α-L-iduronidase fused with humanized anti-human transferrin receptor antibody (lepunafusp alfa) for mucopolysaccharidosis type I: A phase 1/2 trial.

Mucopolysaccharidosis type I (MPS I) causes systemic accumulation of glycosaminoglycans due to a genetic deficiency of α-L-iduronidase (IDUA), which results in progressive systemic symptoms affecting multiple organs, including the central nervous system (CNS). Because the blood-brain barrier (BBB) prevents enzymes from reaching the brain, enzyme replacement therapy is effective only against the somatic symptoms. Hematopoietic stem cell transplantation can address the CNS symptoms, but the risk of complications limits its applicability. We have developed a novel genetically modified protein consisting of IDUA fused with humanized anti-human transferrin receptor antibody (lepunafusp alfa; JR-171), which has been shown in nonclinical studies to be distributed to major organs, including the brain, bringing about systemic reductions in heparan sulfate (HS) and dermatan sulfate concentrations. Subsequently, a first-in-human study was conducted to evaluate the safety, pharmacokinetics, and exploratory efficacy of JR-171 in 18 patients with MPS I. No notable safety issues were observed. Plasma drug concentration increased dose dependently and reached its maximum approximately 4 h after the end of drug administration. Decreased HS in the cerebrospinal fluid suggested successful delivery of JR-171 across the BBB, while suppressed urine and serum concentrations of the substrates indicated that its somatic efficacy was comparable to that of laronidase.

BCL6B Contributes to Ocular Vascular Diseases via Notch Signal Silencing.

BACKGROUND: Endothelial cell activation is tightly controlled by the balance between VEGF (vascular endothelial cell growth factor) and Notch signaling pathway. VEGF destabilizes blood vessels and promotes neovascularization, which are common features of sight-threatening ocular vascular disorders. Here, we show that BCL6B (B-cell CLL/lymphoma 6 member B protein), also known as BAZF, ZBTB28, and ZNF62, plays a pivotal role in the development of retinal edema and neovascularization. METHODS: The pathophysiological physiological role of BCL6B was investigated in cellular and animal models mimicking 2 pathological conditions: retinal vein occlusion and choroidal neovascularization. An in vitro experimental system was used in which human retinal microvascular endothelial cells were supplemented with VEGF. Choroidal neovascularization cynomolgus monkey model was generated to investigate the involvement of BCL6B in the pathogenesis. Mice lacking BCL6B or treated with BCL6B-targeting small-interfering ribose nucleic acid were examined for histological and molecular phenotypes. RESULTS: In retinal endothelial cells, the BCL6B expression level was increased by VEGF. BCL6B-deficient endothelial cells showed Notch signal activation and attenuated cord formation via blockage of the VEGF-VEGFR2 signaling pathway. Optical coherence tomography images showed that choroidal neovascularization lesions were decreased by BCL6B-targeting small-interfering ribose nucleic acid. Although BCL6B mRNA expression was significantly increased in the retina, BCL6B-targeting small-interfering ribose nucleic acid suppressed ocular edema in the neuroretina. The increase in proangiogenic cytokines and breakdown of the inner blood-retinal barrier were abrogated in BCL6B knockout (KO) mice via Notch transcriptional activation by CBF1 (C promotor-binding factor 1) and its activator, the NICD (notch intracellular domain). Immunostaining showed that Müller cell activation, a source of VEGF, was diminished in BCL6B-KO retinas. CONCLUSIONS: These data indicate that BCL6B may be a novel therapeutic target for ocular vascular diseases characterized by ocular neovascularization and edema.

Effect of anti-claudin 18.2 monoclonal antibody zolbetuximab alone or combined with chemotherapy or programmed cell death-1 blockade in syngeneic and xenograft gastric cancer models.

