Predicting successful ageing among older adults seems possible even as far as two decades ahead.

BACKGROUND: Successful ageing is the term often used for depicting exceptional ageing and can be measured with multidimensional models including physical, psychological and social wellbeing. The aim of this study was to test multidimensional successful ageing models to investigate whether these models can predict successful ageing, and which individual subcomponents included in the models are most significantly associated with successful ageing. METHODS: Successful ageing was defined as the ability to live at home without daily care at the age of 84 years or over. Data on the participants' physical, psychological and social wellbeing were gathered at baseline and the follow-up period was 20 years. Four successful ageing models were constructed. Backward stepwise logistic regression analysis was used to identify the individual subcomponents of the models which best predicted successful ageing. RESULTS: All successful ageing models were able to predict ageing successfully after the 20-year follow-up period. After the backward stepwise logistic regression analysis, three individual subcomponents of four models remained statistically significant and were included in the new model: having no heart disease, having good self-rated health and feeling useful. As a model, using only these three subcomponents, the association with successful ageing was similar to using the full models. CONCLUSIONS: Multidimensional successful ageing models were able to predict successful ageing after a 20-year follow-up period. However, according to the backward stepwise logistic regression analysis, the three subcomponents (absence of heart disease, good self-rated health and feeling useful) significantly associated with successful ageing performed as well as the multidimensional successful ageing models in predicting ageing successfully.

Re-examination of successful agers with lower biological than chronological age still after a 20-year follow-up period.

BACKGROUND: Successful ageing is the term often used for depicting exceptional ageing but a uniform definition is lacking. The aim was to re-examine and describe the successful agers living at home at the age of 84 years or over after a 20-year follow-up. The purpose was also to identify possible factors leading to their successful ageing. METHODS: Successful ageing was defined as the ability to live at home without daily care. Data on the participants' functional ability, objective health, self-rated health and satisfaction with life were gathered at baseline and after a 20-year follow-up period. A measurement of personal biological age (PBA) was established and the difference between the PBA and the chronological age (CA) was counted. RESULTS: The participants' mean age was 87.6 years (Standard deviation 2.5, range 84-96). All analyzed variables depicted poorer physical ability and subjective health at re-examination than at baseline. Still, 99% of the participants were at least moderately satisfied with their lives. The PBA at baseline was 6.5 years younger than CA, and at re-examination, the difference was even more pronounced at 10.5 years. DISCUSSION: Even though the participants were chronologically older, had poorer physical ability and subjective health, they were still satisfied with their lives indicating possible psychological resilience. The difference between the PBA and CA was greater at re-examination than at baseline indicating that they were also biologically successful agers. CONCLUSIONS: Successful agers were satisfied with life despite hardships and had a lower biological than chronological age. Further research is needed to evaluate causality.

A novel easy-to-use index to predict institutionalization and death in older population - a 10-year population-based follow-up study.

BACKGROUND: Various indexes have been developed to estimate the risk for mortality, institutionalization, and other adverse outcomes for older people. Most indexes are based on a large number of clinical or laboratory parameters. An index based on only a few parameters would be more practical to use in every-day clinical practice. Our aim was to create an index to predict the risk for mortality and institutionalization with as few parameters as possible without compromising their predictive ability. METHODS: A prospective study with a 10-year follow-up period. Thirty-six clinical and fourteen laboratory parameters were combined to form an index. Cox regression model was used to analyze the association of the index with institutionalization and mortality. A backward statistical method was used to reduce the number of parameters to form an easy-to-use index for predicting institutionalization and mortality. RESULTS: The mean age of the participants (n = 1172) was 73.1 (SD 6.6, range 64‒97) years. Altogether, 149 (14%) subjects were institutionalized, and 413 (35%) subjects deceased during the follow-up. Institutionalization and mortality rates increased as index scores increased both for the large 50-parameter combined index and for the reduced indexes. After a backward variable selection in the Cox regression model, three clinical parameters remained in the index to predict institutionalization and six clinical and three laboratory parameters in the index to predict mortality. The reduced indexes showed a slightly better predictive value for both institutionalization and mortality compared to the full index. CONCLUSIONS: A large index with fifty parameters included many unimportant parameters that did not increase its predictive value, and therefore could be replaced with a reduced index with only a few carefully chosen parameters, that were individually associated with institutionalization or death.

