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Brain-derived neurotrophic factor (BDNF), which facilitates neuroplasticity and synaptogenesis, may be decreased in bipolar disorder, but has not been systematically investigated in people with newly diagnosed bipolar disorder and unaffected first-degree relatives.
To compare BDNF levels in patients with newly diagnosed bipolar disorder, their unaffected first-degree relatives and healthy controls.
The study investigated plasma BDNF levels in patients (n = 371) with newly diagnosed bipolar disorder, their unaffected first-degree relatives (n = 98) and healthy controls (n = 200) using enzyme-linked immunosorbent assay. We further investigated associations between BDNF levels and illness-related variables and medication status.
BDNF levels were found to be 22.0% (95% CI 1.107–1.343) higher in patients with bipolar disorder compared with healthy controls (P < 0.001) and 15.6% higher in unaffected first-degree relatives compared with healthy controls (95% CI 1.007–1.327, P = 0.04), when adjusting for age and gender. Further, BDNF levels were positively associated with duration of illness at a trend level (P = 0.05), age (P = 0.001) and use of anti-epileptic medication (P = 0.05).
These findings suggest that BDNF levels are not decreased in the early stages of bipolar disorder and in unaffected first-degree relatives contrasting with prior findings during later stages of the illness.
Previous literature has demonstrated a strong association between cigarette smoking, suicidal ideation and suicide attempts. This association has not previously been examined in a causal inference framework and could have important implications for suicide prevention strategies.
We aimed to examine the evidence for an association between smoking behaviours (initiation, smoking status, heaviness, lifetime smoking) and suicidal thoughts or attempts by triangulating across observational and Mendelian randomisation analyses.
First, in the UK Biobank, we calculated observed associations between smoking behaviours and suicidal thoughts or attempts. Second, we used Mendelian randomisation to explore the relationship between smoking and suicide attempts and ideation, using genetic variants as instruments to reduce bias from residual confounding and reverse causation.
Our observational analysis showed a relationship between smoking behaviour, suicidal ideation and attempts, particularly between smoking initiation and suicide attempts (odds ratio, 2.07; 95% CI 1.91–2.26; P < 0.001). The Mendelian randomisation analysis and single-nucleotide polymorphism analysis, however, did not support this (odds ratio for lifetime smoking on suicidal ideation, 0.050; 95% CI −0.027 to 0.127; odds ratio on suicide attempts, 0.053; 95% CI, −0.003 to 0.110). Despite past literature showing a positive dose-response relationship, our results showed no clear evidence for a causal effect of smoking on suicidal ideation or attempts.
This was the first Mendelian randomisation study to explore the effect of smoking on suicidal ideation and attempts. Our results suggest that, despite observed associations, there is no clear evidence for a causal effect.
Observational studies have linked elevated homocysteine to vascular conditions. Folate intake has been associated with lower homocysteine concentration, although randomised controlled trials of folic acid supplementation to decrease the incidence of vascular conditions have been inconclusive. We investigated determinants of maternal homocysteine during pregnancy, particularly in a folic acid-fortified population.
Data were from the Ottawa and Kingston Birth Cohort of 8085 participants. We used multivariable regression analyses to identify factors associated with maternal homocysteine, adjusted for gestational age at bloodwork. Continuous factors were modelled using restricted cubic splines. A subgroup analysis examined the modifying effect of MTHFR 677C>T genotype on folate, in determining homocysteine concentration.
Participants were recruited in Ottawa and Kingston, Canada, from 2002 to 2009.
Women were recruited when presenting for prenatal care in the early second trimester.
In 7587 participants, factors significantly associated with higher homocysteine concentration were nulliparous, smoking and chronic hypertension, while factors significantly associated with lower homocysteine concentration were non-Caucasian race, history of a placenta-mediated complication and folic acid supplementation. Maternal age and BMI demonstrated U-shaped associations. Folic acid supplementation of >1 mg/d during pregnancy did not substantially increase folate concentration. In the subgroup analysis, MTHFR 677C>T modified the effect of folate status on homocysteine concentration.
