Breathing irregularities before sleep onset on polysomnography in patients with heart diseases.

PURPOSE: Severe cardiac dysfunction can manifest with diurnal breathing irregularity. However, it remains to be clarified whether or not diurnal breathing irregularity is observed in patients with heart diseases, including relatively mild chronic heart failure (CHF), compared to those without heart diseases. METHODS: In this cross-sectional study, consecutive inpatients who were admitted for evaluation of sleep-disordered breathing were enrolled. We extracted 3.5 min of stable respiratory signals before sleep onset using polysomnography, analyzed the airflow data using fast Fourier transform, and quantified breathing irregularities using Shannon entropy S. RESULTS: A total of 162 subjects were evaluated. Among these, 39 subjects had heart diseases, including ischemic heart disease (IHD), atrial fibrillation (Af), CHF, and a history of aortic dissection. The values of Shannon entropy S of airflow signals in subjects with heart diseases were significantly higher than in those without heart diseases (p < 0.001). After excluding CHF, the Shannon entropy S was also significantly higher in subjects with heart diseases than in those without heart diseases (p < 0.001). The values of Shannon entropy S were significantly correlated with plasma brain natriuretic peptide levels (r = 0.443, p < 0.001). Although the values were also significantly correlated with body mass index, the presence of heart diseases was independently associated with breathing irregularity in the multiple logistic analysis. Matching analysis revealed consistent differences between subjects with heart diseases and without heart diseases. CONCLUSION: Breathing irregularity was observed before sleep onset in subjects with heart diseases who underwent polysomnography to diagnose sleep-disordered breathing.

Influence of oral health on frailty in patients with type 2 diabetes aged 75 years or older.

BACKGROUND: Poor oral health conditions are known to affect frailty in the older adults. Diabetes is a risk factor for both poor oral health and frailty, therefore, oral health status may affect frailty in diabetic patients more than in the general population. The purpose of this study was to evaluate the influence of oral health and other factors on frailty and the relationship among oral health, diabetes and frailty in older adult patients with type 2 diabetes. METHODS: Patients with type 2 diabetes aged 75 years or older were included in this cross-sectional study. Eligible patients were surveyed by questionnaire for frailty, oral health status, and cognitive and living functions. Factors influencing pre-frailty, frailty, and individual frailty screening index (FSI) classes were evaluated. RESULTS: Of the 111 patients analyzed, 66 cases (59.5%) were categorized as robust, 33 cases (29.7%) as pre-frailty, and 12 cases (10.8%) as frailty. The oral frailty index, the cognitive and living functions score, and BMI were found to be factors influencing pre-frailty or frailty. In the evaluation of individual FSI classes, BMI had an influence on those with a FSI ≤2. The cognitive and living functions score was a factor influencing those with FSI ≤3. The oral frailty index was found to have a significant influence on all FSI classes. CONCLUSIONS: Poor oral health has an influence on frailty in patients with type 2 diabetes aged ≥75. In this patient population, as frailty progresses, the impact of oral health on frailty may increase. TRIAL REGISTRATION: This study was retrospectively registered in UMIN-CTR ( UMIN000044227 ).

Evaluation of an advance care planning training program for practice professionals in Japan incorporating shared decision making skills training: a prospective study of a curricular intervention.

BACKGROUND: We developed a novel training program for health care professionals that incorporated shared decision making (SDM) skills training into an advance care planning (ACP) training course, the first in Japan. This study aimed to assess the training program's impact on health care professionals' knowledge, skill, attitudes, and confidence to initiate ACP. METHODS: Using the novel Japanese educational program, we evaluated the effect of 8-month programs conducted eight community training sites of professionals who can practice ACP in a local area in Aichi Prefecture (the Aichi ACP Project). SDM skills training was provided during the workshops conducted in the ACP training course, and the participants' satisfaction and understanding of the training were assessed. After the completion of two workshops, information on SDM skill results from the training and submitted assignments were collected anonymously from the training sites. RESULT: A total of 404 participants completed all education programs. After the first workshop, at least 95% of trainees stated that they were satisfied with the training and that it was useful for ACP practice. The evaluation of the results between the first and second workshops indicated improvement in SDM skills on some items of the SDM measures. In the second workshop, at least 90% of participants submitted implementation reports, and after the second workshop, a survey of confidence in ACP practice was administered, with responses indicating improvement. There were high levels of interest in education related to the ACP practices of oneself and others. CONCLUSIONS: This educational program can be an effective for developing professionals who can practice ACP with SDM skills.

