Genetic variation in the LDL receptor-related protein 5 (LRP5) gene : Association with bone health and metabolic parameters

Bone mass accrual and maintenance are regulated by a complex interplay between genetic and environmental factors. Recent studies have revealed an important role for the low-density lipoprotein receptor-related protein 5 (LRP5) in this process. The aim of this thesis study was to identify novel variants in the LRP5 gene and to further elucidate the association of LRP5 and its variants with various bone health related clinical characteristics. The results of our studies show that loss-of-function mutations in LRP5 cause severe osteoporosis not only in homozygous subjects but also in the carriers of these mutations, who have significantly reduced bone mineral density (BMD) and increased susceptibility to fractures. In addition, we demonstrated for the first time that a common polymorphic LRP5 variant (p.A1330V) was associated with reduced peak bone mass, an important determinant of BMD and osteoporosis in later life. The results from these two studies are concordant with results seen in other studies on LRP5 mutations and in association studies linking genetic variation in LRP5 with BMD and osteoporosis. Several rare LRP5 variants were identified in children with recurrent fractures. Sequencing and multiplex ligation-dependent probe amplification (MLPA) analyses revealed no disease-causing mutations or whole-exon deletions. Our findings from clinical assessments and family-based genotype-phenotype studies suggested that the rare LRP5 variants identified are not the definite cause of fractures in these children. Clinical assessments of our study subjects with LPR5 mutations revealed an unexpectedly high prevalence of impaired glucose tolerance and dyslipidaemia. Moreover, in subsequent studies we discovered that common polymorphic LRP5 variants are associated with unfavorable metabolic characteristics. Changes in lipid profile were already apparent in pre-pubertal children. These results, together with the findings from other studies, suggest an important role for LRP5 also in glucose and lipid metabolism. Our results underscore the important role of LRP5 not only in bone mass accrual and maintenance of skeletal health but also in glucose and lipid metabolism. The role of LRP5 in bone metabolism has long been studied, but further studies with larger study cohorts are still needed to evaluate the specific role of LRP5 variants as metabolic risk factors.

Oral health and menopause

Hormone therapy (HT) is widely used to relieve climacteric symptoms in order to increase the well-being of the women. The benefits as well as side-effects of HT are well documented. The principal menopausal oral symptoms are dry mouth (DM) and sensation of painful mouth (PM) due to various causes. Profile studies have indicated that HT users are more health-conscious than non-users. The hypothesis of the present study was that there are differences in oral health between woman using HT and those not using HT. A questionnaire study of 3173 women of menopausal age (50-58 years old) was done to investigate the prevalence of self-assessed sensations of PM and DM. Of those women participating in the questionnaire study, a random sample of 400 (200 using, 200 not using HT) was examined clinically in a 2-year follow-up study. Oral status was recorded according to WHO methods using DMFT and CPITN indices. The saliva flows were measured, salivary total protein, albumin and immunoglobulin concentrations and selected periodontal micro-organisms were analysed, and panoramic tomography of the jaws was taken. The patients filled in a structured questionnaire on their systemic health, medication and health habits. According to our questionnaire study there was no significant difference in the occurrence of self- assessed PM or DM between the HT users and non-users. According to logistic regression analyses, climacteric complaints significantly correlated with the occurrence of PM (p=0.000) and DM (p=0.000) irrespective of the use of HT, indicating that PM and DM are associated with climacteric symptoms in general. There was no difference between the groups in DMFT index values at follow up. The number of filled teeth (FT) showed a significant (p<0.05) increase in the HT group at follow-up. Periodontitis was diagnosed in 79% of HT users at baseline and in 71% at the follow-up. The values for non-HT users were 80% vs. 76%, respectively (Ns.). The mean numbers of ≥ 6 mm deep periodontal pockets were 0.9 ± 1.7 at baseline vs. 1.1 ± 2.1 two years later in the HT group, and 1.0 ± 1.7 vs. 1.2 ± 1.9, respectively, in the non-HT group. In a large Finnish national health survey, the prevalence of peridontitis of women of this age group was lower, but the prevalence of severe periodontitis seemed to be higher than in our study. Salivary albumin, IgG and IgM concentrations decreased in the HT group during the 2-year follow up (p<0.05), possibly indicating an improvement in epithelial integrity. No difference was found in any other salivary parameters or in the prevalence of the periodontal bacteria between or within the groups. In conclusion, the present findings showed that 50 to 58 year old women living in Helsinki have fairly good oral and dental health. The occurrence of PM and DM seemed to be associated with climacteric symptoms in general, and the use of HT did not affect the oral symptoms studied.