Ceramides and Phosphatidylcholines Associate with Cardiovascular Diseases in the Elderly.

BACKGROUND: The ceramide- and phospholipid-based cardiovascular risk score (CERT2) has been found to predict the risk for cardiovascular disease (CVD) events, especially cardiovascular mortality. In the present study, our aim was to estimate the predictive ability of CERT2 for mortality of CVD, coronary artery disease (CAD), and stroke in the elderly and to compare these results with those of conventional lipids. METHODS: We conducted a prospective study with an 18-year follow-up period that included a total of 1260 participants ages ≥64 years. Ceramides and phosphatidylcholines were analyzed using a LC-MS. Total cholesterol and triglycerides were performed by enzymatic methods and HDL cholesterol was determined by a direct enzymatic method. Concentrations of LDL-cholesterol were calculated according to the Friedewald formula. RESULTS: A higher score of CERT2 was significantly associated with higher CVD, CAD, and stroke mortality during the 18-year follow-up both in unadjusted and adjusted Cox regression models. The unadjusted hazard ratios (HRs) of CERT2 (95% CI) per SD for CVD, CAD, and stroke were 1.72 (1.52-1.96), 1.76 (1.52-2.04), and 1.63 (1.27-2.10), respectively, and the corresponding adjusted HRs (95% CI) per SD for CERT2 were 1.48 (1.29-1.69), 1.50 (1.28-1.75), and 1.41 (1.09-1.83). For conventional lipids, HRs per SD were lower than for CERT2. CONCLUSIONS: The risk score CERT2 associated strongly with CVD, CAD, and stroke mortality in the elderly, while the association between these events and conventional lipids was weak.

Subjective and objective health predicting mortality and institutionalization: an 18-year population-based follow-up study among community-dwelling Finnish older adults.

BACKGROUND: Objective health measures, such as registered illnesses or frailty, predict mortality and institutionalization in older adults. Also, self-reported assessment of health by simple self-rated health (SRH) has been shown to predict mortality and institutionalization. The aim of this study was to assess the association of objective and subjective health with mortality and institutionalization in Finnish community-dwelling older adults. METHODS: In this prospective study with 10- and 18-year follow-ups, objective health was measured by registered illnesses and subjective health was evaluated by simple SRH, self-reported walking ability (400 m) and self-reported satisfaction in life. The participants were categorized into four groups according to their objective and subjective health: 1. subjectively and objectively healthy, 2. subjectively healthy and objectively unhealthy, 3. subjectively unhealthy and objectively healthy and 4. subjectively and objectively unhealthy. Cox regression model was used in the analyses. Death was used as a competing factor in the institutionalization analyses. RESULTS: The mean age of the participants (n = 1259) was 73.5 years (range 64.0-100.0). During the 10- and 18-year follow-ups, 466 (37%) and 877 (70%) died, respectively. In the institutionalization analyses (n = 1106), 162 (15%) and 328 (30%) participants were institutionalized during the 10- and 18-year follow-ups, respectively. In both follow-ups, being subjectively and objectively unhealthy, compared to being subjectively and objectively healthy, was significantly associated with a higher risk of institutionalization in unadjusted models and with death both in unadjusted and adjusted models. CONCLUSIONS: The categorization of objective and subjective health into four health groups was good at predicting the risk of death during 10- and 18-year follow-ups, and seemed to also predict the risk of institutionalization in the unadjusted models during both follow-ups. Poor subjective health had an additive effect on poor objective health in predicting mortality and could therefore be used as part of an older individual's health evaluation when screening for future adverse outcomes.

A practical laboratory index to predict institutionalization and mortality - an 18-year population-based follow-up study.