The development of targeted cancer therapies based on monoclonal antibodies against tumor-associated antigens has progressed markedly over recent decades. This approach is dependent on the identification of tumor-specific, normal tissue-sparing antigenic targets. The transmembrane protein claudin-18 splice variant 2 (CLDN18.2) is frequently and preferentially displayed on the surface of primary gastric adenocarcinomas, making it a promising monoclonal antibody target. Phase 3 studies of zolbetuximab, a chimeric immunoglobulin G1 monoclonal antibody targeting CLDN18.2, combined with 5-fluorouracil/leucovorin plus oxaliplatin (modified FOLFOX6) or capecitabine plus oxaliplatin (CAPOX) in advanced or metastatic first-line gastric or gastroesophageal junction (G/GEJ) adenocarcinoma have demonstrated favorable clinical results with zolbetuximab. In studies using xenograft or syngeneic models with gastric cancer cell lines, zolbetuximab mediated death of CLDN18.2-positive human cancer cell lines via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro and demonstrated anti-tumor efficacy as monotherapy and combined with chemotherapy in vivo. Mice treated with zolbetuximab plus chemotherapy displayed a significantly higher frequency of tumor-infiltrating CD8+ T cells versus vehicle/isotype control-treated mice. Furthermore, zolbetuximab combined with an anti-mouse programmed cell death-1 antibody more potently inhibited tumor growth compared with either agent alone. These results support the potential of zolbetuximab as a novel treatment option for G/GEJ adenocarcinoma.

Urinary podocyte markers of disease activity, therapeutic efficacy, and long-term outcomes in acute and chronic kidney diseases.

A critical degree of podocyte depletion causes glomerulosclerosis, and persistent podocyte loss in glomerular diseases drives the progression to end-stage kidney disease. The extent of podocyte injury at a point in time can be histologically assessed by measuring podocyte number, size, and density ("Biopsy podometrics"). However, repeated invasive renal biopsies are associated with increased risk and cost. A noninvasive method for assessing podocyte injury and depletion is required. Albuminuria and proteinuria do not always correlate with disease activity. Podocytes are located on the urinary space side of the glomerular basement membrane, and as they undergo stress or detach, their products can be identified in urine. This raises the possibility that urinary podocyte products can serve as clinically useful markers for monitoring glomerular disease activity and progression ("Urinary podometrics"). We previously reported that urinary sediment podocyte mRNA reflects disease activity in both animal models and human glomerular diseases. This includes diabetes and hypertension which together account for 60% of new-onset dialysis induction patients. Improving approaches to preventing progression is an urgent priority for the renal community. Sufficient evidence now exists to indicate that monitoring urinary podocyte markers could serve as a useful adjunctive strategy for determining the level of current disease activity and response to therapy in progressive glomerular diseases.

Concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer: A multicenter, retrospective, observational study.

OBJECTIVES: There is concern that hydroxyzine exacerbates delirium, but a recent preliminary study suggested that the combination of haloperidol and hydroxyzine was effective against delirium. This study examined whether the concomitant use of hydroxyzine and haloperidol worsened delirium in patients with cancer. METHODS: This retrospective, observational study was conducted at 2 general hospitals in Japan. The medical records of patients with cancer who received haloperidol for delirium from July to December 2020 were reviewed. The treatments for delirium included haloperidol alone or haloperidol combined with hydroxyzine. The primary outcome was the duration from the first day of haloperidol administration to the resolution of delirium, defined as its absence for 2 consecutive days. The time to delirium resolution was analyzed to compare the haloperidol group and hydroxyzine combination group using the log-rank test with the Kaplan-Meier method. Secondary outcomes were (1) the total dose of antipsychotic medications, including those other than haloperidol (measured in chlorpromazine-equivalent doses), and (2) the frequencies of detrimental incidents during delirium, specifically falls and self-removal of drip infusion lines. The unpaired t-test and Fisher's exact test were used to analyze secondary outcomes. RESULTS: Of 497 patients who received haloperidol, 118 (23.7%) also received hydroxyzine. No significant difference in time to delirium resolution was found between the haloperidol group and the hydroxyzine combination group (log-rank test, P = 0.631). No significant difference between groups was found in either chlorpromazine-equivalent doses or the frequency of detrimental incidents. SIGNIFICANCE OF RESULTS: This study showed that the concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer.

