Search

BackgroundMutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reduce the efficacy of neutralizing monoclonal antibody therapy against coronavirus disease 2019 (COVID-19). We here evaluated the efficacy of casirivimab-imdevimab in patients with mild-to-moderate COVID-19 during the Delta variant surge in Fukushima Prefecture, Japan.MethodsWe enrolled 949 patients with mild-to-moderate COVID-19 who were admitted to hospital between July 24, 2021 and September 30, 2021. Clinical deterioration after admission was compared between casirivimab-imdevimab users (n = 314) and non-users (n = 635).ResultsThe casirivimab-imdevimab users were older (P < 0.0001), had higher body temperature (≥ 38°C) (P < 0.0001) and greater rates of history of cigarette smoking (P = 0.0068), hypertension (P = 0.0004), obesity (P < 0.0001), and dyslipidemia (P < 0.0001) than the non-users. Multivariate logistic regression analysis demonstrated that receiving casirivimab-imdevimab was an independent factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.263–0.763; P = 0.0023). Furthermore, in 222 patients who were selected from each group after matching on the propensity score, deterioration was significantly lower among those receiving casirivimab-imdevimab compared to those not receiving casirivimab-imdevimab (7.66% vs 14.0%; p = 0.021).ConclusionThis real-world study demonstrates that casirivimab-imdevimab contributes to the prevention of deterioration in COVID-19 patients after hospitalization during a Delta variant surge.SummaryThis real-world retrospective study demonstrates the contribution of treatment with casirivimab-imdevimab to the prevention of deterioration in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) even during the Delta variant pandemic.

Background It is unclear whether molnupiravir has a beneficial effect on vaccinated patients infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We here evaluated the efficacy of molnupiravir in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron variant surge in Fukushima Prefecture, Japan. Methods We enrolled patients with mild-to-moderate COVID-19 who were admitted to hospitals between January and April, 2022. Clinical deterioration after admission was compared between molnupiravir users (n = 281) and non-users (n = 1,636). Results The molnupiravir users were older (P

Context Advance care planning (ACP) is vital for end-of-life care management. Experiences as informal family caregivers might act as a catalyst to promote ACP. Objectives We investigated the association between ACP discussions and caregiving experiences. Methods A nationwide survey in Japan was conducted in December 2016 using a quota sampling method to select a sample representative of the general Japanese population. The responses of 3167 individuals aged 20–84 years (mean age: 50.9 ± 16.8) were analyzed. The outcome was measured by asking if respondents had ever engaged in ACP discussions. The exposure was measured by asking whether and for how long respondents had experience as informal caregivers for family members. We analyzed informal caregiving experience related to the occurrence of ACP discussions using multivariable logistic regression models that adjusted for possible covariates. Results Respondents with informal caregiving experience had significantly higher odds of having ACP discussions than those without caregiving experience (adjusted odds ratio: 1.93, 95% CI = 1.63, 2.29). Stronger effects were identified in younger adults (aged 20–65 years) and those with a higher education level (education duration > 12 years) than in older adults (aged ≥65 years) and those with a lower education level, respectively. Conclusion Experiences as informal caregivers for family members may facilitate ACP discussions among Japanese adults, especially younger adults with higher educational attainment. Our findings may help health-care providers screen those at risk for inadequate ACP discussions, and informal caregiving experience should be considered when health-care providers initiate discussions of end-of-life care.

Objective: To evaluate the added value of inflammatory markers to vital signs to predict mortality in patients suspected of severe infection. Methods: This study was conducted at an acute care hospital (471-bed capacity). Consecutive adult patients suspected of severe infection who presented to either ambulatory care or the emergency department from April 2015 to March 2017 were retrospectively evaluated. A prognostic model for predicting 30-day in-hospital mortality based on previously established vital signs (systolic blood pressure, respiratory rate, and mental status) was compared with an extended model that also included four inflammatory markers (C-reactive protein, neutrophil-lymphocyte ratio, mean platelet volume, and red cell distribution width). Measures of interest were model fit, discrimination, and the net percentage of correctly reclassified individuals at the pre-specified threshold of 10% risk. Results: Of the 1015 patients included, 66 (6.5%) died. The extended model including inflammatory markers performed significantly better than the vital sign model (likelihood ratio test: p < 0.001), and the c-index increased from 0.69 (range 0.67–0.70) to 0.76 (range 0.75–0.77) (p = 0.01). All included markers except C-reactive protein showed significant contribution to the model improvement. Among those who died, 9.1% (95% CI −2.8–21.8) were correctly reclassified by the extended model at the 10% threshold. Conclusions: The inflammatory markers except C-reactive protein showed added predictive value to vital signs. Future studies should focus on developing and validating prediction models for use in individualized predictions including both vital signs and the significant markers.

