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1.
Acta Psychiatr Scand ; 149(2): 124-132, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38072006

ABSTRACT

OBJECTIVE: Information on borderline personality disorder (BPD) and its comorbidities is often limited to concentrate on a few diagnoses. The aim of the study was to use national register data to investigate all diagnostic co-occurring mental health disorders and somatic diseases 3 years before and after initial BPD diagnosis compared with a matched control group. METHOD: The study was a register-based cohort of 2756 patients with incident BPD (ICD F60.3) and 11,024 matched controls, during 2002-2016. Comorbidity data were classified into main disease groups, in accordance with the World Health Organization ICD-10 criteria. RESULTS: Almost half the patients had been diagnosed with mental and behavioral disorders before the BPD diagnosis as compared to 3% in the control group. Further, the co-occurrence of diseases due to external causes of morbidity, including injury, self-harm, and poisoning were more represented in the BPD group before diagnosis as compared to the control group. In addition, co-occurring morbidity related to diseases in the circulatory, the respiratory, the digestive, the musculoskeletal, and the genitourinary system was more represented in the BPD group. After diagnosis, the proportion of patients with co-occurring morbidity increased further in all main disease groups in the BPD group. As many as 87% of patients had mental and behavioral co-occurring morbidity and 15% nervous diseases as compared with 3% and 4%, respectively, in the control group. Also, comorbidities related to external causes of morbidity, including for example, injury and self-harm were more represented in the BPD group. The BPD group had more somatic co-occurring morbidity, especially digestive, respiratory, circulatory, and endocrine diseases. Finally, the mortality over 12 years was statistically significantly higher in people with BPD than in the control group. CONCLUSION: Patients with BPD have higher odds for multiple physical health conditions and co-occurrence of mental health disorders.


Subject(s)
Borderline Personality Disorder , Humans , Borderline Personality Disorder/diagnosis , Borderline Personality Disorder/epidemiology , Borderline Personality Disorder/psychology , Prospective Studies , Mental Health , Comorbidity
2.
Public Health ; 207: 88-93, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35594807

ABSTRACT

OBJECTIVE: Heart failure (HF) imposes a major economic burden; however, the individual management for patients varies, potentially leading to large cost heterogeneity. The aim of this study was to investigate the spectrum of health cost by patients with HF and factors associated with high direct health cost. STUDY DESIGN: This was a nationwide, retrospective longitudinal study. METHODS: Using Danish nationwide registries from 2012 to 2015, we identified all patients aged >18 years with a first-time diagnosis of HF. Total health costs were investigated using two perspectives-at index and during 3 years of follow-up. Patients were investigated by decile cost groups. A multivariable logistic regression was used to identify variables associated with being in the highest cost decile compared with the rest (90%). RESULTS: A total of 11,170 patients with HF were included, and those in the highest cost decile (n = 1117, 10%) were younger (69 vs. 75 years), fewer were females (34% vs. 43%), and more were inpatients (83% vs. 70%) compared with the rest of the patients with HF (n = 10,053, 90%). Patients in the highest cost decile (10%) incurred a 30 times higher cost with a mean total health cost in index year of €86,607 compared with €2893 for patients in lowest cost decile (10%). The results were similar for 3 years aggregated (€139,473 vs. €4086), corresponding to a 34 times higher cost. CONCLUSION: In patients with HF, a large total health cost heterogeneity exists with younger age, inpatient admittance, male sex, and comorbidities being associated with a higher likelihood of belonging to the highest cost group.


Subject(s)
Heart Failure , Hospitalization , Female , Health Care Costs , Heart Failure/therapy , Humans , Longitudinal Studies , Male , Retrospective Studies
3.
Pilot Feasibility Stud ; 7(1): 168, 2021 Sep 03.
Article in English | MEDLINE | ID: mdl-34479646

