The aim of this study was to determine reference intervals in an outpatient population from Vall d'Hebron laboratory using an indirect approach previously described in a Dutch population (NUMBER ...project). We used anonymized test results from individuals visiting general practitioners and analysed during 2018. Analytical quality was assured by EQA performance, daily average monitoring and by assessing longitudinal accuracy between 2018 and 2020 (using trueness verifiers from Dutch EQA). Per test, outliers by biochemically related tests were excluded, data were transformed to a normal distribution (if necessary) and means and standard deviations were calculated, stratified by age and sex. In addition, the reference limit estimator method was also used to calculate reference intervals using the same dataset. Finally, for standardized tests reference intervals obtained were compared with the published NUMBER results. Reference intervals were calculated using data from 509,408 clinical requests. For biochemical tests following a normal distribution, similar reference intervals were found between Vall d'Hebron and the Dutch study. For creatinine and urea, reference intervals increased with age in both populations. The upper limits of Gamma-glutamyl transferase were markedly higher in the Dutch study compared to Vall d'Hebron results. Creatine kinase and uric acid reference intervals were higher in both populations compared to conventional reference intervals. Medical test results following a normal distribution showed comparable and consistent reference intervals between studies. Therefore a simple indirect method is a feasible and cost-efficient approach for calculating reference intervals. Yet, for generating standardized calculated reference intervals that are traceable to higher order materials and methods, efforts should also focus on test standardization and bias assessment using commutable trueness verifiers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
CONTEXT Data regarding the association between subclinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospective cohort studies. This might reflect differences in ...participants' age, sex, thyroid-stimulating hormone (TSH) levels, or preexisting cardiovascular disease. OBJECTIVE To assess the risks of coronary heart disease (CHD) and total mortality for adults with subclinical hypothyroidism. DATA SOURCES AND STUDY SELECTION The databases of MEDLINE and EMBASE (1950 to May 31, 2010) were searched without language restrictions for prospective cohort studies with baseline thyroid function and subsequent CHD events, CHD mortality, and total mortality. The reference lists of retrieved articles also were searched. DATA EXTRACTION Individual data on 55 287 participants with 542 494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospective cohorts in the United States, Europe, Australia, Brazil, and Japan. The risk of CHD events was examined in 25 977 participants from 7 cohorts with available data. Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Subclinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations. RESULTS Among 55 287 adults, 3450 had subclinical hypothyroidism (6.2%) and 51 837 had euthyroidism. During follow-up, 9664 participants died (2168 of CHD), and 4470 participants had CHD events (among 7 studies). The risk of CHD events and CHD mortality increased with higher TSH concentrations. In age- and sex-adjusted analyses, the hazard ratio (HR) for CHD events was 1.00 (95% confidence interval CI, 0.86-1.18) for a TSH level of 4.5 to 6.9 mIU/L (20.3 vs 20.3/1000 person-years for participants with euthyroidism), 1.17 (95% CI, 0.96-1.43) for a TSH level of 7.0 to 9.9 mIU/L (23.8/1000 person-years), and 1.89 (95% CI, 1.28-2.80) for a TSH level of 10 to 19.9 mIU/L (n = 70 events/235; 38.4/1000 person-years; P <.001 for trend). The corresponding HRs for CHD mortality were 1.09 (95% CI, 0.91-1.30; 5.3 vs 4.9/1000 person-years for participants with euthyroidism), 1.42 (95% CI, 1.03-1.95; 6.9/1000 person-years), and 1.58 (95% CI, 1.10-2.27, n = 28 deaths/333; 7.7/1000 person-years; P = .005 for trend). Total mortality was not increased among participants with subclinical hypothyroidism. Results were similar after further adjustment for traditional cardiovascular risk factors. Risks did not significantly differ by age, sex, or preexisting cardiovascular disease. CONCLUSIONS Subclinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels, particularly in those with a TSH concentration of 10 mIU/L or greater.
Objectives
To examine the Framingham Stroke Risk Profile (FSRP); the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) risk score, and oxi‐inflammatory load (cumulative risk score ...of three blood biomarkers—homocysteine, interleukin‐6, C‐reactive protein) for associations with cognitive decline using three cohort studies of very old adults and to examine whether incorporating these biomarkers with the risk scores can affect the association with cognitive decline.
