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1.  Differences in risk factors for self-harm with and without suicidal intent: Findings from the ALSPAC cohort 
Journal of Affective Disorders  2014;168(100):407-414.
Background
There is a lack of consensus about whether self-harm with suicidal intent differs in aetiology and prognosis from non-suicidal self-harm, and whether they should be considered as different diagnostic categories.
Method
Participants were 4799 members of the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK population-based birth cohort who completed a postal questionnaire on self-harm with and without suicidal intent at age 16 years. Multinomial logistic regression analyses were used to examine differences in the risk factor profiles of individuals who self-harmed with and without suicidal intent.
Results
Many risk factors were common to both behaviours, but associations were generally stronger in relation to suicidal self-harm. This was particularly true for mental health problems; compared to those with non-suicidal self-harm, those who had harmed with suicidal intent had an increased risk of depression (OR 3.50[95% CI 1.64, 7.43]) and anxiety disorder (OR 3.50[95% CI 1.72, 7.13]). Higher IQ and maternal education were risk factors for non-suicidal self-harm but not suicidal self-harm. Risk factors that appeared specific to suicidal self-harm included lower IQ and socioeconomic position, physical cruelty to children in the household and parental self-harm.
Limitations
i) There was some loss to follow-up, ii) difficulty in measuring suicidal intent, iii) we cannot rule out the possibility of reverse causation for some exposure variables, iv) we were unable to identify the subgroup that had only ever harmed with suicidal intent.
Conclusion
Self-harm with and without suicidal intent are overlapping behaviours but with some distinct characteristics, indicating the importance of fully exploring vulnerability factors, motivations, and intentions in adolescents who self harm.
doi:10.1016/j.jad.2014.07.009
PMCID: PMC4160300  PMID: 25108277
ALSPAC; Adolescent; Self-harm; Suicide attempt; Longitudinal
2.  Reporting of drug induced depression and fatal and non-fatal suicidal behaviour in the UK from 1998 to 2011 
Background
Psychiatric adverse drug reactions (ADRs) are distressing for patients and have important public health implications. We identified the drugs with the most frequent spontaneous reports of depression, and fatal and non-fatal suicidal behaviour to the UK’s Yellow Card Scheme from 1998 to 2011.
Methods
We obtained Yellow Card data from the Medicines and Healthcare products Regulatory Agency for the drugs with the most frequent spontaneous reports of depression and suicidal behaviour from 1964 onwards. Prescribing data were obtained from the NHS Information Centre and the Department of Health. We examined the frequency of reports for drugs and estimated rates of reporting of psychiatric ADRs using prescribing data as proxy denominators from 1998 to 2011, as prescribing data were not available prior to 1998.
Results
There were 110 different drugs with ≥ 20 reports of depression, 58 with ≥10 reports of non-fatal suicidal behaviour and 33 with ≥5 reports of fatal suicidal behaviour in the time period. The top five drugs with the most frequent reports of depression were the smoking cessation medicines varenicline and bupropion, followed by paroxetine (a selective serotonin reuptake inhibitor), isotretinoin (used in acne treatment) and rimonabant (a weight loss drug). Selective serotonin reuptake inhibitors, varenicline and the antipsychotic medicine clozapine were included in the top five medicines with the most frequent reports of fatal and non-fatal suicidal behaviour. Medicines with the highest reliably measured reporting rates of psychiatric ADRs per million prescriptions dispensed in the community included rimonabant, isotretinoin, mefloquine (an antimalarial), varenicline and bupropion. Robust denominators for community prescribing were not available for two drugs with five or more suicide reports, efavirenz (an antiretroviral medicine) and clozapine.
Conclusions
Depression and suicide-related ADRs are reported for many nervous system and non-nervous system drugs. As spontaneous reports cannot be used to determine causality between the drug and the ADR, psychiatric ADRs which can cause significant public alarm should be specifically assessed and reported in all randomised controlled trials.
doi:10.1186/2050-6511-15-54
PMCID: PMC4184159  PMID: 25266008
Adverse drug reaction; Suicide; Non-fatal suicidal behaviour; Self injury; Depression; Yellow card; Adverse effects
3.  A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010 
Lim, Stephen S | Vos, Theo | Flaxman, Abraham D | Danaei, Goodarz | Shibuya, Kenji | Adair-Rohani, Heather | Amann, Markus | Anderson, H Ross | Andrews, Kathryn G | Aryee, Martin | Atkinson, Charles | Bacchus, Loraine J | Bahalim, Adil N | Balakrishnan, Kalpana | Balmes, John | Barker-Collo, Suzanne | Baxter, Amanda | Bell, Michelle L | Blore, Jed D | Blyth, Fiona | Bonner, Carissa | Borges, Guilherme | Bourne, Rupert | Boussinesq, Michel | Brauer, Michael | Brooks, Peter | Bruce, Nigel G | Brunekreef, Bert | Bryan-Hancock, Claire | Bucello, Chiara | Buchbinder, Rachelle | Bull, Fiona | Burnett, Richard T | Byers, Tim E | Calabria, Bianca | Carapetis, Jonathan | Carnahan, Emily | Chafe, Zoe | Charlson, Fiona | Chen, Honglei | Chen, Jian Shen | Cheng, Andrew Tai-Ann | Child, Jennifer Christine | Cohen, Aaron | Colson, K Ellicott | Cowie, Benjamin C | Darby, Sarah | Darling, Susan | Davis, Adrian | Degenhardt, Louisa | Dentener, Frank | Des Jarlais, Don C | Devries, Karen | Dherani, Mukesh | Ding, Eric L | Dorsey, E Ray | Driscoll, Tim | Edmond, Karen | Ali, Suad Eltahir | Engell, Rebecca E | Erwin, Patricia J | Fahimi, Saman | Falder, Gail | Farzadfar, Farshad | Ferrari, Alize | Finucane, Mariel M | Flaxman, Seth | Fowkes, Francis Gerry R | Freedman, Greg | Freeman, Michael K | Gakidou, Emmanuela | Ghosh, Santu | Giovannucci, Edward | Gmel, Gerhard | Graham, Kathryn | Grainger, Rebecca | Grant, Bridget | Gunnell, David | Gutierrez, Hialy R | Hall, Wayne | Hoek, Hans W | Hogan, Anthony | Hosgood, H Dean | Hoy, Damian | Hu, Howard | Hubbell, Bryan J | Hutchings, Sally J | Ibeanusi, Sydney E | Jacklyn, Gemma L | Jasrasaria, Rashmi | Jonas, Jost B | Kan, Haidong | Kanis, John A | Kassebaum, Nicholas | Kawakami, Norito | Khang, Young-Ho | Khatibzadeh, Shahab | Khoo, Jon-Paul | Kok, Cindy | Laden, Francine | Lalloo, Ratilal | Lan, Qing | Lathlean, Tim | Leasher, Janet L | Leigh, James | Li, Yang | Lin, John Kent | Lipshultz, Steven E | London, Stephanie | Lozano, Rafael | Lu, Yuan | Mak, Joelle | Malekzadeh, Reza | Mallinger, Leslie | Marcenes, Wagner | March, Lyn | Marks, Robin | Martin, Randall | McGale, Paul | McGrath, John | Mehta, Sumi | Mensah, George A | Merriman, Tony R | Micha, Renata | Michaud, Catherine | Mishra, Vinod | Hanafiah, Khayriyyah Mohd | Mokdad, Ali A | Morawska, Lidia | Mozaff arian, Dariush | Murphy, Tasha | Naghavi, Mohsen | Neal, Bruce | Nelson, Paul K | Nolla, Joan Miquel | Norman, Rosana | Olives, Casey | Omer, Saad B | Orchard, Jessica | Osborne, Richard | Ostro, Bart | Page, Andrew | Pandey, Kiran D | Parry, Charles D H | Passmore, Erin | Patra, Jayadeep | Pearce, Neil | Pelizzari, Pamela M | Petzold, Max | Phillips, Michael R | Pope, Dan | Pope III, C Arden | Powles, John | Rao, Mayuree | Razavi, Homie | Rehfuess, Eva A | Rehm, Jürgen T | Ritz, Beate | Rivara, Frederick P | Roberts, Thomas | Robinson, Carolyn | Rodriguez-Portales, Jose A | Romieu, Isabelle | Room, Robin | Rosenfeld, Lisa C | Roy, Ananya | Rushton, Lesley | Salomon, Joshua A | Sampson, Uchechukwu | Sanchez-Riera, Lidia | Sanman, Ella | Sapkota, Amir | Seedat, Soraya | Shi, Peilin | Shield, Kevin | Shivakoti, Rupak | Singh, Gitanjali M | Sleet, David A | Smith, Emma | Smith, Kirk R | Stapelberg, Nicolas J C | Steenland, Kyle | Stöckl, Heidi | Stovner, Lars Jacob | Straif, Kurt | Straney, Lahn | Thurston, George D | Tran, Jimmy H | Van Dingenen, Rita | van Donkelaar, Aaron | Veerman, J Lennert | Vijayakumar, Lakshmi | Weintraub, Robert | Weissman, Myrna M | White, Richard A | Whiteford, Harvey | Wiersma, Steven T | Wilkinson, James D | Williams, Hywel C | Williams, Warwick | Wilson, Nicholas | Woolf, Anthony D | Yip, Paul | Zielinski, Jan M | Lopez, Alan D | Murray, Christopher J L | Ezzati, Majid
Lancet  2012;380(9859):2224-2260.
Summary
Background
Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time.
Methods
We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden.
Findings
In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania.
Interpretation
Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children.
Funding
Bill & Melinda Gates Foundation.
doi:10.1016/S0140-6736(12)61766-8
PMCID: PMC4156511  PMID: 23245609
4.  Childhood traumatic events and adolescent overgeneral autobiographical memory: Findings in a UK cohort 
Background
Overgeneral autobiographical memory has repeatedly been identified as a risk factor for adolescent and adult psychopathology but the factors that cause such over-generality remain unclear. This study examined the association between childhood exposure to traumatic events and early adolescent overgeneral autobiographical memory in a large population sample.
Methods
Thirteen-year-olds, n = 5,792, participating in an ongoing longitudinal cohort study (ALSPAC) completed a written version of the Autobiographical Memory Test. Performance on this task was examined in relation to experience of traumatic events, using data recorded by caregivers close to the time of exposure.
Results
Results indicated that experiencing a severe event in middle childhood increased the likelihood of an adolescent falling into the lowest quartile for autobiographical memory specificity (retrieving 0 or 1 specific memory) at age 13 by approximately 60%. The association persisted after controlling for a range of potential socio-demographic confounders.
Limitations
Data on the traumatic event exposures was limited by the relatively restricted range of traumas examined, and the lack of contextual details surrounding both the traumatic event exposures themselves and the severity of children's post-traumatic stress reactions.
Conclusions
This is the largest study to date of the association between childhood trauma exposure and overgeneral autobiographical memory in adolescence. Findings suggest a modest association between exposure to traumatic events and later overgeneral autobiographical memory, a psychological variable that has been linked to vulnerability to clinical depression.
Highlights
•Overgeneral autobiographical memory has been linked to trauma in childhood.•We examined associations between low AMT score and trauma exposure at age 13.•A severe middle childhood life event increased likelihood of low AMT by 60%.•This association was not appreciably attenuated after adjustment for confounders.
doi:10.1016/j.jbtep.2014.02.004
PMCID: PMC4053588  PMID: 24657714
Memory; Adolescence; Trauma; Depression; ALSPAC
5.  Suicide and the 2008 economic recession: Who is most at risk? Trends in suicide rates in England and Wales 2001–2011 
Social Science & Medicine (1982)  2014;117(100):76-85.
The negative impacts of previous economic recessions on suicide rates have largely been attributed to rapid rises in unemployment in the context of inadequate social and work protection programmes. We have investigated trends in indicators of the 2008 economic recession and trends in suicide rates in England and Wales in men and women of working age (16–64 years old) for the period 2001–2011, before, during and after the economic recession, our aim was to identify demographic groups whose suicide rates were most affected. We found no clear evidence of an association between trends in female suicide rates and indicators of economic recession. Evidence of a halt in the previous downward trend in suicide rates occurred for men aged 16–34 years in 2006 (95% CI Quarter 3 (Q3) 2004, Q3 2007 for 16–24 year olds & Q1 2005, Q4 2006 for 25–34 year olds), whilst suicide rates in 35–44 year old men reversed from a downward to upward trend in early 2010 (95% CI Q4 2008, Q2 2011). For the younger men (16–34 years) this change preceded the sharp increases in redundancy and unemployment rates of early 2008 and lagged behind rising trends in house repossessions and bankruptcy that began around 2003. An exception were the 35–44 year old men for whom a change in suicide rate trends from downwards to upwards coincided with peaks in redundancies, unemployment and rises in long-term unemployment. Suicide rates across the decade rose monotonically in men aged 45–64 years. Male suicide in the most-to-medium deprived areas showed evidence of decreasing rates across the decade, whilst in the least-deprived areas suicide rates were fairly static but remained much lower than those in the most-deprived areas. There were small post-recession increases in the proportion of suicides in men in higher management/professional, small employer/self-employed occupations and fulltime education. A halt in the downward trend in suicide rates amongst men aged 16–34 years, may have begun before the 2008 economic recession whilst for men aged 35–44 years old increased suicide rates mirrored recession related unemployment. This evidence suggests indicators of economic strain other than unemployment and redundancies, such as personal debt and house repossessions may contribute to increased suicide rates in younger-age men whilst for men aged 35–44 years old job loss and long-term unemployment is a key risk factor.