Masticatory performance in oral function assessment: Alternative methods.

BACKGROUND: Masticatory function declines with age or disease, implicating a poor chewing efficiency and an often-unconscious change for a less healthy, yet easy to chew diet. Timely screening of masticatory function may foster an early-onset diagnosis and potential treatment. The aim of this study was to compare alternative diagnostic tools for masticatory function to a Jelly-scan test. MATERIALS AND METHODS: Patients aged 70 years and older who were hospitalised for rehabilitation were recruited for this study. A total of four different tests for masticatory function were administered. The Japanese Society of Gerodontology glucose extraction test (Jelly-scan) was used as reference to compare a colour-changing gum test (Gum1-colour) as well as a mixing ability test with a visual (Gum2-visual) and opto-electronical (Gum2-digital) analyses. Receiver operating characteristic (ROC) curves were used to establish the discriminative value, kappa-values were used to estimate individual agreements and correlations were verified using Spearman's tests. RESULTS: Sixty-one patients (Men n = 23, Women n = 38) aged 82.4 ± 6.8 years participated in the experiments. The average number of natural teeth was 16.5 ± 10.5, 34.4% of the participants wore removable dentures. For all tests, the sum of sensitivity and specificity was >150%. All test correlated with Jelly-scan (absolute Rho >0.5). With Jelly-scan 51 participants (83.6%) were diagnosed with "masticatory hypofunction". After reducing the cut-off value of the test from 100 mg/dL to 65 mg/dL, only 33 participants (54%) fulfilled the diagnosis. This post-hoc analysis increased the sensitivity of the Gum2-tests and the agreement to kappa >0.5 for all three tests. CONCLUSION: All three tests can be considered useful screening alternatives. In its original version, Jelly-scan may tend to over-diagnose masticatory hypofunction, hence a novel cut-off with better agreement between tests is suggested.

Effect of the denture adhesive for dry mouth on the retentive force of the experimental palatal plates: a pilot controlled clinical trial.

BACKGROUND: A denture adhesive for dry mouth with good cleaning properties has recently been developed. While previous studies on models have shown the effectiveness of denture adhesives in terms of retention and cleanability, no reports have evaluated their effectiveness in the oral cavity. The aim of this study was to compare and investigate the retention and usability of an experimental palatal plate in the dentulous jaw using a denture adhesive for dry mouth, a conventional cream-type denture adhesive, an oral moisturizer, and a denture moisturizer. METHODS: Ten healthy dentulous participants (mean age 27.2 ± 1.6 years) were included in the study. Palatal plates were fabricated. Four test samples were used: denture adhesive for dry mouth, conventional denture adhesive (cream type), oral moisturizer, and denture moisturizer. The sample was applied to the inner surface of the palatal plates, and the retentive force of the palatal plate was measured every 10 min for 30 min. After the measurements, the study participants were asked to rinse the palatal plate with water and subjectively evaluate the samples used. RESULTS: The conventional denture adhesive (cream type) showed increased retentive force over time, with the maximum retentive force obtained after 10 min of application. However, its washability was rated second lowest. The denture adhesive for dry mouth showed the highest retentive force immediately after application. Its washability was also good. CONCLUSIONS: The results suggest that the denture adhesive for dry mouth has reasonable retentive force in the oral cavity and cleaning properties compared to the conventional cream-type denture adhesive.

Potent bactericidal activity of reduced cryptdin-4 derived from its hydrophobicity and mediated by bacterial membrane disruption.