ABSTRACT

BACKGROUND: People with severe mental illness (SMI) have an increased risk of premature mortality, predominantly due to somatic health conditions. Evidence indicates that primary and tertiary prevention and improved treatment of somatic conditions in patients with SMI could reduce this excess mortality. This paper reports a protocol designed to evaluate the feasibility of a coordinated co-produced care program (SOFIA model, a Danish acronym for Severe Mental Illness and Physical Health in General Practice) in the general practice setting to reduce mortality and improve quality of life in patients with severe mental illness. METHODS: The SOFIA pilot trial is designed as a cluster randomized controlled trial targeting general practices in two regions in Denmark. We aim to include 12 practices, each of which is instructed to recruit up to 15 community-dwelling patients aged 18 and older with SMI. Practices will be randomized by a computer in a ratio of 2:1 to deliver a coordinated care program or usual care during a 6-month study period. A randomized algorithm is used to perform randomization. The coordinated care program includes educational training of general practitioners and their clinical staff educational training of general practitioners and their clinical staff, which covers clinical and diagnostic management and focus on patient-centered care of this patient group, after which general practitioners will provide a prolonged consultation focusing on individual needs and preferences of the patient with SMI and a follow-up plan if indicated. The outcomes will be parameters of the feasibility of the intervention and trial methods and will be assessed quantitatively and qualitatively. Assessments of the outcome parameters will be administered at baseline, throughout, and at end of the study period. DISCUSSION: If necessary the intervention will be revised based on results from this study. If delivery of the intervention, either in its current form or after revision, is considered feasible, a future, definitive trial to determine the effectiveness of the intervention in reducing mortality and improving quality of life in patients with SMI can take place. Successful implementation of the intervention would imply preliminary promise for addressing health inequities in patients with SMI. TRIAL REGISTRATION: The trial was registered in Clinical Trials as of November 5, 2020, with registration number NCT04618250 . Protocol version: January 22, 2021; original version.

4.
Mult Scler Relat Disord ; 46: 102567, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33296969

ABSTRACT

BACKGROUND: Primary progressive multiple sclerosis (PPMS) is characterized by development of more chronic neurological manifestations from disease onset compared with relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) but the following socioeconomic consequences have never been described in a nation-wide patient population. OBJECTIVE: To determine if socioeconomic burden of PPMS is increased compared with RRMS and SPMS. METHODS: We included patients from The Danish Multiple Sclerosis Registry diagnosed between 1998 and 2015. Yearly average health costs, public transfers and earned income was calculated from the index diagnosis date, and each year in a five-year period before and after index diagnosis date, for the three patient groups. A regression model estimating the odds ratio (OR) with PPMS as the comparator, was used to analyze the differences between PPMS vs. RRMS and PPMS vs. SPMS controlling for age and sex. RESULTS: In total, 9563 MS patients were identified (1998-2015), with a characteristic distribution between different disease courses: 7012 patients with RRMS (73%), 1099 patients with PPMS (11%) and 1452 patients with SPMS (15%). Total health costs were lower in RRMS vs. PPMS (OR 0.76; 95% CI 0.74-0.78; p<0.0001) but not in SPMS vs. PPMS (OR 1.06; 95% CI 1.03-1.09; p<0.0001). Especially homecare costs were lower in RRMS vs. PPMS (OR 0.17; 95% CI 0.17-0.18; p<0.0001), less pronounced in SPMS vs. PPMS (OR 0.93; 95% CI 0.90-0.97; p = 0.0001). OR for health costs before and after diagnosis was significantly lower in RRMS vs. PPMS regarding most variables, less pronounced in SPMS vs. PPMS. CONCLUSION: This nation-wide population-based study show that socioeconomic burden is significantly higher in PPMS relative to RRMS, but less pronounced compared with SPMS.


Subject(s)
Multiple Sclerosis, Chronic Progressive , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Denmark/epidemiology , Disease Progression , Humans , Multiple Sclerosis, Chronic Progressive/epidemiology , Socioeconomic Factors
5.
Osteoarthritis Cartilage ; 28(7): 907-916, 2020 07.
Article in English | MEDLINE | ID: mdl-32243994

ABSTRACT

OBJECTIVE: To assess the 24-month cost-effectiveness of supervised treatment compared to written advice in knee osteoarthritis (OA). DESIGN: 100 adults with moderate-severe OA not eligible for total knee replacement (TKR) randomized to a 12-week individualized, supervised treatment (exercise, education, diet, insoles and pain medication) or written advice. Effectiveness was measured as change in quality-adjusted life years (QALYs) from baseline to 24 months, including data from baseline, 3, 6, 12 and 24 months, while healthcare costs and transfer payments were derived from national registries after final follow-up. Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. A sensitivity analysis resampling existing data was conducted and the probability of cost-effectiveness was estimated using a 22,665 Euros/QALY threshold. In a sensitivity analysis, cost-effectiveness was calculated for different costs of the supervised treatment (actual cost in study; cost in private practice; and in-between cost). RESULTS: Average costs were similar between groups (6,758 Euros vs 6,880 Euros), while the supervised treatment were close to being more effective (incremental effect (95% CI) of 0.075 (-0.005 to 0.156). In the primary analysis excluding deaths, this led the supervised treatment to be cost-effective, compared to written advice. The sensitivity analysis demonstrated that the results were sensitive to changes in the cost of treatment, but in all scenarios the supervised treatment was cost-effective (ICERs of 6,229 to 20,688 Euros/QALY). CONCLUSIONS: From a 24-month perspective, a 12-week individualized, supervised treatment program is cost-effective compared to written advice in patients with moderate-severe knee OA not eligible for TKR. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01535001.


Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Exercise Therapy/methods , Health Care Costs , Osteoarthritis, Knee/rehabilitation , Patient Education as Topic/methods , Quality-Adjusted Life Years , Aged , Analgesics, Non-Narcotic/economics , Cost-Benefit Analysis , Denmark , Diet Therapy/economics , Diet Therapy/methods , Exercise Therapy/economics , Female , Foot Orthoses/economics , Humans , Ibuprofen/economics , Ibuprofen/therapeutic use , Male , Middle Aged , Motivational Interviewing , Osteoarthritis, Knee/economics , Overweight/diet therapy , Patient Education as Topic/economics , Physical Therapy Modalities/economics , Sick Leave/economics , Treatment Outcome
6.
Acta Psychiatr Scand ; 140(5): 458-467, 2019 11.
Article in English | MEDLINE | ID: mdl-31483859

ABSTRACT

OBJECTIVE: Information on societal cost of patients with Borderline Personality Disorder (BPD) and spouses is limited. The aim was to investigate factual societal costs before and after initial BPD diagnosis. METHOD: A register-based cohort study of 2756 patients with incident BPD (ICD F60.3) with spouses and 11 024 matched controls, during 2002-2016. RESULTS: Total direct healthcare costs and lost productivity costs amounted €40 441 for patients with BPD, which was more than 16 times higher than the matched controls. Somatic and psychiatric health care costs and costs of lost productivity were increased during 5 years before initial diagnosis of BPD. Before and after initial diagnosis, health care costs and lost productivity were increased among spouses of patients with BPD. CONCLUSION: Patients with BPD differed substantially from the general population with respect to all included costs. The study documented a significant burden on their spouses. Besides the early onset of BPD, which implies that patients are affected before they finish school and enter labor market, the neurocognitive impairment and fundamental symptoms of BPD, e.g. unstable, intense relationships, impulsivity, and lack of stable sense of self together with psychiatric and somatic comorbidity are part of explanation of the excess costs of BPD.


Subject(s)
Borderline Personality Disorder/economics , Cost of Illness , Health Care Costs/statistics & numerical data , Registries , Spouses/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Denmark , Efficiency , Female , Humans , Male , Middle Aged , Young Adult
7.
Br J Dermatol ; 180(1): 100-107, 2019 01.
Article in English | MEDLINE | ID: mdl-29947129

ABSTRACT

BACKGROUND: There are limited data regarding causes of mortality in patients with psoriasis or psoriatic arthritis (PsA). OBJECTIVES: This retrospective cohort study evaluated the risk and leading causes of mortality in patients with psoriasis or PsA. METHODS: Individuals with a hospital-based diagnosis of PsA or psoriasis were identified using the Danish National Patient Registry. Matched control individuals were identified from the general population. The main outcome measures were risk of death and cause-specific mortality in patients with psoriasis or PsA. RESULTS: Death rates per 1000 patient-years (with 95% confidence intervals) vs. controls were 22·3 (19·7-24·9) vs. 13·9 (11·8-16·0) for patients with psoriasis and 10·8 (8·9-12·8) vs. 11·6 (9·6-13·6) for patients with PsA. Survival, according to stratified hazard ratios (HRs), was significantly lower in patients with psoriasis than in controls (HR 1·74, P < 0·001), but not in patients with PsA (HR 1·06, P = 0·19). Significantly increased risk of death was observed in patients with psoriasis vs. controls due to a number of causes; the highest risks were observed for diseases of the digestive system; endocrine, nutritional and metabolic diseases; and certain infectious and parasitic diseases (HRs 3·61, 3·02 and 2·71, respectively). In patients with PsA, increased mortality was observed only for certain infectious and parasitic diseases (HR 2·80) and diseases of the respiratory system (HR 1·46). Patients with psoriasis died at a younger age than controls (mean age 71·0 vs. 74·5 years, P < 0·001). CONCLUSIONS: Patients with severe psoriasis have increased mortality risk compared with matched controls, due to a number of causes. Evidence to support an increased risk for patients with PsA was less convincing.