Highlights
•Indicators showed economic hardship was increasing 5 years prior to the 2008 economic recession.•The downward trends in younger male suicide rates (16–34 year olds) halted around 2006.•Economic strain and unemployment may contribute to rises in suicide rates in men aged 35–44 years old.•There was no clear evidence of an impact of the 2008 economic recession on suicide rates in females.
doi:10.1016/j.socscimed.2014.07.024
PMCID: PMC4151136  PMID: 25054280
Suicide rates; suicide trends; Economic recession; England and Wales; Risk; Joinpoint regression
6.  Risk factors for suicidal thoughts in adolescence-a prospective cohort study: the Young-HUNT study 
BMJ Open  2014;4(8):e005867.
Objectives
Examining the associations between health and lifestyle factors recorded in the participants’ early teens and development of suicidal thoughts recorded 4 years later.
Design
Population-based prospective cohort study.
Settings
All students in the two relevant year classes in Nord-Trøndelag County were invited, 80% attended both waves of data collection.
Participants
2399 secondary school students who participated in the Young-HUNT1 study in 1995–1997 (13–15 years old) were included in a follow-up study 4 years later (17–19 years old).
Primary outcome measure
Suicidal thoughts reported at age 17–19 years.
Results
408 (17%, 95% CI 15.5% to 18.5%) of the adolescents reported suicidal thoughts at follow-up, 158 (14.2%, CI 13.6% to 16.4%) boys and 250 (19.5%, CI 18.8% to 22.0%) girls. Baseline anxiety and depressive symptoms (adjusted OR (aOR) 1.9, CI 1.4 to 2.6), conduct problems (aOR 1.8, CI 1.3 to 2.6), overweight (aOR 1.9 CI 1.4 to 2.4), and muscular pain and tension (aOR 1.8, CI 1.4 to 2.4), were all associated with reporting suicidal thoughts at follow-up.
Conclusions
One in six young adults experienced suicidal thoughts, girls predominating. Suicidal thoughts were most strongly associated with symptoms of anxiety/depression, conduct problems, pain/tension and overweight reported when participants were 13–15 years old. Specific preventive efforts in these groups might be indicated. Future research should investigate whether similar associations are seen with suicide/suicidal attempts as endpoints.
doi:10.1136/bmjopen-2014-005867
PMCID: PMC4139646  PMID: 25142264
Preventive Medicine
7.  Suicide in Sri Lanka 1975–2012: age, period and cohort analysis of police and hospital data 
BMC Public Health  2014;14(1):839.
Background
Sri Lanka has experienced major changes in its suicide rates since the 1970s, and in 1995 it had one of the highest rates in the world. Subsequent reductions in Sri Lanka’s suicide rates have been attributed to the introduction of restrictions on the availability of highly toxic pesticides. We investigate these changes in suicide rates in relation to age, gender, method specific trends and birth-cohort and period effects, with the aim of informing preventative strategies.
Methods
Secular trends of suicide in relation to age, sex, method, birth-cohort and period effects were investigated graphically using police data (1975–2012). Poisoning case-fatality was investigated using national hospital admission data (2004–2010).
Results
There were marked changes to the age-, gender- and method-specific incidence of suicide over the study period. Year on year declines in rates began in 17–25 year olds in the early 1980s. Reduction in older age groups followed and falls in all age groups occurred after all class I (the most toxic) pesticides were banned. Distinct changes in the age/gender pattern of suicide are observed: in the 1980s suicide rates were highest in 21–35 year old men; by the 2000s, this pattern had reversed with a stepwise increase in male rates with increasing age. Throughout the study period female rates were highest in 17–25 year olds. There has been a rise in suicide by hanging, though this rise is relatively small in relation to the marked decline in self-poisoning deaths. The patterns of suicides are more consistent with a period rather than birth-cohort effect.
Conclusions
The epidemiology of suicide in Sri Lanka has changed noticeably in the last 30 years. The introduction of pesticide regulations in Sri Lanka coincides with a reduction in suicide rates, with evidence of limited method substitution.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2458-14-839) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2458-14-839
PMCID: PMC4148962  PMID: 25118074
Sri Lanka; Pesticide poisoning; Suicide; Period effects; Birth-cohort effects
8.  Associations between APOE and low-density lipoprotein cholesterol genotypes and cognitive and physical capability: the HALCyon programme 
Age  2014;36(4):9673.
The APOE ε2/3/4 genotype has been associated with low-density lipoprotein cholesterol (LDL-C) and Alzheimer disease. However, evidence for associations with measures of cognitive performance in adults without dementia has been mixed, as it is for physical performance. Associations may also be evident in other genotypes implicated in LDL-C levels. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, genotypic information was obtained for APOE ε2/3/4, rs515135 (APOB), rs2228671 (LDLR) and rs629301 (SORT1) from eight cohorts of adults aged between 44 and 90 + years. We investigated associations with four measures of cognitive (word recall, phonemic fluency, semantic fluency and search speed) and physical capability (grip strength, get up and go/walk speed, timed chair rises and ability to balance) using meta-analyses. Overall, little evidence for associations between any of the genotypes and measures of cognitive capability was observed (e.g. pooled beta for APOE ε4 effect on semantic fluency z score = −0.02; 95 % CI = −0.05 to 0.02; p value = 0.3; n = 18,796). However, there was borderline evidence within studies that negative effects of APOE ε4 on nonverbal ability measures become more apparent with age. Few genotypic associations were observed with physical capability measures. The findings from our large investigation of middle-aged to older adults in the general population suggest that effects of APOE on cognitive capability are at most modest and are domain- and age-specific, while APOE has little influence on physical capability. In addition, other LDL-C-related genotypes have little impact on these traits.
Electronic supplementary material
The online version of this article (doi:10.1007/s11357-014-9673-9) contains supplementary material, which is available to authorized users.
doi:10.1007/s11357-014-9673-9
PMCID: PMC4150901  PMID: 25073452
Ageing; Apolipoprotein E; Cognition; Single nucleotide polymorphism
9.  Challenges and opportunities of a paperless baseline survey in Sri Lanka 
BMC Research Notes  2014;7:452.