Defensin is a cysteine-rich antimicrobial peptide with three disulphide bonds under normal oxidative conditions. Cryptdin-4 (Crp4) is a defensin secreted by Paneth cells in the small intestine of mice, and only reduced Crp4 (Crp4red) shows activity against enteric commensal bacteria, although both oxidised Crp4 (Crp4ox) and Crp4red can kill non-commensal bacteria. To investigate the molecular factors that affect the potent antimicrobial activity of Crp4red, the bactericidal activities of Crp4ox and Crp4red, Crp4 with all Cys residues substituted with Ser peptide (6C/S-Crp4), and Crp4 with all thiol groups modified by N-ethylmaleimide (NEM-Crp4) were assessed. All peptides showed bactericidal activity against non-commensal bacteria, whereas Crp4red and NEM-Crp4 showed bactericidal activity against commensal bacteria. These potent peptides exhibited high hydrophobicity, which was strongly correlated with membrane insertion. Intriguingly, Crp4ox formed electrostatic interactions with the membrane surface of bacteria, even without exerting bactericidal activity. Moreover, the bactericidal activity of both oxidised and reduced forms of Crp4 was abolished by inhibition of electrostatic interactions; this finding suggests that Crp4red targets bacterial membranes. Finally, a liposome leakage assay against lipids extracted from commensal bacteria demonstrated a correlation with bactericidal activity. These results suggest that the potent bactericidal activity of Crp4red is derived from its hydrophobicity, and the bactericidal mechanism involves disruption of the bacterial membrane. Findings from this study provide a better understanding of the bactericidal mechanism of both Crp4ox and Crp4red.

Distinct Expression of SLM2 Underlies Splicing-Dependent Trans-Synaptic Signaling of Neurexin Across GABAergic Neuron Subtypes.

The mammalian brain contains multiple types of neuronal cells with complex assemblies and distinct structural and functional properties encoded by divergent gene programs. There is increasing evidence that alternative splicing (AS) plays fundamental roles in transcriptomic diversity and specifying synaptic properties of each neuronal cell type. However, the mechanisms underlying AS regulation and whether it controls synapse formation across GABAergic interneurons have not been fully elucidated. Here we show the differential expression levels of Sam68-like molecule 2 (SLM2), a major splicing regulator of neurexin (NRX), in GABAergic neuronal subtypes and its contribution to GABAergic synapse specification. Cortical SLM2 is strongly expressed not only in excitatory neurons but also in a subpopulation of GABAergic interneurons, especially in VIP-positive neurons that are originated from late-born caudal ganglionic eminence (GE)- derived cells. Using artificial synapse formation assay, we found that GE containing cortices form a strong synapse with LRRTM2, a trans-synaptic receptor of the alternatively spliced segment 4 (AS4)(-) of NRX. SLM2 knock-down reduced the NRX AS4(-) isoform expression and hence weaken LRRTM2-induced synapse formation. The addition of NRX AS4(-) was sufficient to rescue the synaptic formation by LRRTM2 in SLM2 knock-down neurons. Thus, our findings suggest a novel function of SLM2 in modifying network formation of a specific population of GABAergic interneurons and contribute to a better understanding of the roles AS plays in regulating synapse specificity and neuronal molecular diversity.

Evaluation of a Capillary Microsampling Device for Analyzing Plasma Lenvatinib Concentration in Patients With Hepatocellular Carcinoma.

BACKGROUND: The anticancer drug, Lenvima (lenvatinib), has severe side effects. Therapeutic drug monitoring helps ensure its efficacy and safety. Regular and optimally timed blood sampling is tough, especially when lenvatinib is self-medicated. Microsampling using the easy to handle Microsampling Wing (MSW) may help circumvent this problem. However, current lenvatinib detection methods are not sensitive enough to detect its concentrations in microsamples (<50-250 µL). Thus, the aim of this study was 2-fold (1) develop an analytic method to estimate plasma lenvatinib concentrations in microsamples and (2) verify whether this method works on micro (5.6 µL) blood plasma samples obtained clinically through MSW from patients with unresectable hepatocellular carcinoma (HCC). METHODS: A simple, highly sensitive, and specific liquid chromatography-electrospray ionization tandem mass spectrometry method was developed. Using this novel protocol, the trough blood plasma concentration of lenvatinib was measured for both blood sampled conventionally and that using MSW. Thirty-five venous whole blood samples were obtained from 11 patients with HCC. Furthermore, the stability of lenvatinib in MSW samples during storage was evaluated. RESULTS: The mean plasma lenvatinib concentration estimates were not significantly different between the MSW and conventional venous blood samples. CV for interday and intraday assays was low. Up to day 5, the lenvatinib concentration in the MSW samples was 85%-115% of the initial day concentration (when stored at 25°C or 4°C). The interference of endogenous matrix components in the human plasma was low. CONCLUSIONS: These results indicate that the novel mass spectrometry protocol accurately measures lenvatinib in human plasma and is reproducible. Thus, MSW could be a useful microsampling device for lenvatinib therapeutic drug monitoring in patients with HCC when used in combination with this novel liquid chromatography-electrospray ionization tandem mass spectrometry detection method.