The impact of economic crises on social inequalities in health: what do we know so far?

Since 2008, Western countries are going through a deep economic crisis whose health impacts seem to be fundamentally counter-cyclical: when economic conditions worsen, so does health, and mortality tends to rise. While a growing number of studies have presented evidence on the effect of crises on the average population health, a largely neglected aspect of research is the impact of crises and the related political responses on social inequalities in health, even if the negative consequences of the crises are primarily borne by the most disadvantaged populations. This commentary will reflect on the results of the studies that have analyzed the effect of economic crises on social inequalities in health up to 2013. With some exceptions, the studies show an increase in health inequalities during crises, especially during the Southeast Asian and Japanese crises and the Soviet Union crisis, although it is not always evident for both sexes or all health or socioeconomic variables. In the Nordic countries during the nineties, a clear worsening of health equity did not occur. Results about the impacts of the current economic recession on health equity are still inconsistent. Some of the factors that could explain this variability in results are the role of welfare state policies, the diversity of time periods used in the analyses, the heterogeneity of socioeconomic and health variables considered, the changes in the socioeconomic profile of the groups under comparison in times of crises, and the type of measures used to analyze the magnitude of social inequalities in health. Social epidemiology should further collaborate with other disciplines to help produce more accurate and useful evidence about the relationship between crises and health equity.

Fragilidade em idosos brasileiros: avaliação de sua prevalência pelos critérios propostos pela Escala de Fragilidade do Cardiovascular Health Study em uma população da cidade do Rio de Janeiro

A síndrome de fragilidade pode ser definida como um estado de vulnerabilidade a agentes estressores, um resultado de declínios orgânicos observados em múltiplos sistemas, comprometendo a habilidade do indivíduo em manter a homeostase. O objetivo deste estudo transversal foi avaliar a prevalência desta condição através da Escala de Fragilidade proposta pelo Cardiovascular Health Study em uma população de idosos, clientes de uma operadora de saúde, que vivem na zona norte da cidade do Rio de Janeiro, além de observar o comportamento deste instrumento em uma amostra brasileira. 754 indivíduos foram avaliados quanto aos cinco critérios da escala além de variáveis sociodemográficas, capacidade funcional, quedas, perfil cognitivo e comorbidades relatadas. Foram considerados Frágeis aqueles que apresentaram três ou mais dos seguintes critérios: a) lentificação da velocidade da marcha; b) reduzida força de preensão palmar; c) sensação de exaustão; d) baixa atividade física; e) perda de peso. Os resultados apontam que, dentre os avaliados, 9,2% eram Frágeis. Estes eram mais idosos, com pior status socioeconômico, com pior desempenho cognitivo e maior comprometimento funcional (p< 0,05). Entre os 9,2% de Frágeis, 87% apresentaram alteração da velocidade da marcha, 79,7% da força de preensão palmar, 66,8% baixa atividade física, 52,2% relato de sensação de exaustão e 36,2% relato de perda de peso. A distribuição de suas frequências quando comparado ao estudo original foi bastante semelhante. Vários estudos partem do postulado que a fragilidade pode ser identificada através de medidas clínicas. Através de sua identificação precoce, é possível reconhecer uma entidade potencialmente reversível, reduzindo morbidade e mortalidade na população idosa, no entanto é fundamental um estudo acurado sobre como esta entidade será mensurada e quais serão os critérios adotados para defini-la. Maiores estudos são necessários para realizar, no Brasil, uma análise mais aprofundada desta pertinente questão.

Collaboration on procurement of e-content between the National Health Service and higher education in the UK

Urquhart, C. J., Cox, A. M.& Spink, S. (2007). Collaboration on procurement of e-content between the National Health Service and higher education in the UK. Interlending & Document Supply, 35(3), 164-170. Sponsorship: JISC, LKDN

An empirical examination of risk equalisation in a regulated community rated health insurance market