Subject(s)
Cause of Death , Psoriasis/mortality , Adult , Age Factors , Aged , Case-Control Studies , Denmark/epidemiology , Female , Humans , Male , Middle Aged , Registries/statistics & numerical data , Retrospective Studies , Risk Factors , Survival Analysis
8.
Acta Neurol Scand ; 136(6): 715-720, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28677318

ABSTRACT

AIMS AND OBJECTIVES: Based on class-I studies, sodium oxybate is regarded as a first-line treatment for both EDS and cataplexy. The cost-effectiveness of sodium oxybate is largely unknown, though. In this study, we estimate the cost-effectiveness of sodium oxybate as treatment for patients with narcolepsy as compared to standard treatment, by calculating incremental cost-effectiveness ratios (cost per quality-adjusted life year, QALY) for patients in a Swedish setting. MATERIALS AND METHODS: Calculations were performed using a Markov model with a 10-year time horizon. The study population consisted of adult patients treated for narcolepsy with cataplexy. Healthcare utilization and quality-adjusted life years (QALYs) for each treatment alternative were calculated assuming no treatment effect on survival. Sensitivity analyses were performed for treatment effectiveness and healthcare cost parameters. RESULTS: The cost per additional quality-adjusted life year was estimated at SEK 563,481. The cost-effectiveness measure was demonstrated to be particularly sensitive to the duration of the relative quality-of-life improvements accruing to patients treated with sodium oxybate. CONCLUSIONS: The estimated cost per additional QALY for the sodium oxybate treatment alternative compared with standard treatment was estimated above the informal Swedish willingness-to-pay threshold (SEK 500,000). The estimated cost per additional QALY obtained here is likely to overestimate the true cost-effectiveness ratio as potentially beneficial effects on productivity of treatment with sodium oxybate were not included (due to lack of data).


Subject(s)
Anesthetics, Intravenous/economics , Cost-Benefit Analysis , Narcolepsy/drug therapy , Sodium Oxybate/economics , Adult , Anesthetics, Intravenous/therapeutic use , Female , Humans , Sodium Oxybate/therapeutic use , Sweden
9.
Eur J Neurol ; 24(2): 326-333, 2017 02.
Article in English | MEDLINE | ID: mdl-27869331

ABSTRACT

BACKGROUND AND PURPOSE: In the world today 10-20 million people are still living with late effects of poliomyelitis (PM), but the long-term consequences of the disease are not well known. The aim of this study was to describe lifelong morbidity and mortality among Danes who survived PM. METHODS: Data from official registers for a cohort of 3606 Danes hospitalized for PM in the period 1940-1954 were compared with 13 762 age- and gender-matched controls. RESULTS: Compared with controls, mortality was moderately increased for both paralytic as well as non-paralytic PM cases; Hazard Ratio, 1.31 (95% confidence interval, 1.18-1.44) and 1.09 (95% confidence interval, 1.00-1.19), respectively. Hospitalization rates were approximately 1.5 times higher among both paralytic and non-paralytic PM cases as compared with controls. Discharge diagnoses showed a broad spectrum of diseases. There were no major differences in morbidities between paralytic and non-paralytic PM cases. CONCLUSIONS: Poliomyelitis has significant long-term consequences on morbidity and mortality of both paralytic and non-paralytic cases.


Subject(s)
Poliomyelitis/epidemiology , Poliomyelitis/mortality , Age Factors , Aged , Aged, 80 and over , Denmark/epidemiology , Female , Follow-Up Studies , Hospitalization/statistics & numerical data , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Paralysis/complications , Paralysis/epidemiology
10.
Osteoporos Int ; 27(12): 3535-3541, 2016 12.
Article in English | MEDLINE | ID: mdl-27394414