Background
Personal digital assistants (PDAs) have been shown to reduce costs associated with survey implementation and digitisation, and to improve data quality when compared to traditional paper based data collection. Few studies, however, have shared their experiences of the use of these devices in rural settings in Asia. This paper reports on our experiences of using a PDA device for data collection in Sri Lanka as part of a large cluster randomised control trial.
Findings
We found that PDAs were useful for collecting data for a baseline survey of a large randomised control trial (54,000 households). We found that the PDA device and survey format was easy to use by inexperienced field staff, even though the survey was programmed in English. The device enabled the rapid digitisation of survey data, providing a good basis for continuous data quality assurance, supervision of staff and survey implementation. An unexpected advantage was the improved community opinion of the research project as a result of the device, because the use of the technology gave data collectors an elevated status amongst the community. In addition the global positioning system (GPS) functionality of the device allowed precise mapping of households, and hence distinct settlements to be identified as randomisation clusters. Future users should be mindful that to save costs the piloting should be completed before programming. In addition consideration of a local after-care service is important to avoid costs and time delays associated with sending devices back to overseas providers.
Discussion
Since the start of this study, PDA devices have rapidly developed and are increasingly used. The use of PDA or similar devices for research is not without its problems; however we believe that the universal lessons learnt as part of this study are even more important for the effective utilisation of these rapidly developing technologies in resource poor settings.
doi:10.1186/1756-0500-7-452
PMCID: PMC4118630  PMID: 25027231
Sri Lanka; Computer; Handheld; Data collection; Randomised control trial; Epidemiology
10.  Validation of suicide and self-harm records in the Clinical Practice Research Datalink 
Aims
The UK Clinical Practice Research Datalink (CPRD) is increasingly being used to investigate suicide-related adverse drug reactions. No studies have comprehensively validated the recording of suicide and nonfatal self-harm in the CPRD. We validated general practitioners' recording of these outcomes using linked Office for National Statistics (ONS) mortality and Hospital Episode Statistics (HES) admission data.
Methods
We identified cases of suicide and self-harm recorded using appropriate Read codes in the CPRD between 1998 and 2010 in patients aged ≥15 years. Suicides were defined as patients with Read codes for suicide recorded within 95 days of their death. International Classification of Diseases codes were used to identify suicides/hospital admissions for self-harm in the linked ONS and HES data sets. We compared CPRD-derived cases/incidence of suicide and self-harm with those identified from linked ONS mortality and HES data, national suicide incidence rates and published self-harm incidence data.
Results
Only 26.1% (n = 590) of the ‘true’ (ONS-confirmed) suicides were identified using Read codes. Furthermore, only 55.5% of Read code-identified suicides were confirmed as suicide by the ONS data. Of the HES-identified cases of self-harm, 68.4% were identified in the CPRD using Read codes. The CPRD self-harm rates based on Read codes had similar age and sex distributions to rates observed in self-harm hospital registers, although rates were underestimated in all age groups.
Conclusions
The CPRD recording of suicide using Read codes is unreliable, with significant inaccuracy (over- and under-reporting). Future CPRD suicide studies should use linked ONS mortality data. The under-reporting of self-harm appears to be less marked.
doi:10.1111/bcp.12059
PMCID: PMC3703237  PMID: 23216533
Clinical Practice Research Datalink; General Practice Research Database; nonfatal self-harm; suicide; validation
11.  Body Mass Index in Young Adulthood and Suicidal Behavior up to Age 59 in a Cohort of Swedish Men 
PLoS ONE  2014;9(7):e101213.
An association of higher body mass index (BMI) with lower risk of attempted and completed suicide has been reported. In contrast, increasing BMI has been found to be associated with depression and other risk factors for suicidal behavior. We aimed to investigate this possible paradox in a cohort comprising 49 000 Swedish men. BMI, mental health, lifestyle and socioeconomic measures were recorded at conscription in 1969–70, at ages 18–20. Information on attempted suicide 1973–2008 and completed suicide 1971–2008 was obtained from national records. Hazard ratios (HR) were estimated by Cox proportional hazard models. We found that each standard deviation (SD) increase in BMI was associated with a 12% lower risk of later suicide attempt (HR 0.88, 95% CI 0.83–0.94). Associations were somewhat weaker for completed suicide and did not reach conventional levels of statistical significance (HR 0.93, 95% CI 0.85–1.01). Adjustment for a wide range of possible confounding factors had little effect on the associations. Lower BMI at conscription was also associated with higher prevalence of psychiatric diagnoses, low emotional control and depressed mood. Our results confirm previous findings regarding the association of higher BMI with a reduced risk of suicide, extending them to show similar findings in relation to suicide attempts. The associations were little affected by adjustment for a range of possible confounding factors. However, we found no evidence that high BMI was associated with an increased risk of depression cross-sectionally or longitudinally.
doi:10.1371/journal.pone.0101213
PMCID: PMC4077734  PMID: 24983947
12.  Suicidal behaviour across the African continent: a review of the literature 
BMC Public Health  2014;14:606.
Background
Suicide is a major cause of premature mortality worldwide, but data on its epidemiology in Africa, the world’s second most populous continent, are limited.
Methods
We systematically reviewed published literature on suicidal behaviour in African countries. We searched PubMed, Web of Knowledge, PsycINFO, African Index Medicus, Eastern Mediterranean Index Medicus and African Journals OnLine and carried out citation searches of key articles. We crudely estimated the incidence of suicide and suicide attempts in Africa based on country-specific data and compared these with published estimates. We also describe common features of suicide and suicide attempts across the studies, including information related to age, sex, methods used and risk factors.
Results
Regional or national suicide incidence data were available for less than one third (16/53) of African countries containing approximately 60% of Africa’s population; suicide attempt data were available for <20% of countries (7/53). Crude estimates suggest there are over 34,000 (inter-quartile range 13,141 to 63,757) suicides per year in Africa, with an overall incidence rate of 3.2 per 100,000 population. The recent Global Burden of Disease (GBD) estimate of 49,558 deaths is somewhat higher, but falls within the inter-quartile range of our estimate. Suicide rates in men are typically at least three times higher than in women. The most frequently used methods of suicide are hanging and pesticide poisoning. Reported risk factors are similar for suicide and suicide attempts and include interpersonal difficulties, mental and physical health problems, socioeconomic problems and drug and alcohol use/abuse. Qualitative studies are needed to identify additional culturally relevant risk factors and to understand how risk factors may be connected to suicidal behaviour in different socio-cultural contexts.