BACKGROUND: Previously, several indexes based on a large number of clinical and laboratory tests to predict mortality and frailty have been produced. However, there is still a need for an easily applicable screening tool for every-day clinical practice. METHODS: A prospective study with 10- and 18-year follow-ups. Fourteen common laboratory tests were combined to an index. Cox regression model was used to analyse the association of the laboratory index with institutionalization and mortality. RESULTS: The mean age of the participants (n = 1153) was 73.6 (SD 6.8, range 64.0-100.0) years. Altogether, 151 (14.8%) and 305 (29.9%) subjects were institutionalized and 422 (36.6%) and 806 (69.9%) subjects deceased during the 10- and 18-year follow-ups, respectively. Higher LI (laboratory index) scores predicted increased mortality. Mortality rates increased as LI scores increased both in unadjusted and in age- and gender-adjusted models during both follow-ups. The LI did not significantly predict institutionalization either during the 10- or 18-year follow-ups. CONCLUSIONS: A practical index based on routine laboratory tests can be used to predict mortality among older people. An LI could be automatically counted from routine laboratory results and thus an easily applicable screening instrument in clinical settings.

Frailty, walking ability and self-rated health in predicting institutionalization: an 18-year follow-up study among Finnish community-dwelling older people.

BACKGROUND: In clinical practice, there is a need for an instrument to screen older people at risk of institutionalization. AIMS: To analyze the association of frailty, walking-ability and self-rated health (SRH) with institutionalization in Finnish community-dwelling older people. METHODS: In this prospective study with 10- and 18-year follow-ups, frailty was assessed using FRAIL Scale (FS) (n = 1087), Frailty Index (FI) (n = 1061) and PRISMA-7 (n = 1055). Walking ability was assessed as self-reported ability to walk 400 m (n = 1101). SRH was assessed by a question of general SRH (n = 1105). Cox regression model was used to analyze the association of the explanatory variables with institutionalization. RESULTS: The mean age of the participants was 73.0 (range 64.0‒97.0) years. Prevalence of institutionalization was 40.8%. In unadjusted models, frailty was associated with a higher risk of institutionalization by FS in 10-year follow-up, and FI in both follow-ups. Associations by FI persisted after age- and gender-adjustments in both follow-ups. By PRISMA-7, frailty predicted a higher risk of institutionalization in both follow-ups. In unadjusted models, inability to walk 400 m predicted a higher risk of institutionalization in both follow-ups and after adjustments in 10-year follow-up. Poor SRH predicted a higher risk of institutionalization in unadjusted models in both follow-ups and after adjustments in 10-year follow-up. DISCUSSION: Simple self-reported items of walking ability and SRH seemed to be comparable with frailty indexes in predicting institutionalization among community-dwelling older people in 10-year follow-up. CONCLUSIONS: In clinical practice, self-reported walking ability and SRH could be used to screen those at risk.

Gender-specific change in leptin concentrations during long-term CPAP therapy.

PURPOSE: Nasal continuous positive airway pressure (CPAP) alleviates sleepiness in patients with obstructive sleep apnoea syndrome (OSAS), but part of OSAS patients keep gaining weight. Leptin and insulin-like growth factor-1 (IGF-1) interact with energy balance, and CPAP therapy has been suggested to influence these endocrine factors. We hypothesised that leptin would decrease during long-term CPAP therapy, and weight gain would associate with OSAS severity, lower CPAP adherence, lower IGF-1, and leptin concentrations. METHODS: Consecutive patients (n = 223) referred to sleep study with suspected OSAS were enrolled. Patients underwent cardiorespiratory polygraphy at baseline. Questionnaires were completed, and blood samples were drawn both at baseline and after 3 years. A total of 149 (67%; M 65, F 84) patients completed the follow-up. Plasma samples were available from 114 patients, 109 of which with CPAP adherence data (49 CPAP users, 60 non-users). RESULTS: At baseline, the CPAP users were more obese and had more severe OSAS than the non-users. Leptin concentrations did not differ. After follow-up, leptin concentrations were higher in CPAP users (30.2 ng/ml vs. 16.8 ng/ml; p = 0.001). In regression analysis, increase in leptin concentrations was independent of age, baseline body mass index (BMI), or the change in BMI. Leptin concentrations increased among females (- 8.9 vs. 12.7 ng/ml; p < 0.001); whereas in men, CPAP did not have an effect, if not opposed the natural decrease in leptin observed in men not using CPAP. Change in IGF-1 levels did not differ. CONCLUSIONS: Our results suggest increase in leptin concentrations during long-term CPAP therapy among females.