Respiratory rate measurement is one of the core nursing skills for early detection of deterioration of a patient's condition. Nevertheless, it is sometimes bothersome to visually measure respiratory rate over 1 min. Respiratory rate measurement using a mobile phone application "RRate" has been reported to be accurate and completed in a short time. However, it has only been investigated in children. The aim of this study was to validate the "RRate" compared with the 1-min method in adult patients.This was a cross-sectional study in the setting of a nursing school. Videos of the movement of the thorax during respiration of adult patients were made. Nursing students watched these videos and measured respiratory rate with each method. Bland-Altman analysis was used to calculate bias and limits of agreement. The times taken for the measurements were compared using a t test.A total of 59 nursing students participated. When compared to the reference measurement, the one measured using "RRate" and the one measured over 1 min showed a bias of 0.40 breaths per minute and 0.65 breaths per minute, limits of agreement of -2.86 to 3.67 breaths per minute and -2.11 to 3.41 breaths per minute, respectively. The mean measurement time for "RRate" was 22.8 s (95% CI 13.9-36.6), which was significantly shorter than the 65.8 s (95% CI 61.0-73.2) for the measurement over 1 min (p .001).Respiratory rate can be measured accurately in a shorter time using a mobile phone application in adult patients.

Aspiration pneumonia (AP) is a public health concern among older adults. Previous studies have reported the association between oral intake initiation within 48 h after hospital admission and better in-hospital outcomes among patients with AP. We investigated the association between initiation of oral intake within 24 h and in-hospital outcomes of older patients with AP undergoing dysphagia rehabilitation.This retrospective cohort study was conducted from April 2015 to September 2020. Door-to-oral time (D2O) was defined as the time from hospital arrival to the first oral intake and was divided into early (within 24 h), middle (between 24 and 48 h), and late (over 48 h). We examined the associations between D2O and in-hospital outcomes: discharge with oral intake (by logistic regression analysis), length of stay, and days from the first oral intake to discharge (by fitting the general linear models with robust variance estimation).Among the 398 patients with AP, 142 (35.7%) were classified into early, 111 (27.9%) into middle, and 145 (36.4%) into late groups. Compared with the late group, we found insufficient evidence that early D2O was associated with a greater likelihood of discharge with oral intake (adjusted odds ratio = 1.09; 95% confidence interval [95% CI]: 0.50 to 2.38). The early group was associated with a shorter length of stay (adjusted length difference [aLD] = -7.14 days; 95% CI: -10.80 to -3.42) but not with shorter days from first oral intake to discharge (aLD = -3.34 days; 95% CI: -6.91 to 0.24).While D2O within 24 h among patients with AP was not associated with a decreased likelihood of discharge with oral intake, it was associated with a shorter length of stay. To improve outcomes without compromising the quality of AP care, early oral intake should be decided based on careful swallowing function assessment.