Conclusions
Our estimate is somewhat lower than GBD, but still clearly indicates suicidal behaviour is an important public health problem in Africa. More regional studies, in both urban and rural areas, are needed to more accurately estimate the burden of suicidal behaviour across the continent. Qualitative studies are required in addition to quantitative studies.
doi:10.1186/1471-2458-14-606
PMCID: PMC4067111  PMID: 24927746
Suicide; Suicide attempts; Africa; Review; Incidence; Risk factor; Sex; Method
13.  Regional Changes in Charcoal-Burning Suicide Rates in East/Southeast Asia from 1995 to 2011: A Time Trend Analysis 
PLoS Medicine  2014;11(4):e1001622.
Using a time trend analysis, Ying-Yeh Chen and colleagues examine the evidence for regional increases in charcoal-burning suicide rates in East and Southeast Asia from 1995 to 2011.
Please see later in the article for the Editors' Summary
Background
Suicides by carbon monoxide poisoning resulting from burning barbecue charcoal reached epidemic levels in Hong Kong and Taiwan within 5 y of the first reported cases in the early 2000s. The objectives of this analysis were to investigate (i) time trends and regional patterns of charcoal-burning suicide throughout East/Southeast Asia during the time period 1995–2011 and (ii) whether any rises in use of this method were associated with increases in overall suicide rates. Sex- and age-specific trends over time were also examined to identify the demographic groups showing the greatest increases in charcoal-burning suicide rates across different countries.
Methods and Findings
We used data on suicides by gases other than domestic gas for Hong Kong, Japan, the Republic of Korea, Taiwan, and Singapore in the years 1995/1996–2011. Similar data for Malaysia, the Philippines, and Thailand were also extracted but were incomplete. Graphical and joinpoint regression analyses were used to examine time trends in suicide, and negative binomial regression analysis to study sex- and age-specific patterns. In 1995/1996, charcoal-burning suicides accounted for <1% of all suicides in all study countries, except in Japan (5%), but they increased to account for 13%, 24%, 10%, 7%, and 5% of all suicides in Hong Kong, Taiwan, Japan, the Republic of Korea, and Singapore, respectively, in 2011. Rises were first seen in Hong Kong after 1998 (95% CI 1997–1999), followed by Singapore in 1999 (95% CI 1998–2001), Taiwan in 2000 (95% CI 1999–2001), Japan in 2002 (95% CI 1999–2003), and the Republic of Korea in 2007 (95% CI 2006–2008). No marked increases were seen in Malaysia, the Philippines, or Thailand. There was some evidence that charcoal-burning suicides were associated with an increase in overall suicide rates in Hong Kong, Taiwan, and Japan (for females), but not in Japan (for males), the Republic of Korea, and Singapore. Rates of change in charcoal-burning suicide rate did not differ by sex/age group in Taiwan and Hong Kong but appeared to be greatest in people aged 15–24 y in Japan and people aged 25–64 y in the Republic of Korea. The lack of specific codes for charcoal-burning suicide in the International Classification of Diseases and variations in coding practice in different countries are potential limitations of this study.
Conclusions
Charcoal-burning suicides increased markedly in some East/Southeast Asian countries (Hong Kong, Taiwan, Japan, the Republic of Korea, and Singapore) in the first decade of the 21st century, but such rises were not experienced by all countries in the region. In countries with a rise in charcoal-burning suicide rates, the timing, scale, and sex/age pattern of increases varied by country. Factors underlying these variations require further investigation, but may include differences in culture or in media portrayals of the method.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, almost one million people die by suicide globally; suicide is the fifth leading cause of death in women aged 15–49 and the sixth leading cause of death in men in the same age group. Most people who take their own life are mentally ill. For others, stressful events (the loss of a partner, for example) have made life seem worthless or too painful to bear. Strategies to reduce suicide rates include better treatment of mental illness and programs that help people at high risk of suicide deal with stress. Suicide rates can also be reduced by limiting access to common suicide methods. These methods vary from place to place. Hanging is the predominant suicide method in many countries, but in Hong Kong, for example, jumping from a high building is the most common method. Suicide methods also vary over time. For example, after a woman in Hong Kong took her life in 1998 by burning barbecue charcoal in a sealed room (a process that produces the toxic gas carbon monoxide), charcoal burning rapidly went from being a rare method of killing oneself in Hong Kong to the second most common suicide method.
Why Was This Study Done?
Cases of charcoal-burning suicide have also been reported in several East and Southeast Asian countries, but there has been no systematic investigation of time trends and regional patterns of this form of suicide. A better understanding of regional changes in the number of charcoal-burning suicides might help to inform efforts to prevent the emergence of other new suicide methods. Here, the researchers investigate the time trends and regional patterns of charcoal-burning suicide in several countries in East and Southeast Asia between 1995 and 2011 and ask whether any rises in the use of this method are associated with increases in overall suicide rates. The researchers also investigate sex- and age-specific time trends in charcoal-burning suicides to identify which groups of people show the greatest increases in this form of suicide across different countries.
What Did the Researchers Do and Find?
The researchers analyzed method-specific data on suicide deaths for Hong Kong, Japan, the Republic of Korea, Taiwan, and Singapore between 1995/1996 and 2011 obtained from the World Health Organization Mortality Database and from national death registers. In 1995/1996, charcoal-burning suicides accounted for less than 1% of all suicides in all these countries except Japan (4.9%). By 2011, charcoal-burning suicides accounted for between 5% (Singapore) and 24% (Taiwan) of all suicides. Rises in the rate of charcoal-burning suicide were first seen in Hong Kong in 1999, in Singapore in 2000, in Taiwan in 2001, in Japan in 2003, and in the Republic of Korea in 2008. By contrast, incomplete data from Malaysia, the Philippines, and Thailand showed no evidence of a marked increase in charcoal-burning suicide in these countries over the same period. Charcoal-burning suicides were associated with an increase in overall suicide rates in Hong Kong in 1998–2003, in Taiwan in 2000–2006, and in Japanese women after 2003. Finally, the annual rate of change in charcoal-burning suicide rate did not differ by sex/age group in Taiwan and Hong Kong, whereas in Japan people aged 15–24 and in the Republic of Korea people aged 25–64 tended to have the greatest rates of increase.
What Do These Findings Mean?