Frailty and mortality: an 18-year follow-up study among Finnish community-dwelling older people.

BACKGROUND: There is a lack of agreement about applicable instrument to screen frailty in clinical settings. AIMS: To analyze the association between frailty and mortality in Finnish community-dwelling older people. METHODS: This was a prospective study with 10- and 18-year follow-ups. Frailty was assessed using FRAIL scale (FS) (n = 1152), Rockwood's frailty index (FI) (n = 1126), and PRISMA-7 (n = 1124). To analyze the association between frailty and mortality, Cox regression model was used. RESULTS: Prevalence of frailty varied from 2 to 24% based on the index used. In unadjusted models, frailty was associated with higher mortality according to FS (hazard ratio 7.96 [95% confidence interval 5.10-12.41] in 10-year follow-up, and 6.32 [4.17-9.57] in 18-year follow-up) and FI (5.97 [4.13-8.64], and 3.95 [3.16-4.94], respectively) in both follow-ups. Also being pre-frail was associated with higher mortality according to both indexes in both follow-ups (FS 2.19 [1.78-2.69], and 1.69 [1.46-1.96]; FI 1.81[1.25-2.62], and 1.31 [1.07-1.61], respectively). Associations persisted even after adjustments. Also according to PRISMA-7, a binary index (robust or frail), frailty was associated with higher mortality in 10- (4.41 [3.55-5.34]) and 18-year follow-ups (3.78 [3.19-4.49]). DISCUSSION: Frailty was associated with higher mortality risk according to all three frailty screening instrument used. Simple and fast frailty indexes, FS and PRISMA-7, seemed to be comparable with a multidimensional time-consuming FI in predicting mortality among community-dwelling Finnish older people. CONCLUSIONS: FS and PRISMA-7 are applicable frailty screening instruments in clinical setting among community-dwelling Finnish older people.

Detection of Group A Streptococcus from Pharyngeal Swab Samples by Bacterial Culture Is Challenged by a Novel mariPOC Point-of-Care Test.

mariPOC is a novel point-of-care test system for rapid detection of respiratory tract infections. We compared the performance of the mariPOC test to that of bacterial culture for detecting group A streptococcus (GAS) in 219 pharyngitis patients (ages 1-64 years) and 109 healthy asymptomatic controls (ages 19-69 years). In addition, 42 patient samples were analyzed by quantitative PCR (qPCR). Of the 219 pharyngeal patient samples, 32 were positive in a GAS bacterial culture (prevalence 15%) and 65 (30%) in the mariPOC test. The amount of GAS in samples reported positive by the mariPOC test and negative by culture was, on average, 10-fold less than that of those positive in both methods. This indicated that the negative results in bacterial cultures were due to lower sensitivity. The qPCR results were positive and in line with the mariPOC results in 43% of the discordant samples studied. Two GAS culture-positive samples were negative by the mariPOC test. The prevalences of GAS in the control subjects were 2% and 6% by culture and mariPOC results, respectively. We conclude that the mariPOC antigen detection test is more sensitive than the conventional bacterial culture for the detection of GAS among symptomatic pharyngitis patients. The higher prevalence of GAS by the mariPOC test among symptomatic patients was probably not due to carriership, since among the control patients, the difference in the prevalence of GAS by the mariPOC test and culture was not nearly as high, 15% versus 4%, respectively. Clinical trials are needed to show the clinical importance of our findings.