Despite universal access entitlements to the public healthcare system in Ireland, over half the population is covered by voluntary private health insurance. The market operates on the basis of community rating, open enrolment and lifetime cover. A set of minimum benefits also exists, and two risk equalisation schemes have been put in place but neither was implemented. These schemes have proved highly controversial. To date, the debate has primarily consisted of qualitative arguments. This study adds a quantitative element by analysing a number of pertinent issues. A model of a community rated insurance market is developed, which shows that community rating can only be maintained in a competitive market if all insurers in the market have the same risk profile as the market overall. This has relevance to the Irish market in the aftermath of a Supreme Court decision to set aside risk equalisation. Two reasons why insurers’ risk profiles might differ are adverse selection and risk selection. Evidence is found of the existence of both forms of selection in the Irish market. A move from single rate community rating to lifetime community rating in Australia had significant consequences for take-up rates and the age profile of the insured population. A similar move has been proposed in Ireland. It is found that, although this might improve the stability of community rating in the short term, it would not negate the need for risk equalisation. If community rating were to collapse then risk rating might result. A comparison of the Irish, Australian and UK health insurance markets suggests that community rating encourages higher take-up among older consumers than risk rating. Analysis of Irish hospital discharge figures suggests that this yields significant savings for the Irish public healthcare system. This thesis has implications for government policy towards private health insurance in Ireland.

Health in the medieval world: Regionality and the bioarchaeology of Ireland and Britain

This study assesses regional health patterns in early medieval Ireland and Britain by analysing and interpreting palaeopathological indicators of stress. This was achieved by incorporating the results of demographic and palaeopathological study into the specific historical contexts. Although relatively small islands, both are home to unique and diverse cultural, physical, and political landscapes, which could potentially affect the general health of the population in different ways. To accurately answer the research question, a bioarchaeological survey of six regions within both islands was carried out, specifically analysing and comparing the demographic profile and general health trends within each region with one another. Results from the analysis have demonstrated statistically significant differences within and between the islands. Inferring that even the more subtle differences observed within the cultural, physical, and political landscapes, such as in the case of Ireland and Britain, can and do affect general health trends. The health of early medieval Ireland and Britain appears to be significantly affected by the physical landscape, specifically a north/south divide. The most northerly regions, Scotland South and Ireland North, manifested higher levels of stress indicators when compared to the more southerly positioned regions. Although it can only be hypothesised what factors within these regions are causing, enhancing or buffering stress, the study has established the potential and necessity for regional work to be continued when interpreting the historical past of these two islands.

Young caregivers in the end-of-life setting: a population-based profile of an emerging group.

PURPOSE: Little is known about young caregivers of people with advanced life-limiting illness. Better understanding of the needs and characteristics of these young caregivers can inform development of palliative care and other support services. METHODS: A population-based analysis of caregivers was performed from piloted questions included in the 2001-2007 face-to-face annual health surveys of 23,706 South Australians on the death of a loved one, caregiving provided, and characteristics of the deceased individual and caregiver. The survey was representative of the population by age, gender, and region of residence. FINDINGS: Most active care was provided by older, close family members, but large numbers of young people (ages 15-29) also provided assistance to individuals with advanced life-limiting illness. They comprised 14.4% of those undertaking "hands-on" care on a daily or intermittent basis, whom we grouped together as active caregivers. Almost as many young males as females participate in active caregiving (men represent 46%); most provide care while being employed, including 38% who work full-time. Over half of those engaged in hands-on care indicated the experience to be worse or much worse than expected, with young people more frequently reporting dissatisfaction thereof. Young caregivers also exhibited an increased perception of the need for assistance with grief. CONCLUSION: Young people can be integral to end-of-life care, and represent a significant cohort of active caregivers with unique needs and experiences. They may have a more negative experience as caregivers, and increased needs for grief counseling services compared to other age cohorts of caregivers.

Effect of heat treatment on the antioxidant activity, color, and free phenolic acid profile of malt

Green malt was kilned at 95 degrees C following two regimens: a standard regimen (SKR) and a rapid regimen (RKR). Both resulting malts were treated further in a tray dryer heated to 120 degrees C, as was green malt previously dried to 65 degrees C (TDR). Each regimen was monitored by determining the color, antioxidant activity (by both ABTS(center dot+) and FRAP methods), and polyphenolic profile. SKR and RKR malts exhibited decreased L* and increased b* values above approximately 80 degrees C. TDR malts changed significantly less, and color did not develop until 110 degrees C, implying that different chemical reactions lead to color in those malts. Antioxidant activity increased progressively with each regimen, although with TDR malts this became significant only at 110-120 degrees C. The RKR malt ABTS(center dot+) values were higher than those of the SKR malt. The main phenolics, that is, ferulic, p-coumaric, and vanillic acids, were monitored throughout heating. Ferulic acid levels increased upon heating to 80 degrees C for SKR and to 70 degrees C for RKR, with subsequent decreases. However, the levels for TDR malts did not increase significantly. The increase in free phenolics early in kilning could be due to enzymatic release of bound phenolics and/or easier extractability due to changes in the matrix. The differences between the kilning regimens used suggest that further modification of the regimens could lead to greater release of bound phenolics with consequent beneficial effects on flavor stability in beer and, more generally, on human health.

