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1.
Epidemiol Psychiatr Sci ; 32: e46, 2023 Jul 12.
Article in English | MEDLINE | ID: mdl-37434513

ABSTRACT

AIMS: Preventing the occurrence of depression/anxiety and suicide during adolescence can lead to substantive health gains over the course of an individual person's life. This study set out to identify the expected population-level costs and health impacts of implementing universal and indicated school-based socio-emotional learning (SEL) programs in different country contexts. METHODS: A Markov model was developed to examine the effectiveness of delivering universal and indicated school-based SEL programs to prevent the onset of depression/anxiety and suicide deaths among adolescents. Intervention health impacts were measured in healthy life years gained (HLYGs) over a 100-year time horizon. Country-specific intervention costs were calculated and denominated in 2017 international dollars (2017 I$) under a health systems perspective. Cost-effectiveness findings were subsequently expressed in terms of I$ per HLYG. Analyses were conducted on a group of 20 countries from different regions and income levels, with final results aggregated and presented by country income group - that is, low and lower middle income countries (LLMICs) and upper middle and high-income countries (UMHICs). Uncertainty and sensitivity analyses were conducted to test model assumptions. RESULTS: Implementation costs ranged from an annual per capita investment of I$0.10 in LLMICs to I$0.16 in UMHICs for the universal SEL program and I$0.06 in LLMICs to I$0.09 in UMHICs for the indicated SEL program. The universal SEL program generated 100 HLYGs per 1 million population compared to 5 for the indicated SEL program in LLMICs. The cost per HLYG was I$958 in LLMICS and I$2,006 in UMHICs for the universal SEL program and I$11,123 in LLMICs and I$18,473 in UMHICs for the indicated SEL program. Cost-effectiveness findings were highly sensitive to variations around input parameter values involving the intervention effect sizes and the disability weight used to estimate HLYGs. CONCLUSIONS: The results of this analysis suggest that universal and indicated SEL programs require a low level of investment (in the range of I$0.05 to I$0.20 per head of population) but that universal SEL programs produce significantly greater health benefits at a population level and therefore better value for money (e.g., less than I$1,000 per HLYG in LLMICs). Despite producing fewer population-level health benefits, the implementation of indicated SEL programs may be justified as a means of reducing population inequalities that affect high-risk populations who would benefit from a more tailored intervention approach.


Subject(s)
Cost-Effectiveness Analysis , Suicide , Humans , Adolescent , Depression/prevention & control , Anxiety , Anxiety Disorders
2.
Lancet Glob Health ; 9(3): e291-e300, 2021 03.
Article in English | MEDLINE | ID: mdl-33341152

ABSTRACT

BACKGROUND: Reducing suicides is a key Sustainable Development Goal target for improving global health. Highly hazardous pesticides are among the leading causes of death by suicide in low-income and middle-income countries. National bans of acutely toxic highly hazardous pesticides have led to substantial reductions in pesticide-attributable suicides across several countries. This study evaluated the cost-effectiveness of implementing national bans of highly hazardous pesticides to reduce the burden of pesticide suicides. METHODS: A Markov model was developed to examine the costs and health effects of implementing a national ban of highly hazardous pesticides to prevent suicides due to pesticide self-poisoning, compared with a null comparator. We used WHO cost-effectiveness and strategic planning (WHO-CHOICE) methods to estimate pesticide-attributable suicide rates for 100 years from 2017. Country-specific costs were obtained from the WHO-CHOICE database and denominated in 2017 international dollars (I$), discounted at a 3% annual rate, and health effects were measured in healthy life-years gained (HLYGs). We used a demographic projection model beginning with the country population in the baseline year (2017), split by 1-year age group and sex. Country-specific data on overall suicide rates were obtained for 2017 by age and sex from the Global Burden of Disease Study 2017 Data Resources. The analysis involved 14 countries spanning low-income to high-income settings, and cost-effectiveness ratios were analysed at the country-specific level and aggregated according to country income group and the proportion of suicides due to pesticides. FINDINGS: Banning highly hazardous pesticides across the 14 countries studied could result in about 28 000 (95% uncertainty interval [UI] 24 000-32 000) fewer suicide deaths each year at an annual cost of I$0·007 per capita (95% UI 0·006-0·008). In the population-standardised results for the base case analysis, national bans produced cost-effectiveness ratios of $94 per HLYG (95% UI 73-123) across low-income and lower-middle-income countries and $237 per HLYG (95% UI 191-303) across upper-middle-income and high-income countries. Bans were more cost-effective in countries where a high proportion of suicides are attributable to pesticide self-poisoning, reaching a cost-effectiveness ratio of $75 per HLYG (95% UI 58-99) in two countries with proportions of more than 30%. INTERPRETATION: National bans of highly hazardous pesticides are a potentially cost-effective and affordable intervention for reducing suicide deaths in countries with a high burden of suicides attributable to pesticides. However, our study findings are limited by imperfect data and assumptions that could be improved upon by future studies. FUNDING: WHO.