New reference limits for cardiac troponin T and N-terminal b-type natriuretic propeptide in elders.

BACKGROUND AND AIMS: Our aim was to define reference limits for cardiac troponin T (cTnT) and N-terminal pro B-type natriuretic peptide (proBNP) that would better reflect their concentrations in older people. In addition, the incidence of acute myocardial infarctions (AMIs) was studied using these reference limits in an older population with and without previous heart diseases. MATERIALS AND METHODS: A population-based study with a ten-year follow-up. The reference population was formed by 763 individuals aged over 64 years, with no diagnoses of heart or kidney diseases. RESULTS: There was a significant increase in cTnT and proBNP concentrations with age. The 99 % reference limits for cTnT were 25 ng/L, 28 ng/l, 38 ng/l, and 71 ng/l for men in five-year-intervals starting from 64 to 69 years to 80 years and older, and 18 ng/L, 22 ng/l, 26 ng/l, and 52 ng/L for women, respectively. The 97.5 % reference limits for proBNP were 272 ng/L, 287 ng/l, 373 ng/l and 686 ng/L for men, and 341 ng/L, 377 ng/l, 471 ng/l, and 794 ng/L for women, respectively. Elevated proBNP was statistically significantly associated with future AMIs in subjects with and without a previous heart disease. CONCLUSIONS: Age-specific reference limits for cTnT and proBNP are needed to better evaluate cardiac symptoms.

Circulating oxidised LDL lipids, when proportioned to HDL-c, emerged as a risk factor of all-cause mortality in a population-based survival study.

BACKGROUND AND OBJECTIVE: the data concerning the predictive role of oxidised LDL (ox-LDL) in all-cause mortality are scarce. We investigated whether circulating ox-LDL would stand out as a risk factor of total mortality in the elderly. Study subjects, design and methods: a total of 1,260 elderly inhabitants (533 men, 727 women) aged 64 years or more from Lieto, South-Western Finland participated the study in 1998-99. Medical records were re-examined approximately a decade later in January 2009. Circulating ox-LDL lipids were used as the main outcome measure. The comparisons were obtained by the Cox hazard ratio model. RESULTS: during the 10-year follow-up, 467 participants had died (37%), of whom 36% had died of atherosclerotic cardiovascular diseases. Ox-LDL was a significant predictor of all-cause mortality, when proportioned to low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c) or apolipoprotein A1 (apoA1). These findings were independent of age, sex, body mass index, smoking, blood pressure and diabetes (P < 0.05 for all). CONCLUSION: circulating ox-LDL lipids, when proportioned to LDL-c, HDL-c or apoaA1, stand out as a risk factor for all-cause mortality independent of major confounding attributes. In the prospective survival and increasing disease burden caused by accumulating age, oxidative stress may have a considerable role.

Does high sensitive CRP improve cardiovascular risk prediction in metabolic syndrome among the aged?

OBJECTIVES: To analyze whether an elevated level of high hsCRP has an additive effect on metabolic syndrome (MetS) in predicting future cardiovascular events (CVEs) as well as on all-cause mortality among the aged subjects. DESIGN: A prospective, population-based study with a 9-year follow-up. The study population consisted of persons aged 64 and above in 1998-99 without vascular disease and CRP less than 10 mg/l at baseline (n = 733). Adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) for CVEs and all-cause mortality predicted by baseline MetS (defined by both International Diabetes Federation (IDF) and World Health Organization (WHO)) and hsCRP-level were estimated. RESULTS: During the 9-year follow-up, a total of 142 CVEs and 206 deaths occurred. After multivariable adjustment, no significant interactions were found between hsCRP and MetS in CVEs (IDF: p = 0.828; WHO: p = 0.572) or in all-cause mortality (IDF: p = 0.113; WHO: p = 0.374). HsCRP was not associated with the occurrence of CVEs (IDF: HR = 1.10, 95% CI = 0.92-1.32, p = 0.281; WHO: HR = 1.10, 95% CI = 0.93-1.32, p = 0.247) or with all-cause mortality (IDF: HR = 1.12, 95% CI = 0.97-1.29, p = 0.134; WHO: HR = 1.11, 95% CI = 0.96-1.28, p = 0.146). CONCLUSIONS: It seems that hsCRP does not give any extra value in evaluation of CVE risk or all-cause mortality of older subjects with MetS.