These findings show that charcoal-burning suicides increased markedly in several but not all East and Southeast Asian countries during the first decade of the 21st century. Moreover, in countries where there was an increase, the timing, scale, and sex/age pattern of the increase varied by country. The accuracy of these findings is likely to be limited by several aspects of the study. For example, because of the way that method-specific suicides are recorded in the World Health Organization Mortality Database and national death registries, the researchers may have slightly overestimated the number of charcoal-burning suicides. Further studies are now needed to identify the factors that underlie the variations between countries in charcoal-burning suicide rates and time trends reported here. However, the current findings highlight the need to undertake surveillance to identify the emergence of new suicide methods and the importance of policy makers, the media, and internet service providers working together to restrict graphic and detailed descriptions of new suicide methods.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001622.
A PLOS Medicine research article by Shu-Sen Chang and colleagues investigates time trends and regional patterns of charcoal-burning suicide in Taiwan
The World Health Organization provides information on the global burden of suicide and on suicide prevention (in several languages); it also has an article on international patterns in methods of suicide
The US National Institute of Mental Health provides information on suicide and suicide prevention
The UK National Health Service Choices website has detailed information about suicide and its prevention
MedlinePlus provides links to further resources about suicide (in English and Spanish)
The International Association for Suicide Prevention provides links to crisis centers in Asia
The charity Healthtalkonline has personal stories about dealing with suicide
doi:10.1371/journal.pmed.1001622
PMCID: PMC3972087  PMID: 24691071
14.  Hospital Presenting Self-Harm and Risk of Fatal and Non-Fatal Repetition: Systematic Review and Meta-Analysis 
PLoS ONE  2014;9(2):e89944.
Background
Non-fatal self-harm is one of the most frequent reasons for emergency hospital admission and the strongest risk factor for subsequent suicide. Repeat self-harm and suicide are key clinical outcomes of the hospital management of self-harm. We have undertaken a comprehensive review of the international literature on the incidence of fatal and non-fatal repeat self-harm and investigated factors influencing variation in these estimates as well as changes in the incidence of repeat self-harm and suicide over the last 30 years.
Methods and Findings
Medline, EMBASE, PsycINFO, Google Scholar, article reference lists and personal paper collections of the authors were searched for studies describing rates of fatal and non-fatal self-harm amongst people who presented to health care services for deliberate self-harm. Heterogeneity in pooled estimates of repeat self-harm incidence was investigated using stratified meta-analysis and meta-regression. The search identified 177 relevant papers. The risk of suicide in the 12 months after an index attempt was 1.6% (CI 1.2–2.4) and 3.9% (CI 3.2–4.8) after 5 years. The estimated 1 year rate of non-fatal repeat self-harm was 16.3% (CI 15.1–17.7). This proportion was considerably lower in Asian countries (10.0%, CI 7.3–13.6%) and varies between studies identifying repeat episodes using hospital admission data (13.7%, CI 12.3–15.3) and studies using patient report (21.9%, CI 14.3–32.2). There was no evidence that the incidence of repeat self-harm was lower in more recent (post 2000) studies compared to those from the 1980s and 1990s.
Conclusions
One in 25 patients presenting to hospital for self-harm will kill themselves in the next 5 years. The incidence of repeat self-harm and suicide in this population has not changed in over 10 years. Different methods of identifying repeat episodes of self-harm produce varying estimates of incidence and this heterogeneity should be considered when evaluating interventions aimed at reducing non-fatal repeat self-harm.
doi:10.1371/journal.pone.0089944
PMCID: PMC3938547  PMID: 24587141
15.  Diurnal variation in probability of death following self-poisoning in Sri Lanka—evidence for chronotoxicity in humans 
Background The absorption, distribution, metabolism and elimination of medicines are partly controlled by transporters and enzymes with diurnal variation in expression. Dose timing may be important for maximizing therapeutic and minimizing adverse effects. However, outcome data for such an effect in humans are sparse, and chronotherapeutics is consequently less practised. We examined a large prospective Sri Lankan cohort of patients with acute poisoning to seek evidence of diurnal variation in the probability of survival.
Methods In all, 14 840 patients admitted to hospital after yellow oleander (Cascabela thevetia) seed or pesticide [organophosphorus (OP), carbamate, paraquat, glyphosate] self-poisoning were investigated for variation in survival according to time of ingestion.
Results We found strong evidence that the outcome of oleander poisoning was associated with time of ingestion (P < 0.001). There was weaker evidence for OP insecticides (P = 0.041) and no evidence of diurnal variation in the outcome for carbamate, glyphosate and paraquat pesticides. Compared with ingestion in the late morning, and with confounding by age, sex, time of and delay to hospital presentation and year of admission controlled, case fatality of oleander poisoning was over 50% lower following evening ingestion (risk ratio = 0.40, 95% confidence interval 0.26–0.62). Variation in dose across the day was not responsible.
Conclusions We have shown for the first time that timing of poison ingestion affects survival in humans. This evidence for chronotoxicity suggests chronotherapeutics should be given greater attention in drug development and clinical practice.
doi:10.1093/ije/dys191
PMCID: PMC3535746  PMID: 23179303
Circadian rhythm; self-injurious behaviour; toxicology; poisoning; Cascabela thevetia; pesticides; Sri Lanka
16.  Physicians' prescribing preferences were a potential instrument for patients' actual prescriptions of antidepressants☆ 
Journal of Clinical Epidemiology  2013;66(12):1386-1396.
Objectives
To investigate whether physicians' prescribing preferences were valid instrumental variables for the antidepressant prescriptions they issued to their patients.
Study Design and Setting
We investigated whether physicians' previous prescriptions of (1) tricyclic antidepressants (TCAs) vs. selective serotonin reuptake inhibitors (SSRIs) and (2) paroxetine vs. other SSRIs were valid instruments. We investigated whether the instrumental variable assumptions are likely to hold and whether TCAs (vs. SSRIs) were associated with hospital admission for self-harm or death by suicide using both conventional and instrumental variable regressions. The setting for the study was general practices in the United Kingdom.
Results
Prior prescriptions were strongly associated with actual prescriptions: physicians who previously prescribed TCAs were 14.9 percentage points (95% confidence interval [CI], 14.4, 15.4) more likely to prescribe TCAs, and those who previously prescribed paroxetine were 27.7 percentage points (95% CI, 26.7, 28.8) more likely to prescribe paroxetine, to their next patient. Physicians' previous prescriptions were less strongly associated with patients' baseline characteristics than actual prescriptions. We found no evidence that the estimated association of TCAs with self-harm/suicide using instrumental variable regression differed from conventional regression estimates (P-value = 0.45).