Design
Three longitudinal, population‐based cohort studies.
Setting
Newcastle‐upon‐Tyne, United Kingdom; Leiden, the Netherlands; and Lakes and Bay of Plenty District Health Board areas, New Zealand.
Participants
Newcastle 85+ Study participants (n = 616), Leiden 85‐plus Study participants (n = 444), and Life and Living in Advanced Age, a Cohort Study in New Zealand (LiLACS NZ Study) participants (n = 396).
Measurements
FSRP, CAIDE risk score, oxi‐inflammatory load, FSRP incorporating oxi‐inflammatory load, and CAIDE risk score incorporating oxi‐inflammatory load. Oxi‐inflammatory load could be calculated only in the Newcastle 85+ and the Leiden 85‐plus studies. Measures of global cognitive function were available for all three data sets. Domain‐specific measures were available for the Newcastle 85+ and the Leiden 85‐plus studies.
Results
Meta‐analysis of pooled results showed greater risk of incident global cognitive impairment with higher FSRP (hazard ratio (HR) = 1.46, 95% confidence interval (CI) = 1.08–1.98), CAIDE (HR = 1.53, 95% CI = 1.09–2.14), and oxi‐inflammatory load (HR = 1.73, 95% CI = 1.04–2.88) scores. Adding oxi‐inflammatory load to the risk scores increased the risk of cognitive impairment for the FSRP (HR = 1.65, 95% CI = 1.17–2.33) and the CAIDE model (HR = 1.93, 95% CI = 1.39–2.67).
Conclusion
Adding oxi‐inflammatory load to cardiovascular risk scores may be useful for determining risk of cognitive impairment in very old adults.
American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but ...without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between subclinical thyroid dysfunction and heart failure events.
We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and subclinical hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had subclinical hypothyroidism and 648 (2.6%) had subclinical hyperthyroidism. In age- and sex-adjusted analyses, risks of heart failure events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01); the hazard ratio was 1.01 (95% confidence interval, 0.81-1.26) for TSH of 4.5 to 6.9 mIU/L, 1.65 (95% confidence interval, 0.84-3.23) for TSH of 7.0 to 9.9 mIU/L, 1.86 (95% confidence interval, 1.27-2.72) for TSH of 10.0 to 19.9 mIU/L (P for trend <0.01) and 1.31 (95% confidence interval, 0.88-1.95) for TSH of 0.10 to 0.44 mIU/L and 1.94 (95% confidence interval, 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors.
Risks of heart failure events were increased with both higher and lower TSH levels, particularly for TSH ≥10 and <0.10 mIU/L.
IMPORTANCE: It is unclear whether levothyroxine treatment provides clinically important benefits in adults aged 80 years and older with subclinical hypothyroidism. OBJECTIVE: To determine the ...association of levothyroxine treatment for subclinical hypothyroidism with thyroid-related quality of life in adults aged 80 years and older. DESIGN, SETTING, AND PARTICIPANTS: Prospectively planned combined analysis of data involving community-dwelling adults aged 80 years and older with subclinical hypothyroidism. Data from a randomized clinical trial were combined with a subgroup of participants aged 80 years and older from a second clinical trial. The trials were conducted between April 2013 and May 2018. Final follow-up was May 4, 2018. EXPOSURES: Participants were randomly assigned to receive levothyroxine (n = 112; 52 participants from the first trial and 60 from the second trial) or placebo (n = 139; 53 participants from the first trial and 86 from the second trial). MAIN OUTCOMES AND MEASURES: Co-primary outcomes were Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire scores for the domains of hypothyroid symptoms and tiredness at 1 year (range, 0-100; higher scores indicate worse quality of life; minimal clinically important difference, 9). RESULTS: Of 251 participants (mean age, 85 years; 118 47% women), 105 were included from the first clinical trial and 146 were included from the second clinical trial. A total of 212 participants (84%) completed the study. The hypothyroid symptoms score decreased from 21.7 at baseline to 19.3 at 12 months in the levothyroxine group vs from 19.8 at baseline to 17.4 at 12 months in the placebo group (adjusted between-group difference, 1.3 95% CI, −2.7 to 5.2; P = .53). The tiredness score increased from 25.5 at baseline to 28.2 at 12 months in the levothyroxine group vs from 25.1 at baseline to 28.7 at 12 months in the placebo group (adjusted between-group difference, −0.1 95% CI, −4.5 to 4.3; P = .96). At least 1 adverse event occurred in 33 participants (29.5%) in the levothyroxine group (the most common adverse event was cerebrovascular accident, which occurred in 3 participants 2.2%) and 40 participants (28.8%) in the placebo group (the most common adverse event was pneumonia, which occurred in 4 3.6% participants). CONCLUSIONS AND RELEVANCE: In this prospectively planned analysis of data from 2 clinical trials involving adults aged 80 years and older with subclinical hypothyroidism, treatment with levothyroxine, compared with placebo, was not significantly associated with improvement in hypothyroid symptoms or fatigue. These findings do not support routine use of levothyroxine for treatment of subclinical hypothyroidism in adults aged 80 years and older. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01660126; Netherlands Trial Register: NTR3851