Subject(s)
Developing Countries , Government Regulation , Pesticides/poisoning , Suicide Prevention , Age Factors , Cost-Benefit Analysis , Global Health , Humans , Markov Chains , Models, Economic , Sex Factors , Socioeconomic Factors
3.
Eur Arch Psychiatry Clin Neurosci ; 271(6): 1017-1025, 2021 Sep.
Article in English | MEDLINE | ID: mdl-32270290

ABSTRACT

Quality indicators are vital for monitoring the transformation of institution-based mental health services towards the provision of person-centered mental healthcare. While several mental healthcare quality indicators have been identified as relevant and valid, their actual usability and utility for routine monitoring healthcare quality over time is significantly determined by the availability and trustworthiness of the underlying data. In this feasibility study, quality indicators that have been systematically identified for use in the Danube region countries of Bulgaria, the Czech Republic, Hungary, and Serbia were measured on the basis of existing mental healthcare data in the four countries. Data were collected retrospectively by means of the best available, most standardized, trustworthy, and up-to-date data in each country. Out of 21 proposed quality indicators, 18 could be measured in Hungary, 17 could be measured in Bulgaria and in the Czech Republic, and 8 could be measured in Serbia. The results demonstrate that a majority of quality indicators can be measured in most of the countries by means of already existing data, thereby demonstrating the feasibility of quality measurement and regular quality monitoring. However, data availability and usability are scattered across countries and care sectors, which leads to variations in the quality of the quality indicators themselves. Making the planning and outputs of national mental healthcare reforms more transparent and evidence-based requires (trans-)national standardization of healthcare quality data, their routine availability and standardized assessment, and the regular reporting of quality indicators.


Subject(s)
Mental Disorders , Mental Health Services , Quality Indicators, Health Care , Europe , Feasibility Studies , Humans , Mental Disorders/therapy , Pilot Projects , Retrospective Studies
4.
Int J Ment Health Syst ; 12: 74, 2018.
Article in English | MEDLINE | ID: mdl-30534197

ABSTRACT

BACKGROUND: In spite of the pronounced adverse economic consequences of mental, neurological, and substance use disorders on households in most low- and middle-income countries, service coverage and financial protection for these families is very limited. The aim of this study was to generate potential strategies for sustainably financing mental health care in Uganda in an effort to move towards increased financial protection and service coverage for these families. METHODS: The process of identifying potential strategies for sustainably financing mental health care in Uganda was guided by an analytical framework developed by the Emerging Mental health systems in low and middle income countries (EMERALD project). Data were collected through a situational analysis (public health burden assessment, health system assessment, macro fiscal assessment) and eight key informant interviews with selected stakeholders from sectors including health, finance and civil society. The situational analysis provided contextualization for the strategies, and was complimented by views from key informant interviews. RESULTS: Findings indicate that the following strategies have the greatest potential for moving towards more equitable and sustainable mental health financing in the Uganda context: implementing National Health Insurance Scheme; shifting to Results Based Financing; decentralizing mental health services that can be provided at community level; and continued advocacy with decision makers with evidence through research. CONCLUSION: Although several options were identified for sustainably financing mental health care in Uganda, the National Health Insurance Scheme seemed the most viable option. However, for the scheme to be effective, there is need for scale up to community health facilities and implementation in a manner that explicitly includes community level facilities.

