Simple mathematical model for predicting COVID-19 outbreaks in Japan based on epidemic waves with a cyclical trend.

BACKGROUND: Several models have been used to predict outbreaks during the COVID-19 pandemic, with limited success. We developed a simple mathematical model to accurately predict future epidemic waves. METHODS: We used data from the Ministry of Health, Labour and Welfare of Japan for newly confirmed COVID-19 cases. COVID-19 case data were summarized as weekly data, and epidemic waves were visualized and identified. The periodicity of COVID-19 in each prefecture of Japan was confirmed using time-series analysis and the autocorrelation coefficient, which was used to investigate the longer-term pattern of COVID-19 cases. Outcomes using the autocorrelation coefficient were visualized via a correlogram to capture the periodicity of the data. An algorithm for a simple prediction model of the seventh COVID-19 wave in Japan comprised three steps. Step 1: machine learning techniques were used to depict the regression lines for each epidemic wave, denoting the "rising trend line"; Step 2: an exponential function with good fit was identified from data of rising straight lines up to the sixth wave, and the timing of the rise of the seventh wave and speed of its spread were calculated; Step 3: a logistic function was created using the values calculated in Step 2 as coefficients to predict the seventh wave. The accuracy of the model in predicting the seventh wave was confirmed using data up to the sixth wave. RESULTS: Up to March 31, 2023, the correlation coefficient value was approximately 0.5, indicating significant periodicity. The spread of COVID-19 in Japan was repeated in a cycle of approximately 140 days. Although there was a slight lag in the starting and peak times in our predicted seventh wave compared with the actual epidemic, our developed prediction model had a fairly high degree of accuracy. CONCLUSION: Our newly developed prediction model based on the rising trend line could predict COVID-19 outbreaks up to a few months in advance with high accuracy. The findings of the present study warrant further investigation regarding application to emerging infectious diseases other than COVID-19 in which the epidemic wave has high periodicity.

Effect of Ankle Weights as a Frailty Prevention Strategy in the Community-Dwelling Elderly: A Preliminary Report.

Since the start of the COVID-19 pandemic, many healthy older adults have been less willing to engage in group exercise for fear of contracting this illness. Therefore, there is a need for an effective home-based exercise program to prevent frailty in the elderly. In this study, we assessed the effectiveness of ankle weights as a frailty prevention device for older adults. The study participants were aged 50−90 years and were screened for falls using the Motor Fitness Scale. Participants were divided into two age groups (≤70 and >70 years) for analysis. Older community-dwelling adults were invited to use ankle weights for 3 months. Seventy-four people responded to the invitation. Physical and cognitive status and performance (body composition, grip strength, standing on one leg with eyes open, the 30 s chair stand test (CS-30), Timed Up and Go test, walking speed, body sway, Japanese version of the Montreal Cognitive Assessment) were assessed before and after 3 months of intervention. CS-30 performance improved during the study. CS-30 reflects lower limb/trunk muscle strength and can be used to indicate the risk of falls. Wearing ankle weights can be recommended for strengthening the muscles of the lower limb and trunk in the elderly.

Gosha-Jinki-Gan Improved Erectile Dysfunction Caused by Anti-Cancer Agent Oxaliplatin by Decreasing Transcriptional Expression of Phosphodiesterase-5 in Rats.

