship between fitness, working hours and risk of death. As a prospective study, it selected a group of people, assessed their risk factors (work hours and fitness) and then followed them over time to assess any future outcomes. This means that the data collected on physical fitness and work hours should be more reliable than if men or their families were asked to recall what they had done in the past.

What did the research involve?

The researchers enrolled working men aged 40 to 59 years old. They performed physical fitness tests and reported how many hours a week they worked. The men were then followed up over 30 years to determine which of them died and the causes of their deaths. The researchers then looked at whether the risk of death was increased in men with different fitness levels and longer working hours.

From 1970 to 1971, researchers enrolled men from 14 companies in Copenhagen, covering a range of industries including the railway, public road construction, the military, postal service, telephone companies, customs, national banking and the medical industry. Men who agreed to participate filled in questionnaires about themselves, detailing their working hours and physical activity at work and in their leisure time. They were also given a clinical examination, including a physical fitness test. Men who already had cardiovascular disease at the start of the study were excluded, as were men who could not complete the fitness test or who provided incomplete information. The final analyses included 4,943 men.

The researchers identified any deaths among the participants during the 30-year follow-up period that ended in 2001 using national registers. They also used these records to identify the causes of any deaths. The researchers were particularly interested in deaths from ischaemic heart disease (deaths from heart attack) as these are known to be related to a lack of physical activity.

Physical fitness was assessed based on estimates of the participants’ maximum volume of oxygen usage (VO2 max) during a standard stationary bicycling test. Based on their results in this test, men were classified into three fitness groups: the least fit (VO2 max range 15 to 26), those with intermediate fitness (VO2 max range 27 to 38) and the most fit (VO2 max range 39 to 78).

Within each fitness level, the researchers compared the risk of death in those men working more than 45 hours a week, 41-45 hours a week and less than 40 hours a week. In their analyses, they took into account other factors which could affect results (called confounders), including age, smoking, alcohol consumption, blood pressure at the start of the study, body mass index, treatment for high blood pressure or diabetes, physical demands of their work, and social class.

What were the basic results?

During the 30 years of follow-up, 2,663 out of the 4,943 men (54%) died. Of these, 587 (11.9%) died from ischaemic heart disease. The researchers then looked at how rates of death were related to length of working hours and physical fitness at the start of the study. Among the groups of men who worked different numbers of hours a week, ischaemic heart disease killed:

• 10.4% of men who worked more than 45 hours a week
• 13.0% of those who worked 41 to 45 hours a week
• 8.5% of those who worked up to 40 hours a week

Among the groups of men with different levels of physical fitness, ischaemic heart disease killed:

• 16.6% of those who were least physically fit
• 11.7% of those with intermediate fitness
• 8.4% of the most fit men

The researchers then carried out analyses with adjustments to account for potential confounders, such as smoking and social class. They found that:

• Men in the least fit group who worked more than 45 hours a week were over twice as likely to die from heart disease as those working 40 hours a week or less (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.10 to 4.73).
• Working more than 45 hours a week was not associated with an increased risk of death from heart disease in men of intermediate or high fitness.
• Men who worked 41 to 45 hours a week had no greater risk of death from heart disease than men who worked 40 hours a week or less at any of the fitness levels.

How did the researchers interpret the results?

The researchers concluded that men with low physical fitness are at increased risk of death due to ischaemic heart disease from working long hours. They say that “men working long hours should be physically fit”.

Conclusion

These findings suggest that long working hours may have the greatest effect on mortality risk in men who are physically unfit. There are some points to note:

• It is possible that the results were influenced by factors other than the hours men worked and their fitness levels. Although the researchers took into account some factors which could affect results, these or other unknown or unmeasured factors could still have an effect. For example, while the researchers made adjustments to account for the influence of smoking, smoking was recorded as current, previous or never, rather than by the number of cigarettes smoked. Smoking rates were also unusually high at 65-70% in some analysis groups.
• Physical fitness and working hours were only assessed at the start of the study. These measurements might not be representative of physical fitness and working hours in the men’s earlier lives or during the 30-year follow-up.
• These results were obtained in Caucasian men aged over 40 years old. Results may differ for different population groups, such as younger men, women or people from different ethnic groups.
• Some of the information was based only on the men’s reports, for example their working hours and whether they had been treated for diabetes or high blood pressure. There could be some inaccuracy in their reports.
• There were relatively small numbers of men in some groups. For example, there were only 110 men in the group who were the least fit and worked 40 hours a week or less. Only 150 men in the least fit group worked more than 45 hours a week. These small numbers mean that the analyses involving these groups may be less reliable.

Further studies are needed to prove conclusively whether long working hours only affect the risk of death from heart disease in the least fit individuals. However, we know that keeping physically fit reduces the risk of cardiovascular disease, and people should make time to keep fit whenever possible.

Links To The Headlines

Unfit men working long hours 'twice as likely' to die of heart problems. The Daily Telegraph, September 7 2010

Unfit men working long hours face greater heart risk, study shows. The Guardian, September 7 2010

Links To Science

Holtermann A, Mortensen OS, Burr H et al. Long work hours and physical fitness: 30-year risk of ischaemic heart disease and all-cause mortality among middle-aged Caucasian men. Heart, September 6 2010 (published online first)