BACKGROUNDDue to the dissemination of vaccination against severe acute respiratory syndrome coronavirus 2 in the elderly, the virus-susceptible subjects have shifted to unvaccinated non-elderlies. The risk factors of COVID-19 deterioration in non-elderly patients without respiratory failure have not yet been determined. This study was aimed to create simple predicting method to identify such patients who have high risk for exacerbation.METHODSWe analyzed the data of 1,675 patients aged under 65 years who were admitted to hospitals with mild-to-moderate COVID-19. For validation, 324 similar patients were enrolled. Disease progression was defined as administration of medication, oxygen inhalation and mechanical ventilator starting one day or longer after admission.RESULTSThe patients who exacerbated tended to be older, male, had histories of smoking, and had high body temperatures, lower oxygen saturation, and comorbidities such as diabetes/obesity and hypertension. Stepwise logistic regression analyses revealed that comorbidities of diabetes/obesity, age ≥ 40 years, body temperature ≥ 38°C, and oxygen saturation < 96% (DOATS) were independent risk factors of worsening COVID-19. As a result two predictive scores were created: DOATS score, which includes all the above risk factors; and DOAT score, which includes all factors except for oxygen saturation. In the original cohort, the areas under the receiver operating characteristic curve of the DOATS and DOAT scores were 0.789 and 0.771, respectively. In the validation, the areas were 0.702 and 0.722, respectively.CONCLUSIONWe established two simple prediction scores that can quickly evaluate the risk of progression of COVID-19 in non-elderly, mild/moderate patients.SummaryThe risk stratification models using independent risks, namely comorbidity of diabetes or obesity, age ≥ 40 years, high body temperature ≥ 38□, and oxygen saturation < 96%, DOATS and DOAT scores, predicted worsening COVID-19 in patients with mild-to-moderate cases.

Background In older adults, the diagnosis of acute pyelonephritis is challenging because of non-specific symptoms and false-positive urine test results. Few studies have investigated the diagnostic performance of computed tomography (CT) signs. Purpose To evaluate the diagnostic performance of CT signs for acute pyelonephritis in older patients suspected of infection with unknown focus. Material and Methods This cross-sectional study was conducted between 2015 and 2018. Patients aged ≥65 years who underwent blood cultures, urine culture, and non-contrast or contrast-enhanced CT on admission were included. Cases with clinically presumable infection focus before CT were excluded. Two radiologists blinded to clinical information independently reviewed five CT signs: perirenal fat stranding; pelvicalyceal wall thickening and enhancement; renal enlargement; thickening of Gerota’s fascia; and area(s) of decreased attenuation. The final diagnoses were made by a clinical expert panel. Results Among 473 eligible patients, 61 were diagnosed with acute pyelonephritis. When the laterality of findings between the left and right kidneys were considered, the positive and negative likelihood ratios of perirenal fat stranding were 4.0 (95% confidence interval [CI] = 2.3–7.0) and 0.8 (95% CI = 0.7–0.9) in non-contrast CT, respectively. The other signs in non-contrast CT showed similar diagnostic performance with positive and negative likelihood ratios of 3.5–11.3 and 0.8–0.9, respectively. Conclusion CT signs can help physicians diagnose acute pyelonephritis in older patients suspected of infection with unknown focus.

Aim This study was conducted to investigate the association between the use of physical restraint and functional decline in older inpatients admitted with pneumonia in an acute care setting. Although several adverse effects related to restraint use have been reported, few researchers have examined this subject in acute care settings. Methods This retrospective cohort study was conducted at a 471-bed, acute care hospital in Japan. Patients 65 years old and older who were admitted with pneumonia between April 2015 and September 2017 were included. The use of restraints (belts and/or mittens) was recorded for every 8-hour shift. The number of shifts during which each patient was restrained was used as an explanatory variable. The primary outcome was the Katz ADL score at discharge. We used multiple linear regression analysis to adjust for confounding factors. Results Of 403 patients, 94 required physical restraints. The mean age was 84.5 years (standard deviation [SD] 8.2); 44.4% were women. The mean Katz score on admission was 2.7 (SD 2.4). For multiple linear regression analysis, the coefficient of the number of restraints used was -0.024 (95% confidence interval: -0.044, -0.003, p = .022). Consequently, the restraint use for 13.9 days was associated with the decrease in the Katz score by 1.0. Conclusions Results suggest that physical restraint use is associated with functional decline among older inpatients admitted with pneumonia in acute care settings.