A Profile of Adolescent Cocaine Use in Northern Ireland.

Background: The image of cocaine as a 'party' drug used by more affluent members of society has begun to change as the levels of use of the drug rise amongst school aged young people. Methods: Cocaine use patterns amongst young people aged 13-16 years who were participating in the Belfast Youth Development Study, a longitudinal study of adolescent drug use was explored. Data was collected through an annual datasweep in participating schools. This paper includes data collected in years 3, 4 and 5 of the study. Results: The results show higher levels of cocaine use amongst this age group than reported in much of the existing harm reduction literature. Lifetime use was 3.8% at age 13-14 years, rising to 7.5% at 15-16 years. The profile indicated that adolescent cocaine users were more likely to be female, live in disrupted families and experience social deprivation which is similar to existing adolescent drug use profiles. There was also some evidence of experimental cocaine use amongst the sample. Conclusions: These findings provide further evidence for the development of age appropriate school focused harm reduction initiatives and continued monitoring of contemporary trends of use of cocaine amongst school aged young people.

Psychological and social profile of family caregivers upon commencement of palliative care provision

Context
Palliative care services are required to support patients who have advanced, life-threatening, noncurable disease, and their family caregivers. Comprehensive psychological and social support for bereaved family members also is expected. However, recent systematic reviews have demonstrated significant gaps in evidence-based approaches for such support. Furthermore, a comprehensive understanding of the psychological and social response to the family caregiver role is required for support to be optimized.

Objectives
We sought to examine the psychological and social profile of family caregivers on commencement of receiving palliative care services.

Methods
A self-report questionnaire was administered to primary family caregivers of patients within two weeks of admission to three palliative care services in Melbourne, Australia. The questionnaire incorporated six instruments that measured 11 family caregiver-related psychosocial factors; four instruments that measured caregiver psychological distress factors; 14 mental health lifetime risk factors; and a sociodemographic questionnaire.

Results
Three hundred and two family caregivers participated. Nearly half (44%) of the caregivers had a probable anxiety and/or depressive disorder, with 40% scoring more than the cutoff score for probable anxiety and 20% scoring more than the cutoff score for probable depression. Additionally, approximately 15% of caregivers met the criteria for pre-loss grief, and around 10% reported moderate to severe levels of demoralization. Caregivers who had a probable anxiety and/or depressive disorder also reported higher levels of pre-loss grief.

Conclusion
This study provides further evidence of the prevalence of poor psychosocial well-being in this population. The results reinforce the need to develop suitable strategies for psychological and social support for family caregivers.

Short-term phytoestrogen supplementation alters insulin-like growth factor profile but not lipid or antioxidant status

Phytoestrogens are plant compounds that have been proposed to have a variety of health benefits. The aim of this study was to assess the effects of these compounds on a number of physiological endpoints. Subjects were given a single intake of a phytoestrogen-rich (80 mg total phytoestrogens) supplement containing soy, rye and linseed (Phase 1), followed by a week-long intervention using the same supplement (Phase 2) (80 mg total phytoestrogens daily). A number of biochemical endpoints were assessed including urinary phytoestrogen metabolites, lipids, antioxidant status, DNA damage and insulin-like growth factor-1 (IGF-1) and IGF binding protein-1 (IGFBP-1) and -3 (IGFBP-3). Ten healthy female subjects took part in the study. Excretion of the isoflavones genistein, daidzein and equol in urine increased in both phases of the study. No other endpoint was altered in Phase 1. However, in Phase 2, concentrations of IGF-1 and IGFBP-3 were increased by phytoestrogen supplementation [IGF-1, median (IQ range), baseline 155 (123, 258), postweek 265 (228, 360) ng/ml, P

Utility, Caller, and Patient Profile of a Novel Chemotherapy Telephone Helpline Service Within a Regional Cancer Centre in Northern Ireland

Background: The telephone is an accepted and useful means of communication for the management of patient care. The Chemotherapy Telephone Helpline (CTH) service, located in a large inner-city Trust within the United Kingdom, is a unique nurse-led service within Northern Ireland.