Adapting the patient and physician versions of the 9-item shared decision making questionnaire for other healthcare providers in Japan.

BACKGROUND: In Japan, the number of older people with various health problems and difficulties in living is increasing. In order to practice patient-centered care for them, not only medical professionals but also multidisciplinary teams including care professionals and patients need to practice shared decision making (SDM) in the context of long-term care. For this reason, a measure of SDM in consultations with healthcare professionals (HCPs) other than physicians is needed. Therefore, this study aimed at adapting the patient and physician versions of the 9-item Shared Decision Making Questionnaire (SDM-Q-9, SDM-Q-Doc) for consultations with HCPs other than physicians in Japan. METHODS: A pair of SDM measures that can be used by HCPs other than physicians, "Care SDM-Questionnaire for care receivers (SDM-C-patient)" and "Care SDM-Questionnaire for care providers (SDM-C-provider)" were prepared based on the Japanese versions of the SDM-Q-9 and SDM-Q-Doc. The internal consistency and conceptual structure of these measures were tested by secondary analysis of data from 496 participants from a workshop on SDM for different HCPs. Measurement invariance were tested by multigroup confirmatory factor analysis (CFA) for the patient (SDM-C-patient and SDM-Q-9) and provider (SDM-C-provider vs. SDM-Q-Doc) versions. RESULTS: Both the Japanese SDM-C-patient and SDM-C-provider demonstrated high internal consistencies (Cronbach's α coefficient was 0.90 and McDonald's ω coefficient was 0.90 for both measures). CFA showed one-factor structures for both measures and original measures for physicians. Moreover, multigroup CFA showed configural and metric invariance between the novel care measures and original physician's measures. CONCLUSIONS: Thus, the novel SDM measures for care providers in Japan as well as the original physician's measures could be used in training setting. As these measures were tested only in a training setting, their reliability and validity as new measures for care should be tested in a clinical setting in future.

Improving the quality of community primary palliative care in COPD: A qualitative study of health-care providers.

Primary palliative care is essential for the continuity of care in severe COPD. This study aimed to identify essential factors and aspects to enhance the quality of primary palliative care for adults with severe COPD living in the community. Interviews with medical professionals from six institutions located in two major metropolitan areas in Japan were conducted, and these interviews were analyzed by using a qualitative content analysis approach. Results indicate that effective collaborative communication among team members, long-term care insurance system and related services, and palliative care techniques were the primary themes.

[A systematic review of distress due to pneumonia experienced by older people with end-stage dementia].

AIM: Many older people with end-stage dementia die of pneumonia, but the details of their distress have been unclear. The present study clarified the distress experienced by such individuals due to pneumonia. METHODS: We searched for literature corresponding to 5 clinical questions (CQs) concerning including "What distress is experienced by older people with end-stage dementia due to pneumonia (CQ1) ?" using a search formula with the Web version of the Central Medical Magazine, MEDLINE (STN)/EMBASE (STN), Cochrane Library, and extracted 604 articles. Forty-two articles corresponding to 5 CQs were extracted by primary screening using abstracts, and 17 articles were adopted after the secondary screening. A total of six articles corresponding to CQ1 were ultimately analyzed. RESULTS: Older people with end-stage dementia who died of pneumonia reported more discomfort and dyspnea than those who died of dehydration. Their main symptoms were respiratory symptoms, such as cough, sputum, and dyspnea, a fever and somnolence. Distress such as dyspnea and discomfort among older people with end-stage dementia recovering from pneumonia peaked on the day of the diagnosis. Furthermore, in older people with end-stage dementia dying of pneumonia, distresses began approximately one week before death and peaked on the day before death. A few days before death, several distressing symptoms, such as pain, dyspnea and restlessness/agitation, were often observed at the same time. CONCLUSIONS: If older people with end-stage dementia contract pneumonia and die from it, attentive palliative care is needed to manage their severe discomfort, dyspnea and other sources of distress.

Large Long-Distance Contributions to the Electric Dipole Moments of Charged Leptons in the Standard Model.

We reevaluate the electric dipole moment (EDM) of charged leptons in the standard model using hadron effective models. We find unexpectedly large EDM generated by the hadron level long-distance effect, d_{e}=5.8×10^{-40}, d_{µ}=1.4×10^{-38}, and d_{τ}=-7.3×10^{-38} e cm, with an error bar of 70%, exceeding the conventionally known four-loop level elementary contribution by several orders of magnitude.

Polysomnographic features of low arousal threshold in overlap syndrome involving obstructive sleep apnea and chronic obstructive pulmonary disease.