Objectives: This study aimed to reveal the features of older adults’ advance care planning (ACP) discussions by identifying psychosocial factors related to their discussions in Japan, where people value family-centered decision making. Methods: A qualitative study using in-depth interviews was conducted with 39 participants (aged ≥65 years) recruited from the outpatient department of a community hospital in Fukushima, Japan. Data were analyzed using the grounded theory approach. Results: Through experiences of family caregiving, participants became aware of their own feelings about the end of life. Equal relationship with family members was important for lowering the threshold for having discussions. Some participants and their families in the same generation reached agreements on ACP; however, they were willing to yield to children’s decision making despite these discussions. Discussions: These findings provide insights into the psychosocial factors in relation to ACP discussions and support for the role of ACP discussions in the family-centered decision-making culture.

Supplemental material, Revised_supplementary_meterial for How Psychosocial Factors Contribute to Japanese Older Adults’ Initiation of Advance Care Planning Discussions: A Qualitative Study by Jun Miyashita, Ayako Kohno, Yosuke Yamamoto, Sayaka Shimizu, Teruhisa Azuma, Toshihiko Takada, Michio Hayashi and Shunichi Fukuhara in Journal of Applied Gerontology

Interest in the use of incentives to promote health behavior change has been growing worldwide. However, to develop an effective incentive program, accurate information regarding individual preferences is essential. Therefore, the aim of this study was to clarify determinants of incentive preferences for health behavior change. A self-completed questionnaire survey regarding incentives for health behavior change was conducted in a Japanese village in 2015. The outcome measures were individual preferences for features of incentives, including item, frequency, type and value. The types of incentives were defined as follows: assured-type (given for participation); effort-type (given if participants make some kind of effort); and outcome-type (given if participants make achievements decided a priori). The associations with respondents’ sex, age, presence of lifestyle-related disease and stage in the transtheoretical model of health behavior change were investigated using multivariate analysis. A total of 1469 residents responded to the survey. Significant associations with preference for different incentive features were found as follows: for monetary items, female and elderly; for high frequency, female and maintenance stage; for effort-type, male, action stage and contemplation stage; and for outcome-type, maintenance stage and action stage. Our results appeared to identify determinants of incentive preferences for health behavior change. These findings are expected to promote the development of an incentive program more in tune with individual preferences.

Objective: Quality indicators (QIs) are tools that standardize evaluations in terms of the minimum acceptable quality of care, presumably contributing for the better management of patients with systemic lupus erythematosus (SLE). This study aimed to develop QIs for SLE using electronic health data.Methods: The modified RAND/UCLA Appropriateness Method was used to develop the QIs. First, a literature review was conducted. Second, the candidate QI items that were available to be evaluated using the electronic health data were extracted. Third, the appropriateness of the items was assessed via rating rounds and panelists' discussions.Results: We found 3621 articles in the initial search. Finally, 34 studies were reviewed, from which 17 potential indicators were extracted as candidate QIs. Twelve indicators were selected as the final QI set through the process of appropriateness. The median appropriateness of these 12 indicators was at least 7.5, and all of them were without disagreement. The QI included assessment of disease activity, treatment of SLE, drug toxicity monitoring, treatment of glucocorticoid complications, and assessment of SLE complications.Conclusion: We formulated 12 QIs for the assessment of patients with SLE based on electronic medical data. Our QI set would be a practical tool as a quality measure.

Background: Older adults’ discussions with family, or with physicians, or with both, about advance care planning (ACP) are increasingly regarded as important for the management of end-of-life care, and yet the factors that induce older adults to engage in ACP discussions are poorly understood. For example, in older adults, is stronger connectedness with family and friends (stronger “networks”) associated with ACP discussions? By facilitating, or by impeding ACP discussions? We sought to evaluate the associations between ACP discussions and social networks in Japanese older adults. Methods: In July 2016 we conducted a cross-sectional survey on 355 community-dwelling patients aged ≥65 years visiting community hospital clinics in Fukushima, Japan. We used the Lubben Social Network Scale (LSNS-6, the shortest available LSNS scale) to assess social networks and recorded two components of social network structure, marital status (dichotomized as “married” vs. “single, other”) and living status (“living with others” vs. “living alone”). One item asked if patients had had ACP discussions. We analyzed the LSNS-6 social network and marital and living status data in relation to the occurrence of ACP discussions using multiple logistic regression models with adjustments for possible confounding factors. Results: Respondents’ social network was “limited” in 16% of cases; 61% had had ACP discussions. Respondents with a limited social network had a significantly lower tendency to have had ACP discussions than respondents with an “adequate” social network (adjusted odds ratio [AOR]: 0.35; 95% confidence interval [CI]: 0.18–0.66; P < 0.001). Marital status and living status were not significantly associated with ACP discussion. Conclusions: Among Japanese older adults, weaker social networks may be associated with a lower tendency to discuss ACP. Our findings may help practitioners to quickly screen populations at risk for inadequate ACP discussion by using the LSNS-6.

