Development of an instrument for the identification of frail older people as a target population for integrated care

Background

Primary care is increasingly interested in the identification of frailty, as it selects the target population for integrated care. However, instruments for the identification of frailty specifically validated for use in primary care are scarce. This study developed the Easycare Two-step Older persons Screening (Easycare-TOS), which provides a valid, efficient, and pragmatic screening procedure to identify frail older people.

Aim

This paper aims to describe the development of the Easycare-TOS and the data from the pilot studies.

Design and setting

Observational pilot study in seven academic GP practices in and around Nijmegen, The Netherlands.

Method

The Easycare-TOS was developed in a cyclic process with the input of stakeholders. In every cycle, the requirements were first defined, then translated into a prototype that was tested in a pilot study. The Easycare-TOS makes optimal use of prior knowledge of the GP, and the professionals’ appraisal is decisive in the frailty decision, instead of a cut-off score. Further, it considers aspects of frailty, as well as aspects of the care context of the patient.

Results

The pilot data have shown that after step 1, two-thirds of the patients do not need further assessment, because they are judged as not frail, based on prior knowledge of the GP. The overall prevalence of frailty in this pilot study is 24%. Most professionals who participated in the pilot studies considered the time investment acceptable and the method to be of added value.

Conclusion

The Easycare-TOS instrument meets the predefined efficiency, flexibility, and acceptability requirements for use as an identification instrument for frailty in primary care.     

Exercise with low glycogen increases PGC-1α gene expression in human skeletal muscle

Recent studies suggest that carbohydrate restriction can improve the training-induced adaptation of muscle oxidative capacity. However, the importance of low muscle glycogen on the molecular signaling of mitochondrial biogenesis remains unclear. Here, we compare the effects of exercise with low (LG) and normal (NG) glycogen on different molecular factors involved in the regulation of mitochondrial biogenesis. Ten highly trained cyclists (VO_2max 65 ± 1 ml/kg/min, W _max 387 ± 8 W) exercised for 60 min at approximately 64 % VO_2max with either low [166 ± 21 mmol/kg dry weight (dw)] or normal (478 ± 33 mmol/kg dw) muscle glycogen levels achieved by prior exercise/diet intervention. Muscle biopsies were taken before, and 3 h after, exercise. The mRNA of peroxisome proliferator-activated receptor-γ coactivator-1 was enhanced to a greater extent when exercise was performed with low compared with normal glycogen levels (8.1-fold vs. 2.5-fold increase). Cytochrome c oxidase subunit I and pyruvate dehydrogenase kinase isozyme 4 mRNA were increased after LG (1.3- and 114-fold increase, respectively), but not after NG. Phosphorylation of AMP-activated protein kinase, p38 mitogen-activated protein kinases and acetyl-CoA carboxylase was not changed 3 h post-exercise. Mitochondrial reactive oxygen species production and glutathione oxidative status tended to be reduced 3 h post-exercise. We conclude that exercise with low glycogen levels amplifies the expression of the major genetic marker for mitochondrial biogenesis in highly trained cyclists. The results suggest that low glycogen exercise may be beneficial for improving muscle oxidative capacity.     

Spirituality Factors in the Prediction of Outcomes of PTSD Treatment for U.S. Military Veterans

Spirituality is a multifaceted construct that might affect veterans’ recovery from posttraumatic stress disorder (PTSD) in adaptive and maladaptive ways. Using a cross‐lagged panel design, this study examined longitudinal associations between spirituality and PTSD symptom severity among 532 U.S. veterans in a residential treatment program for combat‐related PTSD. Results indicated that spirituality factors at the start of treatment were uniquely predictive of PTSD symptom severity at discharge, when accounting for combat exposure and both synchronous and autoregressive associations between the study variables, βs = .10 to .16. Specifically, veterans who scored higher on adaptive dimensions of spirituality (daily spiritual experiences, forgiveness, spiritual practices, positive religious coping, and organizational religiousness) at intake fared significantly better in this program. In addition, possible spiritual struggles (operationalized as negative religious coping) at baseline were predictive of poorer PTSD outcomes, β = .11. In contrast to these results, PTSD symptomatology at baseline did not predict any of the spirituality variables at posttreatment. In keeping with a spiritually integrative approach to treating combat‐related PTSD, these results suggest that understanding the possible spiritual context of veterans’ trauma‐related concerns might add prognostic value and equip clinicians to alleviate PTSD symptomatology among those veterans who possess spiritual resources or are somehow struggling in this domain.     

