Safety and Effectiveness of OnabotulinumtoxinA in Patients with Laryngeal Dystonia: Final Report of a 52-Week, Multicenter Postmarketing Surveillance Study.

This postmarketing surveillance study was conducted to evaluate the safety and effectiveness of onabotulinumtoxinA in Japanese patients with laryngeal dystonia (LD). Patients receiving onabotulinumtoxinA for the first time were enrolled and observed for up to 12 months following the first injection. Safety assessment included adverse drug reactions (ADRs), and effectiveness assessments included the Voice Handicap Index-10 (VHI-10) and physician's global assessment (PGA). ADRs were observed in 48 (5.8%) of 834 patients in the safety analysis set, including dysphonia in 43 (5.2%) patients and dysphagia in 7 (0.8%) patients. The change in total VHI-10 score (mean) in 790 patients included in the effectiveness analysis set showed that improvement in adductor LD peaked at 2 months after the first injection, while patients with abductor or mixed LD showed a gradual attenuation of effect 2-4 weeks post-injection. The change in total VHI-10 score in subsequent injections was generally similar to that following the first injection. The overall effectiveness rate according to the PGA was 93.4% (738/790 patients). The results demonstrate that onabotulinumtoxinA is a well-tolerated and effective treatment for LD in real-world clinical practice.

Relationship between Streptococcus mutans expressing Cnm in the oral cavity and non-alcoholic steatohepatitis: a pilot study.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a severe state of non-alcoholic fatty liver disease (NAFLD), which is pathologically characterised by steatosis, hepatocyte ballooning, and lobular inflammation. Host-microbial interaction has gained attention as one of the risk factors for NASH. Recently, cnm-gene positive Streptococcus mutans expressing cell surface collagen-binding protein, Cnm (cnm-positive S. mutans), was shown to aggravate NASH in model mice. Here, we assessed the detection rate of cnm-positive S. mutans in oral samples from patients with NASH among NAFLD. METHODS: This single hospital cohort study included 41 patients with NAFLD. NASH was diagnosed histologically or by clinical score. The prevalence of cnm-positive S. mutans, oral hygiene and blood tests, including liver enzymes, adipocytokines and inflammatory and fibrosis markers, were assessed in biopsy-proven or clinically suspected NASH among NAFLD. RESULTS: Prevalence of cnm-positive S. mutans was significantly higher in patients with NASH than patients without NASH (OR 3.8; 95% CI 1.02 to 15.5). The cnm-positive S. mutans was related to decreased numbers of naturally remaining teeth and increased type IV collagen 7S level (median (IQR) 10.0 (5.0-17.5) vs 20.0 (5.0-25.0), p=0.06; 5.1 (4.0-7.9) vs 4.4 (3.7-5.3), p=0.13, respectively). CONCLUSIONS: Prevalence of cnm-positive S. mutans in the oral cavity could be related to fibrosis of NASH among NAFLD.

Constipation in the elderly in a Japanese long-term medical facility: An ultrasonographic investigation.

This study aims to assess the fecal retention in elderly patients using colonic ultrasonography (US) in Japanese long-term care facility and determine the correlation between nutrition management methods and the fecal retention by US. This cross-sectional, single-center study was conducted in a long-term care facility in Japan. Patients with chronic constipation fulfilled the Rome III criteria for the diagnosis of functional constipation. US was performed on constipation patients with 4-day fecal retention before starting the standard management of constipation. After patients had defecated, nurses checked the outside of feces using King's Stool Chart and Bristol Stool Chart. All of 32 patients underwent the management of suppository laxative, the daily life independence level in grade C. In all cases, the King's Stool Chart did not detect > 200 g of fecal matter; the Bristol Stool Chart revealed type 5-7 in 56.2% of patients. The total parenteral nutrition and tube feeding did not completely detect type 1-2 in 0%. While the fecal retention groups comprised 15.6%, the non-fecal retention groups comprised 84.4%. The total parenteral nutrition did not completely detect the fecal retention in 0%. In the non-fecal retention groups, the King's Stool Chart indicated < 100 g in 81.8%, and the Bristol Stool Chart indicated type 5-7 in 100%. In conclusion, fecal properties of elderly constipation patients with the long-term parenteral nutrition should be assessed in follow-up examination by US, which is possible for personalized medical care by US, to avoid the administered regular management of constipation.

Effects of a Skin Barrier Cream on Management of Incontinence-Associated Dermatitis in Older Women: A Cluster Randomized Controlled Trial.