PURPOSE: In patients with overlap syndrome (OVS), the pathophysiologies of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease can interact with one another. Focusing on low arousal threshold, the authors evaluated polysomnographic features of OVS patients. METHODS: This retrospective, multicenter study was conducted at three hospitals in Japan. Patients aged ≥ 60 years who underwent polysomnography and pulmonary function testing were reviewed. Severity of airflow limitation (AFL) was classified according to the Global Initiative for Chronic Obstructive Lung Disease criteria. Low arousal threshold was predicted based on the following polysomnography features: lower apnea-hypopnea index (AHI); higher nadir oxygen saturation, and larger hypopnea fraction of total respiratory events. These features were compared among patients with only OSA (n = 126), OVS with mild AFL (n = 16), and OVS with moderate/severe AFL (n = 22). RESULTS: A low arousal threshold was more frequently exhibited by OVS patients with moderate/severe AFL than by those with OSA only (p = 0.016) and OVS with mild AFL (p = 0.026). As forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) decreased in OVS patients, the mean length of apnea decreased (r = 0.388, p = 0.016), hypopnea fractions increased (r = - 0.337, p = 0.039), and AHI decreased (r = 0.424, p = 0.008). FEV1/FVC contributed to low arousal threshold independent of age, sex, smoking history, hospital, or body mass index in all subjects (OR 0.946 [95% CI 0.909-0.984]) and in OVS patients (OR 0.799 [95% CI 0.679-0.940]). CONCLUSIONS: This study first described peculiar polysomnographic features in OVS patients with moderate/severe AFL, suggesting a high prevalence of low arousal threshold.

Silodosin as second-line α-blocker monotherapy in patients with benign prostatic hyperplasia: A prospective observational study.

OBJECTIVE: To assess the efficacy of silodosin as second-line α-blocker monotherapy in patients with lower urinary tract symptoms as a result of benign prostatic hyperplasia. METHODS: Men who were given an α-blocker other than silodosin for ≥8 weeks, aged ≥50 years, had a total International Prostate Symptom Score ≥13 and quality of life index ≥4 were enrolled. After treatment with 8 mg/day silodosin for 8 weeks, symptoms and treatment satisfaction were assessed. If the patients still complained and hoped for readministration of the first-line α-blocker, the previous medication was administered again for 8 weeks in the case of persisting symptoms, and efficacy was again evaluated. RESULTS: A total of 73 patients were enrolled and analyzed at 8 weeks. Silodosin administration significantly improved the International Prostate Symptom Score and Overactive Bladder Symptom Score. The quality of life index was improved by at least 1 point in 49.3% patients, and its mean change was significantly greater in the group with previous naftopidil treatment than in those with tamsulosin. A total of 59 patients hoped to continue silodosin, and 13 requested administration of the first-line α-blocker. Previously taking naftopidil and having a shorter duration of prior α-blocker treatment at baseline were associated with silodosin continuation. Although prior α-blocker readministration in the 13 patients did not show significant efficacy, six preferred to continue the previous α-blocker. CONCLUSIONS: Silodosin represents an effective second-line α-blocker monotherapy, even in those who still have moderate lower urinary tract symptoms.

[The development of pneumothorax in an elderly woman during treatment for nontuberculous mycobacterium].

We report the case of an 82-year-old woman who developed pneumothorax during treatment for nontuberculous mycobacterium (NTM). In year X, she was diagnosed with NTM at another hospital after abnormalities were pointed out on a chest X-ray. She received no treatment for NTM at that time. Antibiotic treatment was introduced at the department of respiratory medicine in our hospital in year X+15. The regimen was composed of clarithromycin (800 mg/day), ethambutol (750 mg/day) and rifampicin (600 mg/day); however, treatment with the three-drug antibiotic regimen was canceled at her request and changed to erythromycin. She was then referred to our department. However, right-side cavity wall thickening was detected on chest CT in year X+17.We resumed clarithromycin (600 mg/day), ethambutol (750 mg/day) and rifampicin (450 mg/day). On the 43rd day after treatment with three types of antibiotics, she felt dyspnea and she was admitted to the hospital and was diagnosed with right-side pneumothorax. The pneumothorax was thought to have been caused by a break in the adhesion of the cavity wall. The visceral pleura was weakened by the exacerbation of NTM and the thickness of the cavity wall was improved after the resumption of antibiotic therapy. This report is considered to be an important case in which pneumothorax developed as a complication in an elderly patient during treatment for NTM.