Background
The broad concept of health as “the ability to adapt and self‐manage in the face of social, physical and emotional challenges” has been operationalized by “Positive Health,” a framework ...increasingly used in the Netherlands. We explored to what degree the impact of the COVID‐19 pandemic and preventive measures on Positive Health differed between community‐dwelling older adults without, with mild and with complex health problems, as well as differences flowing from their use of preventive measures.
Methods
During the second wave in the Netherlands (November 2020–February 2021), a convenience sample of adults aged ≥65 years completed an online questionnaire. Positive Health impact was measured based on self‐reported change of current health status, across six dimensions, compared to before the pandemic (decreased/unchanged/increased). The complexity of health problems (past month) was assessed using the validated ISCOPE tool, comparing subgroups without, with mild or with complex health problems. High use of preventive measures was defined as ≥9 of 13 measures and compared to low use (<9 measures).
Results
Of the 2397 participants (median age 71 years, 60% female, and 4% previous COVID‐19 infection), 31% experienced no health problems, 55% mild health problems, and 15% complex health problems. Overall, participants reported a median decrease in one Positive Health dimension (IQR 1–3), most commonly in social participation (68%). With an increasing complexity of health problems, subjective Positive Health declined more often across all six dimensions, ranging from 3.3% to 57% in those without, from 22% to 72% in those with mild, and from 47% to 75% in those with complex health problems (p‐values for trend <0.001; independent of age and sex). High users of preventive measures more often experienced declined social participation (72% vs. 62%, p < 0.001) and a declined quality of life (36% vs. 30%, p = 0.007) than low users, especially those with complex health problems.
Conclusion
As the complexity of health problems increased, the adverse impact of the COVID‐19 pandemic and related preventive measures was experienced more frequently across all dimensions of Positive Health. Acknowledging this heterogeneity is pivotal to the effective targeting of prevention and healthcare to those most in need.
Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk ...of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF.
We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF.
Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4;
for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease.
In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.
Abstract Purpose Hypertension trials often exclude patients with complex health problems and lack generalizability. We aimed to determine if systolic blood pressure (SBP) in patients undergoing ...antihypertensive treatment is associated with 1-year changes in cognitive/daily functioning or quality of life (QoL) in persons aged ≥75 years with or without complex health problems. Methods We analyzed data from a population-based prospective cohort study (Integrated Systematic Care for Older Persons ISCOPE) with a 1-year follow-up. Stratified by SBP level in the year before baseline, we used mixed-effects linear regression models to evaluate the change from baseline to 1-year follow-up in outcome measures (Mini-Mental State Examination MMSE, Groningen Activity Restriction Scale GARS, and EQ-5D-3L). We adjusted for age, sex, and baseline MMSE/GARS/EQ-5D-3L scores and stratified for complex health problems as a proxy for frailty. Results Participant (n = 1,266) age averaged 82.4 (SD 5) years, and 874 (69%) were women. For participants undergoing antihypertensive therapy (1,057; 83.5%) and with SBP <130 mm Hg, crude cognitive decline was 0.90 points MMSE, whereas in those with SBP >150 mm Hg, it was 0.14 points MMSE (ie, 0.76-point less decline; P for trend = .013). Complex health problems modified the association of SBP with cognition; the association was seen in those with antihypertensive treatment ( P for trend <.001), not in those without ( P for trend = .13). Daily functioning/QoL did not differ across the strata of SBP or antihypertensive treatment. Conclusions Participants aged ≥75 years undergoing antihypertensive treatment, with SBP ≥130 mm Hg compared to <130 mm Hg, showed less cognitive decline after 1 year, without loss of daily functioning or QoL. This effect was strongest in participants with complex health problems. More studies should be conducted to determine if there is a causal relation and to understand the mechanism of the association observed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Urinary tract infections (UTI) are common among the oldest old and may lead to a few days of illness, delirium or even to death. We studied the incidence and predictive factors of UTI among the ...oldest old in the general population.