PURPOSE: The purpose of this study was to examine the effects of a skin barrier cream with moisturization and skin-protectant characteristics for improving the severity of incontinence-associated dermatitis (IAD) pertaining to the skin physiology and appearance. We measured the following outcomes: (1) skin physiological characteristics indicating skin protection and enhancement of the skin's moisture barrier (stratum corneum hydration, dermis hydration level, transepidermal water loss, and skin pH); and (2) changes in skin appearance (the degree of erythema and pigmentation, and the sulcus cutis condition). DESIGN: Single-blind, cluster randomized controlled trial. SUBJECTS AND SETTING: The study was conducted in a long-term care facility in Japan between November 7, 2011, and May 6, 2012. We used block randomization to obtain a random sample of 6 (4 experimental and 2 control) out of 10 available wards. All subjects were elderly women with IAD of the buttock or inner thigh. We assessed 295 patients, but only 33 met inclusion criteria; 18 were allocated to the experimental group and 15 were allocated to the control group. METHODS: All participants were managed with cleansing with a skin cleanser and application of a moisturizer daily. In addition, a skin barrier cream designed to enhance the skin's moisture barrier and act as a protective barrier was applied to the skin of patients in the experimental group 3 times a day when absorptive briefs were changed. Skin physiological and appearance characteristics were scored only at the buttock or thigh area. All data were collected on days 1 and 14 of the study. RESULTS: Univariate analysis found that the erythema index was lower in the intervention group than in the control group at day 14 (P = .004). Multivariate analysis found significant associations between use of the skin barrier cream and increased stratum corneum hydration (ß= .443, P = .031), decreased skin pH (ß=-.439, P = .020), and magnitude of erythema (ß=-.451, P = .018). CONCLUSIONS: Study findings suggest that a barrier cream designed to enhance the skin's moisture barrier and act as a skin protectant increased stratum corneum hydration, reduced cutaneous pH, and reduced erythema.

Exploring the prevalence of skin tears and skin properties related to skin tears in elderly patients at a long-term medical facility in Japan.

The identification of appropriate skin tear prevention guidelines for the elderly requires clinicians to focus on local risk factors such as structural alterations of the epidermis and dermis related to skin tears. The aim of this cross-sectional study is to explore the prevalence of skin tears and to explore skin properties related to skin tears in elderly Japanese patients at a long-term medical facility. After doing the prevalence study, 18 participants with skin tears and 18 without were recruited and an evaluation of their skin properties using 20-MHz ultrasonography, skin blotting and also Corneometer CM-825, Skin-pH-meterPH905, VapoMeter, Moisture Meter-D and CutometerMPA580 was undertaken. A total of 410 patients were examined, the median age was 87 years and 73·2% were women. The prevalence of skin tears was 3·9%, and 50% of skin tears occurred on the dorsal forearm. The changes in skin properties associated with skin tears included increased low-echogenic pixels (LEP) by 20-MHz ultrasonography, decreased type IV collagen and matrix metalloproteinase-2, and increased tumour necrosis factor-α by skin blotting. In conclusion, this study suggests that increased dermal LEP, including solar elastosis, may represent a risk factor for skin tears; this indicates that skin tear risk factors might not only represent chronological ageing but also photoageing.

The nature of sleep in 10 bedridden elderly patients with disorders of consciousness in a Japanese hospital.

No previous study has satisfactorily clarified the nature of sleep in elderly bedridden people with disorders of consciousness (DOC). The objective of the present study was to clarify the sleep states of 10 elderly bedridden patients with DOC in a Japanese hospital to facilitate provision of evidence-based nursing care and appropriate adjustment of patients' environments. Nocturnal polysomnography recordings were analyzed according to the standard scoring criteria, and the patients' sleep stages and quality were investigated. Of the 10 patients, 9 showed slow wave sleep (SWS), 4 showed very high values for sleep efficiency (96-100%), and in 3 of these patients, the percentage of SWS was ≥ 20%. Furthermore, three of these four patients had 200 or more changes in sleep stage. Although the mechanism is unknown, the amount of SWS combined with the value of sleep efficiency suggests that the quality of sleep is poor in elderly bedridden patients with DOC. Further study is needed to determine better indicators of good sleep in this population.

Controlled release of insulin from self-assembling nanofiber hydrogel, PuraMatrix™: application for the subcutaneous injection in rats.