This study investigated the association between the daily salt intake of 3-year-old children and that of their mothers. A total of 641 children were studied. The daily salt intake of the children and their mothers was estimated by morning and spot urine methods, respectively. In the multivariable analysis, a 1 g higher maternal daily salt intake was associated with a 0.14 g (95% confidence interval [CI], 0.07-0.22, P

Objective To prevent functional decline in older inpatients, identification of high-risk patients is crucial. The aim of this study was to develop and validate a prediction model to assess the risk of functional decline in older medical inpatients. Methods In this retrospective cohort study, patients ≥65 years admitted acutely to medical wards were included. The healthcare database of 246 acute care hospitals (n = 229,913) was used for derivation, and two acute care hospitals (n = 1767 and 5443, respectively) were used for validation. Data were collected using a national administrative claims and discharge database. Functional decline was defined as a decline of the Katz score at discharge compared with on admission. Results About 6% of patients in the derivation cohort and 9% and 2% in each validation cohort developed functional decline. A model with 7 items, age, body mass index, living in a nursing home, ambulance use, need for assistance in walking, dementia, and bedsore, was developed. On internal validation, it demonstrated a c-statistic of 0.77 (95% confidence interval (CI) = 0.767–0.771) and good fit on the calibration plot. On external validation, the c-statistics were 0.79 (95% CI = 0.77–0.81) and 0.75 (95% CI = 0.73–0.77) for each cohort, respectively. Calibration plots showed good fit in one cohort and overestimation in the other one. Conclusions A prediction model for functional decline in older medical inpatients was derived and validated. It is expected that use of the model would lead to early identification of high-risk patients and introducing early intervention.

ObjectiveDiagnosis of community-acquired pneumonia (CAP) in the elderly is often delayed because of atypical presentation and non-specific symptoms, such as appetite loss, falls and disturbance in consciousness. The aim of this study was to investigate the external validity of existing prediction models and the added value of the non-specific symptoms for the diagnosis of CAP in elderly patients.DesignProspective cohort study.SettingGeneral medicine departments of three teaching hospitals in Japan.ParticipantsA total of 109 elderly patients who consulted for upper respiratory symptoms between 1 October 2014 and 30 September 2016.Main outcome measuresThe reference standard for CAP was chest radiograph evaluated by two certified radiologists. The existing models were externally validated for diagnostic performance by calibration plot and discrimination. To evaluate the additional value of the non-specific symptoms to the existing prediction models, we developed an extended logistic regression model. Calibration, discrimination, category-free net reclassification improvement (NRI) and decision curve analysis (DCA) were investigated in the extended model.ResultsAmong the existing models, the model by van Vugt demonstrated the best performance, with an area under the curve of 0.75(95% CI 0.63 to 0.88); calibration plot showed good fit despite a significant Hosmer-Lemeshow test (p=0.017). Among the non-specific symptoms, appetite loss had positive likelihood ratio of 3.2 (2.0–5.3), negative likelihood ratio of 0.4 (0.2–0.7) and OR of 7.7 (3.0–19.7). Addition of appetite loss to the model by van Vugt led to improved calibration at p=0.48, NRI of 0.53 (p=0.019) and higher net benefit by DCA.ConclusionsInformation on appetite loss improved the performance of an existing model for the diagnosis of CAP in the elderly.

