Evaluation of hospital pharmacists' activities using additional reimbursement for infection prevention as an indicator in small and medium-sized hospitals.

BACKGROUND: Hospitals in Japan established the healthcare delivery system from FY 2018 to 2021 by acquiring an additional reimbursement for infection prevention (ARIP) of category 1 or 2. However, research on outcomes of ARIP applications related to the practice of hospital pharmacists is scarce. METHODS: This study assessed the activities performed by hospital pharmacists in hospitals with 100 to 299 beds, using ARIP acquirement as an indicator, using data from an annual questionnaire survey conducted in 2020 by the Japanese Society of Hospital Pharmacists on the status of hospital pharmacy departments. Out of the survey items, this study used those related to hospital functions, number of beds, number of pharmacists, whether the hospital is included in the diagnosis procedure combination (DPC) system, average length of stay, and nature of work being performed in the analysis. The relationship between the number of beds per pharmacist and state of implementation of pharmacist services or the average length of hospital stay was considered uncorrelated when the absolute value of the correlation coefficient was within 0-0.2, whereas the relationship was considered to have a weak, moderate, or strong correlation when the absolute value ranged at 0.2-0.4, 0.4-0.7, or 0.7-1, respectively. RESULTS: Responses were received from 3612 (recovery rate: 43.6%) hospitals. Of these, 210 hospitals meeting the criteria for ARIP 1 with 100-299 beds, and 245 hospitals meeting the criteria for ARIP 2 with 100-299 beds, were included in our analysis. There was a significant difference in the number of pharmacists, with a larger number in ARIP 1 hospitals. For the pharmacist services, significant differences were observed, with a more frequency in ARIP 1 hospitals in pharmaceutical management and guidance to pre-hospitalization patients, sterile drug processing of injection drugs and therapeutic drug monitoring. In DPC hospitals with ARIP 1 (173 hospitals) and 2 (105 hospitals), the average number of beds per pharmacist was 21.7 and 24.7, respectively, while the average length of stay was 14.3 and 15.4 d, respectively. Additionally, a weak negative correlation was observed between the number of pharmacist services with "Fairly well" or "Often" and the number of beds per pharmacist for both ARIP 1 (R = -0.207) and ARIP 2 (R = -0.279) DPC hospitals. Furthermore, a weak correlation (R = 0.322) between the average number of beds per pharmacist and the average length of hospital stay was observed for ARIP 2 hospitals. CONCLUSIONS: Our results suggest that lower beds per pharmacist might lead to improved pharmacist services in 100-299 beds DPC hospitals with ARIP 1 or 2. The promotion of proactive efforts in hospital pharmacist services and fewer beds per pharmacist may relate to shorter hospital stays especially in small and medium-sized hospitals with ARIP 2 when ARIP acquisition was used as an indicator. These findings may help to accelerate the involvement of hospital pharmacists in infection control in the future.

Cost-Effectiveness Analysis of Cyclin-Dependent Kinase 4/6 Inhibitor Palbociclib for Inoperable or Recurrent Breast Cancer.

BACKGROUND: Palbociclib and endocrine therapy has been approved to treat hormone receptor-positive/human epidermal growth factor receptor 2-negative inoperable or recurrent breast cancer in Japan. However, this cotherapy imposes an economic burden on both patients and society because of its high cost. In this study, we assessed the cost-effectiveness of cotherapy with palbociclib and fulvestrant compared to fulvestrant monotherapy for inoperable or recurrent breast cancer. METHODS: The three-state Markov model was built by taking into count health stats in inoperable or recurrent breast cancer. The clinical outcomes of the therapies were drawn from published randomized controlled trials. Total regimen cost was calculated from medical receipts of patients at the Yamagata University Hospital. The cost-effectiveness was evaluated by the incremental cost-effectiveness ratio(ICER), in case that it was below 400,000 Yen per month. Markov chain Monte Carlo simulation was performed to assess probability. RESULTS: Acquisition cost of palbociclib and fulvestrant and fulvestrant monotherapy was 6,209,554 JPY and 780,870 JPY, and 25.7 and 22.8 months were achieved, respectively. ICER for the cotherapy was 1,847,721 JPY/quality adjusted life month(QALM)gained. CONCLUSIONS: The palbociclib and fulvestrant therapy provided better health outcomes than conventional fulvestrant monotherapy, but were costly and suggested to be less cost-effective.

