Evaluation of Efficacy of Adding Aprepitant to Palonosetron and Dexamethasone in Carboplatin and Etoposide Therapy.

Although carboplatin (CBDCA) is classified as a moderately emetogenic agent, the majority of guidelines recommend the use of a neurokinin-1 receptor antagonist in addition to a 5-hydroxytryptamine type 3 receptor antagonist with dexamethasone (DEX) for CBDCA-containing chemotherapy because of its higher emetogenic risk. However, the additional efficacy of aprepitant (APR) in CBDCA-containing treatment remains controversial, and data on multiple-day treatments are limited. Etoposide (ETP) was administered on days 1-3 in the CBDCA + ETP regimen, and it is important to evaluate suitable antiemetic therapy for the regimen. Therefore, we evaluated the efficacy of additional APR in CBDCA + ETP. Patients were divided into two groups and retrospectively evaluated. One was the control group, which was prophylactically administered palonosetron (PALO) and DEX, and the other was the APR group, which received APR orally with PALO and DEX. The primary endpoint was complete response (CR) between the groups. The overall CR rates were 75.0 and 76.4% in the control and APR groups, respectively, with no significant difference (p = 1.00). In the acute phase, it was 88.9 and 97.2%, respectively, and 86.1 and 79.2% in the delayed phase, respectively, without significant differences (p = 0.10 and 0.38, respectively). The incidence and severity of nausea, vomiting, and anorexia were not significantly different between the two groups in the acute and delayed phases. Our findings suggest that combining APR with PALO and DEX does not improve the CR rate in CBDCA + ETP therapy.

Risk factor analysis for taxane-associated acute pain syndrome under the dexamethasone prophylaxis.

PURPOSE: Taxane-associated acute pain syndrome (T-APS) reportedly occurs in approximately 70% of patients undergoing therapy. We have previously reported that additional dexamethasone (DEX) administration attenuates T-APS. The aim of this study was to reveal risk factor(s) associated with the incidence of T-APS under prophylactic DEX administration. METHODS: In total, 143 patients with breast cancer who received docetaxel (75 mg/m2) or paclitaxel (175 mg/m2)-containing treatment regimens were enrolled. DEX (4-8 mg) was orally administered on days 2-4. Risk factors for the incidence of ≥ G2 and all-grade T-APS, as well as T-APS incidence between taxane-containing regimens in the first cycle, were retrospectively evaluated. RESULTS: Approximately 90% of the patients received taxanes for adjuvant or neoadjuvant chemotherapy. Overall, 55% of patients administered 4 mg DEX, whereas 45% received 8 mg DEX. Pegfilgrastim was administered in 27% of patients. Incidence of ≥ G2 and all-grade T-APS was 23.8%, and 69.2%, respectively. Univariate and multivariate analyses revealed that administration of pegfilgrastim is an independent risk factor for the incidence of ≥ G2 and all-grade T-APS; age younger than 55 years is also a risk factor for all-grade T-APS. Moreover, the incidence of ≥ G2 and all-grade T-APS was 45.5% and 81.8% in a paclitaxel regimen, and 22.0% and 68.2% in docetaxel-including regimens, respectively, revealing increased tendency with paclitaxel administration, with no significant differences. CONCLUSION: Pegfilgrastim co-administration is an independent risk factor for ≥ G2 and all-grade T-APS, and age younger than 55 years is a risk factor of all-grade T-APS under prophylactic DEX administration.

Evaluation of Chemotherapy Regimen Management Practice by Oncology-Specialized and Non-specialized Pharmacists Collaboration.

Chemotherapy regimen management is one of the most important oncology pharmacy practices, because chemotherapy is conducted according to the registered regimens. In this study, we evaluated the pharmaceutical practice that assumes the initial confirmation of chemotherapy regimens and the quality of practice sharing between oncology-specialized and non-specialized pharmacists in regimen management committee. Pharmacists initially confirmed the applied regimen prescribed by physicians regarding chemotherapeutic agents and prophylactic supportive care medicines. Following confirmation, the regimens were reviewed by the Hokkaido University Hospital Regimen Management Committee. A total of 233 regimens were reviewed by the committee over three years. In total, 110 pharmaceutical inquiries were conducted, 45% of inquiries were concerning chemotherapeutic agents, of which approximately half were regarding supportive care medicines. Most inquiries were regarding premedication, followed by those on administration time, solvent of infusion medicines, and dosage. Correction was performed for 84.5% of inquiries. There was no significant difference in inquiry rates between practice and trial regimens. We have entrusted the first basic regimen review according to the checklist, creation of the chemotherapy plan document, and registry of the adopted regimens in the ordering system from oncology-certified pharmacists to non-certified pharmacists. Basic regimen review was well conducted by a non-certified pharmacist, and a more advanced review was additionally performed by certified pharmacists. In conclusion, we demonstrated the utility of pharmaceutical confirmation in a chemotherapeutic regimen review, suitable review coverage, and quality practice sharing between oncology-certified and non-certified pharmacists, which is one of the recommended methods in chemotherapy regimen review.