5.
Epidemiol Psychiatr Sci ; : 1-12, 2017 Mar 13.
Article in English | MEDLINE | ID: mdl-28287062

ABSTRACT

AIMS: The World Health Organization (WHO)'s Mental Health Atlas series has established itself as the single most comprehensive and most widely used source of information on the global mental health situation. The data derived from the latest Mental Health Atlas survey carried out in 2014 describes the availability and delivery of mental health services in the WHO's Member States, focussing on differences by country's income level. METHODS: The data contained in this paper are mainly derived from questions relating to mental health service availability and uptake, as well as on financial and human resources for mental health. Results are presented as median values and analysed by World Bank income group. Interquartile ranges are also provided as measures of statistical dispersion. RESULTS: In total, 171 out of WHO's 194 Member States were able to at least partially complete the Atlas questionnaire. The results highlight a wide gap between high and low-medium income countries in a number of areas: for example, high-income countries have 20 times more beds in community-based inpatient units and 30 times more admissions; the rate of patients cared by outpatient facilities is 40 times higher; and there are 66 times more community outpatient contacts and 15 times more mental health staff at outpatient level. Overall resources for mental health are not distributed efficiently: globally about 60% of financial resources and over two-thirds of all available mental health staff are concentrated in mental hospitals, which serve only a small proportion of patients. Results indicate that outpatient care is the only effective means of increasing the coverage for mental disorders and is expanding, but it is strongly influenced by country income level. Two elements of the network of mental health facilities are particularly scarce in low- and middle-income countries: day treatment facilities and community residential facilities. CONCLUSIONS: The WHO Mental Health Atlas 2014 survey provides basic mental health information at the level of WHO's Member States, concerning mental health resources and activities. Atlas promotes the use of information, usually underestimated not only in low- and middle-income countries but also in high-income countries. Information is needed not only for monitoring the scaling up of the mental health system at country level, but also for improving transparency and accountability for users, families and the public.

6.
Epidemiol Psychiatr Sci ; 26(3): 234-244, 2017 06.
Article in English | MEDLINE | ID: mdl-27641074

ABSTRACT

BACKGROUND: Although financing represents a critical component of health system strengthening and also a defining concern of efforts to move towards universal health coverage, many countries lack the tools and capacity to plan effectively for service scale-up. As part of a multi-country collaborative study (the Emerald project), we set out to develop, test and apply a fully integrated health systems resource planning and health impact tool for mental, neurological and substance use (MNS) disorders. METHODS: A new module of the existing UN strategic planning OneHealth Tool was developed, which identifies health system resources required to scale-up a range of specified interventions for MNS disorders and also projects expected health gains at the population level. We conducted local capacity-building in its use, as well as stakeholder consultations, then tested and calibrated all model parameters, and applied the tool to three priority mental and neurological disorders (psychosis, depression and epilepsy) in six low- and middle-income countries. RESULTS: Resource needs for scaling-up mental health services to reach desired coverage goals are substantial compared with the current allocation of resources in the six represented countries but are not large in absolute terms. In four of the Emerald study countries (Ethiopia, India, Nepal and Uganda), the cost of delivering key interventions for psychosis, depression and epilepsy at existing treatment coverage is estimated at US$ 0.06-0.33 per capita of total population per year (in Nigeria and South Africa it is US$ 1.36-1.92). By comparison, the projected cost per capita at target levels of coverage approaches US$ 5 per capita in Nigeria and South Africa, and ranges from US$ 0.14-1.27 in the other four countries. Implementation of such a package of care at target levels of coverage is expected to yield between 291 and 947 healthy life years per one million populations, which represents a substantial health gain for the currently neglected and underserved sub-populations suffering from psychosis, depression and epilepsy. CONCLUSIONS: This newly developed and validated module of OneHealth tool can be used, especially within the context of integrated health planning at the national level, to generate contextualised estimates of the resource needs, costs and health impacts of scaled-up mental health service delivery.


Subject(s)
Delivery of Health Care , Depression/therapy , Epilepsy/therapy , Health Resources , Mental Health Services/organization & administration , Psychotic Disorders/therapy , Africa South of the Sahara , Asia , Delivery of Health Care/methods , Delivery of Health Care/organization & administration , Health Care Costs , Health Services Research , Humans , Strategic Planning
8.
East Mediterr Health J ; 21(7): 486-92, 2015 Sep 28.
Article in English | MEDLINE | ID: mdl-26442888

ABSTRACT

For EMR countries to deliver the expectations of the Global Mental Health Action Plan 2013-2020 & the ongoing move towards universal health coverage, all health & social care providers need to innovate and transform their services to provide evidence-based health care that is accessible, cost-effective & with the best patient outcomes. For the primary and community workforce, this includes general medical practitioners, practice & community nurses, community social workers, housing officers, lay health workers, nongovernmental organizations & civil society, including community spiritual leaders/healers. This paper brings together the current best evidence to support transformation & discusses key approaches to achieve this, including skill mix and/or task shifting and integrated care. The important factors that need to be in place to support skill mix/task shifting and good integrated care are outlined with reference to EMR countries.