Actual status of patient information sharing among healthcare delivery facilities: a survey by the third subcommittee, committee on academic research, the Japanese society of hospital pharmacists.

BACKGROUND: Information sharing among medical professionals is important for providing quality medical care. The purpose of the present study was to elucidate the actual status of information sharing between hospitals and other healthcare delivery facilities by surveying information sharing among the pharmaceutical departments of Japanese hospitals in 2020 conducted by the Japanese Society of Hospital Pharmacists. METHODS: Responses were received from 3612 (43.6%) of the 8278 target medical institutions between May 2020 and August 2020. RESULTS: The proportions of hospitals that shared information with community pharmacies, other hospitals, and long-term nursing homes were 40.6%, 36.4%, and 27.3%, respectively. While tracing reports were the most common tool used by hospitals for information sharing with community pharmacies (54.3%), drug summaries were used for sharing information with other hospitals and long-term nursing homes (77.4% and 78.0%, respectively). The proportion of hospitals sharing information with community pharmacies and other hospitals showed a tendency to increase as the number of hospital beds increased. No relationship could be established between the number of hospital beds and the proportion of hospitals sharing information with long-term nursing homes. CONCLUSION: Information between hospitals and community pharmacies was shared primarily using tracing reports, whereas information between hospitals and other hospitals and long-term nursing homes was primarily shared via drug summaries.

The safety of pranlukast and montelukast during the first trimester of pregnancy: A prospective, two-centered cohort study in Japan.

For leukotriene receptor antagonists (LTRAs), especially pranlukast, safety data during pregnancy is limited. Therefore, we conducted a prospective, two-centered cohort study using data from teratogen information services in Japan to clarify the effects of LTRA exposure during pregnancy on maternal and fetal outcomes. Pregnant women who being counseled on drug use during pregnancy at two facilities were enrolled. The primary outcome of this study was major congenital anomalies. The incidence of major congenital anomalies in women exposed to montelukast or pranlukast during the first trimester of pregnancy was compared with that of controls. Logistic regression analysis was performed to analyze the effects of maternal LTRA use during the first trimester of pregnancy on major congenital anomalies. The outcomes of 231 pregnant women exposed to LTRAs (montelukast n = 122; pranlukast n = 106; both n = 3) and 212 live births were compared with those of controls. The rate of major congenital anomalies in the LTRA group was 1.9%. Multivariable logistic regression analysis revealed that LTRA exposure was not a risk factor for major congenital anomalies (adjusted odds ratio, 0.78; 95% confidence interval, 0.23-2.05; p = 0.653). In addition, no significant difference was detected in stillbirth, spontaneous abortion, preterm birth, and low birth weight between the two groups. The present study revealed that montelukast and pranlukast were not associated with the risk of major congenital anomalies. Our findings suggest that LTRAs could be safely employed for asthma therapy during pregnancy.

Characteristics of hospitals that report adverse drug reactions: Results of a nationwide survey in Japan.

WHAT IS KNOWN AND OBJECTIVE: Adverse drug reactions (ADRs) are one of the primary reasons for hospitalization. The spontaneous reporting of ADRs by healthcare professionals is important for issuing post-marketing drug safety measures. The Japanese Society of Hospital Pharmacists (JSHP) conducts a nationwide survey annually. Using data from this large-scale survey, we identified the characteristics of hospitals that reported ADRs to regulatory authorities and pharmaceutical companies. METHODS: Data were obtained from annual surveys conducted by JSHP from 2015 to 2020. All variables were expressed as categorical variables and tabulated. The Chi-square test was used to compare the categorical variables. The Cochran-Armitage trend test was used to identify significant trends in the proportion of hospitals reporting ADRs. RESULTS AND DISCUSSION: From 2015 to 2020, 22,362 responses were recorded. There was a significant increase in the proportion of hospitals that reported ADRs with an increase in number of beds and pharmacists (p < 0.0001). The proportion of hospitals reporting ADRs to regulatory authorities was also significantly higher in those charging an additional fee for pharmacist-performed ward operations and in those with an ADR data management section than in hospitals without these attributes (p < 0.0001). WHAT IS NEW AND CONCLUSION: Hospitals that submitted ADR reports to the regulatory authorities and pharmaceutical companies charged an additional fee for pharmacist-performed ward operations, had a central ADR data management section, and had fewer beds per pharmacist. This trend was similar, regardless of the size of the hospital.