Endogenous testosterone and brachial artery endothelial function in middle-aged men with symptoms of late-onset hypogonadism.

In aging men, serum endogenous testosterone is inversely associated with common carotid intima-media thickness (IMT) and directly with beneficial plasma lipid levels; however, the relationship to endothelial function is poorly characterized. We examined the association between serum testosterone and endothelium-dependent brachial artery flow-mediated dilatation (FMD) in middle-aged to elderly men. A group of 83 men aged 40?69 years (mean 55.9 ± 7.5 [SD]) with andropausal symptoms were studied. We measured their serum lipids, testosterone, luteinizing hormone, mean carotid IMT and brachial artery FMD by high resolution B-mode ultrasound. Brachial FMD correlated inversely with vessel diameter (r = -0.38, p = 0.0004), alcohol consumption (r = -0.22, p = 0.047) and serum testosterone (r = -0.27, p = 0.01), but not with luteinizing hormone. In multivariate analysis, FMD was explained by testosterone (ß = -0.17, p = 0.0226), high density lipoprotein cholesterol (ß = 4.17, p = 0.0312) and vessel diameter (ß = -4.37, p < 0.0001) when adjusted for age, body mass index, triglycerides, blood pressure, carotid IMT, smoking, alcohol consumption, cardiovascular diseases and use of lipid lowering medication (HMG-CoA reductase inhibitors). In middle-aged to elderly men, there is an inverse correlation between serum testosterone and brachial FMD. These data suggest that testosterone may have an adverse effect on systemic endothelial function.

Chronic conditions and multimorbidity associated with institutionalization among Finnish community-dwelling older people: an 18-year population-based follow-up study.

PURPOSE: The ageing population is increasingly multimorbid. This challenges health care and elderly services as multimorbidity is associated with institutionalization. Especially dementia increases with age and is the main risk factor for institutionalization. The aim of this study was to assess the association of chronic conditions and multimorbidity with institutionalization in home-dwelling older people, with and without dementia. METHODS: In this prospective study with 18-year follow-up, the data on participants' chronic conditions were gathered at the baseline examination, and of conditions acquired during the follow-up period from the municipality's electronic patient record system and national registers. Only participants institutionalized or deceased by the end of the follow-up period were included in this study. Different cut-off-points for multimorbidity were analyzed. Cox regression model was used in the analyses. Death was used as a competing factor. RESULTS: The mean age of the participants (n = 820) was 74.7 years (64.0‒97.0). During the follow-up, 328 (40%) were institutionalized. Dementia, mood disorders, neurological disorders, and multimorbidity defined as five or more chronic conditions were associated with a higher risk of institutionalization in all the participants. In people without dementia, mood disorders and neurological disorders increased the risk of institutionalization. CONCLUSION: Having dementia, mood or neurological disorder and/or five or more chronic conditions were associated with a higher risk of institutionalization. These risk factors should be recognized when providing and targeting care and support for older people still living at home.

Blood cell and iron status analytes of preterm and full-term infants from 20 weeks onwards during the first year of life.

