rebeccalawn – Page 2

Later menopause linked with lower risk of depression

Posted on May 13, 2016 by rebeccalawn

by Meg Fluharty @MegEliz_

This blog originally appeared on the Mental Elf site on 17th February 2016.

Women have twice the risk of developing major depression compared to men. This difference is most noticeable during the reproductive period years (Soares et al, 2008) (e.g. premenstrual, during pregnancy and postpartum, and perimenopause) when women are subject to large fluctuations of ovarian hormones.

Additionally, oestrogens are believed to utilise neuroprotective and antidepressive actions within the the brain (Arevalo et al, 2015), and transitioning to the postmenopausal period is associated with a large drop in oestrogen production (Burger al al., 2007).

Therefore, the authors, Georgakis et al (2016), are using ‘age at menopause’ and ‘duration of reproductive age’ as two markers of lifelong oestrogen exposure to measure the association with risk of depression in postmenopausal women.

Research shows that the median age for final menstrual period is 52.5 years, and that 90% of women have their final period by the age of 56.

Methods

Search criteria

The authors conducted a search in MEDLINE using the following keywords: menopause, climacteric, reproductive period, depression, and mood disorders. The authors then searched reference lists of included studies to identify additional studies. There was no restriction on language, publication year or study design. Cross sectional and cohort studies were obviously going to be helpful, but randomised controlled trials were also considered for eligibility if they included depression measurements before intervention.

Definition of variables

Age of menopause was defined as 1 year following last menstruation (although studies examining age at final menstruation were also considered)
Duration of reproductive period was defined as age of menopause minus age of menarche
Diagnosis of depression was defined by clinical diagnosis or validated questionnaire

Excluded studies

Studies were excluded if they used questionnaires without defined cut-offs, or self-reported depression as a single question. Studies including only women with depression were excluded as were those which also had severe psychiatric disorders. Case series, case reports, in vitro and animal studies were excluded. Studies limited to perimenopausal (the period leading up to menopause) women, breast cancer survivors with medically induced menopause, or women with surgically induced menopausal transition were excluded.

Statistical analysis

The odds ratios (OR) and confidence intervals (CI) were pooled across the identified studies, and the analysis was conducted separately for the two exposure variables (age of menopause and duration of reproductive period). The variables were first analysed as continuous variables in 2 year increments, and age of menopause was analysed again as a categorical variables (≥40 vs <40).

Results

A total of 67,714 women were included across 10 cross sectional and 4 cohort studies.

12 studies used self-report diagnosis of depression
1 study used DSM-III-R diagnosis
1 study used physician diagnosis.

Women without a diagnosis of depression were used as the control group.

Age at menopause

Pooling the effect estimates across 13 studies which treated age at menopause as a continuous variable (e.g. 2 year increments); increased age of menopause was associated with 2% decrease in risk of postmenopausal depression (OR, 0.98; 95% CI 0.96 to 0.99 heterogeneity I²=7.6%; P=.37). Sensitivity analyses for hormone therapy, premenopausal depression, or defining age at menopause as 1 year following last menstruation did alter the association.

In 4 studies with data on premature menopause (<40 years), twice the risk of depression was found compared to women with menopause onset over 40 years (OR, 0.49; 95% CI 0.29 to 0.81; heterogeneity I²=54.2%, p=.09).

Reproductive period

Pooling the effect estimates across 5 studies that includes reproductive period as a continuous variable (e.g. 2 year incriminates); found similar associations to age at menopause: a 2% decrease in risk of postmenopausal depression for an increase in reproductive period of 2 years (OR, 0.98; 95% CI 0.94 to 1.01; heterogeneity I²=0.0%; P=.41).

This evidence suggests that women who have the menopause later in life, are less likely to experience depression in their postmenopausal years.

Discussion

This meta-analysis displayed an inverse relationship between the age of menopause and subsequent risk of postmenopausal depression, which prevailed after controlling for hormone therapy and premenopausal depression. Additionally, a similar effect was found within an analysis of the duration of reproductive period. These findings indicate that shorter exposure to endogenous oestrogen is associated with oestrogen deficiency and consequently heightened risk of depression after menopause.

To put it another way, the longer the period between menarche (first menses) and menopause (defined as final menstrual period or 1 year after final menstrual period), the lower the risk that the woman will experience depression in her postmenopausal years.