Effect of palonosetron and dexamethasone administration on the prevention of gastrointestinal symptoms in hepatic arterial chemoembolization with epirubicin.

PURPOSE: There are several studies on premedication to prevent postembolization syndromes which occurs after transcatheter arterial chemoembolization (TACE), but the medication to be used is still not established. This study aimed to examine the effect of palonosetron and dexamethasone on the prevention of gastrointestinal symptoms induced by TACE. METHODS: Patients with hepatocellular carcinoma who were treated with TACE with epirubicin were retrospectively evaluated. The complete response rate of antiemetic drugs and incidence and severity of gastrointestinal symptoms were compared between the antiemetic group (AE group), which includes 51 patients prophylactically administered with palonosetron 0.75 mg and dexamethasone 9.9 mg intravenously before TACE on day 1 and dexamethasone 6.6 mg intravenously on days 2 and 3, and control group with 101 patients without antiemetic premedication. RESULTS: Complete response rate in the entire evaluation period was significantly higher in the AE group compared with that in the control group. In the acute phase, the incidence and severity of nausea, vomiting, and anorexia significantly decreased in the AE group, but only anorexia improved in the delay phase. Additionally, postembolization syndromes, such as abdominal pain and fever, were significantly attenuated in the AE group; however, constipation worsened in this group. CONCLUSIONS: Premedication of palonosetron and dexamethasone significantly prevents the incidence and reduces the severity of gastrointestinal symptoms especially in the acute phase. Further studies will be needed to determine the most recommended 5-HT3 antagonist or dosage of dexamethasone in establishing the optimal antiemetic regimen.

Pharmaceutical Care Contributes to the Advanced Management of Patients Receiving Immune Checkpoint Inhibitors.

We previously reported that successive pharmaceutical care by oncology pharmacy specialists contributes to quality outpatient chemotherapy. However, there are a few reports regarding such care during immune checkpoint inhibitors (ICIs) treatment, despite increasing patients being treated with ICIs and the profile of immune-related adverse events being quite different from that of the adverse effects of cytotoxic agents. We retrospectively evaluated the effectiveness of continuous pharmaceutical care in outpatient ICI treatment, focusing especially on the period of providing pharmaceutical recommendations. The adoption rate, efficacy, and period of pharmaceutical interventions, such as prescription questions and pharmaceutical recommendations, were evaluated. A total of 3597 ICI administrations (366 patients) were evaluated. We performed 2625 face-to-face medication counseling. A total of 282 prescription questions and 147 pharmaceutical recommendations were conducted. Approximately 70% of the questions were regarding ordering of laboratory examination, and 86.5% of these questions were adopted. Pharmaceutical recommendations were categorized into medication recommendations (81.1%), examination recommendations (10.8%), and recommendation of expert consultation (8.1%). The adoption rate of pharmaceutical recommendations was 96.0, and 70% of the medication recommendations attenuated the symptoms. Finally, the provision rate of pharmaceutical recommendations was significantly higher in the first 3 months after ICI treatment initiation. We found that pharmaceutical care contributes to an improved quality of outpatient ICI treatment, and face-to-face pharmaceutical counseling up to 3 months after ICI treatment initiation is the most important.

Dietary patterns and serum gamma-glutamyl transferase in Japanese men and women.