Objective: The objective of the study was to investigate the utility, caller, and patient profile of a novel CTH.

Methods: This was a retrospective study of telephone contacts during 2007 to the CTH. Calls were categorized by caller and patient characteristics, reason for call, and subsequent action.

Results: A total of 7498 calls were made to the CTH during 2007. Of these, 25.6% occurred outside 8AM-4PM. Callers included patients (45.8%), lay carers (31%), and health care professionals (20.5%); 35.2% of calls concerned patients with polysymptomatic problems; 36.8% of calls led directly to patients being medically assessed.

Conclusions: The utility of the CTH service confirms the need of this nurse-led service. This service facilitates access to specialist advice and support for patients, their families, and allied health care professionals.

Implications for Practice: The international significance of these findings for practice includes its demonstration of the multifaceted symptom experience of patients receiving chemotherapy and highlights the importance of rapid access to specialist cancer services for patients and their lay and professional carers. In addition, it demonstrates the capacity of helplines to identify gaps in professional skills and training.

Subjective impact of minimally invasive dentistry in the oral health of older patients

OBJECTIVES: The aim of this study was to investigate if a minimally invasive oral health package with the use of atraumatic restorative treatment (ART) or a conventional restorative technique (CT) would result in any perceived benefit from the patients' perspective and if there would be any difference between the two treatment groups.

MATERIALS AND METHODS: In this randomised clinical trial, 99 independently living older adults (65-90 years) with carious lesions were randomly allocated to receive either ART or conventional restorations using minimally invasive/intervention dentistry (MID) principles. Patients completed an Oral Health Impact Profile (OHIP)-14 questionnaire before and 2 months after treatment. They were also asked to complete a global transition question about their oral health after treatment.

RESULTS: At baseline, the mean OHIP-14 scores recorded were 7.34 (ART) and 7.44 (CT). Two months after treatment intervention, 90 patients answered the OHIP-14 and the mean scores were 7.23 (not significant (n.s.)) and 10.38 (n.s.) for the ART and CT groups, respectively. Overall, 75.5 % of patients stated that their oral health was better compared to the beginning of treatment.

CONCLUSIONS: Although not shown by the OHIP-14, patients perceived an improvement in their overall oral status after treatment, as demonstrated by the global transition ratings in both groups.

CLINICAL RELEVANCE: Dental treatment using minimally invasive techniques might be a good alternative to treat older individuals, and it can improve their oral health both objectively and subjectively.

The impact of rehabilitation using removable partial dentures and functionally orientated treatment on oral health-related quality of life: a randomised controlled clinical trial

OBJECTIVES: This study aimed to compare two different tooth replacement strategies for partially dentate older patients; namely functionally orientated treatment according to the principles of the shortened dental arch (SDA) and conventional treatment using removable partial dentures (RPDs) using a randomised controlled clinical trial. The primary outcome measure for this study was impact on oral health-related quality of life (OHRQoL) measured using the short form of the oral health impact profile (OHIP-14).

METHODS: Patients aged 65 years and older were randomly allocated to two different treatment groups: the RPD group and the SDA group. For the RPD group each patient was restored to complete arches with cobalt-chromium RPDs used to replace missing teeth. For the SDA group, patients were restored to a premolar occlusion of 10 occluding pairs of natural and replacement teeth using resin bonded bridgework (RBB). OHRQoL was measured using the OHIP-14 questionnaire administered at baseline, 1 month, 6 months and 12 months after treatment intervention.

RESULTS: In total, 89 patients completed the RCT: 44 from the RPD group and 45 from the SDA group. Analysis using a mixed model of covariance (ANCOVA) illustrated that treatment according to the SDA concept resulted in significantly better mean OHIP-14 scores compared with RPD treatment (p<0.05). This result was replicated in both treatment centres used in the study.

CONCLUSIONS: In terms of impact on OHRQoL, treatment based on the SDA concept achieved significantly better results than that based on RPDs 12 months after treatment intervention (trial registration no. ISRCTN26302774).

CLINICAL SIGNIFICANCE: Functionally orientated treatment delivery resulted in significantly better outcomes compared to removable dentures in terms of impact on OHRQoL.