BACKGROUND: A platinum-containing anti-cancer agent, oxaliplatin (L-OHP), is known to induce peripheral neuropathy, including erectile dysfunction (ED) as a side effect, while Gosha-jinki-gan (GJG) is a traditional Japanese herbal medicine mainly used for peripheral neuropathy. AIM: To investigate the effect of GJG on L-OHP-induced ED in rats. METHODS: Twelve-week-old male Wister/ST rats were categorized into the following groups: Sham, Sham+GJG, L-OHP, and L-OHP+GJG (each n = 10). The L-OHP and L-OHP+GJG groups were injected intravenously with L-OHP (4 mg/kg) for 2 consecutive days in the first week. Statistical significance was determined using Bonferroni's multiple comparison test. OUTCOMES: At the end of the study period, erectile function was evaluated by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP) after cavernous nerve stimulation. Western blot analysis was used to assess the neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) levels, and quantitative polymerase chain reaction was used to assess the expression of phosphodiesterase-5 (PDE-5) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1. RESULTS: The ICP/MAP ratio of L-OHP rats (0.34 ± 0.06) was significantly lower than that of Sham rats (0.67 ± 0.03, P < .01), however, the ICP/MAP ratio of L-OHP+GJG rats (0.55 ± 0.01) was significantly higher than that of L-OHP rats (P < .01). There were no significant differences in the nNOS and eNOS protein expression between both groups (P > .05). GJG administration significantly decreased PDE-5 and NADPH oxidase-1 messenger RNA expressions in the L-OHP+GJG group. CLINICAL TRANSLATION: This animal model study suggests that GJG might be effective for erectile function in cancer survivors. STRENGTHS & LIMITATIONS: Our study identified that GJG had no notable side effects in the treated group. Further investigation of the cavernous nerve would also help elucidate the mechanism of GJG effect, which is a limitation of this study. CONCLUSION: We found that GJG administration improved L-OHP-induced ED by improving transcriptional PDE-5 expression. Kataoka T, Kawaki Y, Kito Y, et al. Gosha-Jinki-Gan Improved Erectile Dysfunction Caused by Anti-Cancer Agent Oxaliplatin by Decreasing Transcriptional Expression of Phosphodiesterase-5 in Rats. Sex Med 2022;10:100484.

Influence of anticancer agents on sexual function: An in vivo study based on the US FDA Adverse Event Reporting System.

BACKGROUND: Patients with cancer are treated with chemotherapeutics that cause adverse effects, including erectile dysfunction (ED). OBJECTIVES: We investigated erectile function in rats after the administration of anticancer agents based on data retrieved through mining of the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database. MATERIALS AND METHODS: The statistical signal strength for the association between anticancer drugs and ED was calculated using the reporting odds ratio (ROR). A drug-event combination was detected when the lower limit of the 95% confidence interval (CI) of the ROR exceeded 1.00. Rats were administered anticancer agents detected in the FDA AERS analysis. Erectile function was assessed using intracavernous pressure (ICP) and mean arterial pressure (MAP) analysis after electrical stimulation of the cavernous nerve. Statistical significance was determined using Welch's t-test or two-way ANOVA. RESULTS: Melphalan (L-PAM; ROR = 4.72, 95% CI = 2.78-8.00), vincristine (VCR; ROR = 2.47, 95% CI = 1.54-3.97), docetaxel (DTX; ROR = 2.25, 95% CI = 1.28-3.95), methotrexate (MTX; ROR = 1.96, 95% CI = 1.39-2.75), and doxorubicin (DOX; ROR = 1.82, 95% CI = 1.07-3.19) enhanced ED risk. L-PAM and MTX decreased the ICP/MAP ratio 1 week after administration. VCR and DOX decreased erectile function 4 weeks after administration. DTX decreased erectile function at all assessed time points. DISCUSSION AND CONCLUSION: Certain anticancer agents should be considered risk factors for ED. Our results provide possible treatment strategies for maintaining erectile function in cancer survivors, including careful erectile function monitoring after treatment.

Knowledge, attitudes, and practices regarding COVID-19 among pharmacists partnering with community residents: A national survey in Japan.

BACKGROUND: Community pharmacists play an important role in reducing COVID-19-related secondary health problems. However, the knowledge, attitudes, and practices (KAP) regarding COVID-19 among pharmacists in Japan have not yet been elucidated. METHODS: We conducted a web-based questionnaire survey among 1,137 pharmacists working in health support pharmacies (HSPs) in Japan. These pharmacists are responsible for providing health consultations to community residents. We assessed COVID-19-related KAP among pharmacists and compared the results for two age groups: ≤49 years and ≥50 years. We used multiple regression analysis to examine which factors influence KAP scores regarding COVID-19. RESULTS: From among the 2,141 HSPs in Japan, a total of 1,137 pharmacists, each representing a different HSP, responded to the survey. The results indicated that since the beginning of the COVID-19 pandemic, pharmacists have been providing consultations about COVID-19 to local residents, covering topics such as "Effective infection prevention methods" (60.6%) and "What the COVID-19 pandemic would be" (48.8%). Importantly, 73.5% of the pharmacists felt they "did not have enough information about COVID-19." The main information resources about COVID-19 were Internet (91.2%) and television (78.9%). Across all respondents, the mean knowledge score (4.17/10) was lower than the mean scores for attitudes (7.26/10) and practices (5.79/10). Multiple regression analysis showed that having enough information about COVID-19 was a factor strongly associated with total KAP scores (p<0.001; 95% confidence interval, -1.344 to -0.540). CONCLUSIONS: Pharmacists working in community pharmacies provide residents with information related to COVID-19. In this role as a health partner, these pharmacists need a way to strengthen and expand their knowledge, and moreover, their ability to support community residents. Learning more about the available academic and scientific information, as well as having access to accurate epidemiological information, can offer a means of reaching these goals.