Association between oral health and advisability of oral feeding in advanced cancer patients receiving palliative care: a cross-sectional study.

PURPOSE: Maintenance of oral feeding is important in terms of maintaining and improving the quality of life in terminal cancer patients receiving palliative care. Although adequate oral health status is essential for oral feeding in hospitalized patients, the relationship between oral health and oral feeding in patients receiving palliative care remains unclear. This cross-sectional study aimed to examine how the general condition and oral health status of these patients relate to decisions regarding their nutritional intake methods. METHODS: This retrospective cross-sectional study included 103 terminal cancer patients (59 men and 44 women; mean age, 73.8 ± 10.9 years) who received palliative care between April 2017 and August 2019. The nutritional method was assessed using the Functional Oral Intake Scale (FOIS). We assessed two types of nutritional methods: (1) the method advised by the attending physician until the initial dental examination (FOIS-I) and (2) the recommended method based on consultation with a palliative care doctor and dentist after the initial oral examination (FOIS-R). Furthermore, the participants' basic information and Dysphagia Severity Scale (DSS) and Oral Health Assessment Tool (OHAT) scores were assessed. RESULTS: There was a divergence between FOIS-I and FOIS-R. FOIS-R was significantly higher than FOIS-I (p < 0.001). Multiple regression analysis revealed that the time until death, DSS score, and OHAT score had a significant impact on determining the food form for oral feeding. CONCLUSIONS: Appropriate oral health assessment is important in determining the food form and indication for oral feeding among patients receiving palliative care.

Factors affecting the oral health of inpatients with advanced cancer in palliative care.

PURPOSE: Patients with terminal cancer undergoing multidisciplinary palliative care often have oral health problems, but these details are still unclear. This cross-sectional study aimed to elucidate the oral health of patients with terminal-stage cancer who are inpatient recipients of acute-phase palliative care, and to unveil the factors affecting their oral health. METHODS: Participants were 121 patients with terminal-stage cancer (68 males, 53 females, mean age: 73.6 ± 11.1 years) and oral health complaints. They received palliative care at Tokyo Medical and Dental University Medical Hospital between April 2017 and August 2019. Their demographic and medical details were extracted, retrospectively, from their medical records, and their oral health status, such as the number of natural teeth, removable denture usage, Oral Health Assessment Tool (OHAT), and Dysphagia Severity Scale, were evaluated. All outcomes were assessed by a dentist from the palliative care team. RESULTS: The problems with soft tissue, saliva, and oral cleanliness were observed. The absence of posterior occlusal support was common, and the use of removable dentures was often inadequate. In contrast, swallowing function was relatively well-conserved and 46.3% of the participants were capable of nutrition intake solely by mouth. Multiple regression analysis revealed a significant association between total OHAT score and age, consciousness level, prognostic level, and method of nutritional intake. CONCLUSION: The results revealed that the oral health of terminal cancer patients under palliative care declined despite receiving routine oral care from nurses, and suggest the importance of including dental professionals in multidisciplinary palliative care.

Iduronate-2-sulfatase fused with anti-hTfR antibody, pabinafusp alfa, for MPS-II: A phase 2 trial in Brazil.