The Leiden 85-plus Study is a population-based prospective follow-up study of 86-year-old subjects in Leiden, The Netherlands. Information on the diagnosis of UTI was obtained annually during four years of follow-up from the medical records and interviews of treating physicians. A total of 157 men and 322 women aged 86 years participated in the study. Possible predictive factors were collected at baseline, including history of UTI between the age of 85 and 86 years, aspects of functioning (cognitive impairment (Mini-Mental State Examination (MMSE) < 19), presence of depressive symptoms (Geriatric Depression Scale (GDS) > 4), disability in activities of daily living (ADL)), and co-morbidities.
The incidence of UTI from age 86 through 90 years was 11.2 (95% confidence interval (CI) 9.4, 13.1) per 100 person-years at risk. Multivariate analysis showed that history of UTI between the age of 85 and 86 years (hazard ratio (HR) 3.4 (95% CI 2.4, 5.0)), impaired cognitive function (HR 1.9 (95% CI 1.3, 2.9)), disability in daily living (HR 1.7 (95% CI 1.1, 2.5)) and urine incontinence (HR 1.5 (95% CI 1.0, 2.1)) were independent predictors of an increased incidence of UTI from age 86 onwards.
Within the oldest old, a history of UTI between the age of 85 and 86 years, cognitive impairment, ADL disability and urine incontinence are independent predictors of developing UTI. These predictive factors could be used to target preventive measures to the oldest old at high risk of UTI.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Context:
Subclinical hypothyroidism has been associated with increased risk of coronary heart disease (CHD), particularly with thyrotropin levels of 10.0 mIU/L or greater. The measurement of thyroid ...antibodies helps predict the progression to overt hypothyroidism, but it is unclear whether thyroid autoimmunity independently affects CHD risk.
Objective:
The objective of the study was to compare the CHD risk of subclinical hypothyroidism with and without thyroid peroxidase antibodies (TPOAbs).
Data Sources and Study Selection:
A MEDLINE and EMBASE search from 1950 to 2011 was conducted for prospective cohorts, reporting baseline thyroid function, antibodies, and CHD outcomes.
Data Extraction:
Individual data of 38 274 participants from six cohorts for CHD mortality followed up for 460 333 person-years and 33 394 participants from four cohorts for CHD events.
Data Synthesis:
Among 38 274 adults (median age 55 y, 63% women), 1691 (4.4%) had subclinical hypothyroidism, of whom 775 (45.8%) had positive TPOAbs. During follow-up, 1436 participants died of CHD and 3285 had CHD events. Compared with euthyroid individuals, age- and gender-adjusted risks of CHD mortality in subclinical hypothyroidism were similar among individuals with and without TPOAbs hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.87–1.53 vs HR 1.26, CI 1.01–1.58, P for interaction = .62, as were risks of CHD events (HR 1.16, CI 0.87–1.56 vs HR 1.26, CI 1.02–1.56, P for interaction = .65). Risks of CHD mortality and events increased with higher thyrotropin, but within each stratum, risks did not differ by TPOAb status.
Conclusions:
CHD risk associated with subclinical hypothyroidism did not differ by TPOAb status, suggesting that biomarkers of thyroid autoimmunity do not add independent prognostic information for CHD outcomes.
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