Oxaliplatin, an Anticancer Agent, Causes Erectile Dysfunction in Rats due to Endothelial Dysfunction.

BACKGROUND: Chemotherapeutics, one of the standard treatment options for cancer worldwide, have various adverse effects, including erectile dysfunction (ED). AIM: To investigate erectile function in an animal model after administration of the anticancer agent oxaliplatin (L-OHP). METHODS: Male Wistar/ST rats were divided into 2 groups: L-OHP rats (n = 21), which were intravenously administered L-OHP (4 mg/kg; twice a week for 4 weeks), and Control rats (n = 21), which were injected with the same volume of 5% glucose solution, using the same dosing schedule. At the end of the study period, erectile function was evaluated by measuring intracavernous pressure (ICP) and mean arterial pressure (MAP) after cavernous nerve stimulation (n = 9-10). Endothelial function was evaluated with an isometric tension study using corpus cavernosum strips (n = 11). Western blot analysis was used to assess neuronal nitric oxide (nNOS) and endothelial NO synthase (eNOS) protein levels (n = 7). Real-time quantitative polymerase chain reaction (qRT-PCR) was used to assess the expression of inflammation- and oxidative stress-related markers (nicotinamide adenine dinucleotide phosphate oxidase-1, p22phox, interleukin [IL]-6, and nuclear factor-kappa B) (n = 6). Statistical significance was determined using the Student's t-test. OUTCOMES: The L-OHP group had a significantly lower ICP:MAP ratio than the control group (P < .05). Compared to the Control group, the L-OHP group exhibited significantly lower responses to ACh and eNOS protein levels and significantly higher inflammatory biomarker levels. CLINICAL TRANSLATION: The results based on this animal model indicate that use of the anticancer agent L-OHP should be considered as a risk factor for ED occurring via reduction of NO bioavailability in humans; our results provide possible treatment strategies for maintaining the erectile function of cancer survivors. STRENGTHS AND LIMITATIONS: Our study showed that the anticancer agent L-OHP has the propensity to cause ED in rats. A major limitation of this study is the lack of an established cure for ED associated with L-OHP and the lack of clinical evidence. CONCLUSIONS: L-OHP causes ED in rats via reduction of NO bioavailability caused by endothelial dysfunction. Kataoka T, Mori T, Suzuki J, et al. Oxaliplatin, an Anticancer Agent, Causes Erectile Dysfunction in Rats due to Endothelial Dysfunction. J Sex Med 2021;18:1337-1345.

Iron deposition in autopsied liver specimens from older patients receiving intravenous iron infusion.