We identified determinants of maternal homocysteine relevant to the lowering of homocysteine in the post-folic acid fortification era, characterised by folate-replete populations. A focus on periconceptional folic acid supplementation and improving health status may form an effective approach to lower homocysteine.
The cost-effectiveness of molecular pathology testing is highly context dependent. The field is fast-moving, and national health technology assessment may not be relevant or timely for local decision makers. This study illustrates a method of context-specific economic evaluation that can be carried out in a limited timescale without extensive resources.
We established a multi-disciplinary group including an oncologist, pathologists and a health economist. We set out diagnostic and treatment pathways and costs using registry data, health technology assessments, guidelines, audit data, and estimates from the group. Sensitivity analysis varied input parameters across plausible ranges. The evaluation setting was the West of Scotland and UK NHS perspective was adopted. The evaluation was assessed against the AdHopHTA checklist for hospital-based health technology assessment.
A context-specific economic evaluation could be carried out on a timely basis using limited resources. The evaluation met all relevant criteria in the AdHopHTA checklist. Health outcomes were expected to be at least equal to the current strategy. Annual cost savings of £637,000 were estimated resulting primarily from a reduction in the proportion of patients receiving intravenous infusional chemotherapy regimens. The result was not sensitive to any parameter. The data driving the main cost saving came from a small clinical audit. We recommended this finding was confirmed in a larger population.
The method could be used to evaluate testing changes elsewhere. The results of the case study may be transferable to other jurisdictions where the organization of cancer services is fragmented.
Studies involving clinically recruited samples show that genetic liability to schizophrenia overlaps with that for several psychiatric disorders including bipolar disorder, major depression and, in a population study, anxiety disorder and negative symptoms in adolescence.
We examined whether, at a population level, association between schizophrenia liability and anxiety disorders continues into adulthood, for specific anxiety disorders and as a group. We explored in an epidemiologically based cohort the nature of adult psychopathology sharing liability to schizophrenia.
Schizophrenia polygenic risk scores (PRSs) were calculated for 590 European-descent individuals from the Christchurch Health and Development Study. Logistic regression was used to examine associations between schizophrenia PRS and four anxiety disorders (social phobia, specific phobia, panic disorder and generalised anxiety disorder), schizophrenia/schizophreniform disorder, manic/hypomanic episode, alcohol dependence, major depression, and – using linear regression – total number of anxiety disorders. A novel population-level association with hypomania was tested in a UK birth cohort (Avon Longitudinal Study of Parents and Children).
Schizophrenia PRS was associated with total number of anxiety disorders and with generalised anxiety disorder and panic disorder. We show a novel population-level association between schizophrenia PRS and manic/hypomanic episode.
The relationship between schizophrenia liability and anxiety disorders is not restricted to psychopathology in adolescence but is present in adulthood and specifically linked to generalised anxiety disorder and panic disorder. We suggest that the association between schizophrenia liability and hypomanic/manic episodes found in clinical samples may not be due to bias.
In 2012, Massachusetts enacted school competitive food and beverage standards similar to national Smart Snacks. These standards aim to improve the nutritional quality of competitive snacks. It was previously demonstrated that a majority of foods and beverages were compliant with the standards, but it was unknown whether food manufacturers reformulated products in response to the standards. The present study assessed whether products were reformulated after standards were implemented; the availability of reformulated products outside schools; and whether compliance with the standards improved the nutrient composition of competitive snacks.
An observational cohort study documenting all competitive snacks sold before (2012) and after (2013 and 2014) the standards were implemented.
The sample included thirty-six school districts with both a middle and high school.
After 2012, energy, saturated fat, Na and sugar decreased and fibre increased among all competitive foods. By 2013, 8 % of foods were reformulated, as were an additional 9 % by 2014. Nearly 15 % of reformulated foods were look-alike products that could not be purchased at supermarkets. Energy and Na in beverages decreased after 2012, in part facilitated by smaller package sizes.
Massachusetts’ law was effective in improving the nutritional content of snacks and product reformulation helped schools adhere to the law. This suggests fully implementing Smart Snacks standards may similarly improve the foods available in schools nationally. However, only some healthier reformulated foods were available outside schools.