If these findings are confirmed within culturally diverse studies, they can be used to identify at-risk women for postmenopausal depression whom may benefit from either psychological monitoring or oestrogen-based therapy (Georgakis et al 2016).

Strengths and limitations

This systematic review featured a well-conducted meta-analysis, including a total of 67,714 women across 14 studies; and took important confounders into consideration (age, obesity, hormone therapy, smoking, and marital status). The authors conducted sensitivity analyses where necessary and there was no evidence of publication bias in the ‘age at menopause’ studies.

However, there were some limitations to consider:

Limiting their literature search just to the MEDLINE database will have resulted in many trials been missed, which is clearly a big weakness for any systematic review.
12 of the 14 included studies used a self-report diagnosis of depression, rather than a diagnosis reached by a validated diagnostic instrument.
There were differences in the definition of depression, and depression cut-offs across studies.
The association of pre-existing depression and hormone therapy use on later depression should be considered; however the authors did conduct sensitivity analyses where possible.

Many women report a huge lack of information about the menopause, fuelled by a continuing stigma relating to this ubiquitous part of female human existence. This study provides some important pointers to risk factors and later life mental illness, which could be used to help educate women about their risk of depression as they age. However, given the limitations of this current review, we should look for further confirmation of these findings before we consider this question well and truly answered.

Do you talk to your female friends about the menopause?

Links

Primary paper

Georgakis MK, Thomopoulos TP, Diamantaras A, et al. (2015) Association of Age at Menopause and Duration of Reproductive Period With Depression After Menopause: A Systematic Review and Meta-analysis. JAMA Psychiatry. Published online January 06, 2016. doi:10.1001/jamapsychiatry.2015.2653. [Abstract]

Other references

Soares CN, Zitek B. (2008) Reproductive hormone sensitivity and risk for depression across the female life cycle: a continuum of vulnerability? J Psychiatry Neurosci. 2008;33(4):331-343.

Arevalo MA, Azcoitia I, Garcia-Segura LM. (2015) The neuroprotective actions of oestradiol and oestrogen receptors. Nat Rev Neurosci. 2015;16(1): 17-29. [PubMed abstract]

Burger HG, Hale GE, Robertson DM, Dennerstein L. (2007) A review of hormonal changes during the menopausal transition: focus on findings from the Melbourne Women’s Midlife Health Project. Hum Reprod Update. 2007;13(6):559-565. [PubMed abstract]

If you’re looking for a good overview of recent evidence-based research, please read the Evidently Cochrane blogs on the Menopause.

Photo credits

– See more at: http://www.nationalelfservice.net/mental-health/depression/later-menopause-linked-with-lower-risk-of-depression/#sthash.v4Zbt9Fx.dpuf

The European Tobacco Products Directive and the future of e-cigarettes in the UK

Posted on May 6, 2016June 16, 2016 by rebeccalawn

By Jasmine Khouja @Jasmine_Khouja

E-cigarettes have become a popular product among smokers and ex-smokers, and Action on Smoking and Health (ASH) estimates that there are 2.6 million current users of e-cigarettes in the UK. As an alternative to tobacco smoking, research commissioned by Public Health England estimates that e-cigarettes are likely to be roughly 95% less harmful. The evidence supporting these popular and effective quitting aids suggests that e-cigarettes could be a powerful tool for harm reduction amongst current smokers but there is still uncertainty over the safety of e-cigarettes. Limited research concerning the effects of long-term use and the current lack of strict regulation of the products has fuelled this uncertainty but new regulations have been introduced into the pre-existing European Tobacco Products Directive (TPD) to rectify this. The updated TPD will come into force on 20^th May 2016 with a transitional period allowed by the TPD. UK e-cigarettes and refill containers which are not in compliance with the TPD will be allowed to be released for sale on the UK market until 20^th November 2016, but from 20^th May 2017 all products sold to consumers will need to be fully compliant with the TPD. The alternative to following the regulations set by the TPD will be for e-cigarettes to gain a medical licence from the Medicines and Healthcare products Regulatory Agency (MHRA) and be regulated as licenced medicinal products to be sold in the UK.