BACKGROUND: Vitamins and minerals are routinely administered by total parenteral nutrition (TPN). However, in Japan, adjustments in iron dosage are difficult because blended mineral preparations are often used. It is therefore unclear whether the iron content is appropriate in cases of long-term TPN. The aim of the study was to assess the influence of iron administration by long-term TPN on iron deposition in post-mortem liver samples isolated from older deceased patients. METHODS: Liver tissues were collected from post-mortem autopsies of 187 patients over a period of 15 years. Samples were stained with Prussian blue and histologically evaluated from Grade 0-V by at least three different observers. Specimens with positive and negative iron staining were compared, and positive samples were grouped according to the level and distribution of the staining. Post-mortem blood obtained from the subclavian vein during autopsy was also analysed. Samples were collected for the measurement of unsaturated serum iron, serum iron, albumin, prealbumin, hepcidin, and IL-6 concentrations. RESULTS: Iron accumulation in the liver was significantly higher in male patients (p = 0.005) with a history of surgery (p = 0.044) or central vein administration of iron (p<0.001). Additionally, the duration of TPN in the iron-positive group was significantly longer than in the iron-negative group (p = 0.038). Serum analysis revealed that unsaturated serum iron was significantly higher in the iron-negative group and that ferritin and serum iron were significantly higher in the iron-positive group. No other statistically significant differences were observed between the two groups. CONCLUSIONS: Chronic intravenous administration of iron was associated with iron deposition in the liver, even when given the minimum recommended dosage. In long-term TPN patients, the iron dose should therefore be carefully considered.

[The consciousness survey and the effect of educational intervention of Advance Care Planning (ACP) including post-mortem to elderly residents living in old New Town of big city].

AIM: Awareness reform aims to enable survival in an aging society, and ultimately, improve healthcare. An ideal way to achieve this is by implementing Advance directive (Ad) and Advance Care Planning (ACP), which do not usually include postmortem events. This study aims to create opportunities for Ad and ACP to include the postmortem period as a trigger for this awareness reform. METHODS: We conducted an Ad/ACP enlightenment lecture, and a questionnaire survey pre- and post-lecture for the elderly in old New Town, which is known for its aging society. The questionnaire comprised 38 multiple-choice questions covering 6 themes assuming an advanced state of dementia. RESULTS: There were 35 participants (7 men and 22 women) aged 40-89 years. Several people left during the lecture, making it difficult to capture the precise transformation effect with regard to changing of mind. However, the effect of enlightenment was identified as a result of the consciousness survey. A statistically significant change in consciousness occurred in response to social contribution after death. Furthermore, notably more people wanted emergency transportation compared to those wanting resuscitation and extension of life. CONCLUSIONS: The medical treatment desired might vary over time. Even the desire for life extension may differ significantly among individuals. This survey indicated a divergent view between the general public and medical staff, regarding a series of medical actions. We must persistently promote opportunities for enlightenment in cooperation with the general public (i.e., the communities and families we serve).

Hepatitis B infection reported with cancer chemotherapy: analyzing the US FDA Adverse Event Reporting System.

We conducted data mining using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database on spontaneously reported adverse events to evaluate the association between anticancer drug therapy and hepatitis B infection. Reports of hepatitis B infection were retrieved from the FAERS database. The reporting odds ratio (ROR) was used to estimate the association between hepatitis B infection and various anticancer agents and drug combinations. We detected statistically significant risk signals of hepatitis B for 33 of 64 anticancer agents by ROR (26 cytotoxicity drugs and seven molecular-targeted drugs). We focused on molecular-targeted drugs and assessed the risk of hepatitis B from specific anticancer drug combinations. The frequency of hepatitis B infection was significantly high for drugs such as rituximab, bortezomib, imatinib, and everolimus. The addition of cyclophosphamide, doxorubicin, and fludarabine to drug combinations additively enhanced the frequency of hepatitis B infection. There were no reports on hepatitis B infection associated with trastuzumab or azacitidine monotherapy. However, trastuzumab-containing regimens (e.g., combinations with docetaxel or paclitaxel) were correlated with the incidence of hepatitis B infection, similar to azacitidine monotherapy. Our findings suggest that the concomitant use of anticancer drugs, such as trastuzumab, taxane, and azacitidine, may contribute to the risk of hepatitis B infection. The unique signals detected from the public database might provide clues to eliminate the threat of HBV in oncology.

Determination of methylmalonyl coenzyme A by ultra high-performance liquid chromatography tandem mass spectrometry for measuring propionyl coenzyme A carboxylase activity in patients with propionic acidemia.