In Hunter syndrome (mucopolysaccharidosis II [MPS-II]), systemic accumulation of glycosaminoglycans (GAGs) due to a deficiency of iduronate-2-sulfatase (IDS), caused by mutations in the IDS gene, leads to multiple somatic manifestations and in patients with the severe (neuronopathic) phenotype, also to central nervous system (CNS) involvement. These symptoms cannot be effectively treated with current enzyme-replacement therapies, as they are unable to cross the blood-brain barrier (BBB). Pabinafusp alfa, a novel IDS fused with an anti-human transferrin receptor antibody, was shown to penetrate the BBB and to address neurodegeneration in preclinical studies. Subsequent phase 1/2 and 2/3 clinical studies in Japan have shown marked reduction of GAG accumulation in the cerebrospinal fluid (CSF), along with favorable clinical responses. A 26-week, open-label, randomized, parallel-group phase 2 study was conducted in Brazil to further evaluate the safety and efficacy of intravenously administered pabinafusp alfa at 1.0, 2.0, and 4.0 mg/kg/week in MPS-II patients. The safety profiles in the three dosage groups were similar. Neurodevelopmental evaluation suggested positive neurocognitive signals despite a relatively short study period. The 2.0-mg/kg group, which demonstrated marked reductions in substrate concentrations in the CSF, serum, and urine, was considered to provide the best combination regarding safety and efficacy signals.

A Phase 2/3 Trial of Pabinafusp Alfa, IDS Fused with Anti-Human Transferrin Receptor Antibody, Targeting Neurodegeneration in MPS-II.

Pabinafusp alfa (JR-141) is a novel enzyme drug that crosses the blood-brain barrier by transcytosis via transferrin receptors. In order to establish its efficacy and safety, a multicenter, single-arm, open-label phase 2/3 clinical trial was conducted in 28 Japanese patients with mucopolysaccharidosis II (MPS-II, Hunter syndrome) by intravenous administrations of 2.0 mg/kg of pabinafusp alfa for 52 weeks. The primary efficacy endpoint was changes in heparan sulfate (HS) concentrations in the cerebrospinal fluid (CSF). Secondary endpoints included assessments of neurocognitive development for central efficacy, and changes in plasma HS and dermatan sulfate (DS) concentrations for peripheral efficacy. HS concentrations in the CSF significantly decreased from baseline to week 52 (p < 0.001), suggesting continuous inhibition of substrate accumulations in the CNS, i.e., hitherto unaddressed progressive neurodegeneration. Evaluations of neurocognitive developments showed positive changes in 21 of the 28 patients. Serum HS and DS concentrations, liver and spleen volumes, and other assessments suggested the peripheral efficacy of pabinafusp alfa was comparable to that of idursulfase. Drug-related adverse events were mild or moderate in severity, transient, and manageable. The results establish delivery across the BBB of pabinafusp alfa as an effective therapeutic for treating both the CNS and peripheral symptoms of patients with MPS-II.

Drug delivery for neuronopathic lysosomal storage diseases: evolving roles of the blood brain barrier and cerebrospinal fluid.

Whereas significant strides have been made in the treatment of lysosomal storage diseases (LSDs), the neuronopathy associated with these diseases remains impervious mainly because of the blood-brain barrier (BBB), which prevents delivery of large molecules to the brain. However, 100 years of research on the BBB since its conceptualization have clarified many of its functional and structural characteristics, spurring recent endeavors to deliver therapeutics across it to treat central nervous system (CNS) disorders, including neuronopathic LSDs. Along with the BBB, the cerebrospinal fluid (CSF) also functions to protect the microenvironment of the CNS, and it is therefore deeply involved in CNS disorders at large. Recent research aimed at developing therapeutics for neuronopathic LSDs has uncovered a number of critical roles played by the CSF that require further clarification. This review summarizes the most up-to-date understanding of the BBB and the CSF acquired during the development of therapeutics for neuronopathic LSDs, and highlights some of the associated challenges that require further research.