ABSTRACT

We estimated the rate of compliance with oral bisphosphonates among Danish women and examined its association with health care resource use and cost. Approximately 30 % of Danish females aged >55 who take bisphosphonates are noncompliant, and noncompliance is significantly associated with increased health care resource use and cost. INTRODUCTION: Two objectives of this study were to estimate the rate of oral bisphosphonate compliance among Danish women and to examine the association of noncompliance with health care resource use and cost. METHODS: Women ≥55 with an index prescription claim for an oral bisphosphonate were identified from Danish national health registries between 2003 and 2008. Compliance was measured as the medication possession ratio (MPR) during the first 12 months post-index. Cost and health care resource use were collected for the following 12 months. RESULTS: Among the 38,234 women meeting the study inclusion criteria, 29.9 % were noncompliant (MPR <70 %). Younger age was associated with higher odds of compliance (OR [95 % CI] 1.22 [1.15-1.29] for ages 55-64 and 1.18 [1.12-1.24] for ages 65-74; reference age group ≥75 years). Rates of all-cause health care resource use were significantly higher in noncompliant subjects: 28.9 versus 23.0 % had inpatient admissions, 16.5 versus 13.0 % had emergency room visits, and 48.7 versus 43.3 % used outpatient services (P < 0.001 for all comparisons). The total mean (SD) all-cause cost per patient (excluding office visits) was €626 (2344) and €4178 (7854), respectively. The mean (SD) osteoporosis-related cost per patient (excluding office visits) was €572 (2085) and €754 (2857) for compliant and non-compliant subjects, respectively. The compliant subjects accrued significantly lower all-cause and OP-related cost than noncompliant subjects, regardless of whether the total cost or medical cost only was considered. CONCLUSIONS: Approximately 30 % of Danish females aged 55 or older who take bisphosphonates are noncompliant. Noncompliance is significantly associated with increased health care resource use and cost.


Subject(s)
Diphosphonates/therapeutic use , Health Care Costs , Health Resources/statistics & numerical data , Osteoporosis/economics , Patient Compliance , Aged , Denmark , Female , Humans , Middle Aged , Osteoporosis/drug therapy , Registries , Retrospective Studies
11.
Eur J Neurol ; 23(9): 1400-7, 2016 09.
Article in English | MEDLINE | ID: mdl-27297659

ABSTRACT

BACKGROUND AND PURPOSE: Dementia causes morbidity, disability and mortality, and as the population ages the societal burden will grow. The direct health costs and indirect costs of lost productivity and social welfare of dementia were estimated compared with matched controls in a national register based cohort study. METHODS: Using records from the Danish National Patient Registry (1997-2009) all patients with a diagnosis of Alzheimer's disease, vascular dementia or dementia not otherwise specified and their partners were identified and compared with randomly chosen controls matched for age, gender, geographical area and civil status. Direct health costs included primary and secondary sector contacts, medical procedures and medication. Indirect costs included the effect on labor supply. All cost data were extracted from national databases. The entire cohort was followed for the entire period - before and after diagnosis. RESULTS: In all, 78 715 patients were identified and compared with 312 813 matched controls. Patients' partners were also identified and matched with a control group. Patients had lower income and higher mortality and morbidity rates and greater use of medication. Social- and health-related vulnerability was identified years prior to diagnosis. The average annual additional cost of direct healthcare costs and lost productivity in the years before diagnosis was 2082 euros per patient over and above that of matched controls, and 4544 euros per patient after the time of diagnosis. CONCLUSIONS: Dementias cause significant morbidity and mortality, consequently generating significant socioeconomic costs.


Subject(s)
Dementia/economics , Adult , Age Factors , Aged , Aged, 80 and over , Alzheimer Disease/economics , Alzheimer Disease/epidemiology , Alzheimer Disease/psychology , Cohort Studies , Cost of Illness , Dementia/epidemiology , Dementia/psychology , Dementia, Vascular/economics , Dementia, Vascular/epidemiology , Dementia, Vascular/psychology , Denmark/epidemiology , Employment , Female , Health Care Costs , Humans , Male , Middle Aged , Registries , Sex Factors , Socioeconomic Factors , Survival Analysis , Young Adult
13.
Acta Neurol Scand ; 127(4): 242-50, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22812660

ABSTRACT

OBJECTIVES: Optic neuritis (ON) often precedes multiple sclerosis (MS). MS is associated with a significant socioeconomic burden. However, the burden of ON with and without MS before and after its diagnosis has never been calculated. METHODS: Using complete national records from the Danish National Patient Registry (1998-2006), we identified 1677 patients with ON and compared them with 6708 randomly selected citizens matched for age, sex and geography. A societal perspective is taken towards the cost analyses. Costs included in the analysis are those of the health sector, including all contacts with primary and secondary sectors, and the use and costs of drugs. Productivity losses included labour supply and income. All social transfer payments were also calculated. RESULTS: Patients with ON had higher rates of contact with healthcare services, medication use and income from employment, all of which incurred a higher socioeconomic cost. Employed patients had lower income than control subjects. The total annual excess costs relative to matched controls were €3501 for ON patients and €9215 for patients with a dual diagnosis of ON and MS. The ON and ON+MS patients received an annual mean excess social transfer income of €1175 and €4619. ON/ON+MS patients presented social and economic consequences up to 8 years before diagnosis, and these increased after the diagnosis was established. CONCLUSIONS: ON, especially if combined with a diagnosis of MS, has a significant socioeconomic consequence for the individual patient and for society. Productivity losses are a far more important economic factor than health sector costs.