As I am about to commence a PhD investigating the reasons for e-cigarette use, I am interested in what the implications of the directive will be in the UK; will it encourage smokers to switch to e-cigarettes, consequently reducing harm to themselves and others, or will it result in a reduction of available products and cause an increase in relapses to smoking?

I have read the directive and listed some of the key changes that will happen and added my own thoughts on what may happen as a result.

CHANGE: New e-cigarette products must be notified to the MHRA six months before their release to the public. E-cigarette companies will be charged £150 to notify MHRA of a new product and £80 for a modification to an existing product, and will then be charged £60 annually thereafter. POSSIBLE OUTCOMES: The MHRA should have more control over the products on the market and be able to prevent unsafe products entering the market but it may take longer for new products to become available to buy. Additionally, some existing products will be unavailable from 20^th May 2017 if they do not to comply with the regulations by 20^th November 2016.

CHANGE: Under the TPD, e-liquids will only be allowed where the nicotine concentration does not exceed 20 mg of nicotine per ml of liquid. E-liquids containing more than 20 mg of nicotine per ml of liquid will have to gain a medical licence authorised by the MHRA. POSSIBLE OUTCOMES: People may reduce their doses of nicotine and reduce their addiction if their preferred dosage is no longer available. Fewer high dosage products may be available as gaining a medical licence is an expensive process (estimated between £87,000 and £266,000 annually over ten years for a single device). When current products with high dosages such as 36 mg of nicotine per ml of liquid become unavailable, people may use lower dosages such as 20 mg of nicotine per ml of liquid as a substitute and inhale twice as much vapour to get the same nicotine hit. Nicotine is not the only constituent of vapour though; there are low concentrations of other toxicants, so inhaling more vapour means inhaling more toxicants. Alternatively, current higher dosage users may relapse to tobacco smoking if they feel the lower dosages do not effectively deliver the nicotine hit they need.

CHANGE: Products regulated under the TPD must provide information to the MHRA on the safety and contents of e-cigarette products (including ingredients, toxicants and emissions). Health warnings, instructions for use, information on addictiveness and toxicity must also appear on the packaging and accompanying information leaflet. POSSIBLE OUTCOMES: This should allow e-cigarette users to make informed choices. The notification fees mentioned above will include the storage of this information but the companies may have to bear extra costs in testing their products for the amount of toxicants and emissions produced. These tests will have to comply with the standards set in the TPD and by the MHRA which may prove too costly for smaller e-cigarette companies, forcing them to withdraw products from the market. This could leave the market open to the tobacco industry who generally have greater financial resources available to them. The tobacco industry have to also sustain the tobacco market; a consequence of this may be the deliberate placement of ineffective e-cigarette products on the market to encourage current smokers continue to smoke tobacco and ex-smokers using e-cigarettes relapse.

CHANGE: E-cigarette products will be child-safe, will not break or leak during the refill process, and containers will not exceed 10 ml (refill cartridges will not exceed 2 ml). POSSIBLE OUTCOMES: This should prevent accidents involving children consuming dangerous levels of nicotine. Most changes will be made to newer devices, which require e-liquid refills. If these modifications aren’t made by 20^th November 2016 the products will be removed from the market by 20^th May 2017.

CHANGE: Under the TPD, cross-border advertising will be banned, which includes in newspapers, radio and TV, but not on billboards and posters. Products will not be allowed to make smoking cessation or health claims. Advertising of products with a medicinal license will be allowed under “over the counter” medicine rules. POSSIBLE OUTCOMES: This should minimise the amount of e-cigarette advertising seen by those who should not use e-cigarettes such as children and non-smokers. However, only e-cigarette companies who can afford a medical licence will be able to advertise on TV and this could mislead people into thinking that these products are more effective than other products.

A possible outcome for many of these changes is the loss of products from the market because of non-compliance with the regulations. Although increased reassurance that e-cigarettes on the market meet certain quality standards may encourage new users, the removal of any e-cigarette product from the market will provide an opportunity for e-cigarette users to relapse to smoking; without their favourite brand or flavour, it may be easier for them to resume smoking again than to find a replacement that suits their needs and taste. This in turn could lead to increased levels of smoking, and therefore harms to both individuals and society as a whole. Additionally, high nicotine dosage e-cigarette users may be encouraged to inhale more vapour and therefore unnecessary amounts of other constituents. However, recent preliminary research findings from ASH UK suggest there are few high dosage users meaning that this should not affect many.