The concept of this research is, using the acetyl-(Arg-Ala-Asp-Ala)4-CONH2 peptide hydrosol (PuraMatrix™, PM), to develop an new injectable formula of controlled insulin delivery for subcutaneous injection. PM has sol-gel phase transition behavior, and was developed as a scaffold in the field of tissue engineering. The aqueous media of the PM including insulin changed from a sol to a gel phase with increasing ion strength of phosphate ion and pH in working environments in vitro and in vivo. In this study, we examined the in vitro insulin dissolution behavior and the in vivo pharmacokinetics and pharmacodynamics after subcutaneous administration of PM-insulin sol (PM-Isol). In the in vitro release study, after PM-Isol was converted to a gel phase (PM-Igel), PM concentration-dependent and controlled release of insulin were observed at the final concentrations of PM between 0.1% and 2.0% (w/v). The PM-Isol is changed to gel form in vivo, and exhibited a sustained-release pharmacokinetics of insulin, where PM concentration-dependent prolongation of efficacy was found. The plasma glucose level markedly decreased, and the lowest plasma glucose level was maintained up to 24h when 2.0% (w/v) PM-Isol was administered subcutaneously to rats. The PM-Isol, we developed here, is applicable for the wild-type of insulin, and increased the bioavailability and hypoglycemic efficacy of insulin after subcutaneous injection. Hence, the PM is a useful inactive ingredient to produce various types of control-released system of insulin by making just a few changes in PM content of the formulation.

Vibration therapy accelerates healing of Stage I pressure ulcers in older adult patients.

OBJECTIVE: The present study investigated whether vibration therapy using a vibrator could facilitate the healing of Stage I pressure ulcers (PrUs) in older adults. METHODS: The study had a nonrandomized, blinded, controlled design. The subjects were hospital patients in long-term-care facilities with Stage I PrUs. In the experimental group, a vibrator (RelaWave; Matsuda Micronics Corp, Chiba, Japan) was used to apply vibration (frequency: 47 Hz; time: 10 seconds; amplitude modulation cycle: 15 seconds) for 15 minutes 3 times a day for up to 7 days, until Stage I PrUs healed. Apart from the vibration therapy, the experimental and control groups received the same care, which was provided according to PrU care guidelines. The number of healed ulcers was compared between 2 groups. RESULTS: The experimental group consisted of 16 patients with 20 Stage I PrUs; the control group consisted of 15 patients with 21 Stage I PrUs. In the experimental group, 8 (40.0%) PrUs healed; in the control group, 2 (9.5%) PrUs healed. The number of healed ulcers was significantly higher in the experimental group than in the control group (P = .033). The healing rate during the study period was significantly higher in the experimental group than in the control group (P = .018, logrank test). The hazard ratio adjusted for baseline risk factors was 0.031 (95% confidence intervals: 0.002-0.594, P = .021). The mean relative changes per day in wound area and intensity of redness were significantly greater in the experimental group than in the control group (P = .007, and P = .023, respectively). CONCLUSION: Based on these results, the use of the vibrator may facilitate the healing of Stage I PrUs.

Evaluation of comfort in bedridden older adults using an air-cell mattress with an automated turning function: measurement of parasympathetic activity during night sleep.

This study objectively evaluated the degree of comfort in bedridden older adults using an air-cell mattress with an automated turning mechanism. The sample included 10 bedridden women with verbal communication difficulties. The high frequency (HF) components of heart rate variability, which reflect parasympathetic nervous activity, were compared for the manual and automated turning periods. No significant differences in the HF component were observed in 5 of the participants. Significant increases in the HF component associated with automated turning were observed in 3 participants; however, the two participants with the lowest body mass index values exhibited a significant reduction in the HF component during the automated turning period. The results revealed that comfort might not be disturbed during the automated turning period.

A prospective cohort study of lower-extremity pressure ulcer risk among bedfast older adults.