BACKGROUND: The goal of this study was to evaluate the dynamics of blood cell and iron status laboratory analytes in preterm and full-term infants during the first year of life. METHODS: This was a prospective study of 100 preterm and 50 full-term infants. Preterm infants received iron supplementation beginning at 3 weeks of age. Laboratory tests were serially analyzed up to 12 months of corrected age. RESULTS: Estimated means and the 95% reference intervals (RIs) from 20 weeks of age and onwards are presented separately for preterm and full-term infants. At the age of 20 weeks, mean hemoglobin (Hb) in preterm infants was lower than mean Hb in full-term infants, but this difference changed during follow-up. Ferritin concentrations were initially lower in preterm infants, but decreased to similar levels in both groups. Estimated mean values for transferrin receptor and reticulocyte Hb content were quite stable between the ages of 20 and 55 weeks in both groups. CONCLUSIONS: Our study suggests that the same RIs for preterm and full-term infants can be used from the age of 20 or 30 weeks onwards, depending on the analyte. The RIs will help physicians detect iron deficiency or other problems of erythropoiesis in infants.

24-hour serum levels of growth hormone, prolactin, and cortisol in pre- and postmenopausal women: the effect of combined estrogen and progestin treatment.

OBJECTIVE: Our objective was to study the 24-h profiles of GH, prolactin (PRL), and cortisol concentrations in older postmenopausal and middle-aged premenopausal women, before and after estrogen-progestin treatment (EPT). DESIGN: The study was a randomized, placebo-controlled, double-blind trial. GH, PRL, and cortisol were sampled every 20 min for 24 h in 18 postmenopausal (aged 58-70 yr) and 17 premenopausal (aged 45-51 yr) women before and after 6 months of EPT. RESULTS: The mean 24-h GH (1.0 vs. 1.8 mU/liter, P = 0.033) and PRL (6.8 vs. 10.0 ng/ml, P = 0.009) concentrations were lower in postmenopausal than in premenopausal women. After EPT, the postmenopausal GH and PRL did not differ from premenopausal baseline levels. Postmenopausal mean 24-h GH (P < 0.001) and PRL (P = 0.002), daytime GH (P < 0.001) and nighttime PRL (P = 0.004) were higher during EPT compared with placebo. Cortisol levels did not differ. Premenopausal mean nighttime PRL (P = 0.026) and cortisol (P = 0.018) were higher during EPT compared with placebo. Postmenopausal PRL and premenopausal GH and PRL concentrations were higher at night than during the day. EPT did not alter this pattern. CONCLUSIONS: Menopause was associated with decreased 24-h levels of GH and PRL, which were reversible with EPT. In contrast, cortisol levels were not affected by menopause or EPT. In middle-aged premenopausal women, the studied effects of EPT were limited to nighttime increases of PRL and cortisol.

Frequency and clinical relevance of drug interactions with lovastatin and simvastatin: an observational database study.

BACKGROUND: Concomitantly used cytochrome P450 (CYP) 3A4 inhibitors and inducers have been shown to alter the plasma concentrations of the HMG-CoA reductase inhibitors ('statins') lovastatin and simvastatin. Myopathy is a serious adverse effect of statins. Concurrent use of statins with fibrates in particular seems to increase the risk of this adverse effect. OBJECTIVE: To evaluate the incidence and clinical consequences of the use of lovastatin or simvastatin with concomitant CYP3A4 inhibitors and inducers, and with fibrates. METHODS: An observational database study of hospitalized patients treated in Turku University Hospital, Turku, Finland, covering the period 1 July 1996 to 30 June 2003, and of nationwide community data from the Finnish Prescription Register over the period 1 April to 30 June 2001 was conducted. In the hospital setting, the study population comprised 71 025 patients (93 467 treatment periods) over 7 years, with a total of 5320 treatment periods of lovastatin or simvastatin. The community-based, nationwide survey included all reimbursed prescriptions of lovastatin and simvastatin (n = 91 656) in Finland during a 3-month period. The frequency of drug-drug interactions involving lovastatin or simvastatin was studied. The efficacy and safety of the various statin/concomitant drug combinations was estimated by evaluating patients' laboratory data. RESULTS: Concomitant use of lovastatin or simvastatin with interacting medication was detected in 13.3% (704) and 6.9% (6338) of patients in hospital and community settings, respectively. Co-administration of lovastatin or simvastatin with CYP3A4 inhibitors or inducers did not have a clinically significant effect on serum lipid values. Plasma creatine kinase (CK) activity was significantly higher in patients receiving a statin and a fibrate compared with a statin only (433 U/L vs 209 U/L, p = 0.053). Co-administration of a statin and a CYP3A4 inhibitor did not increase CK activity. CONCLUSION: Although the pharmacokinetic interactions between lovastatin or simvastatin and CYP3A4 inhibitors and inducers are substantial, their clinical relevance seems to be limited, at least with lower statin doses. However, combining statins with fibrates, especially gemfibrozil, clearly increases the potential for muscular toxicity.