The withdrawal of products is likely to be determined by the cost of making products compliant. Tobacco companies generally have greater financial resources than e-cigarette companies, with the top companies making billions in profit each year, meaning they can afford to make the necessary changes to meet the new regulations. The few e-cigarette companies that are owned by tobacco companies mainly produce ‘cigalikes’ which are the least effective design of e-cigarettes and there is a higher chance of relapsing to smoking when using them compared to later-generation devices. Given that the tobacco-owned e-cigarette companies will probably have greater resources available to them, they could end up with a monopoly on the e-cigarette industry. In fact, this may already be happening; the first medically licensed e-cigarette is a ‘cigalike’ owned by British American Tobacco. This means British American Tobacco could own the only TV-advertised e-cigarette (until another company gains a licence). Consequently, smokers looking to try e-cigarettes may choose less effective devices because they are more widely advertised.

These changes may reassure the general public that the devices will be safe but may lead to many ex-smokers relapsing because they are forced to use e-cigarettes and e-liquids that do not meet their needs, all the while lining the pockets of the tobacco industry by allowing them a monopoly on higher nicotine dosage products. Of course, the possible outcomes stated here are speculative; research will need to be undertaken to evaluate the ongoing impact of the new guidelines.

Links

Photo Credits

http://ecigarettereviewed.com/ – Lindsay Fox

The Rosalind Franklin Appathon Prize and Tech day: A celebration of pioneering women in STEMM past, present and future.

Posted on March 4, 2016March 4, 2016 by rebeccalawn

by Sarah Griffiths @SarahGriff90

Last week Angela Attwood and I attended the Rosalind Franklin Appathon Prize and Tech day. The appathon was set up by UCL Professor Rachel McKendry with funds from her Royal Society Rosalind Franklin Award. The Rosalind Franklin Award recognises outstanding women in science with an idea for how to raise the profile of other women in their field. Professor McKendry’s idea was to hold an appathon with two challenges. The first challenge was to invent an app that would empower women to become leaders in STEMM (science, technology engineering, mathematics and medicine). The second challenge was to recognise a woman who had pioneered a new app for research, societal good or enterprise. Marcus had nominated me for the second challenge for my work developing the iPad app About Face for teaching emotion recognition to children with autism. Although I was not short listed in the end, I was pleased to be invited along to the prize and tech day to celebrate the winners and their apps.

On the day we were shown videos showcasing the shortlisted apps, some of which you can see here. The winner of Challenge 1 was Amazing STEMM Trailblazers an app for teaching children about influential women in STEMM through games. The runner up was STEMM Role Models, an app for finding female experts to speak at conferences. My personal favourite in this category was EyeSTEMM an app which suggests STEMM careers for young users based on photos they upload to show their interests. There were many exceptional apps shortlisted for Challenge 2, all of which would have been worthy winners. The winner was eSexual Health Clinic, developed by epidemiologist Pam Sonnenberg and her team at UCL. It provides Chlamydia test results and after care, including ordering antibiotic medication to the users local community pharmacy. This app demonstrates the potential of mobile technology to revolutionise health care and reduce strain on the NHS. The runner up was Findme developed by psychologist Sue Fletcher-Watson from Edinburgh University. The app aims to teach children with autism social skills such as following eye gaze and gestures. It was created with consultation with individuals with autism, and the effectiveness of the app has been tested in a randomised control trial. Also shortlisted was Drink Less, which may be of particular interest to readers of this blog. This app was developed by Professor Susan Michie and her team of health psychology researchers at UCL. The app aims to help people keep track of, and to cut down on, their alcohol intake. The data from this app is being used to test how well particular techniques for cutting down work when delivered in an app, rather than by a clinician.

Professor Dame Athene Donald speaking about how to promote women to become leaders in science research.

As well announcing the winning apps, the afternoon also included a number of brilliant talks addressing the challenges and opportunities for women in STEMM industries today. Speakers included Jennifer Glynn, Rosalind Franklin’s sister, who spoke of male-only common rooms in universities which were the norm in the 1950s, reminding us of how far we have come in terms of gender equality in academia. Baroness Martha Lane Fox, founder of lastminute.com, spoke about gender imbalance in the technology industry (only 17% of tech jobs in the UK are held by women) and emphasised the importance of encouraging women to consider STEMM jobs in order to address skills shortages. Finally, Professor Dame Athene Donald gave an inspirational talk about her experiences as a leading female physicist and her ideas for how to promote women in science. This talk I found particularly interesting as a woman seeking a career in this field.