Sleep Apnea and Circadian Extracellular Fluid Change as Independent Factors for Nocturnal Polyuria.

PURPOSE: We investigated the relationships among nocturnal polyuria, sleep apnea and body fluid volume to elucidate the pathophysiology of nocturia in sleep apnea syndrome. MATERIALS AND METHODS: We enrolled 104 consecutive patients who underwent polysomnography for suspected sleep apnea syndrome. Self-assessed symptom questionnaires were administered to evaluate sleep disorder and lower urinary tract symptoms, including nocturia. Voiding frequency and voided volume were recorded using a 24-hour frequency-volume chart. Body fluid composition was estimated in the morning and at night using bioelectric impedance analysis. Frequency-volume chart data were analyzed in 22 patients after continuous positive airway pressure therapy. RESULTS: Patients with nocturnal polyuria showed a higher apnea-hypopnea index (33.9 vs 24.2, p = 0.03) and a larger circadian change in extracellular fluid adjusted to lean body mass (0.22 vs -0.19, p = 0.019) than those without nocturnal polyuria. These relations were more evident in patients 65 years old or older than in those 64 years or younger. A multivariate linear regression model showed an independent relationship of nocturnal polyuria with the apnea-hypopnea index and the circadian change in extracellular fluid adjusted to lean body mass (p = 0.0012 and 0.022, respectively). Continuous positive airway pressure therapy significantly improved nocturnal polyuria and nocturia only in patients with nocturnal polyuria. CONCLUSIONS: This study identified sleep apnea and the circadian change in extracellular fluid as independent factors for nocturnal polyuria.

Isolation and structure of vanitaracin A, a novel anti-hepatitis B virus compound from Talaromyces sp.

Two new tricyclic polyketides, vanitaracin A (1) and B (2), together with three novel compounds 3, 4 and 5, were isolated from a culture broth of a fungus, Talaromyces sp. The chemical structures of these compounds were determined from spectroscopic data (1D/2D NMR, MS and IR). The five isolated compounds were then tested for anti-hepatitis B virus (HBV) activity and vanitaracin A was found to exhibit an IC50 value of 10.5 µM using a HBV-susceptible cell line. By contrast, the derivative 2 displayed weak anti-HBV action, which suggested that the substituents at C-9 in 1 are likely to be important for its antiviral activity. We believe the two vanitaracin derivatives constitute a new class of anti-HBV agents.

Signals of vitellogenesis and estrus in female hawksbill turtles.

This study reports a viable means of identifying the vitellogenic cycle and limited estrus period in hawksbill turtles for the purposes of developing captive breeding program, based on the combination of blood metabolite parameters (triglyceride, total protein, and calcium levels), feeding status, and ovary condition. Follicle size of two focal captive females showed clear seasonal changes, with major development occurring between March and May (19.0-24.4 mm), and exceeding 25 mm between June and September. Triglyceride, total protein, and calcium levels dropped with follicular development and maintenance (March to October), and then began to rise when follicular retraction occurred from October onwards. The two focal turtles reduced food intake during intensive follicular development (April to May). These findings suggest that blood metabolite parameters and feeding conditions are inferred by the vitellogenic cycle. An additional 10 females exhibiting follicular development were mated with a single male for 7-day period between May and June. Follicle size was measured immediately prior to pairing, and a statistically significant difference in follicle size of 10 females was recorded between the seven failed (20.9 mm) and three successful (23.6 mm) mating events. This indicates follicle development is essential to successful mate and monitoring of vitellogenic cycle may help improve the success rates of captive hawksbill breeding programs.

Induction of oviposition by the administration of oxytocin in hawksbill turtles.

We set out to develop an oviposition induction technique for captive female hawksbill turtles Eretmochelys imbricata. The infertile eggs of nine females were induced to develop by the administration of follicle-stimulating hormone, after which we investigated the effects of administering oxytocin on oviposition. Seven of the turtles were held in a stationary horizontal position on a retention stand, and then oxytocin was administrated (0.6-0.8 units/kg of body weight; 5 mL). The seven turtles were retained for a mandatory 2 h period after oxytocin administration, and were then returned to the holding tanks. As the control, normal saline (5 mL) was administered to the other two turtles, followed by the administration of oxytocin after 24 h. The eggs in oviducts of all nine turtles were observed by ultrasonography at 24 h after oxytocin administration. The control experiment validated that stationary retention and normal saline administration had no effect on egg oviposition. Eight of the turtles began ovipositing eggs at 17-43 min after oxytocin administration, while one began ovipositing in the holding tank immediately after retention. All turtles finished ovipositing eggs within 24 h of oxytocin administration. This report is the first to demonstrate successful induced oviposition in sea turtles. We suggest that the muscles in the oviducts of hawksbill turtles may respond to relatively lower doses of oxytocin (inducing contractions) compared to land and freshwater turtles (4-40 units/kg) based on existing studies.