Factors Associated with Food Form in Long-Term Care Insurance Facilities.

We examined factors related to dietary intake status (food form) of long-term care facility (LTCF) residents to identify factors related to proper food form choice for older individuals requiring nursing care. We surveyed 888 residents from 37 LTCFs in Japan. We evaluated basic information (age, sex, body mass index [BMI]), food form (swallowing-adjusted diet class), Barthel Index (BI), Clinical Dementia Rating (CDR), simply evaluated eating and swallowing functions, the number of present/functional teeth, oral diadochokinesis, repetitive saliva swallowing test (RSST), and modified water swallowing test. To clarify factors associated with food form, participants who had good nutrition by oral intake were categorized into the dysphagic diet (DD) and normal diet (ND) groups. Multi-level analyses were used to detect oral functions associated with food form status. Among objective assessments, BMI (odds ratio [OR] 0.979, 95% confidence interval [CI] - 0.022- to 0.006, p = 0.001), BI (OR 0.993, 95% CI - 0.007 to - 0.004, p < 0.001), CDR 3.0 (OR 1.002, 95% CI 0.002‒0.236, p = 0.046), present teeth (OR 0.993, 95% CI - 0.007 to - 0.001, p = 0.011), functional teeth (OR 0.989, 95% CI - 0.011 to - 0.005, p < 0.001), and RSST (OR 0.960, 95% CI - 0.041 to - 0.007, p = 0.006) were significantly associated with DD vs ND discrimination. Simple evaluations of coughing (OR 1.056, 0.054‒0.198, p = 0.001) and rinsing (OR 1.010, 0.010‒0.174, p = 0.029) could also discriminate food form status. These simple evaluations provide insight into the discrepancies between food form status and eating abilities of LTCF residents. Periodic evaluations by the nursing caregiver may help to prevent aspiration by older individuals with dysphagia.

Relationship between two pressure-sensitive films for testing reduced occlusal force in diagnostic criteria for oral hypofunction.

OBJECTIVE: To measure the occlusal force in the same group of patients with the Dental Prescale 50H type R and the Dental Prescale II, examine the association between them, and determine the reference value for Dental Prescale II that corresponds to the 50H type R 200 N reference value used to make a diagnosis of oral hypofunction. BACKGROUND: Reduced occlusal force, a measure of frailty in older persons, was previously determined with Prescale 50H type R pressure-sensitive film, but it has been replaced by the Prescale II. MATERIALS AND METHODS: The study participants were 441 men and women aged ≥ 65 (mean, 71.8 ± 5.3) years. The occlusal force was measured with the two different types of pressure-sensitive film, and their association was examined. Receiver operating characteristic curves for the Prescale II measured values were created with the 200 N reference value used for the 50H type R film as the cut-off value. RESULTS: The analysis set included 391 participants for whom measurements were obtained using both the 50H type R and the Prescale II. Linear regression analysis produced regression equations, and a ROC curve analysis provided reference values of 500 N for the Prescale II (without pressure filter) and 350 N for the Prescale II (with pressure filter). CONCLUSION: In occlusal force tests for making a diagnosis of oral hypofunction, reference values for the Prescale II (without pressure filter) and for the Prescale II (with pressure filter) were determined. The findings suggested that the Prescale II can be used as a diagnostic examination for oral hypofunction.

Impact of oral health guidance on the tongue-lip motor function of outpatients at a dental hospital.