The whole day was very inspiring, both in terms of showing the potential of technology to make positive differences in research, health and education and in terms of showcasing the many women who are playing a leading role in this field. Although there are clearly still challenges being faced by women in STEMM, the message of the day was one of confidence that these can be overcome.

Medication for cognitive impairment in traumatic brain injury: little evidence to support its use

Posted on February 18, 2016February 10, 2016 by rebeccalawn

by Eleanor Kennedy @Nelllor_

This blog originally appeared on the Mental Elf site on 18th January 2016.

Traumatic Brain Injury (TBI) is classified by The World Health Organization as the leading cause of death and disability among children and young adults worldwide (WHO, 2006, p. 164). An estimated 235 per 100,000 Europeans acquire brain injuries each year, with more than 6 million TBI survivors already living in Europe (Tagliaferri et al, 2006).

There are many long-lasting consequences of TBI including cognitive, behavioural and emotional problems (Barnes & Ward, 2005). Pharmacotherapy interventions have been suggested to alleviate cognitive impairment in TBI sufferers. The current review aimed to assess the evidence for such interventions (Dougall et al, 2015).

Traumatic brain injury is the leading cause of death and disability among children and young adults worldwide.

Methods

The Cochrane Dementia and Cognitive Improvement Group’s Specialised Register was searched for studies that examined the effectiveness of pharmacological treatment for cognitive impairment in people with traumatic brain injury. The search included both healthcare databases and trial registers. Studies were included if:

The study design was either a randomised controlled trial (RCT) or cross-over design study
The study investigated one centrally acting pharmacological agent that modulate one or more of the main neurotransmitter systems
Participants had to have experienced the TBI resulting in chronic cognitive impairment at least 12 months prior to assessment

The primary outcomes of interest were performance on psychometric and neuropsychological tests or scores on screening measures that measured memory and cognitive function; global severity of cognitive impairment and global impression of change. Acceptability of treatment (as measured by withdrawal from trial), safety, mortality and subjective benefit were all secondary outcomes.

Analyses were carried out on results from phase one of each included study.

Results

Four studies in total were included in the review (3 from the United States, one from Sweden). Seven RCTs that matched inclusion criteria were found, however, two cross-over design studies could not be included as data for phase one was not available from the authors; another study was not included due to the lack of a placebo control. Table 1 summarises the treatments and participants.

Study	N Participants	Treatment	Duration of treatment
Jhaet al. 2008	51 (age 16 to 65)	Modafinil; effects histaminergic, serotonergic, and glutaminergic activity	4 weeks
Johansson et al. 2012	12 (age 30 to 65)	(−)-OSU6162; monoamine stabiliser agent with dopaminergic and serotonergic effects	4 weeks
Ripley et al. 2014	60 (age 18 to 65)	Atomoxetine; noradrenaline reuptake inhibitor	2 weeks
Silver et al., 2006	157 (age 18 to 50)	Rivastigmine; an acetylcholinesterase and butyrylcholinesterase inhibitor	12 weeks

Primary outcome

Neither modafinil nor atomoxetine demonstrated superiority over placebo on any measure of cognition. The effects of rivastigmine were superior on one measure in the current review (CANTAB RVIP −44.54 milliseconds, 95% CI −88.62 to −0.46), but not in the original trial. Rivastigmine was also effective on the same measure in a subgroup of participants with greater cognitive impairment.

Superiority over placebo for (−)-OSU6162 was demonstrated in Trail Making Test A (−9.20 seconds, 95% CI −12.19 to −6.21), Trail Making Test B (−6.20 seconds, 95%CI,−7.81 to−4.59) and WAIS-III digit symbol coding (8.60, 95% CI 6.47 to 10.73), however the score in Trail Making Test D was higher for placebo (53.80 seconds, 95% CI 36.76 to 70.24) (Johansson 2012).