Disentangling the contribution of the transboundary out-flow from the Asian continent to Tokyo, Japan.

We assessed the contribution of transboundary air pollutants (TAPs) transported from China to Tokyo using the Pb(0.5

Degradation of PAHs during long range transport based on simultaneous measurements at Tuoji Island, China, and at Fukue Island and Cape Hedo, Japan.

We investigated the degradation of polycyclic aromatic hydrocarbons (PAHs) during long-range transport. Aerosols were collected simultaneously at remote sites on Tuoji Island, China; Fukue Island, Japan; and the Cape Hedo Atmosphere and Aerosol Measurement Station (CHAAMS), Okinawa, Japan in April, October, and December from 2012 to 2013. These remote sites were convenient for investigating the degradation of PAHs during long-range transport. PAHs were analyzed via gas chromatography/mass spectrometry. We identified air masses that passed over all sites and combined our measurements with a chemical transport model. We estimated the relative contributions of the PAHs at the three sites by normalizing the PAH concentrations to elemental carbon. Benzo[a]pyrene persisted in 5-16% of samples. The results of this study are consistent with laboratory studies in which secondary organic aerosol (SOA) coatings protected PAHs from degradation by ozone. We detected an inhibition of the degradation PAHs by SOA coatings by collecting PAHs simultaneously at the three sites. To elucidate the major sources of the SOAs, we carried out a positive matrix factorization analysis to identify the major sources of SOA coating, which controls the lifetime of PAHs. In spring and winter, the contribution of vehicle emissions was higher (46%) at Tuoji Island than at CHAAMS (13%). In contrast, the contribution of coal combustion was higher at CHAAMS (59%) than at Tuoji Island (28%). This result implies that during long-range transport, PAHs derived from coal combustion are more slowly degraded than PAHs derived from vehicle emissions. We found that the viscosity of SOA coatings derived from vehicle emissions in China was low, and the corresponding PAHs were rapidly degraded. In contrast, the viscosity of SOA coatings derived from coal combustion was high, and degradation of the corresponding PAHs was relatively slow. These results imply that PAHs derived from coal combustion have long lifetime.

Risk Factors for Severe Hyponatremia Related to Cisplatin: A Retrospective Case-Control Study.

Onset of severe hyponatremia following cisplatin (CDDP) administration has been previously reported. However, the risk factors associated with hyponatremia still remain unclear. We conducted a retrospective, single-center, case-control study to identify independent risk factors of severe hyponatremia in patients with various types of cancers. Adult patients who received intravenous CDDP administration between January 2012 and December 2017 met the inclusion criteria. The investigators recorded patients' demographics and clinical information retrospectively, and assessed the lowest serum sodium level within 21 d of the first CDDP administration. Risk factors for grade ≥3 hyponatremia were examined via a logistic regression analysis. Among a total of 472 patients, fifty patients (10.6%) developed grade ≥3 hyponatremia. Univariate analysis revealed that age (≥65 years), presence of small cell lung or esophageal cancer, and lower sodium concentrations in the serum (<138 mEq/L) were significantly associated with grade 3 and 4 hyponatremia. Additionally, multivariable logistic regression analysis showed that the presence of small cell lung cancer (adjusted odds ratio, 3.26; 95% confidence interval (CI), 1.07-10.00) and lower sodium concentrations in the serum (<138 mEq/L) (adjusted odds ratio, 6.18; 95%CI, 3.21-11.90) were independent risk factors of grade 3 and 4 hyponatremia. Thus, serum sodium concentrations in patients with these risk factors should be closely monitored after CDDP administration.