Conclusion
The main instrumental variable assumptions held, suggesting that physicians' prescribing preferences are valid instruments for evaluating the short-term effects of antidepressants.
doi:10.1016/j.jclinepi.2013.06.008
PMCID: PMC3824069  PMID: 24075596
Instrumental variables; Clinical Practice Research Datalink (CPRD); Physicians' prescribing preferences; Confounding by indication; Causality; Translational epidemiology
17.  Childhood milk consumption is associated with better physical performance in old age 
Age and Ageing  2012;41(6):776-784.
Background: studies have shown that milk and dairy consumption in adulthood have beneficial effects on health.
Methods: we examined the impact of childhood and adult diet on physical performance at age 63–86 years. The Boyd Orr cohort (n = 405) is a 65-year prospective study of children who took part in a 1930's survey; the Caerphilly Prospective Study (CaPS; n = 1,195) provides data from mid-life to old age. We hypothesised that higher intakes of childhood and adult milk, calcium, protein, fat and energy would be associated with a better performance.
Results: in fully adjusted models, a standard deviation (SD) increase in natural log-transformed childhood milk intake was associated with 5% faster walking times from the get-up and go test in Boyd Orr (95% CI: 1 to 9) and 25% lower odds of poor balance (OR: 0.75; 0.55 to 1.02). Childhood calcium intake was positively associated with walking times (4% faster per SD; 0 to 8) and a higher protein intake was associated with lower odds of poor balance (OR: 0.71; 0.54 to 0.92). In adulthood, protein intake was positively associated with walking times (2% faster per SD; 1 to 3; Boyd Orr and CaPS pooled data).
Conclusion: this is the first study to show positive associations of childhood milk intake with physical performance in old age.
doi:10.1093/ageing/afs052
PMCID: PMC3476828  PMID: 22542496
diet; physical performance; walking speed; standing balance; older people
18.  Using natural experiments to evaluate population health interventions: new MRC guidance 
Natural experimental studies are often recommended as a way of understanding the health impact of policies and other large scale interventions. Although they have certain advantages over planned experiments, and may be the only option when it is impossible to manipulate exposure to the intervention, natural experimental studies are more susceptible to bias. This paper introduces new guidance from the Medical Research Council to help researchers and users, funders and publishers of research evidence make the best use of natural experimental approaches to evaluating population health interventions. The guidance emphasises that natural experiments can provide convincing evidence of impact even when effects are small or take time to appear. However, a good understanding is needed of the process determining exposure to the intervention, and careful choice and combination of methods, testing of assumptions and transparent reporting is vital. More could be learnt from natural experiments in future as experience of promising but lesser used methods accumulates.
doi:10.1136/jech-2011-200375
PMCID: PMC3796763  PMID: 22577181
19.  Factors associated with the development of self-harm amongst a socio-economically deprived cohort of adolescents in Santiago, Chile 
Purpose
Studies carried out in the West indicate that the incidence of self-harm (SH) is particularly high amongst adolescents, but few studies have investigated its incidence and aetiology in low-income countries. The purpose of this study was to investigate risk factors associated with new onset episodes of SH, amongst Chilean adolescents from low socio-economic backgrounds.
Methods
Prospective cohort study nested within a cluster randomised controlled trial. A 6-month follow-up for 2,042 adolescents, median age 14 years, from socio-economically deprived areas of Santiago, Chile.
Results
The lifetime prevalence of SH was 23 %. The incidence rate of SH at 6 months was 14 % amongst those reporting no SH at baseline. In multivariable analyses, risk factors for incident SH include depressive symptoms, suicidal thoughts, poor problem-solving skills and cannabis misuse.
Conclusions
The prevalence and incidence of SH in this socio-economically deprived sample differed highly according to gender. Poor problem-solving skills, suicidal thoughts, and cannabis misuse were associated with onset of SH.
Electronic supplementary material
The online version of this article (doi:10.1007/s00127-013-0767-y) contains supplementary material, which is available to authorized users.
doi:10.1007/s00127-013-0767-y
PMCID: PMC3969808  PMID: 24097260
Self-harm; Adolescents; Depression; Prospective; Deprived
20.  Identifying Probable Suicide Clusters in Wales Using National Mortality Data 
PLoS ONE  2013;8(8):e71713.
Background
Up to 2% of suicides in young people may occur in clusters i.e., close together in time and space. In early 2008 unprecedented attention was given by national and international news media to a suspected suicide cluster among young people living in Bridgend, Wales. This paper investigates the strength of statistical evidence for this apparent cluster, its size, and temporal and geographical limits.
Methods and findings
The analysis is based on official mortality statistics for Wales for 2000–2009 provided by the UK's Office for National Statistics (ONS). Temporo-spatial analysis was performed using Space Time Permutation Scan Statistics with SaTScan v9.1 for suicide deaths aged 15 and over, with a sub-group analysis focussing on cases aged 15–34 years. These analyses were conducted for deaths coded by ONS as: (i) suicide or of undetermined intent (probable suicides) and (ii) for a combination of suicide, undetermined, and accidental poisoning and hanging (possible suicides). The temporo-spatial analysis did not identify any clusters of suicide or undetermined intent deaths (probable suicides). However, analysis of all deaths by suicide, undetermined intent, accidental poisoning and accidental hanging (possible suicides) identified a temporo-spatial cluster (p = 0.029) involving 10 deaths amongst 15–34 year olds centred on the County Borough of Bridgend for the period 27th December 2007 to 19th February 2008. Less than 1% of possible suicides in younger people in Wales in the ten year period were identified as being cluster-related.
Conclusions
There was a possible suicide cluster in young people in Bridgend between December 2007 and February 2008. This cluster was smaller, shorter in duration, and predominantly later than the phenomenon that was reported in national and international print media. Further investigation of factors leading to the onset and termination of this series of deaths, in particular the role of the media, is required.
doi:10.1371/journal.pone.0071713
PMCID: PMC3756004  PMID: 24015189
21.  The Impact of Media Reporting on the Emergence of Charcoal Burning Suicide in Taiwan 
PLoS ONE  2013;8(1):e55000.
We investigated the association of the intensity of newspaper reporting of charcoal burning suicide with the incidence of such deaths in Taiwan during 1998–2002. A counting process approach was used to estimate the incidence of suicides and intensity of news reporting. Conditional Poisson generalized linear autoregressive models were performed to assess the association of the intensity of newspaper reporting of charcoal burning and non-charcoal burning suicides with the actual number of charcoal burning and non-charcoal burning suicides the following day. We found that increases in the reporting of charcoal burning suicide were associated with increases in the incidence of charcoal burning suicide on the following day, with each reported charcoal burning news item being associated with a 16% increase in next day charcoal burning suicide (p<.0001). However, the reporting of other methods of suicide was not related to their incidence. We conclude that extensive media reporting of charcoal burning suicides appears to have contributed to the rapid rise in the incidence of the novel method in Taiwan during the initial stage of the suicide epidemic. Regulating media reporting of novel suicide methods may prevent an epidemic spread of such new methods.
doi:10.1371/journal.pone.0055000
PMCID: PMC3559477  PMID: 23383027
22.  How to apply the results of a research paper on diagnosis to your patient 
JRSM Short Reports  2013;4(1):7.