Subject(s)
Delivery of Health Care, Integrated , Health Policy , Health Workforce/organization & administration , Mental Health Services , Cost-Benefit Analysis , Delivery of Health Care, Integrated/economics , Health Priorities , Health Workforce/economics , Humans , Mediterranean Region , Mental Health Services/economics , Organizational Objectives , Program Development , Quality Improvement , World Health Organization
9.
East Mediterr Health J ; 21(7): 512-6, 2015 Sep 28.
Article in English | MEDLINE | ID: mdl-26442892

ABSTRACT

Routine information systems for mental health in many Eastern Mediterranean Region countries are rudimentary or absent, making it difficult to understand the needs of local populations and to plan accordingly. Key components for mental health surveillance and information systems are: national commitment and leadership to ensure that relevant high quality information is collected and reported; a minimum data set of key mental health indicators; intersectoral collaboration with appropriate data sharing; routine data collection supplemented with periodic surveys; quality control and confidentiality; and technology and skills to support data collection, sharing and dissemination. Priority strategic interventions include: (1) periodically assessing and reporting the mental health resources and capacities available using standardized methodologies; (2) routine collection of information and reporting on service availability, coverage and continuity, for priority mental disorders disaggregated by age, sex and diagnosis; and (3) mandatory recording and reporting of suicides at the national level (using relevant ICD codes).


Subject(s)
Information Systems , Mental Disorders/epidemiology , Population Surveillance , Data Collection/methods , Health Services Needs and Demand , Humans , Mediterranean Region/epidemiology , Quality Indicators, Health Care , World Health Organization
11.
J Clin Endocrinol Metab ; 100(11): 4082-91, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26378474

ABSTRACT

CONTEXT: Whereas insulin resistance and obesity coexist, some obese individuals remain insulin sensitive. OBJECTIVE: We examined phenotypic and metabolic factors associated with insulin sensitivity in both muscle and liver in obese individuals. DESIGN AND PARTICIPANTS: Sixty-four nondiabetic obese adults (29 males) underwent hyperinsulinemic (15 and 80 mU/m(2) · min)-euglycemic clamps with deuterated glucose. Top tertile subjects for glucose infusion rate during the high-dose insulin clamp were assigned Musclesen and those in the lower two tertiles were assigned Muscleres. Secondarily, top tertile subjects for endogenous glucose production suppression during the low-dose insulin clamp were deemed Liversen and the remainder Liverres. MAIN OUTCOMES MEASURES: Clinical and laboratory parameters and visceral, subcutaneous, liver, and pancreatic fat were compared. RESULTS: Musclesen and Muscleres had similar body mass index and total fat (P > .16), but Musclesen had lower glycated hemoglobin (P < .001) and systolic (P = .01) and diastolic (P = .03) blood pressure (BP). Despite similar sc fat (P = 1), Musclesen had lower visceral (P < .001) and liver (P < .001) fat. Liversen had lower visceral (P < .01) and liver (P < .01) fat and C-reactive protein (P = .02) than Liverres. When subjects were grouped by both glucose infusion rate during the high-dose insulin clamp and endogenous glucose production suppression, insulin sensitivity at either muscle or liver conferred apparent protection from the adverse metabolic features that characterized subjects insulin resistant at both sites. High-density lipoprotein-cholesterol, 1-hour glucose, systolic BP, and triglycerides explained 54% of the variance in muscle insulin sensitivity. CONCLUSIONS: Obese subjects who were insulin sensitive at muscle and/or liver exhibited favorable metabolic features, including lower BP, liver and visceral adiposity. This study identifies factors associated with, and possibly contributing to, insulin sensitivity in obesity.