Propionic acidemia (PA) is an inherited metabolic disease caused by low activity of propionyl coenzyme A (CoA) carboxylase (PCC), which metabolizes propionyl-CoA into methylmalonyl-CoA. Although many patients with PA have been identified by tandem mass spectrometry since the test was first included in neonatal mass screening in the 1990s, the disease severity varies. Thus, determining the specific level of PCC activity is considered to be helpful to grasp the severity of PA. We developed a new PCC assay method by the determination of methylmalonyl-CoA, which is formed by an enzyme reaction using peripheral lymphocytes, based on ultra high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). With methylmalonyl-CoA concentrations of 0.05, 0.5, and 5µmol/L, the intra-assay coefficients of variation (CVs) were 8.2%, 8.7%, and 5.1%, respectively, and the inter-assay CVs were 13.6%, 10.5%, and 5.9%, respectively. The PCC activities of 20 healthy individuals and 6 PA patients were investigated with this assay. Methylmalonyl-CoA was not detected in one PA patient with a severe form of the disease, but the remaining PA patients with mild disease showed residual activities (3.3-7.8%). These results demonstrate that determination of PCC activity with this assay would be useful to distinguish between mild and severe cases of PA to help choose an appropriate treatment plan.

Light-controlled relaxation of the rat penile corpus cavernosum using NOBL-1, a novel nitric oxide releaser.

PURPOSE: To investigate whether relaxation of the rat penile corpus cavernosum could be controlled with NOBL-1, a novel, light-controllable nitric oxide (NO) releaser. MATERIALS AND METHODS: Fifteen-week-old male Wistar-ST rats were used. The penile corpus cavernosum was prepared and used in an isometric tension study. After noradrenaline (10(-5) M) achieved precontraction, the penile corpus cavernosum was irradiated by light (470-500 nm) with and without NOBL-1 (10(-6) M). In addition, we noted rats' responses to light with vardenafil (10(-6) M), a phosphodiesterase-5 (PDE-5) inhibitor. Next, responses to light in the presence of a guanylate cyclase inhibitor, ODQ (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one) (10(-5) M), were measured. All measurements were performed in pretreated L-NAME (10(-4) M) conditions to inhibit endogenous NO production. RESULTS: Corpus cavernosal smooth muscle, precontracted with noradrenaline, was unchanged by light irradiation in the absence of NOBL-1. However, in the presence of NOBL-1, corpus cavernosal smooth muscle, precontracted with noradrenaline, relaxed in response to light irradiation. After blue light irradiation ceased, tension returned. In addition, the light response was obviously enhanced in the presence of a PDE-5 inhibitor. CONCLUSIONS: This study showed that rat corpus cavernosal smooth muscle relaxation can be light-controlled using NOBL-1, a novel, light sensitive NO releaser. Though further in vivo studies are needed to investigate possible usefulness, NOBL-1 may be prove to be a useful tool for erectile dysfunction therapy, specifically in the field of penile rehabilitation.

Assay for methylmalonyl coenzyme A mutase activity based on determination of succinyl coenzyme A by ultrahigh-performance liquid chromatography tandem mass spectrometry.

Methylmalonic acidemia (MMA) is an inherited metabolic disease. In this condition, metabolism from methylmalonyl coenzyme A (CoA) to succinyl-CoA is inhibited because of either low methylmalonyl-CoA mutase (MCM) activity or adenosylcobalamin deficiency owing to altered vitamin B12 metabolism. A high-precision assay for detecting MCM activity would facilitate not only MMA diagnosis but also the ability to determine the severity of MMA. We developed an MCM assay method based on ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) that involves the determination of succinyl-CoA, which is formed in an enzyme reaction, using peripheral lymphocytes. Using 0.05, 0.5, and 5 µmol/L succinyl-CoA, the intra-assay coefficient of variation (CV) was less than 5.2% and the inter-assay CV was less than 8.7%. The MCM activities of five healthy individuals and four patients were investigated with this assay. The MCM activities of the patients were very low in relation to those of healthy individuals. Together, these results show that the UPLC-MS/MS method is useful for a detailed MCM activity assay.

Outcomes of the implementation of the computer-assisted HBView system for the prevention of hepatitis B virus reactivation in chemotherapy patients: a retrospective analysis.