Subject(s)
Health Expenditures , Health Services/economics , Multiple Sclerosis/economics , National Health Programs/economics , Optic Neuritis/economics , Adolescent , Adult , Age Factors , Aged , Child , Child, Preschool , Cost of Illness , Denmark , Employment , Female , Humans , Income , Infant , Infant, Newborn , Male , Middle Aged , Multiple Sclerosis/complications , Optic Neuritis/complications , Registries/statistics & numerical data , Sex Factors , Young Adult
14.
Acta Neurol Scand ; 121(4): 265-70, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20047573

ABSTRACT

OBJECTIVES: In the absence of socio-economical consequences of hypersomnia this study addresses the factual indirect and direct costs. METHODS: Two thousand two hundred and eight patients with a hypersomnia diagnosis from 1998 to 2005 were identified in the Danish national patient registry (NPR), each compared with 4 age and gender adjusted, randomly chosen citizens selected from the Civil Registration System Statistics. The health cost was decomposed in direct and indirect yearly costs, including labor supply and social transfer payments. Direct costs included frequencies and costs of discharges and outpatient use by cost weights according to diagnosis related groups and specific outpatient prices based on data from The Danish Ministry of Health. The use of and costs of drugs was based on data from the Danish Medicines Agency. The frequencies and costs from primary sectors were based on data from The National Health Security. Indirect costs were based on income data from the coherent social statistics (CSS). RESULTS: Patients with hypersomnia presented significant higher health related contact rate, expenses and medication use. No differences were identified in employment and income. The yearly sum of direct and indirect costs were yearly euro3402 vs. euro1212 in controls (P < 0.001), corresponding to a yearly excess costs euro2190. The patients presented higher transfer income, total euro889. CONCLUSION: Hypersomnia patient present higher health and medication uses, and social transfer income and thus represent a significant socio-economical burden.


Subject(s)
Disorders of Excessive Somnolence/economics , Primary Health Care/economics , Ambulatory Care/economics , Compensation and Redress , Cost of Illness , Denmark , Disorders of Excessive Somnolence/psychology , Drug Costs , Employment/economics , Female , Health Care Costs , Health Expenditures , Humans , Income , Male
15.
BMC Plant Biol ; 7: 64, 2007 Nov 28.
Article in English | MEDLINE | ID: mdl-18045483

ABSTRACT

BACKGROUND: The phospholipids of the plant plasma membrane are synthesized in the endoplasmic reticulum (ER). The majority of these lipids reach the plasma membrane independently of the secretory vesicular pathway. Phospholipid delivery to the mitochondria and chloroplasts of plant cells also bypasses the secretory pathway and here it has been proposed that lysophospholipids are transported at contact sites between specific regions of the ER and the respective organelle, followed by lysophospholipid acylation in the target organelle. To test the hypothesis that a corresponding mechanism operates to transport phospholipids to the plasma membrane outside the secretory pathway, we investigated whether lysolipid acylation occurs also in the plant plasma membrane and whether this membrane, like the chloroplasts and mitochondria, is in close contact with the ER. RESULTS: The plant plasma membrane readily incorporated the acyl chain of acyl-CoA into phospholipids. Oleic acid was preferred over palmitic acid as substrate and acyl incorporation occurred predominantly into phosphatidylcholine (PC). Phospholipase A2 stimulated the reaction, as did exogenous lysoPC when administered in above critical micellar concentrations. AgNO3 was inhibitory. The lysophospholipid acylation reaction was higher in a membrane fraction that could be washed off the isolated plasma membranes after repeated freezing and thawing cycles in a medium with lowered pH. This fraction exhibited several ER-like characteristics. When plasma membranes isolated from transgenic Arabidopsis expressing green fluorescent protein in the ER lumen were observed by confocal microscopy, membranes of ER origin were associated with the isolated plasma membranes. CONCLUSION: We conclude that a lysoPC acylation activity is associated with plant plasma membranes and cannot exclude a PC transacylase activity. It is highly plausible that the enzyme(s) resides in a fraction of the ER, closely associated with the plasma membrane, or in both. We suggest that this fraction might be the equivalent of the mitochondria associated membrane of ER origin that delivers phospholipids to the mitochondria, and to the recently isolated ER-derived membrane fraction that is in close contact with chloroplasts. The in situ function of the lysoPC acylation/PC transacylase activity is unknown, but involvement in lipid delivery from the ER to the plasma membrane is suggested.


