Marieke D. Spreeuwenberg

Predicting ADL disability in community-dwelling elderly people using physical frailty indicators: a systematic review

BackgroundDisability in Activities of Daily Living (ADL) is an adverse outcome of frailty that places a burden on frail elderly people, care providers and the care system. Knowing which physical frailty indicators predict ADL disability is useful in identifying elderly people who might benefit from an intervention that prevents disability or increases functioning in daily life. The objective of this study was to systematically review the literature on the predictive value of physical frailty indicators on ADL disability in community-dwelling elderly people.MethodsA systematic search was performed in 3 databases (PubMed, CINAHL, EMBASE) from January 1975 until April 2010. Prospective, longitudinal studies that assessed the predictive value of individual physical frailty indicators on ADL disability in community-dwelling elderly people aged 65 years and older were eligible for inclusion. Articles were reviewed by two independent reviewers who also assessed the quality of the included studies.ResultsAfter initial screening of 3081 titles, 360 abstracts were scrutinized, leaving 64 full text articles for final review. Eventually, 28 studies were included in the review. The methodological quality of these studies was rated by both reviewers on a scale from 0 to 27. All included studies were of high quality with a mean quality score of 22.5 (SD 1.6). Findings indicated that individual physical frailty indicators, such as weight loss, gait speed, grip strength, physical activity, balance, and lower extremity function are predictors of future ADL disability in community-dwelling elderly people.ConclusionsThis review shows that physical frailty indicators can predict ADL disability in community-dwelling elderly people. Slow gait speed and low physical activity/exercise seem to be the most powerful predictors followed by weight loss, lower extremity function, balance, muscle strength, and other indicators. These findings should be interpreted with caution because the data of the different studies could not be pooled due to large variations in operationalization of the indicators and ADL disability across the included studies. Nevertheless, our study suggests that monitoring physical frailty indicators in community-dwelling elderly people might be useful to identify elderly people who could benefit from disability prevention programs.

The Multiple Propensity Score as Control for Bias in the Comparison of More Than Two Treatment Arms An Introduction From a Case Study in Mental Health

Background and Objective:The propensity score method (PS) has proven to be an effective tool to reduce bias in nonrandomized studies, especially when the number of (potential) confounders is large and dimensionality problems arise. The PS method introduced by Rosenbaum and Rubin is described in detail for studies with 2 treatment options. Since in clinical practice we are often interested in the comparison of multiple interventions, there was a need to extend the PS method to multiple treatments. It has been shown that in theory a multiple PS method is possible. So far, its practical application is rare and a practical introduction lacking. Methods:A practical guideline to illustrate the use of the multiple PS method is provided with data from a mental health study. The multiple PS is estimated with a multinomial logistic regression analysis. The multiple PS is the probability of assignment to each treatment category. Subsequently, to estimate the treatment effects while controlling for initial differences, the multiple PSs, calculated for each treatment category, are included as extra predictors in the regression analysis. Results:With the multiple PS method, balance was achieved in all relevant pretreatment variables. The corrected estimated treatment effects were somewhat different from the results without control for initial differences. Conclusions:Our results indicate that the multiple PS method is a feasible method to adjust for observed pretreatment differences in nonrandomized studies where the number of pretreatment differences is large and multiple treatments are compared.

Exercise testing to estimate survival in pulmonary hypertension.

BACKGROUND : The 6-min walk distance (6MWD) predicts survival in pulmonary hypertension (PH). The peak oxygen consumption (V O2peak) measured during a cardiopulmonary exercise test (CPET) also relates to survival in PH, and it is unknown how the prognostic information from measurements of ventilatory responses and gas exchange during CPET compares to the prognostic information obtained by the 6MWD alone. The aims of our study were to compare prognostic values of different exercise parameters in PH and to assess whether CPET adds prognostic value to the information from the 6MWD. METHODS : After baseline right-heart catheterization and exercise testing, survival was assessed in a cohort of 115 PH patients. RESULTS : During the 4 yr of follow-up, 18 patients died. At baseline, pulmonary arterial pressure was 49 +/- 17 mm Hg, the slope relating minute ventilation to carbon dioxide output (V E/V CO2slope) = 45 +/- 11, V O2peak = 15 +/- 6 mL.kg.min, increase in O2 pulse from rest to peak exercise (DeltaO2 pulse) = 5 +/- 2 mL.beat, and 6MWD = 445 +/- 128 m. For the prediction of mortality, the areas under the receiver operating curves were very similar for the different parameters and ranged from 0.69 to 0.74. Patients with a V E/V CO2slope < 48, V O2peak > 13.2 mL.kg.min, DeltaO2 pulse > 3.3 mL.beat, or a 6MWD > 399 m had a higher cumulative survival (P < 0.05). Multivariable Cox regression with a forward selection procedure showed that only DeltaO2 pulse improved the univariate 6MWD prediction model significantly (P < 0.05). CONCLUSION : CPET parameters predict survival in PH patients and add marginally to the prognostic value of the 6MWD.