Recently, a simple device for self-monitoring of daily salt intake was developed, and it is recommended by The Japanese Society of Hypertension. This study aimed to investigate the effects of this device on salt reduction and on lowering blood pressure. In this single blinded, cluster randomized controlled trial, families were randomly assigned to either an intervention or a control group. Participants in both groups attended lectures about salt reduction, but only the intervention group used the self-monitoring device to estimate their daily salt intake. The main outcome measure was the difference in the estimated daily salt intake by spot urine between the two groups after 4 weeks. The secondary outcome was the difference in blood pressure. A total of 105 families (158 participants) were randomized. The mean daily salt intake was 9.04 (SD 1.77) g/day in the control group and 9.37 (SD 2.13) g/day in the intervention group at baseline. After 4 weeks, the mean daily salt intake was 8.97 (SD 1.97) g/day in the control group and 8.60 (SD 2.25) g/day in the intervention group; the mean difference between the two groups was −0.50 g/day (95% confidence interval (CI) −0.95, −0.05; P = 0.030). The mean difference in systolic blood pressure was −4.4 mm Hg (95% CI −8.7, −0.1; P = 0.044). This is the first randomized controlled trial to demonstrate the effectiveness of a device for self-monitoring of salt intake with a significant reduction in daily salt intake and systolic blood pressure.

A 32-year-old man presented with a fever. A laboratory examination detected atypical lymphocytes and liver enzyme elevation. The serological tests for Epstein-Barr virus (EBV) were consistent with an acute infection pattern. Computed tomograpy showed bowel wall thickening, and colonoscopy revealed numerous ulcerations. The histological findings from the biopsy specimens from the colon were consistent with peripheral T-cell lymphoma (PTCL), and in situ hybridization detected EBER-1 in the atypical lymphocytes. Because his clinical and endoscopic abnormalities improved without medication, we diagnosed the patient with EBV-associated enteropathy. We herein report a rare case of EBV-associated enteropathy that required careful differentiation from PTCL.

[Background] Desire to attend graduate school for academic research training following the mandatory two-year clinical internship is unknown among young Japanese physicians who work at community hospitals after their internship. The aim of this study is to determine opinions and factors regarding pursuing higher education through graduate school among young physicians who work at community hospitals after their two-year internship. [Methods] This cross-sectional survey was conducted among young physicians working at community hospitals after their two-year internship. We examined the percentage of young physicians considering higher education through graduate school, the planned timing and field of enrollment among those wanting to enroll, and reasons for not continuing their education among those with no such plans. The association between desire to enroll in graduate school and background characteristics was examined using modified least-squares regression to estimate proportion difference. [Results] Among 127 (73.2 % internal medicine specialists, median age 30 years) physicians in 33 hospitals, 71 (55.9 %) stated that they wished to enroll in graduate school. The most frequently reported timing was 7–8 years after graduation from medical school. Those who stated no desire to attend graduate school cited concerns about the quality of training or not having enough knowledge to choose an appropriate laboratory or field, among other reasons. Increased number of years since graduating medical school [adjusted proportion difference (PD) −6.0 %, 95 % confidence interval (95 % CI) −9.8 to −2.3 %], being a woman with children [adjusted PD −53.4 %, 95 % CI −87.3 to −19.5 % (vs. a man not having children)], and completing their two-year internship at both university and community hospitals [adjusted PD −40.3 %, 95 % CI −72.5 to −8.0 % (vs. internship only at community hospitals)] were associated with a reduction in desire to enroll in graduate school. [Conclusions] We identified a growing trend in desire among young physicians to attend graduate school. Attracting those young physicians who express no desire to attend graduate school, however, will require establishment of more flexible graduate school programs which address their concerns.