Subject(s)
Insulin Resistance , Obesity/physiopathology , Adipocytes/pathology , Adipocytes/ultrastructure , Adolescent , Adult , Aged , Blood Pressure , Body Mass Index , C-Reactive Protein/metabolism , Cholesterol, HDL/blood , Female , Glucose Clamp Technique , Humans , Hyperinsulinism/metabolism , Liver/metabolism , Male , Middle Aged , Muscles/metabolism , Pancreas/metabolism , Phenotype , Subcutaneous Fat/metabolism , Triglycerides/blood , Young Adult
12.
East. Mediterr. health j ; 21(7): 531-534, 2015.
Article in English | WHO IRIS | ID: who-255249
13.
East. Mediterr. health j ; 21(7): 512-516, 2015.
Article in English | WHO IRIS | ID: who-255245

ABSTRACT

Routine information systems for mental health in many Eastern Mediterranean Region countries are rudimentary or absent, making it difficult to understand the needs of local populations and to plan accordingly. Key components for mental health surveillance and information systems are: national commitment and leadership to ensure that relevant high quality information is collected and reported; a minimum data set of key mental health indicators; intersectoral collaboration with appropriate data sharing; routine data collection supplemented with periodic surveys; quality control and confidentiality; and technology and skills to support data collection, sharing and dissemination. Priority strategic interventions include: [1]periodically assessing and reporting the mental health resources and capacities available using standardized methodologies; [2]routine collection of information and reporting on service availability, coverage and continuity, for priority mental disorders disaggregated by age, sex and diagnosis; and [3]mandatory recording and reporting of suicides at the national level [using relevant ICD codes]


Les systèmes d'information de routine pour la santé mentale dans de nombreux pays de la Région de la Méditerranée orientale sont rudimentaires ou font défaut, ce qui rend difficile la compréhension des besoins des populations locales et la planification correspondante. Les composantes clés des systèmes d'information et de surveillance de la santé mentale sont les suivantes : un engagement et un rôle de premier plan à l'échelle nationale pour garantir que des données pertinentes et de haute qualité sont recueillies et transmises ; un ensemble de données minimales servant d'indicateurs clés pour la santé mentale ; une collaboration intersectorielle permettant le partage approprié des informations ; le recueil de données systématique complété par des enquêtes périodiques ; un contrôle qualité et la confidentialité ; et de la technologie et des compétences pour appuyer le recueil, le partage et la diffusion des données.Parmi les interventions stratégiques prioritaires,on peut citer : 1]l'évaluation périodique des ressources et des capacités en santé mentale disponibles et la notification de ces informations à l'aide de méthodologies normalisées ; 2]le recueil et la notification de données systématiques sur la disponibilité des services, leur couverture et leur pérennité pour les troubles de santé mentale prioritaires,ventilées par âge, sexe et diagnostic ; et 3]l'enregistrement et la notification obligatoires des suicides à l'échelle nationale [à l'aide des codes CIM pertinents]


Subject(s)
Mental Health , Information Systems
14.
East. Mediterr. health j ; 21(7): 486-492, 2015.
Article in English | WHO IRIS | ID: who-255241

ABSTRACT

For EMR countries to deliver the expectations of the Global Mental Health Action Plan 2013-2020 and the ongoing move towards universal health coverage, all health and social care providers need to innovate and transform their services to provide evidence-based health care that is accessible, cost-effective and with the best patient outcomes. For the primary and community workforce, this includes general medical practitioners, practice and community nurses, community social workers, housing officers, lay health workers, nongovernmental organizations and civil society, including community spiritual leaders/healers. This paper brings together the current best evidence to support transformation and discusses key approaches to achieve this, including skill mix and/or task shifting and integrated care. The important factors that need to be in place to support skill mix/task shifting and good integrated care are outlined with reference to EMR countries


Pour que les pays de la Région de la Méditerranée orientale puissent répondre aux attentes créées par le Plan d'action mondial sur la santé mentale 2013-2020 et pour faciliter le mouvement continu vers la couverture sanitaire universelle, tous les acteurs de la prestation de soins socio-sanitaires doivent faire preuve d'innovation et transformer leurs services afin de fournir des soins de santé fondés sur des bases factuelles qui soient accessibles, d'un bon rapport coût-efficacité et procurent les meilleurs résultats pour les patients. Pour ce qui est des personnels aux niveaux primaires et communautaires, ceci concerne les médecins généralistes, les infirmières praticiennes, les infirmières communautaires, les travailleurs sociaux communautaires, les responsables des logements sociaux,les travailleurs de la santé non professionnels, les membres des organisations non gouvernementales et de la société civile, y compris les leaders et les guérisseurs spirituels communautaires.Le présent article rassemble les meilleures bases factuelles actuellement disponibles à l'appui de cette transformation et examine les approches principales à cet égard, y compris l'éventail des compétences et/ou la délégation des tâches et les soins intégrés.Les facteurs importants qui doivent être en place à l'appui de l'éventail des compétences/la délégation des tâches et de bons soins intégrés sont présentés dans le contexte des pays de la Région de la Méditerranée orientale