Seasonal and annual changes in PAH concentrations in a remote site in the Pacific Ocean.

This paper reports the long term observation of particle-associated polycyclic aromatic hydrocarbons (PAHs) at Cape Hedo Atmosphere and Aerosol Monitoring Station, a remote site in the Western Pacific Ocean, from 2008 to 2015. This is the first long-term study that evaluated the contribution of long-range transport of PAHs in East Asia. No obvious trend (P > 0.05) was found in a particular season over the years. However, there are seasonal variations of PAH concentrations with higher in spring and winter. The higher PAH are attributed to air masses from the area including part of China. Source apportionment using three different approaches, i.e., PAH compositional pattern analysis, PAH diagnostic ratio analysis and positive matrix factorization modeling, showed the combined high contribution of biomass burning (18%, 14%) and coal combustion (33%, 24%) in spring and winter. In addition, the contribution of ship emissions (35%) was relatively high in spring, whereas that of vehicle emissions (36%) was relatively high in winter. The contribution of coal combustion to PAH has decreased throughout the years, likely due to changes in energy structure in China. The contribution of biomass burning to PAH has showed no trend, being stable, and that of vehicular emissions has increased.

[Effects of Serum Sodium Concentrations on Nausea and Vomiting after Moderately Emetogenic Chemotherapy].

Chemotherapy-induced nausea and vomiting (CINV) is the most unbearable adverse effect of chemotherapy. The antiemesis guidelines of the National Comprehensive Cancer Network indicate that hyponatremia is a risk factor for CINV, although the relationship between the incidence of CINV and hyponatremia has not been sufficiently studied. This two-center prospective observational study evaluated whether low serum sodium concentrations were a risk factor for CINV. The study included 34 patients who were scheduled to receive first-line carboplatin- or oxaliplatin-based chemotherapy for gynecological or colorectal cancers. Patient diaries were used to record the daily incidences of CINV events during a 5-day period. The patients were divided based on the median serum sodium concentration into a low Na+ group (<141 mEq/L) and a high Na+ group (≥141 mEq/L). The incidences of delayed nausea were 27.8% in the high Na+ group and 62.5% in the low Na+ group (p=0.042), with complete control rates (no vomiting, rescue medication, or grade 2 nausea) of 77.8% and 43.8%, respectively (p=0.042). The time to complete control failure in each group was analyzed using the Kaplan-Meier method, which revealed a significantly shorter time in the low Na+ group (p=0.03). Therefore, these results indicate that low serum sodium concentrations may increase the risk of CINV.

Measurement of hydrogen peroxide and organic hydroperoxide concentrations during autumn in Beijing, China.

Gaseous peroxides play important roles in atmospheric chemistry. To understand the pathways of the formation and removal of peroxides, atmospheric peroxide concentrations and their controlling factors were measured from 7:00 to 20:00 in September, October, and November 2013 at a heavily trafficked residential site in Beijing, China, with average concentrations of hydrogen peroxide (H2O2) and methyl hydroperoxide (MHP) at 0.55ppb and 0.063ppb, respectively. H2O2 concentrations were higher in the afternoon and lower in the morning and evening, while MHP concentrations did not exhibit a regular diurnal pattern. Both H2O2 and MHP concentrations increased at dusk in most cases. Both peroxides displayed monthly variations with higher concentrations in September. These results suggested that photochemical activity was the main controlling factor on variations of H2O2 concentrations during the measurement period. Increasing concentrations of volatile organic compounds emitted by motor vehicles were important contributors to H2O2 and MHP enrichment. High levels of H2O2 and MHP concentrations which occurred during the measurement period probably resulted from the transport of a polluted air mass with high water vapor content passing over the Bohai Bay, China.

Transboundary secondary organic aerosol in western Japan indicated by the δ13C of water-soluble organic carbon and the m/z 44 signal in organic aerosol mass spectra.