BACKGROUND: Although specific foods and nutrients have been examined as potential determinants of serum gamma-glutamyl transferase (GGT) concentrations, the relationship between dietary patterns and GGT remains unknown. The present cross-sectional study aimed to determine relationships between dietary patterns and GGT concentrations, and the effects of lifestyle factors on GGT. METHODS: Relationships between dietary patterns and GGT were analyzed in 9803 Japanese individuals (3723 men and 6080 women age 40-69 years) without a history of liver diseases or elevated serum aminotransferase. We examined major dietary patterns by factor analysis of 46 items determined from a validated, short food frequency questionnaire. RESULTS: We defined dietary patterns as healthy, Western, seafood, bread, and dessert. The healthy pattern was inversely related to GGT in men (odds ratio [OR] for highest vs lowest quartile, 0.72; 95% confidence interval [CI], 0.57-0.92; P < 0.01 for trend) and women (OR 0.82; 95% CI, 0.66-1.0; P = 0.05 for trend), whereas the seafood pattern was positively related to GGT in men (OR 1.27; 95% CI, 1.01-1.61; P = 0.03 for trend) and women (OR 1.21; 95% CI, 0.98-1.49; P = 0.05 for trend). Male-specific inverse associations with GGT were found for bread and dessert patterns (OR 0.63; 95% CI, 0.50-0.80 and OR 0.53; 95% CI, 0.41-0.68, respectively; P < 0.01 for both trends). Seafood or bread patterns and alcohol consumption significantly interacted with GGT in men (P = 0.03 and <0.01 for interaction, respectively) and between the dessert pattern and body mass index or smoking habit in women (P = 0.03 and <0.01, respectively, for interaction). CONCLUSIONS: Dietary patterns may be important determinants of GGT, and their possible clinical implications warrant further investigation.

Objectively measured physical activity and inflammatory cytokine levels in middle-aged Japanese people.

OBJECTIVE: Studies using self-reported physical activity (PA) showed that higher PA is associated with lower circulating levels of C-reactive protein; in contrast, studies investigating associations of objective PA and other inflammatory markers are limited. We investigated cross-sectional associations of accelerometer-determined PA with circulating levels of myokine-type inflammatory cytokines in a middle-aged Japanese population. METHOD: A total of 1838 individuals (737 men and 1101 women) aged 40 to 69 years participated in the baseline survey of a population-based cohort study in Saga, Japan (2005-2007). Habitual PA was assessed by a single-axis accelerometer. Serum interleukin (IL)-4, IL-6, IL-8, IL-15, and tumor necrosis factor (TNF)-α were measured by a multiplex enzyme-linked immunosorbent assay. Associations between PA and cytokine levels were assessed by multiple regression analysis and analysis of covariance, with adjustment for potential confounders. RESULTS: Step count and PA level (PAL) were inversely associated with TNF-α and IL-15 even after adjusting for BMI. Similarly, greater PA indices were also independently associated with a lower level of inflammatory cytokine z score as an index of overall inflammation. CONCLUSION: The current results suggest that greater engagement in daily PA may be linked with reduced levels of myokine-type cytokines including IL-15, irrespective of body weight in middle-aged Japanese people.

Gender-specific associations of perceived stress and coping strategies with C-reactive protein in middle-aged and older men and women.

BACKGROUND: Perceived stress and coping strategies may influence the risk of cardiovascular disease through their possible association with inflammation, but data remain controversial for perceived stress or scanty for coping strategies. PURPOSE: We examined the associations of perceived stress and coping strategies with serum high-sensitivity C-reactive protein (CRP) in a Japanese general population. METHODS: This cross-sectional study included 2,971 men and 4,902 women aged 40-69 years who were enrolled between 2005 and 2007. Subjects with possible inflammation-related disease, CRP levels ≥3,000 ng/mL, or currently used analgesics or lipid-lowering drugs were excluded. Analyses were performed by gender with adjustment for lifestyle, socioeconomic, and psychosocial factors. RESULTS: Unexpectedly, elevated perceived stress was significantly associated with lower CRP levels in men (P trend < 0.001) but not in women (P trend = 0.90) after adjustment for age and covariates. Among five items of coping strategies evaluated, "disengagement" showed a significant inverse association with CRP in men only (P trend = 0.027). In addition, a possible interaction between "emotional support seeking" and perceived stress on CRP was detected in men (P interaction = 0.021); "emotional support seeking" was associated with lower CRP at the high stress level only (P trend = 0.028). CONCLUSIONS: Both perceived stress and coping strategies may be associated with systemic inflammation in Japanese men, yet caution must be exercised before accepting the stress-inflammation-disease pathway.