Subject(s)
Mental Health , Cost-Benefit Analysis , Delivery of Health Care, Integrated
16.
J Viral Hepat ; 21(5): 325-32, 2014 May.
Article in English | MEDLINE | ID: mdl-24716635

ABSTRACT

Chronic hepatitis C (CHC) is associated with lipid-related changes and insulin resistance; the latter predicts response to antiviral therapy, liver disease progression and the risk of diabetes. We sought to determine whether insulin sensitivity improves following CHC viral eradication after antiviral therapy and whether this is accompanied by changes in fat depots or adipokine levels. We compared 8 normoglycaemic men with CHC (genotype 1 or 3) before and at least 6 months post viral eradication and 15 hepatitis C antibody negative controls using an intravenous glucose tolerance test and two-step hyperinsulinaemic-euglycaemic clamp with [6,6-(2) H2 ] glucose to assess peripheral and hepatic insulin sensitivity. Magnetic resonance imaging and spectroscopy quantified abdominal fat compartments, liver and intramyocellular lipid. Peripheral insulin sensitivity improved (glucose infusion rate during high-dose insulin increased from 10.1 ± 1.6 to 12 ± 2.1 mg/kg/min/, P = 0.025), with no change in hepatic insulin response following successful viral eradication, without any accompanying change in muscle, liver or abdominal fat depots. There was corresponding improvement in incremental glycaemic response to intravenous glucose (pretreatment: 62.1 ± 8.3 vs post-treatment: 56.1 ± 8.5 mm, P = 0.008). Insulin sensitivity after viral clearance was comparable to matched controls without CHC. Post therapy, liver enzyme levels decreased but, interestingly, levels of glucagon, fatty acid-binding protein and lipocalin-2 remained elevated. Eradication of the hepatitis C virus improves insulin sensitivity without alteration in fat depots, adipokine or glucagon levels, consistent with a direct link of the virus with insulin resistance.


Subject(s)
Body Fat Distribution , Hepatitis C, Chronic/drug therapy , Insulin Resistance , Adipokines/blood , Adult , Antiviral Agents/therapeutic use , Glucose Tolerance Test , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Spectrum Analysis
17.
J Physiol ; 592(3): 523-35, 2014 Feb 01.
Article in English | MEDLINE | ID: mdl-24297852

ABSTRACT

Calcium cycling is integral to muscle performance during the rapid muscle contraction and relaxation of high-intensity exercise. Ca(2+) handling is altered by diabetes mellitus, but has not previously been investigated in human skeletal muscle. We investigated effects of high-intensity exercise and sprint training on skeletal muscle Ca(2+) regulation among men and women with type 1 diabetes (T1D, n = 8, 3F, 5M) and matched non-diabetic controls (CON, n = 8, 3F, 5M). Secondarily, we examined sex differences in Ca(2+) regulation. Subjects undertook 7 weeks of three times-weekly cycle sprint training. Before and after training, performance was measured, and blood and muscle were sampled at rest and after high-intensity exercise. In T1D, higher Ca(2+)-ATPase activity (+28%) and Ca(2+) uptake (+21%) than in CON were evident across both times and days (P < 0.05), but performance was similar. In T1D, resting Ca(2+)-ATPase activity correlated with work performed until exhaustion (r = 0.7, P < 0.01). Ca(2+)-ATPase activity, but not Ca(2+) uptake, was lower (-24%, P < 0.05) among the women across both times and days. Intense exercise did not alter Ca(2+)-ATPase activity in T1D or CON. However, sex differences were evident: Ca(2+)-ATPase was reduced with exercise among men but increased among women across both days (time × sex interaction, P < 0.05). Sprint training reduced Ca(2+)-ATPase (-8%, P < 0.05), but not Ca(2+) uptake, in T1D and CON. In summary, skeletal muscle Ca(2+) resequestration capacity was increased in T1D, but performance was not greater than CON. Sprint training reduced Ca(2+)-ATPase in T1D and CON. Sex differences in Ca(2+)-ATPase activity were evident and may be linked with fibre type proportion differences.