Charles Jennens's Il Moderato (1740) is the longest English text written ab initio for Handel to set, yet there has been little critical examination of it. That is unsurprising. Modern taste does not warm to its theme or its diction. This chapter seeks to orientate the words of Il Moderato in the taste of Handel's time. It forms one of an intermittent series of attempts to fathom Handel's L'Allegro, il Penseroso ed il Moderato (1740–41), that apparently limpid, yet endlessly referential, composition. It will suggest why, when Handel wrote to Jennens from Dublin, ‘I assure you that the Words of the Moderato are vastly admired’, which is possibly the politest sentence that Handel ever wrote, he may have been quite truthful, rather than polite in the sense of insincerely tactful.
A contemporary reviewer of L'Allegro, il Penseroso ed il Moderato, whose essay includes high praise for Milton's twin poems L'Allegro and Il Penseroso, thought that the words of Il Moderato could well stand comparison with them:
Never was there in any Language so beautiful a Collection of Images suited to each of those Tempers, as in the two original Poems … had they been printed entire, and annex'd to the Drama, in a small Character [font], it would have been an agreeable Compliment paid to the Audience, had heighten'd the Relish of the Musick, and been no Injustice done to the Fitter of them for the Theatre; whose dramatic Moderato (or Mean between them) can very well bear being compared together.
The reviewer wishes that the wordbook had included Milton's original poems, so as to ‘heighten the relish’ of listeners by enabling them to compare Milton with what had been made of him by librettist and composer. The wish contains an assumption that some at least of Handel's audience really did pay attention to his librettists’ words in relation to his settings of them, and suggests that Handel was wise to respond to demands for music united with good English texts. It is in this context of attentive comparison that the reviewer finds that Jennens's words ‘can very well bear being compared’ with Milton's.
To examine the association between BMI and folate concentrations in serum and red blood cells (RBC) in pregnant women.
A cross-sectional comparison of folate concentrations in serum and RBC sampled simultaneously from the same individual.
The Ottawa Hospital and Kingston General Hospital, Ontario, Canada.
Pregnant women recruited between 12 and 20 weeks of gestation.
A total of 869 pregnant women recruited from April 2008 to April 2009 were included in the final analysis. Serum folate was inversely associated and RBC folate positively associated with BMI, after adjusting for folic acid supplementation, age, gestational age at blood sample collection, race, maternal education, annual income, smoking and MTHFR 677C→T genotype. In stratified analyses, this differential association was significant in women with the MTHFR CC variant. In women with the CT and TT variants, the differential associations were in the same direction but not significant. Folic acid supplementation during pregnancy did not alter the differential association of BMI with serum and RBC folate concentration. This indicates that the current RBC folate cut-off approach for assessing risk of neural tube defects in obese women may be limited.
BMI is inversely associated with serum folate and positively associated with RBC folate in pregnant women, especially for those with the MTHFR CC variant.
The overall aim of this study was to evaluate whether attendance at a Sensory Support Centre for people with a sensory impairment living in the Western Isles of Scotland had an impact on their lives.
Demographic forecasts show that the prevalence of sensory impairment in the population will increase, as a significant proportion of sensory loss is age related. People with sensory impairments are more likely to experience social exclusion, and are more at risk of injury and physical and mental illness. Therefore, strategies to improve service access and provision for people with sensory impairments are important to reduce the disability associated with sight and/or hearing loss.
All clients who accessed the service during a six-month period were invited to complete a postal questionnaire about their service experience. Semi-structured individual interviews with clients (n=12) described their experience of living with a sensory impairment and the impact (if any) that access to the Sensory Centre had on their lives. Individual interviews were also conducted with healthcare and social-care professionals (n=7) to ascertain their level of service awareness.
Clients who experienced sensory impairment described how the impairment negatively impacted on their activities of living, safety and independence. Following Sensory Centre assessment and support, some clients were able to identify ways in which interventions had reduced their sense of social isolation, impacted positively on self-confidence and sense of self-esteem and safety. Importantly, interventions had supported greater functional independence in their own homes.
This study provides evidence that access to sensory services are important to people with sensory impairments living in remote areas, and should be considered when planning healthcare services, as they are one way of ameliorating health inequalities in this population group.