Oral Nutritional Supplements Containing (n-3) Polyunsaturated Fatty Acids Affect the Nutritional Status of Patients with Stage III Non-Small Cell Lung Cancer during Multimodality Treatment

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), (n-3) fatty acids from fish oil, have immune-modulating effects and may improve nutritional status in cancer. The objective of this study was to investigate the effects of an oral nutritional supplement containing (n-3) fatty acids on nutritional status and inflammatory markers in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment. In a double-blind experiment, 40 patients with stage III NSCLC were randomly assigned to receive 2 cans/d of a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids (2.0 g EPA + 0.9 g DHA/d) or an isocaloric control supplement. EPA in plasma phospholipids, energy intake, resting energy expenditure (REE), body weight, fat free mass (FFM), mid-upper arm circumference (MUAC), and inflammatory markers were assessed. Effects of intervention were analyzed by generalized estimating equations and expressed as regression coefficients (B). The intervention group (I) had a better weight maintenance than the control (C) group after 2 and 4 wk (B = 1.3 and 1.7 kg, respectively; P < 0.05), a better FFM maintenance after 3 and 5 wk (B = 1.5 and 1.9 kg, respectively; P < 0.05), a reduced REE (B = -16.7% of predicted; P = 0.01) after 3 wk, and a trend for a greater MUAC (B = 9.1; P = 0.06) and lower interleukin-6 production (B = -27.9; P = 0.08) after 5 wk. After 4 wk, the I group had a higher energy and protein intake than the C group (B = 2456 kJ/24 h, P = 0.03 and B = 25.0 g, P = 0.01, respectively). In conclusion, a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids beneficially affects nutritional status during multimodality treatment in patients with NSCLC.

Growth during infancy and early childhood in relation to blood pressure and body fat measures at age 8–18 years of IVF children and spontaneously conceived controls born to subfertile parents

BACKGROUND Little is known about post-natal growth in IVF offspring and the effects of rates of early post-natal growth on blood pressure and body fat composition during childhood and adolescence. METHODS The follow-up study comprised 233 IVF children aged 8-18 years and 233 spontaneously conceived controls born to subfertile parents. Growth data from birth to 4 years of age, available for 392 children (n = 193 IVF, n = 199 control), were used to study early post-natal growth. Furthermore, early post-natal growth velocity (weight gain) was related to blood pressure and skinfold measurements at follow-up. RESULTS We found significantly lower weight, height and BMI standard deviation scores (SDSs) at 3 months, and weight SDS at 6 months of age in IVF children compared with controls. Likewise, IVF children demonstrated a greater gain in weight SDS (P < 0.001), height SDS (P = 0.013) and BMI SDS (P = 0.029) during late infancy (3 months to 1 year) versus controls. Weight gain during early childhood (1-3 years) was related to blood pressure in IVF children (P = 0.014 systolic, 0.04 diastolic) but not in controls. Growth during late infancy was not related to skinfold thickness in IVF children, unlike controls (P = 0.002 peripheral sum, 0.003 total sum). Growth during early childhood was related to skinfold thickness in both IVF and controls (P = 0.005 and 0.01 peripheral sum and P = 0.003 and 0.005 total sum, respectively). CONCLUSIONS Late infancy growth velocity of IVF children was significantly higher compared with controls. Nevertheless, early childhood growth instead of infancy growth seemed to predict cardiovascular risk factors in IVF children. Further research is needed to confirm these findings and to follow-up growth and development of IVF children into adulthood.

Oral nutritional supplements containing n-3 polyunsaturated fatty acids affect quality of life and functional status in lung cancer patients during multimodality treatment: an RCT

Background/Objectives:Our objective was to investigate effects of an oral nutritional supplement containing n-3 polyunsaturated fatty acids (FAs) on quality of life, performance status, handgrip strength and physical activity in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment.Subjects/Methods:In a double-blind experiment, 40 patients with stage III NSCLC were randomised to receive 2 cans/day of a protein- and energy-dense oral nutritional supplement containing n-3 polyunsaturated FAs (2.02 g eicosapentaenoic acid+0.92 g docosahexaenoic acid/day) or an isocaloric control supplement, during multimodality treatment. Quality of life, Karnofsky Performance Status, handgrip strength and physical activity (by wearing an accelerometer) were assessed. Effects of intervention were analysed by generalised estimating equations. P-values <0.05 were regarded as statistically significant.Results:The intervention group reported significantly higher on the quality of life parameters, physical and cognitive function (B=11.6 and B=20.7, P<0.01), global health status (B=12.2, P=0.04) and social function (B=22.1, P=0.04) than the control group after 5 weeks. The intervention group showed a higher Karnofsky Performance Status (B=5.3, P=0.04) than the control group after 3 weeks. Handgrip strength did not significantly differ between groups over time. The intervention group tended to have a higher physical activity than the control group after 3 and 5 weeks (B=6.6, P=0.04 and B=2.5, P=0.05).Conclusion:n-3 Polyunsaturated FAs may beneficially affect quality of life, performance status and physical activity in patients with NSCLC undergoing multimodality treatment.