Scrapie and cellular prion proteins share polypeptide epitopes

Purified preparations of scrapie prions contain one major protein, PrP 27-30, and aggregates of rod-shaped structures. On the basis of the NH2-terminal amino acid sequence of PrP 27-30, a synthetic peptide (PrP-P1) was constructed. Monospecific rabbit antisera to PrP-P1 were found by immunoblotting to react with PrP 27-30 and its precursor (PrP 33-35Sc), as well as with a related protease-sensitive cellular homologue (PrP 33-35C). An enzyme-linked immunosorbent assay showed that rabbit antiserum to PrP 27-30 was more reactive with PrP 27-30 than with PrP-P1; conversely, antiserum to PrP-P1 was more reactive with the peptide than with the prion proteins. In addition, antibodies to PrP-P1 decorate purified prion rods and stain amyloid plaques in scrapie-infected hamster brain. The peptide epitopes shared by PrP 27-30, PrP 33-35Sc, and PrP 33-35C clearly establish a relationship among these three proteins.     

Cell surface peptidase CD26/DPPIV mediates G-CSF mobilization of mouse progenitor cells

CXC ligand 12 (CXCL12; also known as stromal cell-derived factor 1alpha/SDF-1alpha) chemoattracts hematopoietic stem and progenitor cells (HSCs/HPCs) and is thought to play a crucial role in the mobilization of HSCs/HPCs from the bone marrow. CD26 (dipeptidylpeptidase IV [DPPIV]) is a membrane-bound extracellular peptidase that cleaves dipeptides from the N-terminus of polypeptide chains. CD26 has the ability to cleave CXCL12 at its position-2 proline. We found by flow cytometry that CD26 is expressed on a subpopulation of normal Sca-1+c-kit+lin- hematopoietic cells isolated from mouse bone marrow, as well as Sca-1+c-kit-lin- cells, and that these cells possess CD26 peptidase activity. To test the functional role of CD26 in CXCL12-mediated normal HSC/HPC migration, chemotaxis assays were performed. The CD26 truncated CXCL12(3-68) showed an inability to induce the migration of sorted Sca-1+c-kit+lin- or Sca-1+c-kit-lin- mouse marrow cells compared with the normal CXCL12. In addition, CXCL12(3-68) acts as an antagonist, resulting in the reduction of migratory response to normal CXCL12. Treatment of Sca-1+c-kit+lin- mouse marrow cells, and myeloid progenitors within this population, or Sca-1+c-kit-lin- cells with a specific CD26 inhibitor, enhanced the migratory response of these cells to CXCL12. Finally, to test for potential in vivo relevance of these in vitro observations, mice were treated with CD26 inhibitors during granulocyte colony-stimulating factor (G-CSF)-induced mobilization. This treatment resulted in a reduction in the number of progenitor cells in the periphery as compared with the G-CSF regimen alone. This suggests that a mechanism of action of G-CSF mobilization involves CD26.     

Gastroduodenal sensory mechanisms and CCK in inhibition of gastric emptying in response to a meal

The ability of nutrients in the intestinal lumen to exert feedback control over the proximal gastrointestinal tract function is well recognized, yet the control mechanisms are poorly defined. There is evidence that extrinsic sensory pathways from the intestine are required to initiate this regulatory process. Furthermore, CCK appears to be involved in the gastric response to several intestinal stimuli, such as fat, carbohydrate and protein. Our hypothesis is that nutrients release CCK from the intestine, which then stimulates intestinal mucosal afferents to signal reflex changes in gastric motor function and thus inhibit gastric emptying.