Subject(s)
1-Acylglycerophosphocholine O-Acyltransferase/metabolism , Arabidopsis/enzymology , Cell Membrane/enzymology , Endoplasmic Reticulum/enzymology , Phospholipids/metabolism , Acylation , Microscopy, Confocal , Peptides/metabolism
16.
Biochim Biophys Acta ; 1684(1-3): 46-53, 2004 Aug 30.
Article in English | MEDLINE | ID: mdl-15450209

ABSTRACT

Here we report that cytosolic phospholipases are involved in the utilization of phosphatidylcholine (PC) as substrate for chloroplast-localized synthesis of monogalactosyldiacylglycerol (MGDG). Isolated chloroplasts were pre-incubated with lysoPC and [14C]18:0-CoA to form [14C]PC. When soluble plant proteins (cytosol) and UDP-galactose were added, [14C] MGDG was formed. An inhibitor of phospholipase D markedly lowered the formation of [14C]MGDG, whereas thermolysin pretreatment of the chloroplasts was without effect. The cytosolic activity resided in the >100-kDa fraction. In a second approach, [14C]PC-containing lipid mixtures were incubated with cytosol. Degradation of [14C]PC to [14C]diacylglycerol was highest when the lipid composition of the mixture mimicked that of the outer chloroplast envelope. We also investigated whether PC of extraplastidic origin could function as substrate for MGDG synthesis. Isolated chloroplasts were incubated with enriched endoplasmic reticulum containing radiolabelled acyl lipids. In the presence of cytosol and UDP-galactose, there was a time-dependent transfer of [14C]PC from this fraction to chloroplasts, where [14C]MGDG was formed. We conclude that chloroplasts recruit cytosolic phospholipase D and phosphatidic acid phosphatase to convert PC to diacylglycerol. Apparently, these lipases do not interact with chloroplast surface proteins, but rather with outer membrane lipids, either for association to the envelope or for substrate presentation.


Subject(s)
Chloroplasts/metabolism , Cytoplasm/enzymology , Galactolipids/biosynthesis , Intracellular Membranes/metabolism , Lipase/metabolism , Phosphatidylcholines/metabolism , Biological Transport/physiology , Cell Fractionation , Endoplasmic Reticulum/metabolism , Lipid Metabolism , Pisum sativum/cytology , Pisum sativum/metabolism , Plant Proteins/metabolism
17.
Physiol Plant ; 114(1): 142-148, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11982945

ABSTRACT

Proteins binding guanosine triphosphate (GTP) have emerged as important regulators in several cellular processes in plants. To investigate any role of such proteins in chloroplast functions, we subjected envelope, stroma and thylakoid fractions isolated from spinach chloroplasts to two different GTP-binding assays. With both methods, we detected GTP-specific binding only in the envelope fraction. Two chloroplast envelope proteins with the apparent molecular weights of 30.5 and 33.5 kDa, respectively, bound [alpha-32P]GTP after SDS-PAGE followed by electroblotting onto a PVDF-membrane and renaturation. Both proteins were intrinsic proteins located in the outer chloroplast envelope. Also, when the fractions were incubated with [alpha-32P]GTP, followed by periodate oxidation and borohydride reduction to cross-link GTP to proteins, two proteins in the envelope fraction, of apparent molecular weights of 28 and 39 kDa, appeared to specifically bind GTP. When agents that stimulate heterotrimeric G-proteins, cholera toxin or the mastoparan analogue mas7, were added to isolated chloroplast envelope, the binding of radiolabelled GTP to the 39 kDa protein, a protein of the inner chloroplast envelope, was stimulated, whereas GTP-binding of the 28 kDa protein, a protein of the outer envelope, was unchanged. Mas7 also stimulated synthesis of monogalactosyl diacylglycerol in isolated chloroplast envelope. The occurrence and regulation of GTP-binding proteins in the chloroplast envelope suggests that GTP-binding proteins could be involved in communication with the extraplastidic compartment during chloroplast biogenesis and development.