Evaluation of Prediabetes in Cisplatin-induced Nephrotoxicity in the Short Hydration Method: A Subgroup Analysis.

BACKGROUND/AIM: Cisplatin-induced nephrotoxicity (CIN) is one of the most attention-requiring adverse effects. We have reported that diabetes mellitus significantly increases the incidence of CIN in a short hydration method in real-world lung cancer treatment. However, the effect of prediabetes on CIN development remains unclear. This study investigated whether patients with prediabetes exhibit CIN at a greater rate during real-world cisplatin-including treatments as a subgroup analysis. PATIENTS AND METHODS: This retrospective observational study enrolled patients with lung cancer receiving cisplatin treatment (≥75 mg/m2) from May 2014 to January 2021 (n=169). Patients were divided into a prediabetes group (baseline HbA1c 5.7-6.4%) and a control group (baseline HbA1c <5.7%). The primary endpoint of this study was the incidence of CIN in all treatment cycles between the two groups. We also assessed variations in serum creatinine (SCr) levels and creatinine clearance (CCr). RESULTS: CIN occurred in 4.7% of controls and 8.3% of patients with prediabetes in all cycles, with no significant difference (p=0.37). In contrast, variation of SCr levels and CCr was significantly worse in the prediabetes group [median variation level (range) 0.11 mg/dl (-0.11-0.46 mg/dl) and 0.12 mg/dl (-0.02-1.08 mg/d) in controls and prediabetes, p=0.04 for SCr; -12.9 ml/min (-54.1-4.9 ml/min) and -16.3 ml/min (-49.4-3.0 ml/min), p=0.02 for CCr, respectively]. These results were also confirmed during the first cycle of treatment. CONCLUSION: Patients with prediabetes did not develop problematic CIN, although they exhibited significant increases in SCr and decreases in CCr.

Gefitinib-induced Myositis: A Novel Case Report.

Chemotherapy-induced myositis is a severe adverse event caused by chemotherapeutic agents such as immune checkpoint inhibitors (ICIs) or cytotoxic agents. We experienced a patient with gefitinib-induced myositis with symptoms of muscle cramps and stiffness in the limbs, and reported the treatment process. A 70-year-old woman received four courses of carboplatin (CBDCA)+pemetrexed (PEM)+gefitinib (intravenous CBDCA area under the curve (AUC) 5 and PEM 500 mg/m2, every 3 weeks, and oral gefitinib 250 mg daily), for epidermal growth factor receptor (EGFR) mutation-positive stage IV lung cancer treatment; followed by seven courses of PEM+gefitinib, and continued gefitinib monotherapy thereafter. Myositis occurred 5 months after the initiation of gefitinib monotherapy. She developed strong limb cramps despite regular oral administration of 400 mg acetaminophen three times a day and complained of pain on a numeric rating scale of 10/10. Her creatine kinase (CK) was elevated from the second course of CBDCA+PEM+gefitinib but was stable at grade 1-2 thereafter. However, the muscle symptoms disappeared with CK normalization within a few days of gefitinib discontinuation due to disease progression. The Naranjo Adverse Drug Reaction Scale score was 6, suggesting a probable association. Osimertinib (an EGFR tyrosine kinase inhibitor)-induced myositis has been reported, but similar events were first observed with gefitinib in this case. Consequently, when treating with gefitinib, myositis, including the CK variation, should be monitored and appropriately managed with multidirectional treatment.

The Cenozoic palaeoenvironment of the Arctic Ocean.

The history of the Arctic Ocean during the Cenozoic era (0-65 million years ago) is largely unknown from direct evidence. Here we present a Cenozoic palaeoceanographic record constructed from >400 m of sediment core from a recent drilling expedition to the Lomonosov ridge in the Arctic Ocean. Our record shows a palaeoenvironmental transition from a warm 'greenhouse' world, during the late Palaeocene and early Eocene epochs, to a colder 'icehouse' world influenced by sea ice and icebergs from the middle Eocene epoch to the present. For the most recent approximately 14 Myr, we find sedimentation rates of 1-2 cm per thousand years, in stark contrast to the substantially lower rates proposed in earlier studies; this record of the Neogene reveals cooling of the Arctic that was synchronous with the expansion of Greenland ice (approximately 3.2 Myr ago) and East Antarctic ice (approximately 14 Myr ago). We find evidence for the first occurrence of ice-rafted debris in the middle Eocene epoch (approximately 45 Myr ago), some 35 Myr earlier than previously thought; fresh surface waters were present at approximately 49 Myr ago, before the onset of ice-rafted debris. Also, the temperatures of surface waters during the Palaeocene/Eocene thermal maximum (approximately 55 Myr ago) appear to have been substantially warmer than previously estimated. The revised timing of the earliest Arctic cooling events coincides with those from Antarctica, supporting arguments for bipolar symmetry in climate change.