OBJECTIVE: To clarify the effect of oral health guidance on tongue-lip motor function in the outpatients visiting the Showa University Dental Hospital (Tokyo, Japan). BACKGROUND: The management of the oral function of older people visiting a dental hospital is important. Previous studies have revealed that tongue-lip motor function is easy to improve. However, the impact of oral health guidance on tongue-lip motor function in the outpatients of dental hospital requires further elucidation. MATERIALS AND METHODS: The participants (n = 35) included patients who were diagnosed with low tongue-lip motor function on evaluation by oral diadochokinesis (ODK) at the outpatient clinic. They underwent a second examination approximately 6-12 months later. Their demographic characteristics were recorded. Oral health guidance was provided through an educational leaflet on oral hypofunction when the participants visited the clinic. It included content on tongue twisters, voice training and a range of movement and muscle training of the tongue and lip. RESULTS: Following oral health guidance on tongue-lip motor function, the ODK values changed from 5.6 at the first examination to 6.0 at the second for /pa/, from 5.6 to 5.8 for /ta/ and from 5.2 to 5.4 for /ka/. This improvement was not significantly associated with age, sex, measurement period or number of visits. CONCLUSION: The findings of this longitudinal study suggested that oral health guidance using an oral hypofunction educational leaflet may be effective in improving the tongue-lip motor function of outpatients who had low tongue-lip motor function, regardless of the measurement period or the number of visits to the dental hospital.

Oral health status and its association with nutritional support in malnourished patients hospitalised in acute care.

OBJECTIVES: This cross-sectional study aimed to examine the oral health of malnourished acute-care hospital inpatients, who were the subjects of a nutritional support team (NST). We also aimed to elucidate the systemic and nutritional factors associated with the oral health of those patients. BACKGROUND: Interventions by NST are essential for inpatient nutrition management and require the active participation of dental professionals. However, information is limited regarding the state of oral health among acute-stage malnourished inpatients. MATERIALS AND METHODS: We enrolled 255 hospitalised patients (101 women, mean age: 69.7 ± 14.4 years) who were referred to an NST for nutrition management between April 2016 and July 2019. The main outcome was the Oral Health Assessment Tool (OHAT) scores. Moreover, we assessed participants' demographic characteristics, nutritional status, number of natural and functional teeth, posterior occlusal support, denture use, Dysphagia Severity Scale, whether oral health management was needed, and the methods of nutrition intake. RESULTS: Several participants presented with a deteriorated oral health. Consequently, oral health management was often regarded necessary in these patients. Approximately half were fed by parenteral or tube feeding. Multiple regression analysis revealed the OHAT score has a positive association with age (P = .008), and a negative association with body mass index (P = .009) and the method of nutrition intake (P = .028). CONCLUSION: Malnourished inpatients at an acute care hospital who were subject to an NST had a deteriorated oral health status. Additionally, poor oral health was associated with poor nutritional status and nutrition intake methods.

Pneumonia incidence and oral health management by dental hygienists in long-term care facilities: A 1-year prospective multicentre cohort study.

OBJECTIVE: To investigate the association between oral health management (OHM) by dental hygienists and the occurrence of pneumonia, and determine the effectiveness of OHM in pneumonia prevention. BACKGROUND: In long-term care facilities in Japan, the need for professional OHM is increasing with an increase in the number of severely debilitated residents. MATERIALS AND METHODS: A 1-year prospective multicentre cohort study was conducted using data from 504 residents (63 men; mean age: 87.4 ± 7.8 years) in Japanese long-term care facilities. Basic information, medical history, willingness to engage in oral hygiene behaviour, need for OHM and oral conditions were investigated at baseline. In addition, information on the occurrence of pneumonia was collected using a follow-up survey after one year. A Poisson regression analysis with robust standard errors was conducted, with pneumonia as the dependent variable, and factors associated with OHM and pneumonia occurrence as explanatory variables. RESULTS: Overall, 349 (69.2%) residents required OHM by dental hygienists during that year of follow-up. Of those, 238 (68.2%) were provided with OHM, and 18 (7.5%) developed pneumonia. Among the 111 patients (31.8%) who were not provided with OHM, 21 (18.9%) developed pneumonia. The OHM group had lower pneumonia rates than the non-OHM group (prevalence rate ratio: 0.374; 95% CI: 0.210-0.665). CONCLUSION: Oral health management by dental hygienists was associated with a lower incidence of pneumonia among residents of long-term care facilities, underlining the importance of professional OHM for such individuals. It is recommended that OHM be practised routinely in long-term care facilities.