BACKGROUND: Screening for hepatitis B virus (HBV) infection is recommended worldwide for patients receiving systemic chemotherapy in accordance with clinical guidelines, but compliance varies by country and facility. Alert systems may be useful for promoting screening, but it is unclear how effective such systems are. In this study, we investigated HBV screening procedures and their incorporation into treatment regimens following the implementation of an alert system. METHODS: An alert system was introduced at our hospital in April 2012. The rates of HBV screening in the periods before and after the introduction of the alert system (September 2010 to March 2012 and April 2012 to October 2013, respectively) were investigated. We collected data on hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb), and HBV-DNA testing in patients. As a result of this analysis, we developed a system in which pharmacists would intervene to check and confirm whether HBV screening had occurred in patients scheduled to begin treatment with chemotherapy. We named our project the "HBView" project, and the rate of HBV screening and the number of times pharmacists intervened was studied during specific time periods before and after the HBView project commenced (July 2013 to December 2013 and January 2014 to June 2014, respectively). RESULTS: After introducing the alert system, the percentage of patients tested for HBsAb/HBcAb and HBV-DNA increased significantly, from 71.6 % to 84.9 % and from 44.5 % to 69.7 %, respectively. However, the rate of compliance with HBV testing guidelines was not 100 % after interventions. The numbers of patients who were not screened but should have been before and after the introduction of HBView were 6 and 17, respectively. Two patients at risk of HBV reactivation were identified after intervention by pharmacists; their intervention thus prevented HBV reactivation. CONCLUSIONS: Compliance with clinical HBV screening guidelines was not sufficiently improved after the introduction of the automatic alert system; however, the HBView project proved useful in reinforcing the automatic alert system.

[Performance of a portable continuous infusion pump (SUREFUSER A) in continuous infusion of 5-FU].

Therapy with mFOLFOX6/FOLFIRI used in treating colorectal cancer is typical of the regimens performed in outpatient settings. In this therapy, 46-h continuous infusion of 5-fluorouracil (5-FU) with concomitant oxaliplatin and irinotecan hydrochloride is conducted. The portable continuous infusion pump that makes continuous infusion possible has a non-electric structure, so variation in the infusion rate is seen. There are known effects of 5-FU concentration and temperature, and many studies have reported on the precision. In our hospital, we have experienced many cases of incomplete infusion and delays for the above reasons. We changed the specifications of the infusion pump to correspond to the kinematic viscosity of 5-FU and made all drug solution amounts uniform. We measured the time required to administer the drug solution from the time the infusion was started (recorded by a nurse) and the time it was completed (recorded by the patient), and confirmed the precision of the pump after the changes were made. It was found that while there was a decrease in the infusion rate at which the effect of the kinematic viscosity of 5-FU is seen, the mean infusion time was kept to within 46+/-10% hours in more than 90% of patients. There were no effects from concentration differences in 5-FU, and the completion time was reduced. The management and lifestyles of individual patients are potential factors in precision errors, and it is important to explain in advance to patients the necessity of secure fixation and infusion pump problems that might occur.

[Survey on patients' satisfaction with opioid rescue guidance by pharmacists].

To examine the influence of drug therapy guidance by pharmacists on the use of a rescue dose (RD) for opioid analgesics (opioids) and pain as well as drug therapy guidance in cancer pain treatment, we conducted a patient satisfaction survey. The subjects were 56 cancer patients undergoing opioid therapy in hospitals belonging to the Symptom Control Research Group (SCORE-G). The survey period was 2 months (from November 1 until December 31, 2006). Drug therapy guidance regarding the use of RD was performed twice in each patient to evaluate the patients' satisfaction. RD was prescribed in 87.8% of the patients in the first guidance and in 80.5% in the second guidance periods. The proportion of patients who used RD significantly increased from 63.8% to 87.5%. Five items significantly improved in the second guidance period: "marked analgesic effects," "satisfaction with current treatment," "correct understanding of RD usage," "relief through RD," and "appropriate use of RD." On comprehensive evaluation following the second round of guidance, 81% of the patients reported overall satisfaction, and 78% reported the usefulness of guidance in pain treatment. These results suggest that positive guidance by pharmacists increases patients' satisfaction. In providing guidance, it was important to confirm the characteristics and side effects of opioids as well as the necessity of RD to patients accurately and repeatedly.