Late Gadolinium-Enhanced Cardiovascular Magnetic Resonance Evaluation of Infarct Size and Microvascular Obstruction in Optimally Treated Patients after Acute Myocardial Infarction

PURPOSE Cardiovascular magnetic resonance (CMR) is considered the standard imaging modality in clinical trials to monitor patients after acute myocardial infarction (AMI). However, limited data is available with respect to infarct size, presence, and extent of microvascular injury (MVO), and changes over time, in relation to cardiac function in these optimally treated patients. In this study, we prospectively investigate the change of infarct size over time, and the incidence and significance of MVO in a uniform, optimally treated patient group after AMI. METHODS Forty patients underwent cine and late gadolinium-enhanced CMR within 9 days and at 4 months after primary stenting. Left ventricular ejection fraction (LVEF), infarct size (IS) and MVO size were calculated. RESULTS IS decreased with 19.0% at follow-up (p<0.01). The 23 (57.5%) patients with MVO had larger infarct size, higher left ventricular volumes and lower LVEF and more involution of IS at follow-up. Overall, LVEF improved from 42.3+/-9.8% to 44.0+/-9.8% (p=0.06), irrespective of presence or size of MVO. CONCLUSION Infarct size reduces over time by 19.0% in optimally treated patients after AMI. Despite optimal reperfusion, MVO was found in the majority of patients. Although patients with MVO had larger infarcts and worse indices of left ventricular remodelling, functional change at follow-up was comparable to patients without MVO.

Renal injury in children with a solitary functioning kidney—the KIMONO study

BACKGROUND Children with a solitary functioning kidney (SFK) have an increased risk of developing hypertension, albuminuria and chronic kidney disease in later life. This renal injury is hypothesized to be caused by glomerular hyperfiltration that follows renal mass reduction in animal studies. Furthermore, children with an SFK show a high incidence of congenital anomalies of the kidney and urinary tract (CAKUT), which could further compromise renal function. METHODS A retrospective study of renal injury markers was performed in 206 children, divided into groups based on the origin of SFK [primary (congenital) SFK (n = 116) and secondary SFK (n = 90)]. Data on ipsilateral CAKUT were stratified separately. For blood pressure, albuminuria and glomerular filtration rate, longitudinal models were additionally developed using generalized estimated equation analysis. RESULTS Renal injury, defined as the presence of hypertension and/or albuminuria and/or the use of renoprotective medication, was present in 32% of all children with an SFK at a mean age of 9.5 (SD 5.6) years. Children with ipsilateral CAKUT had higher proportions of renal injury (48.3 versus 24.6%, P < 0.05). Furthermore, longitudinal models showed a decrease in glomerular filtration rate in both groups from the beginning of puberty onwards. CONCLUSIONS This large cohort study demonstrates that renal injury is present in children with an SFK at a young age, whereas our longitudinal models show an increased risk for chronic kidney disease in adulthood. Renal injury is even more pronounced in the presence of ipsilateral CAKUT. Therefore, we underline that clinical follow-up of all children with an SFK is needed.

A systematic analysis of the feasibility of four‐dimensional ultrasound imaging using spatiotemporal image correlation in routine fetal echocardiography

To investigate the feasibility of incorporating spatiotemporal image correlation (STIC) into a tertiary fetal echocardiography program.

An overview of L‐2‐hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype–phenotype study

L‐2‐Hydroxyglutaric aciduria (L2HGA) is a rare, neurometabolic disorder with an autosomal recessive mode of inheritance. Affected individuals only have neurological manifestations, including psychomotor retardation, cerebellar ataxia, and more variably macrocephaly, or epilepsy. The diagnosis of L2HGA can be made based on magnetic resonance imaging (MRI), biochemical analysis, and mutational analysis of L2HGDH. About 200 patients with elevated concentrations of 2‐hydroxyglutarate (2HG) in the urine were referred for chiral determination of 2HG and L2HGDH mutational analysis. All patients with increased L2HG (n=106; 83 families) were included. Clinical information on 61 patients was obtained via questionnaires. In 82 families the mutations were detected by direct sequence analysis and/or multiplex ligation dependent probe amplification (MLPA), including one case where MLPA was essential to detect the second allele. In another case RT‐PCR followed by deep intronic sequencing was needed to detect the mutation. Thirty‐five novel mutations as well as 35 reported mutations and 14 nondisease‐related variants are reviewed and included in a novel Leiden Open source Variation Database (LOVD) for L2HGDH variants (http://www.LOVD.nl/L2HGDH). Every user can access the database and submit variants/patients. Furthermore, we report on the phenotype, including neurological manifestations and urinary levels of L2HG, and we evaluate the phenotype–genotype relationship. Hum Mutat 30:1–11, 2010.