Guido Kranenburg

Screening for frailty in primary care: a systematic review of the psychometric properties of the frailty index in community-dwelling older people

BackgroundTo better accommodate for the complex care needs of frail, older people, general practitioners must be capable of easily identifying frailty in daily clinical practice, for example, by using the frailty index (FI). To explore whether the FI is a valid and adequate screening instrument for primary care, we conducted a systematic review of its psychometric properties.MethodsWe searched the Cochrane, PubMed and Embase databases and included original studies focusing on the criterion validity, construct validity and responsiveness of the FI when applied in community-dwelling older people. We evaluated the quality of the studies included using the Quality in Prognosis Studies (QUIPS) tool. This systematic review was conducted based on the PRISMA statement.ResultsOf the twenty studies identified, eighteen reported on FIs derived from research data, one reported upon an FI derived from an administrative database of home-care clients, and one reported upon an FI derived from routine primary care data. In general, the FI showed good criterion and construct validity but lacked studies on responsiveness. When compared with studies that used data gathered for research purposes, there are indications that the FI mean score and range might be different in datasets using routine primary care data; however, this finding needs further investigation.ConclusionsOur results suggest that the FI is a valid frailty screening instrument. However, further research using routine Electronic Medical Record data is necessary to investigate whether the psychometric properties of the FI are generalizable to a primary care setting and to facilitate its interpretation and implementation in daily clinical practice.Trial registrationPROSPERO systematic review register number: CRD42013003737.

Identifying frailty: do the Frailty Index and Groningen Frailty Indicator cover different clinical perspectives? a cross-sectional study

BackgroundEarly identification of frailty is important for proactive primary care. Currently, however, there is no consensus on which measure to use. Therefore, we examined whether a Frailty Index (FI), based on ICPC-coded primary care data, and the Groningen Frailty Indicator (GFI) questionnaire identify the same older people as frail.MethodsWe conducted a cross-sectional, observational study of 1,580 patients aged ≥ 60 years in a Dutch primary care center. Patients received a GFI questionnaire and were surveyed on their baseline characteristics. Frailty-screening software calculated their FI score. The GFI and FI scores were compared as continuous and dichotomised measures.ResultsFI data were available for 1549 patients (98%). 663 patients (42%) returned their GFI questionnaire. Complete GFI and FI scores were available for 638 patients (40.4%), mean age 73.4 years, 52.8% female. There was a positive correlation between the GFI and the FI (Pearson’s correlation coefficient 0.544). Using dichotomised scores, 84.3% of patients with a low FI score also had a low GFI score. In patients with a high FI score, 55.1% also had a high GFI score. A continuous FI score accurately predicted a dichotomised GFI score (AUC 0.78, 95% CI 0.74 to 0.82). Being widowed or divorced was an independent predictor of both a high GFI score in patients with a low FI score, and a high FI score in patients with a low GFI score.ConclusionsThe FI and the GFI moderately overlap in identifying frailty in community-dwelling older patients. To provide optimal proactive primary care, we suggest an initial FI screening in routine healthcare data, followed by a GFI questionnaire for patients with a high FI score or otherwise at high risk as the preferred two-step frailty screening process in primary care.

The relation between HbA1c and cardiovascular events in patients with type 2 diabetes with and without vascular disease.

OBJECTIVE Poor glycemic control is related to vascular events in patients with type 2 diabetes, but the presence of vascular disease might influence this relation. We evaluated the relation between glycemic control (HbA1c level) and new cardiovascular events and mortality in patients with type 2 diabetes, with and without vascular disease. RESEARCH DESIGN AND METHODS In a cohort of 1,687 patients with type 2 diabetes enrolled in the Second Manifestations of Arterial Disease (SMART) study, the continuous relation between HbA1c and cardiovascular events (composite of myocardial infarction, stroke, and vascular mortality) and all-cause mortality was evaluated with Cox proportional hazard analyses stratified for the presence of vascular disease. RESULTS During a median follow-up time of 6.1 years (interquartile range 3.1–9.5 years), a new cardiovascular event developed in 293 patients and 340 patients died. In all patients, the hazard ratio (HR) of the relation between HbA1c level and cardiovascular events was 1.06 (95% CI 0.97–1.17). A 1 percentage point higher HbA1c level was related to a 27% higher risk of a cardiovascular event in patients with type 2 diabetes without vascular disease (HR 1.27 [95% CI 1.06–1.51]), but not in patients with vascular disease (HR 1.03 [95% CI 0.93–1.15], P for interaction = 0.195). A 1 percentage point higher HbA1c level was related to a 16% higher risk of death (HR 1.16 [95% CI 1.06–1.28]) in patients with vascular disease and a nonsignificant 13% higher risk of all-cause mortality (HR 1.13 [95% CI 0.97–1.31]) in patients without vascular disease. CONCLUSIONS In patients with type 2 diabetes, there is a modest, but not statistically significant, relation between HbA1c level and cardiovascular events, and, as there was no statistically significant interaction, this relation was not different for patients with or without clinical manifestation of vascular disease.