Subject(s)
Calcium-Transporting ATPases/metabolism , Calcium/metabolism , Diabetes Mellitus, Type 1/metabolism , Exercise , Muscle, Skeletal/metabolism , Sarcoplasmic Reticulum/metabolism , Adult , Case-Control Studies , Female , Humans , Male , Muscle, Skeletal/physiology , Sex Factors
18.
Diabetologia ; 56(4): 875-85, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23344726

ABSTRACT

AIMS/HYPOTHESIS: Muscle insulin resistance, one of the earliest defects associated with type 2 diabetes, involves changes in the phosphoinositide 3-kinase/Akt network. The relative contribution of obesity vs insulin resistance to perturbations in this pathway is poorly understood. METHODS: We used phosphospecific antibodies against targets in the Akt signalling network to study insulin action in muscle from lean, overweight/obese and type 2 diabetic individuals before and during a hyperinsulinaemic-euglycaemic clamp. RESULTS: Insulin-stimulated Akt phosphorylation at Thr309 and Ser474 was highly correlated with whole-body insulin sensitivity. In contrast, impaired phosphorylation of Akt substrate of 160 kDa (AS160; also known as TBC1D4) was associated with adiposity, but not insulin sensitivity. Neither insulin sensitivity nor obesity was associated with defective insulin-dependent phosphorylation of forkhead box O (FOXO) transcription factor. In view of the resultant basal hyperinsulinaemia, we predicted that this selective response within the Akt pathway might lead to hyperactivation of those processes that were spared. Indeed, the expression of genes targeted by FOXO was downregulated in insulin-resistant individuals. CONCLUSIONS/INTERPRETATION: These results highlight non-linearity in Akt signalling and suggest that: (1) the pathway from Akt to glucose transport is complex; and (2) pathways, particularly FOXO, that are not insulin-resistant, are likely to be hyperactivated in response to hyperinsulinaemia. This facet of Akt signalling may contribute to multiple features of the metabolic syndrome.


Subject(s)
Insulin Resistance , Muscles/physiopathology , Proto-Oncogene Proteins c-akt/metabolism , Adult , Aged , Diabetes Mellitus, Type 2/metabolism , Female , Forkhead Box Protein O1 , Forkhead Transcription Factors/metabolism , Gene Expression Profiling , Humans , Insulin/metabolism , Insulin Secretion , Male , Metabolic Syndrome/metabolism , Middle Aged , Muscles/metabolism , Phosphorylation , Signal Transduction
19.
Psychol Med ; 43(4): 801-11, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22846332

ABSTRACT

BACKGROUND: While bipolar disorder (BD) is a leading cause of disability, and an important contributor to disability in BD is cognitive impairment, there is little systematic research on the longitudinal course of cognitive function and instrumental activities of daily living (IADLs) in late-life. In this report, we characterize the 2-year course of cognitive function and IADLs in older adults with BD. Method We recruited non-demented individuals 50 years and older with BD I or BD II (n = 47) from out-patient clinics or treatment studies at the University of Pittsburgh. Comparator subjects ('controls') were 22 individuals of comparable age and education with no psychiatric or neurologic history, but similar levels of cardiovascular disease. We assessed cognitive function and IADLs at baseline, 1- and 2-year time-points. The neuropsychological evaluation comprised 21 well-established and validated tests assessing multiple cognitive domains. We assessed IADLs using a criterion-referenced, performance-based instrument. We employed repeated-measures mixed-effects linear models to examine trajectory of cognitive function. We employed non-parametric tests for analysis of IADLs. RESULTS: The BD group displayed worse cognitive function in all domains and worse IADL performance than the comparator group at baseline and over follow-up. Global cognitive function and IADLs were correlated at all time-points. The BD group did not exhibit accelerated cognitive decline over 2 years. CONCLUSIONS: Over 2 years, cognitive impairment and associated functional disability of older adults with BD appear to be due to long-standing neuroprogressive processes compounded by normal cognitive aging rather than accelerated cognitive loss in old age.


Subject(s)
Activities of Daily Living , Bipolar Disorder/physiopathology , Cognition Disorders/physiopathology , Disease Progression , Aged , Aged, 80 and over , Aging/physiology , Bipolar Disorder/complications , Bipolar Disorder/psychology , Case-Control Studies , Cognition , Cognition Disorders/etiology , Female , Humans , Interview, Psychological , Linear Models , Longitudinal Studies , Male , Middle Aged , Neuropsychological Tests/statistics & numerical data , Statistics, Nonparametric
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