Late survival of Neanderthals at the southernmost extreme of Europe.

The late survival of archaic hominin populations and their long contemporaneity with modern humans is now clear for southeast Asia. In Europe the extinction of the Neanderthals, firmly associated with Mousterian technology, has received much attention, and evidence of their survival after 35 kyr bp has recently been put in doubt. Here we present data, based on a high-resolution record of human occupation from Gorham's Cave, Gibraltar, that establish the survival of a population of Neanderthals to 28 kyr bp. These Neanderthals survived in the southernmost point of Europe, within a particular physiographic context, and are the last currently recorded anywhere. Our results show that the Neanderthals survived in isolated refuges well after the arrival of modern humans in Europe.

A 5% Glucose Solution for the Liquid Formulation Gemcitabine Solvent Decreases Gemcitabine-induced Vascular Pain.

BACKGROUND/AIM: Gemcitabine (GEM)-induced vascular pain often occurs in patients. A 5% glucose solution for the lyophilized formulation of GEM solvent is known to decrease the frequency of GEM-induced vascular pain compared with saline. In this study, we aimed to examine the availability of glucose for a liquid formulation GEM solvent for the prevention of GEM-induced vascular pain. PATIENTS AND METHODS: In total, 214 patients with bile tract or pancreatic cancer, who received GEM-containing regimens, were enrolled in this retrospective study. The patients were divided into a glucose group, which was administered the liquid formation GEM diluted with glucose, and a saline group. The frequency of GEM-induced vascular pain was compared between them. RESULTS: Glucose significantly decreased the frequency of GEM-induced vascular pain during the first GEM administration (36% vs. 55%, p=0.005). CONCLUSION: Switching the solution for liquid formulation GEM from saline to glucose significantly decreased the frequency of vascular pain.

Diabetes mellitus degenerates cisplatin-induced nephrotoxicity in short hydration method: a propensity score-matching analysis.

Cisplatin (CDDP)-induced nephrotoxicity (CIN) is dose-limiting. We revealed that co-administration of non-steroid anti-inflammatory drugs and baseline comorbidity of diabetes mellitus (DM) are associated with CIN development in the short hydration method; however, the results were accessorily obtained without appropriate power calculation. This study aimed to demonstrate the influence of DM complications on CIN incidence in a real-world setting. Lung cancer patients receiving CDDP (≥ 75 mg/m2)-containing regimens with a short hydration method (n = 227) were retrospectively evaluated. The patients were divided into control and baseline DM complication groups. The primary endpoint was the evaluation of CIN incidence between the groups. Propensity score-matching was performed to confirm the robustness of the primary analysis results. CIN occurred in 6.8% of control and 27.0% of DM patients, respectively, with a significant difference in all-patient populations (P = 0.001). In addition, variation of serum creatinine and creatinine clearance significantly worsened in DM patients. Similar results were obtained in a propensity-matched population. Multivariate logistic regression analysis found that DM complication is a singular risk factor for CIN development (adjusted odds ratio; 4.31, 95% confidence interval; 1.62-11.50, P = 0.003). In conclusion, our study revealed that baseline DM complications significantly worsen CIN.

Sedentary time, physical activity, and serum SPARC in a middle-aged population.