Romosozumab Treatment in Postmenopausal Osteoporosis

To the Editor: Osteoporosis has medical and economic costs that increase greatly with osteoporotic fracture. Many drugs that act at multiple targets in bone metabolism are currently available.1 The article by Cosman et al. (Oct. 20 issue)2 showed that romosozumab decreased the risk of vertebral fractures by 73% as compared with placebo; there was no significant between-group difference in the risk of nonvertebral fractures. The reduction in the risk of vertebral fracture is similar to that currently achieved with available standard treatments.3 In our opinion, it is unethical to randomly assign patients with osteoporosis who are at risk for debilitating fractures to a placebo group given the existence of approved standard therapies.4 We believe that the right way to advance development of a new, promising drug would be to compare it with the standard of care and prove that it is either more efficacious or equally efficacious with a better safety profile — or that it works when all else fails.5

Inter-arm systolic blood pressure differences, relations with future vascular events and mortality in patients with and without manifest vascular disease

BACKGROUND Inter-arm systolic blood pressure difference (SBPD) is an easily obtained patient characteristic which relates to vascular disease. We aimed to identify determinants of large inter-arm SBPD and to investigate the relation between inter-arm SBPD and vascular events in patients with and without manifest vascular disease. METHODS In a cohort of 7344 patients with manifest vascular disease or vascular risk factors alone enrolled in the Second Manifestations of ARTerial disease (SMART) study, single bilateral non-simultaneous blood pressure measurements were performed. Logistic and Cox regression was used to identify determinants of large inter-arm SBPD (≥15mmHg) and to investigate the relation between inter-arm SBPD and vascular events (composite of non-fatal myocardial infarction, stroke, and vascular mortality) and all-cause mortality. RESULTS In all patients the median inter-arm SBPD was 7mmHg (IQR 3-11) and 1182 (16%) patients had inter-arm SBPD ≥15mmHg. Higher age, higher systolic blood pressure, diabetes mellitus, peripheral artery disease, carotid artery stenosis, higher carotid intima-media thickness, and lower ankle-brachial indices were related to large inter-arm SBPD (≥15mmHg). Each 5mmHg increase in inter-arm SBPD was related to a 12% higher risk of vascular events in patients without manifest vascular disease (HR 1.12; 95% CI 1.00-1.27), whereas no relation was apparent in patients with manifest vascular disease (HR 0.98; 95% CI 0.93-1.04, interaction p-value 0.036). Inter-arm SBPD was not related to all-cause mortality (HR 1.05; 95% CI 0.93-1.19). CONCLUSIONS Inter-arm SBPD relates to a higher risk of vascular events in patients without manifest vascular disease, whereas this relation is not apparent in patients with manifest vascular disease.

Cerebral disease in a nationwide Dutch pseudoxanthoma elasticum cohort with a systematic review of the literature

BACKGROUND Pseudoxanthoma elasticum (PXE) is a monogenetic disease with progressive calcification of arteries and potential risk of stroke. To gain insights in the cerebral involvement in PXE, we evaluated prevalence and determinants of cerebral disease in our PXE cohort and performed a systematic review of literature. METHODS Systematic history taking concerning cerebral disorders was performed in our PXE cohort. Cardiovascular risk factors were compared between PXE patients with and without cerebral disease. Additionally, Pubmed, Embase, the Cochrane Library and PsycINFO were systematically reviewed for studies published up to August 2016 about cerebral disease in PXE. RESULTS Of the 178 PXE patients 31 (17%) had cerebral disease including ischemic stroke (n=15, 8%) or transient ischemic attack (n=13, 7%). The cerebral disease group was older (61±12 vs. 52±15years, adjusted p=0.004) and had less favorable profiles of traditional cardiovascular risk factors regarding the use of lipid lowering medication (61% vs. 31%, adjusted p=0.037) and levels of HDL-cholesterol (1.4±0.3 vs. 1.6±0.4mmol/L, adjusted p=0.005). One prospective cohort study reporting an incidence rate of ischemic stroke of 477/100,000/year and two cross-sectional studies with a reported prevalence of ischemic stroke of 14% and 0% were identified. Furthermore, 53 unique cases of cerebral disease in PXE including ischemic stroke (n=16) and transient ischemic attack (n=7) were reported. CONCLUSIONS Physicians and patients should be aware of the prevalent occurrence of cerebrovascular disease in PXE, which further stresses the importance of strict cardiovascular risk management in these patients.

