Validation of a Geriatric Bedside Swallowing Screen (GEBS): Protocol of a Prospective Cohort Study.

BACKGROUND: Demographic changes will raise the need for specialized care of older patients. Oropharyngeal dysphagia has recently been declared a geriatric syndrome reflecting its multifactorial background. Alongside multimorbidity, sarcopenia, frailty, and disability, swallowing disorders increase with advancing age, with prevalence rates reported to be as high as 44% in acute geriatric hospital settings and 80% in long-term care facilities. Hence, systematic screening of older patients to diagnose dysphagia and initiate treatment is of paramount importance to prevent bolus death, aspiration pneumonia, and malnutrition and improve quality of life. Several screening tools have been evaluated in emergency and stroke units. However, no published dysphagia screening tool has been validated in the hospitalized, older adult population using a gold standard in dysphagia diagnostics as a reference test. The validation of the proposed test is a first step. OBJECTIVE: The Geriatric Bedside Swallowing Screen (GEBS) study aims to validate a new screening tool developed specifically for older inpatients against an instrumental swallowing evaluation, the flexible endoscopic evaluation of swallowing (FEES), which is considered a gold standard. Primary outcomes to be evaluated are sensitivity and specificity for the GEBS in the detection of dysphagia in a mixed older adult population. The presence of dysphagia will be defined by an instrumental swallowing evaluation (FEES), analyzed by the standardized penetration-aspiration scale. METHODS: To validate the GEBS, a prospective cohort study will be carried out. Two institutions, an acute geriatric department and a long-term care facility, will aim to recruit a total of 100 patients aged ≥75 years. After giving their informed consent, patients will undergo the full screening protocol described in the GEBS as well as an evaluation of swallowing function using the FEES. Investigators will be blinded to the results of the respective other testing. The analysis of pseudonymized data sets will be done by a third investigator. Outcomes to be considered are sensitivity, specificity, diagnostic odds ratio, positive and negative likelihood quotient, and the reliability of the proposed dysphagia screening tool using the κ coefficient. RESULTS: Recruitment started in October 2022 and will end in April 2024. Data publication is planned for early 2025. CONCLUSIONS: If proven to be a valid screening tool for the early detection of dysphagia, further studies including different older adult populations as well as studies to determine the impact of systematic dysphagia screening on parameters, such as rates of aspiration pneumonia or nutritional status, should be planned. Effective screening of dysphagia will lead to earlier detection of patients with impaired swallowing. Those who fail the screening will be referred to speech language pathology for further diagnosis, thus optimizing care while streamlining personnel resources. TRIAL REGISTRATION: ISCRTN Registry ISRCTN11581931; https://www.isrctn.com/ISRCTN11581931. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46252.

European postgraduate curriculum in geriatric medicine developed using an international modified Delphi technique.

BACKGROUND: the European Union of Medical Specialists (UEMS-GMS) recommendations for training in Geriatric Medicine were published in 1993. The practice of Geriatric Medicine has developed considerably since then and it has therefore become necessary to update these recommendations. METHODS: under the auspices of the UEMS-GMS, the European Geriatric Medicine Society (EuGMS) and the European Academy of Medicine of Ageing (EAMA), a group of experts, representing all member states of the respective bodies developed a new framework for education and training of specialists in Geriatric Medicine using a modified Delphi technique. Thirty-two expert panel members from 30 different countries participated in the process comprising three Delphi rounds for consensus. The process was led by five facilitators. RESULTS: the final recommendations include four different domains: 'General Considerations' on the structure and aim of the syllabus as well as quality indicators for training (6 sub-items), 'Knowledge in patient care' (36 sub-items), 'Additional Skills and Attitude required for a Geriatrician' (9 sub-items) and a domain on 'Assessment of postgraduate education: which items are important for the transnational comparison process' (1 item). CONCLUSION: the current publication describes the development of the new recommendations endorsed by UEMS-GMS, EuGMS and EAMA as minimum training requirements to become a geriatrician at specialist level in EU member states.

Case finding for sarcopenia in geriatric inpatients: performance of bioimpedance analysis in comparison to dual X-ray absorptiometry.

BACKGROUND: Sarcopenia is a common geriatric syndrome associated with serious adverse health outcomes. The European Working Group on Sarcopenia in Older People (EWGSOP) suggests different methods for case finding for sarcopenia. However, data comparing the different methodological options are scarce for geriatric inpatients. METHODS: On the basis of the recommendations of the EWGSOP sixty geriatric inpatients underwent measurement of gait speed, hand grip strength and muscle mass by both, dual X-ray absorptiometry (DXA) and bioimpedance analysis (BIA). By linear regression analysis and Bland-Altman plots muscle mass measurements of DXA and BIA were compared. Outcomes of the DXA- and BIA-based approaches for classifying participants as having normal or reduced muscle mass and sarcopenia according to the EWGSOP case finding algorithm were compared by raw agreement and kappa statistics. Finally, on the hypothetical assumption that the DXA-based approach can be set as reference, the performance of the BIA-based approach is illustrated. RESULTS: Muscle mass measured by BIA was highly correlated to DXA (r > 0.9), but BIA systematically overestimated muscle mass. The mean difference between DXA and BIA was -1.30 kg (p < 0.001) for appendicular and -2.33 kg (p < 0.001) for total muscle mass. The raw agreement between the DXA- and BIA-based approaches for classifying participants as having normal or reduced muscle mass was at best 80 % depending on the BIA cut-offs used. Functional prescreening according to the sarcopenia case finding algorithm of the EWGSOP reduced the need for muscle mass measurement by 37 %, but only marginally changed the agreement between the DXA- and BIA-based approaches. CONCLUSION: Clinicians should be aware that in geriatric inpatients the BIA-based approaches resulted in highly different subgroups of sarcopenic/non-sarcopenic subjects compared to the DXA-based approach following the EWGSOP case finding algorithm. In this pilot-study the BIA-based approach misclassified nearly 1 out of 6 patients if the DXA-based approach is taken as reference.

Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians.

The associations of the adiponectin (APM1) gene with parameters of the metabolic syndrome are inconsistent. We performed a systematic investigation based on fine-mapped single nucleotide polymorphisms (SNPs) highlighting the genetic architecture and their role in modulating adiponectin plasma concentrations in a particularly healthy population of 1,727 Caucasians avoiding secondary effects from disease processes. Genotyping 53 SNPs (average spacing of 0.7 kb) in the APM1 gene region in 81 Caucasians revealed a two-block linkage disequilibrium (LD) structure and enabled comprehensive tag SNP selection. We found particularly strong associations with adiponectin concentrations for 11 of the 15 tag SNPs in the 1,727 subjects (five P values <0.0001). Haplotype analysis provided a thorough differentiation of adiponectin concentrations with 9 of 17 haplotypes showing significant associations (three P values <0.0001). No significant association was found for any SNP with the parameters of the metabolic syndrome. We observed a two-block LD structure of APM1 pointing toward at least two independent association signals, one including the promoter SNPs and a second spanning the relevant exons. Our data on a large number of healthy subjects suggest a clear modulation of adiponectin concentrations by variants of APM1, which are not merely a concomitant effect in the course of type 2 diabetes or coronary artery disease.

PPARgamma controls cell proliferation and apoptosis in an RB-dependent manner.

The nuclear receptor PPARgamma is implicated in the control of cell proliferation and apoptosis. However, the molecular mechanisms by which it controls these processes remain largely elusive. We show here that PPARgamma activation in the presence of the retinoblastoma protein (RB) results in the arrest of cells at the G1 phase of the cell cycle, whereas in the absence of RB, cells accumulate in G2/M, endoreduplicate, and undergo apoptosis. Through the use of HDAC inhibitors and coimmunoprecipitations, we furthermore demonstrate that the effects of RB on PPARgamma-mediated control of the cell cycle and apoptosis depend on the recruitment of histone deacetylase 3 (HDAC3) to PPARgamma. In combination, these data hence demonstrate that the effects of PPARgamma on cell proliferation and apoptosis are dependent on the presence of an RB-HDAC3 complex.

The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation.

The retinoblastoma protein (RB) has previously been shown to facilitate adipocyte differentiation by inducing cell cycle arrest and enhancing the transactivation by the adipogenic CCAAT/enhancer binding proteins (C/EBP). We show here that the peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear receptor pivotal for adipogenesis, promotes adipocyte differentiation more efficiently in the absence of RB. PPARgamma and RB were shown to coimmunoprecipitate, and this PPARgamma-RB complex also contains the histone deacetylase HDAC3, thereby attenuating PPARgamma's capacity to drive gene expression and adipocyte differentiation. Dissociation of the PPARgamma-RB-HDAC3 complex by RB phosphorylation or by inhibition of HDAC activity stimulates adipocyte differentiation. These observations underscore an important function of both RB and HDAC3 in fine-tuning PPARgamma activity and adipocyte differentiation.

The generation of monoclonal antibodies against human peroxisome proliferator-activated receptors (PPARs).

Monoclonal antibodies (Mabs) are valuable reagents for the purification, characterization and immunolocalization of proteins. In this study, we raised Mabs against human peroxisome proliferator-activated receptors (PPARs) using baculovirus particles displaying surface glycoprotein gp64-fusion proteins as the immunizing agent. In this system, to display fusion proteins on the viral surface, the amino terminal sequences of human PPARd and PPARg2 are inserted in-frame between the signal sequence and the mature domain of the gp64 nucleotide sequence.Mabs were raised by immunization with whole virus without a purification of the target antigens. The Mabs generated by this novel method were shown to recognize not only the gp64-PPARs fusion protein, but also mature, expressed proteins by a wide variety of techniques, including immunohistochemistry, immunoblotting, and electrophoretic mobility shift assays (EMSAs). Transfection of the transfer vector containing a nucleotide sequence encoding less than 30 amino acids along with linearized baculovirus DNA allows for the production of a high affinity antibody against the corresponding mature form. This method is of potential utility in that it allows the production of valuable antibodies without the requirement of a protein purification step.