Long-term follow-up of renal function after high-dose methotrexate treatment in children.

BACKGROUND: High-dose methotrexate (HD-MTX) is commonly used in treatment of pediatric leukemias and lymphomas. Transient deterioration in renal function is frequently noted during HD-MTX treatment, but possible long-term changes are less well known. In this study we aimed to study long-term renal prognosis after HD-MTX treatment, and to find possible underlying risk factors for reduced renal function. PROCEDURE: Medical records of pediatric cancer patients treated with HD-MTX were reviewed retrospectively after follow-up of 1-10 years. Renal function before and after chemotherapy was investigated in a total of 28 patients. Assessment of glomerular and tubular function was prospectively evaluated in each case. Glomerular function was evaluated by either (51)Cr-EDTA or (99m)Tc-DTPA clearance methods, and by urinary albumin excretion. Tubular function was assessed by measuring blood electrolyte levels and urinary alpha(1)- or beta(2)-microglobulin. RESULTS: A decrease in glomerular filtration rate (GFR) was statistically significant as follow-up time increased (P = 0.02). Age at the time of diagnosis and exposure to potentially nephrotoxic antibiotics during cancer treatment had no influence on GFR. However, albuminuria was observed more often in patients treated with amphotericin B or gentamycin (P = 0.04). No changes in tubular function were observed. CONCLUSIONS: Our results show that HD-MTX treatment significantly decreases GFR and may cause albuminuria in pediatric cancer patients several years after treatment. Long-term renal follow-up of these patients is therefore important.

Increased carotid atherosclerosis in andropausal middle-aged men.

OBJECTIVES: This study examined the association between carotid artery intima-media thickness (IMT), serum sex hormone levels, and andropausal symptoms in middle-aged men. BACKGROUND: Male sex hormones may play a dual role in the pathogenesis of atherosclerosis in men by carrying both proatherogenic and atheroprotective effects. METHODS: We studied 239 40- to 70-year-old men (mean +/- SD: 57 +/- 8 years) who participated in the Turku Aging Male Study and underwent serum lipid and sex hormone measurements. Ninety-nine men (age 58 +/- 7 years) were considered andropausal (i.e., serum testosterone <9.8 nmol/l or luteinizing hormone [LH] >6.0 U/l and testosterone in the normal range), and in both situations, they had subjective symptoms of andropause (a high symptom score in questionnaire). Three were excluded because of diabetes. The rest of the men (age 57 +/- 8 years) served as controls. Carotid IMT was determined using high-resolution B-mode ultrasound, and serum testosterone, estradiol (E2), LH, and sex hormone-binding globulin were measured using standard immunoassays. RESULTS: Andropausal men had a higher maximal IMT compared with controls in the common carotid (1.08 +/- 0.34 vs. 1.00 +/- 0.23, p < 0.05) and in the carotid bulb (1.44 +/- 0.48 vs. 1.27 +/- 0.35, p = 0.003). Common carotid IMT correlated inversely with serum testosterone (p = 0.003) and directly with LH (p = 0.006) in multivariate models adjusted for age, total cholesterol, body mass index, blood pressure, and smoking. CONCLUSIONS: Middle-aged men with symptoms of andropause, together with absolute or compensated (as reflected by high normal to elevated LH) testosterone deficiency, show increased carotid IMT. These data suggest that normal testosterone levels may offer protection against the development of atherosclerosis in middle-aged men.