The amount of calcifications in pseudoxanthoma elasticum patients is underestimated in computed tomographic imaging; a post-mortem correlation of histological and computed tomographic findings in two cases

ObjectivesPseudoxanthoma elasticum (PXE) is a rare genetic disorder, characterised by elastic fibre degeneration and calcifications in multiple organ systems. Computed tomography (CT) imaging is a potential method to monitor disease progression in PXE patients; however, this method has not been validated. The aim of this study was to correlate histological and computed tomographic findings in PXE patients to investigate the ability of CT scanning to detect these alterations.MethodsPost mortem total body CT scans were obtained from two PXE patients (a 69-year-old male and 77-year-old female). Autopsy was performed, and 38 tissue samples of the first and 45 tissue samples of the second patient were extensively investigated histologically. The findings were compared with the CT scans.ResultsDegenerated and calcified elastic fibres and calcifications were histologically found in the skin, subcutaneous fat, heart, arteries and pleura and around the oesophagus. On CT imaging only the intradermal alterations of the skin and the larger vascular calcifications were detected. The smaller PXE-related abnormalities were not visible on CT.ConclusionsWith CT imaging vascular calcifications and skin alterations can be monitored in PXE patients. However, many of the subtle PXE-related abnormalities found in other organ systems during the autopsy were not visualised by CT scans. Furthermore, we extended the current knowledge on the disease location of PXE with subcutaneous, oesophageal and pleural lesions.Teaching Points• CT can be used to monitor gross vascular calcifications in PXE patients.• Many subtle PXE-related abnormalities are not visualised by CT scans.• PXE-related alterations can also be found in oesophagus, pleura and subcutaneous fat.

Arterial stiffening and thickening in patients with pseudoxanthoma elasticum

BACKGROUND AND AIMS Patients with pseudoxanthoma elasticum (PXE), a monogenetic calcification disease, are at high vascular risk. Although the precise arterial phenotype remains unestablished, it is hypothesized that PXE predominantly affects the medial arterial layer leading to arterial stiffening. We aimed to test this hypothesis by measuring arterial wall characteristics in PXE and comparisons with the general population and diabetes mellitus type 2 (DM2), a condition typically associated with mixed intimal and medial arterial disease. METHODS Extensive arterial wall characterization was performed in 203 PXE patients involving intima-media thickness (IMT), pulse wave velocity (PWV) and pulse pressure (PP) measurements. IMT and PWV in PXE were compared with the general population using age, sex and mean arterial pressure corrected values for each PXE patient. IMT and PP were compared between PXE and DM2 independently of sex, age and systolic blood pressure, using data of DM2 patients (n = 1033) from the Second Manifestations of ARTerial disease (SMART) cohort. RESULTS PXE patients had significantly higher IMT (mean difference 0.09 mm; 95% CI 0.07-0.12 mm) and PWV (mean difference 2.5 m/s; 95% CI 1.9-3.0 m/s) compared to the general population. IMT in PXE was lower compared to DM2 (0.72 mm; 95% CI 0.68-0.75 mm vs. 0.85 mm; 95% CI 0.83-0.87 mm, p-value<0.01), whereas PP in PXE was higher compared to DM2 (60 mmHg; 95% CI 59-62 vs. 57 mmHg; 95% CI 57-58 mmHg, p-value<0.01). CONCLUSIONS PXE patients have thicker arterial walls than the general population, but thinner arterial walls than DM2 patients at similar age. Arterial stiffening is more pronounced in PXE patients compared to DM2 patients.

To the editor: Romosozumab Treatment in Postmenopausal Osteoporosis

To the Editor: Osteoporosis has medical and economic costs that increase greatly with osteoporotic fracture. Many drugs that act at multiple targets in bone metabolism are currently available.1 The article by Cosman et al. (Oct. 20 issue)2 showed that romosozumab decreased the risk of vertebral fractures by 73% as compared with placebo; there was no significant between-group difference in the risk of nonvertebral fractures. The reduction in the risk of vertebral fracture is similar to that currently achieved with available standard treatments.3 In our opinion, it is unethical to randomly assign patients with osteoporosis who are at risk for debilitating fractures to a placebo group given the existence of approved standard therapies.4 We believe that the right way to advance development of a new, promising drug would be to compare it with the standard of care and prove that it is either more efficacious or equally efficacious with a better safety profile — or that it works when all else fails.5

Abnormally high failure rate for femoral angioplasty in patients with pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE) is an inherited disease characterized by skin lesions, central blindness, and progressive peripheral occlusive disease. Severe claudication is a frequent symptom for which angioplasty represents a possible therapeutic avenue. We report the outcomes of four patients with PXE treated by angioplasty and stenting of the superficial femoral artery in two centers. These patients exhibited an abnormal failure rate for angioplasty and stenting of the superficial femoral artery, suggesting an as yet unknown susceptibility in such patients. In the absence of further evidence, we do not recommend arterial angioplasty with stenting as a primary surgical approach in PXE patients with femoral artery lesions.