The stable carbon isotope ratio (δ13C) of low-volatile water-soluble organic carbon (LV-WSOC) was measured in filter samples of total suspended particulate matter, collected every 24 h in the winter of 2010 at an urban site and two rural sites in western Japan. Concentrations of the major chemical species in fine aerosol (<1.0 µm) were also measured in real time by aerosol mass spectrometers. The oxidation state of organic aerosol was evaluated using f44; i.e., the proportion of the signal at m/z 44 (CO2+ ions from the carboxyl group) to the sum of all m/z signals in the organic mass spectra. A strong correlation between LV-WSOC and m/z 44 concentrations was observed, which suggested that LV-WSOC was likely to be associated with carboxylic acids in fine aerosol. Plots of δ13C of LV-WSOC versus f44 showed random variation at the urban site and systematic trends at the rural sites. The systematic trends qualitatively agreed with a simple binary mixture model of secondary organic aerosol with background LV-WSOC with an f44 of ∼0.08 and δ13C of -17‰ or higher. Comparison with reference values suggested that the source of background LV-WSOC was likely to be primary emissions associated with C4 plants.

Effect of ambient-level gas-phase peroxides on foliar injury, growth, and net photosynthesis in Japanese radish (Raphanus sativus).

To investigate the effects of ambient-level gas-phase peroxides concurrent with O(3) on foliar injury, photosynthesis, and biomass in herbaceous plants, we exposed Japanese radish (Raphanus sativus) to clean air, 50 ppb O(3), 100 ppb O(3), and 2-3 ppb peroxides + 50 ppb O(3) in outdoor chambers. Compared with exposure to 100 ppb O(3), exposure to 2-3 ppb peroxides + 50 ppb O(3) induced greater damage in foliar injury, net photosynthetic rates and biomass; the pattern of foliar injury and the cause of net photosynthetic rate reduction also differed from those occurring with O(3) exposure alone. These results indicate for the first time that sub-ppb peroxides + 50 ppb O(3) can cause more severe damage to plants than 100 ppb O(3), and that not only O(3), but also peroxides, could be contributing to the herbaceous plant damage and forest decline observed in Japan's air-polluted urban and remote mountains areas.

Characteristic of organic aerosol in a remote area of Okinawa Island.

A continuous investigation of aerosol pollutants in Cape Hedo, Japan was conducted from October 2005 to August 2006 by Aerodyne aerosol mass spectrometer (AMS). This article focused on the analysis of long-range transport of organic aerosol from continental origin to the remote island. Based on the transport distance and air mass origin, four main air mass origins were considered, including North China, South China, Japan and Korea. Although the mass concentration and air mass origin were quite different during study period, the mass spectrum and size distribution of organic matter and oxidized organics were similar, which showed uni-modal distribution with modal diameter of around 500 nm. The loss rate of organics was (5.15 +/- 0.55) x 10(-6) s(-1) obtained by plotting the concentration against the transport time. Conversion rate of SO2 to sulfate and oxidation rate of organics were (1.07 +/- 0.15) x 10(-5) and (1.09 +/- 0.52) x 10(-6) s(-1), respectively.

Secondary organic aerosol formation during the photooxidation of toluene: NOx dependence of chemical composition.

The photooxidation of toluene is a potential source of secondary organic aerosol (SOA) in urban air, but only a small portion of the compounds present in SOA have been identified. In this study, we analyzed the chemical compositions of SOA produced by photoirradiation of the toluene/NOx/air system in laboratory chamber experiments by a combination of liquid chromatography-mass spectrometry, hybrid high-performance liquid chromatography-mass spectrometry, and iodometry-spectrophotometry. The dependence of the chemical composition on the initial NOx concentration was examined at initial NO concentrations ([NO]0) of 0.2 and 1 ppmv. Fifteen semivolatile products, including aromatic and ring-cleavage compounds, were quantified. However, the quantified products comprised only a small portion ( approximately 1 wt %) of the total aerosol mass. The total SOA yield ( approximately 13 wt %), the ratio of organic peroxides to total SOA mass ( approximately 17 wt %), and the density of SOA ( approximately 1.4 g cm-3) were independent of the NOx level, suggesting that the reaction mechanisms of the formation of major SOA products at [NO]0 = 0.2 and 1 ppmv are essentially the same. The negative-ion mass spectra of SOA samples showed that ion signals attributed to hemiacetal oligomers and/or decomposition products of peroxy hemiacetal oligomers were detected in the range of mass-to-charge ratios (m/z) between 200 and 500. The highest signals were detected at m/z = 155 and 177, and these were tentatively assigned to C7 unsaturated oxacyclic oxocarboxylic acids and C7 unsaturated oxacyclic dicarboxylic acids, respectively. We conclude that the major chemical components of the aerosol are hemiacetal and peroxy hemiacetal oligomers and low-molecular-weight dicarboxylic acids.