Secondary outcomes

Safety and acceptability were two secondary outcomes that were reported on. Participants reported more adverse effects for modafinil and atomoxetine, however this was not statistically supported. One participant required a dose reduction in the (-)-OSU6162 trial due to adverse effects. More participants taking rivastigmine reported nausea compared to those taking placebo (19/80, 23.8%versus 6/77, 7.8%, risk ratio 3.05, 95% CI 1.29 to 7.22). Two people dropped out of the modafinil treatment arm, none in the placebo group. There were no deaths reported in any of the included studies.

Strengths and limitations

The review included only randomised controlled trials to assess the effects of centrally acting pharmacological agents for treatment of chronic cognitive impairment subsequent to traumatic brain injury in adults. There were very strict inclusion criteria and the authors chose to only include data from phase one of the treatment. This is a strength for cross-over design studies particularly as this controls for the possibility of long term treatment effects once a group’s treatment is switched to placebo following pharmacological treatment. However, two studies were excluded because data from phase one were unavailable.

The limited number of included studies, rather than a limitation, is likely to be indicative of a lack of well controlled research into pharmacological treatments for cognitive impairment following TBI.

Conclusions

There was no evidence to support modafinil or atomoxetine as a treatment for cognitive impairment as a result of TBI. There was weak evidence to suggest that rivastigmine may be helpful in the treatment of cognitive impairment in one measure of cognitive functioning in this review, however the same effect was not significant in the original study possibly due to the use of a different statistical test, and the findings that (−)-OSU6162 may be superior to placebo must be interpreted with caution as the sample size in this group was so small (n=6).

Overall the authors concluded that:

there is insufficient evidence to determine whether pharmacological treatment is effective in chronic cognitive impairment in TBI.

Two of the four included studies had fatigue as their primary outcome, which further suggests that more research in the specific area of cognition may be necessary.

In closing, the review highlights a gap in the research in such treatments for TBI, the authors suggest that future research should also focus on outcomes such as neurobehavioral symptoms as well as cognitive impairment and memory performance.

This review highlights a lack of RCTs that explore the potential value of medication for cognitive impairment following traumatic brain injury.

Links

Primary paper

Dougall D, Poole N, Agrawal N. Pharmacotherapy for chronic cognitive impairment in traumatic brain injury. Cochrane Database of Systematic Reviews 2015, Issue 12. Art. No.: CD009221. DOI: 10.1002/14651858.CD009221.pub2.

Other references

Barnes M, Ward A. (2005) Oxford Handbook of Rehabilitation Medicine. Oxford University Press.

Jha A, Weintraub A, Allshouse A, Morey C, Cusick C, Kittelson J, Gerber D. (2008) A randomized trial of modafinil for the treatment of fatigue and excessive daytime sleepiness in individuals with chronic traumatic brain injury. Journal of Head Trauma Rehabilitation, 23(1), 52–63. doi:10.1097/01.HTR.0000308721.77911.ea (PubMed abstract)

Johansson B, Carlsson A, Carlsson ML, Karlsson M, Nilsson MKL, Nordquist-Brandt E, Rönnbäck L. (2012) Placebo-controlled cross-over study of the monoaminergic stabiliser (-)-OSU6162 in mental fatigue following stroke or traumatic brain injury. Acta Neuropsychiatrica, 24, 266–274. doi:10.1111/j.1601-5215.2012.00678.x [PubMed record]

Ripley DL, Morey CE, Gerber D, Harrison-Felix C, Brenner LA, Pretz CR, Wesnes K. (2014) Atomoxetine for attention deficits following traumatic brain injury: Results from a randomized controlled trial. Brain Injury, 28(January 2016), 1514–1522. doi:10.3109/02699052.2014.919530 [PubMed abstract]

Silver JM, Koumaras B, Chen M, Mirski D, Potkin SG, Reyes P, Gunay I. (2006) Effects of rivastigmine on cognitive function in patients with traumatic brain injury. Neurology, 67, 748–755. [PubMed abstract]

Tagliaferri F, Compagnone C, Korsic M, Servadei F, Kraus J. (2006) A systematic review of brain injury epidemiology in Europe. Acta Neurochirurgica, 148(3), 255–68; discussion 268. doi:10.1007/s00701-005-0651-y [PubMed abstract]

WHO. (2006) Neurological Disorders: Public Health Challenges. World Health Organisation (p. 232).http://www.who.int/mental_health/neurology/neurological_disorders_report_web.pdf