Interpreting information on diagnostic accuracy is an area that health professionals struggle with. In this paper, we use the example of Mr Samways, a 45-year-old man with joint symptoms, to illustrate how to apply the results of a diagnostic accuracy study in clinical practice. We consider the various measures used to quantify diagnostic accuracy and discuss their clinical utility. We provide an overview of potential biases to consider when evaluating a diagnostic accuracy study and consider how to determine whether the results can be applied to a particular patient.
doi:10.1258/shorts.2012.012089
PMCID: PMC3572661  PMID: 23413409
23.  Genetic markers of bone and joint health and physical capability in older adults: the HALCyon programme 
Bone  2013;52(1):278-285.
Background
Good bone and joint health is essential for the physical tasks of daily living and poorer indicators of physical capability in older adults have been associated with increased mortality rates. Genetic variants of indicators of bone and joint health may be associated with measures of physical capability.
Methods
As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women aged between 52 and 90 + years from six UK cohorts were genotyped for a polymorphism associated with serum calcium (rs1801725, CASR), two polymorphisms associated with bone mineral density (BMD) (rs2941740, ESR1 and rs9594759, RANKL) and one associated with osteoarthritis risk rs3815148 (COG5). Meta-analysis was used to pool within-study effects of the associations between each of the polymorphisms and measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance.
Results
Few important associations were observed among the several tests. We found that carriers of the serum calcium-raising allele had poorer grip strength compared with non-carriers (pooled p = 0.05, n = 11,239) after adjusting for age and sex. Inconsistent results were observed for the two variants associated with BMD and we found no evidence for an association between rs3815148 (COG5) and any of the physical capability measures.
Conclusion
Our findings suggest elevated serum calcium levels may lead to lower grip strength, though this requires further replication. Our results do not provide evidence for a substantial influence of these variants in ESR1, RANKL and COG5 on physical capability in older adults.
Highlights
► We examined associations between bone-related genotypes and physical capability. ► We conducted a meta-analysis on 12,836 middle-age adults. ► We found CASR may be associated with grip strength. ► No substantial support for specific bone mineral density variants and physical capability.
doi:10.1016/j.bone.2012.10.004
PMCID: PMC3526776  PMID: 23072920
BMD, bone mineral density; OA, osteoarthritis; BMI, body mass index; SNP, single nucleotide polymorphism; CaPS, Caerphilly Prospective Study; ELSA, English Longitudinal Study of Ageing; HAS, Hertfordshire Ageing Study; HCS, Hertfordshire Cohort Study; LBC1921, The Lothian Birth Cohort 1921; NSHD, National Survey of Health and Development; HWE, Hardy–Weinberg equilibrium; WHR, waist–hip ratio; GWAS, genome-wide association studies; Aging; Grip strength; Calcium; Bone mineral density; Osteoarthritis
24.  Vitamin B-12 Status during Pregnancy and Child’s IQ at Age 8: A Mendelian Randomization Study in the Avon Longitudinal Study of Parents and Children 
PLoS ONE  2012;7(12):e51084.
Vitamin B-12 is essential for the development and maintenance of a healthy nervous system. Brain development occurs primarily in utero and early infancy, but the role of maternal vitamin B-12 status during pregnancy on offspring cognitive function is unclear. In this study we assessed the effect of vitamin B-12 status in well-nourished pregnant women on the cognitive ability of their offspring in a UK birth cohort (ALSPAC). We then examined the association of SNPs in maternal genes FUT2 (rs492602) and TCN2 (rs1801198, rs9606756) that are related to plasma vitamin B-12, with offspring IQ. Observationally, there was a positive association between maternal vitamin B-12 intake and child’s IQ that was markedly attenuated after adjustment for potential confounders (mean difference in offspring IQ score per doubling of maternal B-12 intake, before adjustment: 2.0 (95% CI 1.3, 2.8); after adjustment: 0.7 (95% CI −0.04, 1.4)). Maternal FUT2 was weakly associated with offspring IQ: mean difference in IQ per allele was 0.9 (95% CI 0.1, 1.6). The expected effect of maternal vitamin B-12 on offspring IQ, given the relationships between SNPs and vitamin B-12, and SNPs and IQ was consistent with the observational result. Our findings suggest that maternal vitamin B-12 may not have an important effect on offspring cognitive ability. However, further examination of this issue is warranted.
doi:10.1371/journal.pone.0051084
PMCID: PMC3515553  PMID: 23227234
25.  Socioeconomic disadvantage from childhood to adulthood and locomotor function in old age: a lifecourse analysis of the Boyd Orr and Caerphilly prospective studies 
Background
Socioeconomic influences over a lifetime impact on health and may contribute to poor physical functioning in old age.
Methods
We examined the impact of both childhood and adulthood socioeconomic factors on locomotor function at 63-86 years (measured with the get up and go timed walk and flamingo balance test), in the UK-based Boyd Orr (n=405) and Caerphilly (n=1,196) prospective cohorts.
Results
There was a marked reduction in walking speed and balance time with increasing age. Each year of age was associated with a 1.7% slower walk time and a 14% increased odds of poor balance. Participants who moved from a low socioeconomic position in childhood to a high socioeconomic position in adulthood had walking times 3% slower (95% CI: -2%, 8%) than people with high socioeconomic position in both periods. Participants who moved from a high socioeconomic position in childhood to a low adulthood socioeconomic position had walking times 5% slower (95% CI: -2%, 12%). Participants with a low socioeconomic position in both periods had walking times 10% slower (95% CI: 5%, 16%; P for trend <0.001).
In Boyd Orr, low socioeconomic position in childhood was associated with poor balance in old age (OR per worsening category = 1.26; 95% CI 1.01, 1.57; P=0.043), as was socioeconomic position in adulthood (OR = 1.71; 95% CI 1.20, 2.45; P=0.003). Similar associations were not observed in Caerphilly.
Conclusion
Accumulating socioeconomic disadvantage from childhood to adulthood is associated with slower walking time in old age, with mixed results for balance ability.
doi:10.1136/jech.2009.103648
PMCID: PMC3381706  PMID: 20644236
Aged; Gait; Physical performance; Social Class; Socioeconomic Factors

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