The influence of habitual physical activity (PA) on the circulating levels of secreted protein acidic and rich in cysteine (SPARC) remains unclear. The purpose of the current study was to clarify the effects of sedentary time, light-intensity PA (LPA), and moderate- to vigorous-intensity PA (MVPA) on the serum SPARC in a general middle-aged population. The current study is a cross-sectional study of 4,000 men and 6,040 women (40-69 years). Sedentary time, LPA, and MVPA were objectively measured by an accelerometer. The serum SPARC concentration was measured by enzyme-linked immunosorbent assay. Using an isotemporal substitution model, cross-sectional associations of replacing sedentary time with either LPA or MVPA on serum SPARC levels were analysed according to sex. Interactions with subject characteristics, such as the body mass index (BMI), smoking, and alcohol consumption, were also examined. In men, replacing 60 min of sedentary time with 60 min of MVPA was significantly associated with 23 ng/mL lower serum SPARC levels (confidence interval: -43, -2) after adjusting for confounders, including the BMI (P = 0.028). A significant interaction between replacing sedentary behaviour with LPA and the BMI on SPARC was detected in women (P = 0.029), although the stratified associations for each BMI level (<25 or ≥25 kg/m2) did not reach significance. The current study suggests that replacing sedentary time with MVPA is associated with reduced serum SPARC levels in middle-aged men, but not in women. In addition, a potential interaction between LPA and the BMI on SPARC was also found in women.Highlights An isotemporal substitution analysis showed that replacing sedentary behaviour with moderate- to vigorous-intensity physical activity (MVPA) is associated with decreased serum SPARC levels in men.Such an inverse association between replacing sedentary behaviour with MVPA and the SPARC levels was not observed in women.A potential interaction between replacing sedentary behaviour with light-intensity PA and the body mass index on the serum SPARC levels was also found in women.

Association between dietary pattern and serum C-reactive protein in Japanese men and women.

BACKGROUND: Dietary pattern may influence the risks of cardiovascular disease, atherosclerosis, type 2 diabetes, and metabolic syndrome through its effects on inflammation. We evaluated the association between dietary pattern and serum high-sensitivity C-reactive protein (hs-CRP) in a Japanese population. METHODS: In this cross-sectional analysis, we used baseline data from 3905 men and 5640 women (age 40-69 years) who participated in a population-based cohort study between November 2005 and December 2007. Participants with possible inflammation-related diseases, current analgesic use, high hs-CRP levels (≥3000 ng/mL) or extreme dietary energy intake were excluded. We used 46 items from a validated short food frequency questionnaire and examined major dietary patterns by factor analysis. RESULTS: We identified 5 dietary patterns: healthy (high in vegetables and fruit), Western (high in meat and fried foods), seafood (high in shellfish, squid, fish, etc.), bread (high in bread and low in rice), and dessert (high in confections and fruit). After adjustment for age, alcohol use, smoking, physical activity, and body mass index, hs-CRP levels in men were inversely associated with the healthy, bread, and dessert patterns (P-trend: 0.01, 0.06, and <0.01, respectively) and positively associated with the seafood pattern (P-trend = 0.02). In women, hs-CRP levels were inversely associated with the healthy pattern (P-trend = 0.06) and positively associated with the Western pattern (P-trend = 0.06). CONCLUSIONS: The healthy dietary pattern may be associated with suppressed inflammation in Japanese men and women, independently of body mass index and other factors. The sex-specific associations of hs-CRP with other dietary patterns (eg, the seafood pattern) require further study.

Profile of participants and genotype distributions of 108 polymorphisms in a cross-sectional study of associations of genotypes with lifestyle and clinical factors: a project in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.

BACKGROUND: Most diseases are thought to arise from interactions between environmental factors and the host genotype. To detect gene-environment interactions in the development of lifestyle-related diseases, and especially cancer, the Japan Multi-institutional Collaborative Cohort (J-MICC) Study was launched in 2005. METHODS: We initiated a cross-sectional study to examine associations of genotypes with lifestyle and clinical factors, as assessed by questionnaires and medical examinations. The 4519 subjects were selected from among participants in the J-MICC Study in 10 areas throughout Japan. In total, 108 polymorphisms were chosen and genotyped using the Invader assay. RESULTS: The study group comprised 2124 men and 2395 women with a mean age of 55.8 ± 8.9 years (range, 35-69 years) at baseline. Among the 108 polymorphisms examined, 4 were not polymorphic in our study population. Among the remaining 104 polymorphisms, most variations were common (minor allele frequency ≥0.05 for 96 polymorphisms). The allele frequencies in this population were comparable with those in the HapMap-JPT data set for 45 Japanese from Tokyo. Only 5 of 88 polymorphisms showed allele-frequency differences greater than 0.1. Of the 108 polymorphisms, 32 showed a highly significant difference in minor allele frequency among the study areas (P < 0.001). CONCLUSIONS: This comprehensive data collection on lifestyle and clinical factors will be useful for elucidating gene-environment interactions. In addition, it is likely to be an informative reference tool, as free access to genotype data for a large Japanese population is not readily available.