OBJECTIVE: To estimate the incidence and identify risk factors for lower-extremity pressure ulcers in bedfast older adult patients. DESIGN: Prospective cohort study. SETTING: A 500-bed long-term-care facility in Japan. PATIENTS: A total of 259 patients who were aged 65 years or older, confined to bed, and without lower-extremity pressure ulcers at enrollment participated in the study. MAIN OUTCOME MEASURES: Incidence of occurrence, wound characteristics, and risk factors for lower-extremity pressure ulcers. The incidence of lower-extremity pressure ulcers per 100 person-years was 16.8 (n = 33). The most common sites of lesions were the toes and heels. Cox regression analysis indicated that 3 factors were independently related to new lower-extremity pressure ulcer risk: low ankle-brachial index value (hazards ratio 0.075; 95% confidence interval [CI], 0.023-0.242), length of bedfast period (hazards ratio 1.010; 95% CI, 1.004-1.015), and male gender (hazards ratio 2.951; 95% CI, 1.450-6.009). Receiver operating characteristic curve analysis showed the area under the curve was 0.760 (95% CI, 0.675-0.844) for the ankle-brachial index. Therefore, an ankle-brachial index cutoff level of 0.8 provided high sensitivity and adequate specificity. CONCLUSION: Lower-extremity pressure ulcers are a significant problem in bedfast older adult patients aged 65 years or older. Bedfast older adult patients who developed lower-extremity pressure ulcers in this study were believed to have arteriosclerosis; the patients' ulcers exhibited features of ischemic ulcers. The findings of the present study suggest that bedfast older adult patients with a low ankle-brachial index value, a long bedfast period, or male gender should be closely monitored for lower-extremity pressure ulcer development on admission to long-term-care facilities. In particular, the ankle-brachial index is recommended as a screening tool in this practice setting.

Comparison of two pressure ulcer preventive dressings for reducing shear force on the heel.

OBJECTIVE: We compared the shear forces exerted over the heel between a pressure ulcer preventive dressing and a thin-film dressing in a clinical setting. Interface pressures were measured as well. DESIGN: Quasi-experimental clinical trial. SETTING AND SUBJECTS: Participants were 30 elderly patients (5 men, 25 women; mean age, 86.4 +/- 8.0 years) hospitalized in a geriatrics hospital in Japan; all had a Braden score of less than 14 (mean, 10.1 +/- 1.1). Informed consent was obtained from all the patients.A shear force and pressure sensor including a strain gauge, and an oval airbag-type pressure sensor were used. METHODS: The sensor was attached to one heel using double-sided tape; then the target dressing was applied over the sensor and on the opposite heel to avoid the influence of the opposite heel on the shear force measurement. Interface pressures were measured with the patient in a stationary supine position; shear force was then measured at 0.2-second intervals, while the sheet was manually pulled at a velocity of around 5 cm/second. Shear force was determined by averaging the stable shear force lasting for 10 measurement points. RESULTS: The mean interface pressures with the PPD and the film dressings were 70.7 +/- 16.5 and 70.2 +/- 15.2 mmHg, respectively; this difference was not statistically significant. The shear force produced during the pulling of the sheet was 2.2 +/- 1.4 and 11.7 +/- 5.8 N, respectively (P < .001, Wilcoxon signed-rank test). CONCLUSIONS: The results of this study suggest that a dressing with a low-friction external surface (such as the pressure ulcer preventive dressing) can significantly reduce shear force. However, results also suggest that external dressings do not significantly reduce interface pressures and cannot be used as a substitute for heel elevation in an immobile patient.

Expression of hTERT mRNA in a mortal liver cell line during S phase without detectable telomerase activity.

Normal human liver cells have a limited capacity for proliferation due to telomere shortening, whereas immortalized cells prevent shortening of the 3' single strand telomeric repeat by expressing telomerases, including human telomerase reverse transcriptase (hTERT). The hTERT transcript contains three deletion sites that give rise to alternatively spliced variants (ASVs). Recently, hTERT expression was observed in cycling primary presenescent human fibroblasts, which were believed to lack hTERT expression and telomerase activity. hTERT mRNA was expressed in the synthesis (S) phase of the cell cycle. Although hTERT mRNA has eight isoforms, it is not known which of the hTERT ASVs are expressed in S phase. In order to determine the possible relationships between the cell cycle and ASV expressions, we measured the full-length isoform and ASVs of hTERT mRNA in a mortal liver cell line and immortal cell lines that were synchronized in S phase of the cell cycle. Using RT nested-PCR analysis, the full-length isoform and alpha-deletion ASV of hTERT were detected in the LI90 mortal liver cell line at points when cells in S phase represented >48% of the cell population without detectable telomerase activity. hTERT was always expressed in the HLE and Huh-7 hepatocellular carcinoma cell lines, regardless of the cell cycle. Our results suggest the possibility that telomerase is regulated in a cell cycle-dependent manner in normal liver cells.