18.
Acta Anaesthesiol Scand ; 46(1): 68-73, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11903075

ABSTRACT

BACKGROUND: Autologous platelet rich plasma (PRP) harvest with autotransfusion devices has been used for 10 years in cardiac surgery and recently in orthopedics as a blood saving method. The quality of the harvested platelets has not been adequately examined, in part because of methodological difficulties in studying platelet function during surgery. METHODS: Twenty patients undergoing primary total hip replacement (THR) were studied. Ten patients underwent an immediate preoperative platelet apheresis to obtain concentrated platelet rich plasma (c-PRP). The other 10 patients not undergoing apheresis were allocated to a control group. Platelet activation was evaluated as the population expressing P-selectin on the surface of platelets in the c-PRP and in blood samples collected pre-, per- and postoperatively. The method used was flow cytometry. RESULTS AND CONCLUSIONS: A minor population of activated platelets was found to be circulating in the patients' blood, with a highly significant difference between patients (P = 0.005), and with a range of 1-23% in peroperative activation. PRP harvest did not significantly alter platelet activity. The platelet apheresis procedure did not inhibit platelet function in the c-PRP, as judged by a high proportion of platelets that could be activated in ADP stimulation experiments (mean value +/- SD 86% +/- 7.5%).


Subject(s)
Arthroplasty, Replacement, Hip , Platelet Activation , Plateletpheresis , Adenosine Diphosphate/pharmacology , Aged , Blood Platelets/chemistry , Blood Transfusion, Autologous , Humans , Middle Aged , P-Selectin/blood , Platelet Activation/drug effects , Prospective Studies
19.
Plant Physiol ; 127(1): 184-93, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11553746

ABSTRACT

To study the regulation of lipid transport from the chloroplast envelope to the thylakoid, intact chloroplasts, isolated from fully expanded or still-expanding pea (Pisum sativum) leaves, were incubated with radiolabeled lipid precursors and thylakoid membranes subsequently were isolated. Incubation with UDP[(3)H]Gal labeled monogalactosyldiacylglycerol in both envelope membranes and digalactosyldiacylglycerol in the outer chloroplast envelope. Galactolipid synthesis increased with incubation temperature. Transport to the thylakoid was slow below 12 degrees C, and exhibited a temperature dependency closely resembling that for the previously reported appearance and disappearance of vesicles in the stroma (D.J. Morré, G. Selldén, C. Sundqvist, A.S. Sandelius [1991] Plant Physiol 97: 1558-1564). In mature chloroplasts, monogalactosyldiacylglycerol transport to the thylakoid was up to three times higher than digalactosyldiacylglycerol transport, whereas the difference was markedly lower in developing chloroplasts. Incubation of chloroplasts with [(14)C]acyl-coenzyme A labeled phosphatidylcholine (PC) and free fatty acids in the inner envelope membrane and phosphatidylglycerol at the chloroplast surface. PC and phosphatidylglycerol were preferentially transported to the thylakoid. Analysis of lipid composition revealed that the thylakoid contained approximately 20% of the chloroplast PC. Our results demonstrate that lipids synthesized at the chloroplast surface as well as in the inner envelope membrane are transported to the thylakoid and that lipid sorting is involved in the process. Furthermore, the results also indicate that more than one pathway exists for galactolipid transfer from the chloroplast envelope to the thylakoid.


Subject(s)
Chloroplasts/metabolism , Lipid Metabolism , Pisum sativum/metabolism , Thylakoids/metabolism , Acetyl Coenzyme A/pharmacology , Age Factors , Biological Transport, Active , Carbon Radioisotopes , Endoplasmic Reticulum/physiology , Fatty Acids/analysis , Fatty Acids/metabolism , Galactolipids , Glycolipids/metabolism , Phospholipids/metabolism , Plant Leaves/physiology , Plant Proteins/metabolism , Temperature
20.
Semin Oncol Nurs ; 17(2): 138-46, 2001 May.
Article in English | MEDLINE | ID: mdl-11383245

ABSTRACT

OBJECTIVES: Quality of life (QOL) issues are important for patients with prostate cancer because side effects from treatment are substantial, while the disease itself may be indolent. This article reviews prostate cancer QOL studies. DATA SOURCES: Selected studies published on QOL in prostate cancer using validated patient-assessed tools from the last 5 years. CONCLUSIONS: Prostate cancer treatments are associated with side effects: prostatectomy has more urinary and sexual side effects, while external radiation therapy has more bowel symptoms. Side effects are not highly correlated with overall QOL. IMPLICATIONS FOR NURSING PRACTICE: Patients must be made aware of potential gains in life expectancy as well as side effects of treatments to make informed decisions about treatment.


Subject(s)
Prostatic Neoplasms , Quality of Life , Clinical Trials as Topic , Erectile Dysfunction/etiology , Health Knowledge, Attitudes, Practice , Humans , Male , Prostatectomy/adverse effects , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Prostatic Neoplasms/psychology , Prostatic Neoplasms/therapy , Radiotherapy/adverse effects , Rectal Diseases/etiology , Urinary Incontinence/etiology
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