Optimal cutoff values of waist circumference and the discriminatory performance of other anthropometric indices to detect the clustering of cardiovascular risk factors for metabolic syndrome in Japanese men and women.

OBJECTIVE: To evaluate the pertinent cutoffs of waist circumference (WC) and the discriminatory performance of other anthropometric indices to detect clustering cardiovascular risk factors for metabolic syndrome (MetS) in Japan, where the current WC cutoffs for MetS (85 cm for men and 90 cm for women) remain controversial. METHODS: We analyzed the baseline data from 844 subjects (330 men and 514 women) aged 40-69 years who participated in a cohort study in Saga city, Japan, between November 2005 and December 2007. Receiver operating characteristic (ROC) analyses were performed to find an appropriate cutoff (defined as the point nearest to the upper left corner of the ROC curve) of each anthropometric index for the presence of multiple risk factors among dyslipidemia, hypertension, and hyperglycemia [which was defined as hemoglobin A1c (HbA1c) levels at and above 5.2, 5.5, or 5.8%, values approximately corresponding to fasting plasma glucose levels of 100, 110, and 120 mg/dL, respectively]. RESULTS: The optimal WC cutoff was 88 cm (sensitivity 60%, specificity 70%) for men and 82 cm (sensitivity 78%, specificity 62%) for women; changing the HbA1c cutoff affected the results in women only (~85 cm). For the currently defined WC cutoffs in Japan, specificity was low (53-57%) in men, whereas sensitivity was very low (32-42%) in women. Body mass index, proportion of body fat, waist-to-height ratio, and waist-to-hip ratio showed area under the curve values similar to that of WC. CONCLUSION: The current Japanese criteria of WC for MetS may be low for men and too high and insensitive for women in our study population. Other anthropometric indices such as waist-to-height ratio did not confer an improved discriminatory performance compared with WC.

Causes and timing of recurring subarctic Pacific hypoxia.

Several North Pacific studies of the last deglaciation show hypoxia throughout the ocean margins and attribute this phenomenon to the effects of abrupt warming and meltwater inputs. Yet, because of the lack of long records spanning multiple glacial cycles and deglaciation events, it is unclear whether deoxygenation was a regular occurrence of warming events and whether deglaciation and/or other conditions promoted hypoxia throughout time. Here, subarctic Pacific laminated sediments from the past 1.2 million years demonstrate that hypoxic events recurred throughout the Pleistocene as episodes of highly productive phytoplankton growth and were generally associated with interglacial climates, high sea levels, and enhanced nitrate utilization-but not with deglaciations. We suggest that hypoxia was typically stimulated by high productivity from iron fertilization facilitated by redox-remobilized iron from flooded continental shelves.

[Pharmaceutical Intervention According to Strict Management System Can Normalize Decreased Serum Calcium Level by Denosumab and Prevent Its Aggravation].

Denosumab is a fully monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand (RANKL), and prevents skeletal-related events by bone metastasis. Hypocalcemia is the most typical adverse effect of denosumab use. We have developed a management system for the more efficient and safer management of denosumab administration, and evaluated pharmaceutical interventions for the better control of hypocalcemia. All pharmaceutical interventions in the system from April 2016 to March 2020 were retrospectively evaluated. We have also assessed the incidence of hypocalcemia in 158 patients who were administered denosumab for six months or more in the period. A total of 282 pharmaceutical interventions (7.0% of the total administration) were conducted. The most conducted intervention was regarding hypocalcemia, which involved the suspension of the injection and/or the increase of calcium and vitamin D supplement with 65% adoption and 17% temporary treatment suspensions. Other interventions were about hypercalcemia, request of laboratory examination and ordering supplements, dental consultation, and poor renal function. A total of 199 interventions (70.6%) were adopted, with 33 administrations suspended. The frequency of hypocalcemia was 27.8% with just one patient having grade 2 hypocalcemia, suggesting that there were no severe cases. Moreover, hypocalcemia was significantly normalized following pharmaceutical intervention and/or handling by physicians (p=0.02) according to the system. Conversely, the normalization rate in hypercalcemia did not differ according to the countermeasures. In conclusion, pharmaceutical interventions according to our management system benefit safe denosumab treatment, especially in severe hypocalcemia prevention.