To investigate similarities and differences in dietary habits, nutrient intakes and health outcomes of South Asians (SA) and East and South-East Asians (ESEA) and the New Zealand European and Other (NZEO) group, and to examine differences within ‘Asian’ subgroups according to duration of residence.
Nutrient intake data from 24 h diet recalls and data from the dietary habits questionnaire, anthropometry and biochemical analyses from the cross-sectional 2008/09 Adult National Nutrition Survey in New Zealand were compared for participants categorized as SA, ESEA and NZEO.
Adults aged 15 years and older (n 2995).
New Zealand households.
SA were more likely to ‘never’ eat red meat in comparison to NZEO (P<0·001) and among females also in comparison to ESEA (P<0·05). Intakes of fats and some micronutrients (riboflavin, vitamin B6, B12, Se) were lower among SA than NZEO (P<0·05). Lower intakes of Zn and vitamin B12 were reported by SA females compared with ESEA and NZEO females (P<0·05). A higher percentage of SA were obese using ethnic-specific cut-offs, had lower indices of Fe status and reported diagnosed diabetes compared with NZEO and ESEA. Recent SA male migrants had higher intakes of β-carotene, vitamin C and Ca compared with long-term migrants (P<0·05).
The results of the present study indicate that dietary habits, nutrient intakes, blood profile and body size differ significantly between Asian subgroups. It also provides some evidence for changes in dietary intakes according to duration of residence especially for SA males.
To describe treatment and referral patterns and National Health Service resource use in patients with chronic pain associated with low back pain or osteoarthritis, from a Primary Care perspective.
Osteoarthritis and low back pain are the two commonest debilitating causes of chronic pain, with high health and social costs, and particularly important in primary care. Understanding current practice and resource use in their management will inform health service and educational requirements and the design and optimisation of future care.
Multi-centre, retrospective, descriptive study of adults (⩾18 years) with chronic pain arising from low back pain or osteoarthritis, identified through primary care records. Five general practices in Scotland, England (two), Northern Ireland and Wales. All patients with a diagnosis of low back pain or osteoarthritis made on or before 01/09/2006 who had received three or more prescriptions for pain medication were identified and a sub-sample randomly selected then consented to an in-depth review of their medical records (n=264). Data on management of chronic pain were collected retrospectively from patients’ records for three years from diagnosis (‘newly diagnosed’ patients) or for the most recent three years (‘established’ patients).
Patients received a wide variety of pain medications with no overall common prescribing pattern. GP visits represented the majority of the resource use and ‘newly diagnosed’ patients were significantly more likely to visit their GP for pain management than ‘established’ patients. Although ‘newly diagnosed’ patients had more referrals outside the GP practice, the number of visits to secondary care for pain management was similar for both groups.
This retrospective study confirmed the complexity of managing these causes of chronic pain and the associated high resource use. It provides an in-depth picture of prescribing and referral patterns and of resource use.
To investigate: (i) the percentage of the New Zealand (NZ) population reporting fast food/takeaway food and restaurant/café food per day; (ii) examine demographic factors associated with their use; (iii) quantify their contribution to energy intake; and (iv) describe the specific types of foods reported from both sources.
Twenty-four hour diet recalls from the cross-sectional 2008/09 NZ Adult Nutrition Survey were used to identify fast-food and restaurant-food consumers.
Adults aged 15 years and older (n 4721).
Overall 28 % reported consuming at least one fast food and 14 % a restaurant food within the 24 h diet recall. Fast-food consumption was not associated with level of education or an area-based measure of socio-economic status, but a higher education was positively associated with restaurant-food consumption. Individual factors such as ethnicity, household size, age, sex and marital status were found to be important influences on the use of fast food and restaurant food. Fast-food consumption was more prevalent among participants living in urban areas, young adults (19–30 years) and Māori compared with NZ European and Others. The most frequently reported fast foods were bread-based dishes, potatoes (including fries) and non-alcoholic beverages.
Given the high reported consumption of fast food by young adults, health promotion initiatives both to improve the nutritional quality of fast-food menus and to encourage healthier food choices would likely make a large impact on the overall diet quality of this group.