Successful Response to Golimumab in a Case of Relapsing Polychondritis Overlapping with Ulcerative Colitis.

A 51-year-old Japanese man was diagnosed with left-sided ulcerative colitis (UC) at age 41. He was treated with mesalazine and azathioprine and maintained remission. At age 51, the patient developed bloody stools, abdominal pain, scleritis, arthritis, cough, bloody sputum, and pericardial effusion. Considering that pericardial effusion is an atypical extraintestinal complication of UC, and the patient met the diagnostic criteria for relapsing polychondritis (RP), a diagnosis of RP complicating a relapse of UC was made. Steroid therapy was administered, and both diseases improved. Golimumab, an anti-tumor necrosis factor-α inhibitor, was introduced as maintenance therapy for UC. All symptoms, including pericardial effusion, improved. Subsequently, no relapse of UC or RP was observed. As only a few cases of RP overlapping with UC have been reported and no treatment protocol has been established, we considered this case valuable and worthy of publication.

Predictors for the Clinical Efficacy of Tramadol for Cancer Pain.

CONTEXT: Tramadol is conditionally recommended for cancer pain and is a less expensive drug compared to strong opioids. Thus, tramadol may help reduce health care costs. OBJECTIVES: To investigate factors that predict the clinical efficacy of tramadol for cancer pain. METHODS: A retrospective study using electronic medical records was conducted on patients who received tramadol for cancer pain from January 2016 to December 2020. Patients who continued tramadol for >28 days or discontinued tramadol before 28 days owing to pain improvement were considered as clinical efficacy cases. RESULTS: We identified 183 eligible patients; 104 cases had clinical efficacy. The median starting tramadol daily dose was 100 mg, and the median administration duration was 22 days. Overall, 169 patients (92.3%) discontinued tramadol; pain improvement was the most common reason (34.9%). Age (>70 years), a performance status of 0-1, and an albumin-bilirubin grade of 1 were independent predictors for the clinical efficacy of tramadol. Patients with multiple predictors had significantly higher achievement rates than those without. CONCLUSION: Tramadol could have greater clinical efficacy for cancer pain in patients who are elderly, have good performance status, and have good liver function.

Hyperprogressive disease in lung metastases without target lesion progression after durvalumab consolidation therapy: A case report.

Hyperprogressive disease (HPD) is a novel progressive pattern that occurs after immune checkpoint inhibitor (ICI) administration. Here, a 74-year-old woman who had undergone right lower lobectomy for lung cancer received curative chemoradiotherapy followed by consolidation therapy with durvalumab for metastatic recurrence confined to the mediastinal lymph nodes. Three weeks later, multiple randomly distributed nodular shadows appeared on chest CT, and thoracoscopic lung biopsy led to the diagnosis of multiple pulmonary metastases. HPD may be suspected when multiple metastases appear in new organs early after the administration of ICIs. This phenomenon may occur not only with ICI monotherapy but also with the administration of ICIs after chemoradiotherapy. Therefore, patients who have received radiation therapy should also be given similar attention early after the administration of ICIs.

Antimicrobial peptide defensin: identification of novel isoforms and the characterization of their physiological roles and their significance in the pathogenesis of diseases.

Defensins comprise a family of cationic antimicrobial peptides containing a specific six-cysteine motif. Their contribution to the host defense against microbial invasion and the control of normal flora have been previously described. Some of the ß-defensin isoforms are predominantly expressed in the epididymis and showed a region-specific expression pattern in the epididymis, which thus suggested that these isoforms may possess epididymis-specific functions in addition to antimicrobial activities. A sequence variant of the ß-defensin 126 gene has been shown to be associated with reductions in the human sperm function, thus supporting this hypothesis. Furthermore, defensins have the capacity to chemoattract immune cells and induce the secretion of inflammatory cytokines. Mice expressing human neutrophil α-defensin showed more severe lung injuries after the aspiration of acidic contents than did control mice. Recent investigations regarding copy number variations of human defensin genes also suggest the significance of defensin in the pathogenesis or the worsening of chronic obstructive pulmonary diseases, sepsis and psoriasis.