Atmospheric outflow of anthropogenic semivolatile organic compounds from East Asia in spring 2004.

To estimate the emissions of anthropogenic semivolatile organic compounds (SOCs) from East Asia and to identify unique SOC molecular markers in Asian air masses, high-volume air samples were collected on the island of Okinawa, Japan between 22 March and 2 May 2004. Contributions from different source regions (China, Japan, the Koreas, Russia, and ocean/local) were estimated by use of source region impact factors (SRIFs). Elevated concentrations of hexachlorobenzene (HCB), hexachlorcyclohexanes (HCHs), dichlorodiphenyltrichloroethanes (DDTs), and particulate-phase polycyclic aromatic hydrocarbons (PAHs) were attributed to air masses from China. A large proportion of the variation in the current-use pesticides, gas-phase PAHs, and polychlorinated biphenyl (PCB) concentrations was explained by meteorology. Chlordanes showed a technical mixture profile and similar concentrations regardless of source region. alpha/gamma HCH and trans/cis chlordane ratios did not vary significantly with different source regions and had regional averages of 2.5 +/- 1.0 and 1.2 +/- 0.3, respectively. Particulate-phase PAH concentrations were significantly correlated (p value < 0.05) with other incomplete combustion byproduct concentrations, including elemental mercury (Hg0), CO, NOx, black carbon, submicrometer aerosols, and SO2. By use of measured PAH, CO, and black carbon concentrations and estimated CO and black carbon emission inventories, the emission of six carcinogenic particulate-phase PAHs was estimated to be 1518-4179 metric tons/year for Asia and 778-1728 metric tons/year for China, respectively. These results confirm that East Asian outflow contains significant emissions of carcinogenic particulate-phase PAHs.

Aircraft measurement of organic aerosols over China.

Lower to middle (0.5-3.0 km altitude) tropospheric aerosols (PM2.5) collected by aircraft over inland and east coastal China were, for the first time, characterized for organic molecular compositions to understand anthropogenic, natural, and photochemical contribution to the air quality. n-Alkanes, fatty acids, sugars, polyacids are detected as major compound classes, whereas lignin and resin products, sterols, polycyclic aromatic hydrocarbons, and phthalic acids are minor species. Average concentrations of all the identified compounds excluding malic acid correspond to 40-50% of those reported on the ground sites. Relative abundances of secondary organic aerosol (SOA) components such as malic acid are much higher in the aircraft samples, suggesting an enhanced photochemical production over China. Organic carbon (OC) concentrations in summer (average, 24.3 microg m(-3)) were equivalent to those reported on the ground sites. Higher OC/EC (elemental carbon) ratios in the summer aircraft samples also support a significant production of SOA over China. High loadings of organic aerosols in the Chinese troposphere may be responsible to an intercontinental transport of the pollutants and potential impact on the regional and global climate changes.

A calibration method for measurement of small alkyl organic peroxy radicals by chemical amplifier.

A new method is proposed to determine the calibration factor (CF) of methyl and ethyl peroxy radicals in a chemical amplifier. The radical source comes from the reactions of excess methane and ethane, respectively, with known concentrations of OH radicals generated by the photolysis of water vapor at 184.9 nm in air in a flow tube. This yields a mixed radical source with equal amounts of HO2 and RO2 (R = CH3, C2H5). The CF for RO2 can be derived from the CF for HO2 and an average CF for the mixed radicals. The reliability of the method was evaluated by comparing the CF ratios of RO2 to HO2 obtained from both the experiments and theoretical calculations.