Objective To evaluate the efficacy and safety of intensive post-remission chemotherapy for untreated patients aged 15-69 years with adult acute lymphoblastic leukemia and lymphoblastic lymphoma in a multicenter Phase II study. Methods The chemotherapy regimen consisted of induction, post-remission and maintenance for 2 years. The primary endpoint was 5-year progression-free survival, and secondary endpoints included complete remission rate, overall survival and adverse events. Among 115 patients enrolled, 108 eligible patients [median age, 33.5 years (range, 15-69)] including 96 acute lymphoblastic leukemia and 12 lymphoblastic lymphoma were assessed. Other major characteristics were male 50%, T-cell phenotype 21%, Philadelphia chromosome 22%, B-symptom+ 35% and performance status 2/3 22%. Results Eighty-seven patients achieved complete remission (81%; 95% confidence interval 72-88%), while five (5%) died during the chemotherapy protocol. The median overall survival and progression-free survival were 1.8 years (95% confidence interval, 1.5-2.6) and 1.2 years (95% confidence interval, 0.8-1.6), respectively. Their 5-year overall survival and progression-free survival were 29 and 28%, respectively. The 5-year overall survival of 31 patients who underwent allogeneic (n = 19) or autologous (n = 12) stem cell transplantation during first complete response was 51%. Major non-hematologic toxicities of Grade 3 or greater were infections (21%) and pulmonary complications (6%). When compared with the investigators' previous Phase II trials, JCOG9402 improved progression-free survival and overall survival when compared with JCOG8702; however, it did not show improvement when compared with JCOG9004. Conclusions Although the intensified induction and post-remission chemotherapy was feasible and 28% of the patients with adult acute lymphoblastic leukemia or lymphoblastic lymphoma achieved long-term progression-free survival, JCOG9402 did not show improvement.

The prognosis of therapy-related myelodysplastic syndrome and acute leukemia (t-MDS/AL) remains poor. We retrospectively analyzed the data of 47 patients (31 AL and 16 MDS) who were treated at our institute. Thirty-three patients received disease-adapted chemotherapy, with a response rate of 73%, while 14 received no interventions due to an indolent course, such as MDS. The median follow-up of surviving patients was 1.9 years (range 0.1-10.5) after the diagnosis of t-MDS/AL, and the estimated 3-year overall survival (OS) for all patients was 55%. Twenty-seven patients underwent allogeneic hematopoietic stem cell transplantation (HCT), and the 3-year non-relapse mortality was 17%. Twenty patients did not undergo HCT due to various reasons including advanced age or comorbidities. The 3-year OS was better in patients who received HCT than in those who did not (71 vs. 31%; p = 0.018). A multivariate analysis revealed that HCT was associated with a better OS. Although this study has several limitations, including a potential selection bias due to the retrospective nature of the analysis and a small number of patients, the results show that modern HCT may be useful for inducing long-term survival in a fraction of patients suffering from t-MDS/AL. The present findings warrant future prospective studies.

Background Information on the clinical behavior of the recently proposed primary duodenal follicular lymphoma (DFL) is limited. Patients and methods Demographic data, signs, symptoms, disease stage, and treatment of the patients diagnosed in National Cancer Center Hospital from 1999 to 2007 were collected and analyzed. Results Twenty-seven patients were studied. Nineteen patients were asymptomatic at the time of diagnosis. Twenty patients had stage I disease. The histological grade was 1 or 2 in 26 patients. IgH/BCL2 fusion was shown in 20 of the examined 24 cases (83%). Fourteen patients received therapy upon diagnosis (local radiotherapy in 2 patients and chemotherapy in 12 including rituximab therapy), their response rate was 85%, and the estimated progression-free survival (PFS) rate at 3 years was 70%. One patient developed histological transformation. The other 13 patients were followed up; their estimated PFS rate at 3 years was 74%. Five among six cases responded to treatment even after progressive disease. All 27 patients have survived with a median follow-up time of 47.9 months. Conclusions The majority of primary DFL patients have a localized tumor of low-grade histology and are positive for t(14;18). Watchful waiting might be an alternative approach for its indolent course; however, further studies are warranted.

Inotuzumab ozogamicin (CMC-544), an antibody-targeted chemotherapeutic agent composed of an anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic antibiotic, specifically targets the CD22 antigen present in >90% of B-lymphoid malignancies, rendering it useful for treating patients with B-cell non-Hodgkin lymphoma (B-NHL). This phase I study evaluated the safety, tolerability, efficacy, and pharmacokinetics of inotuzumab ozogamicin in Japanese patients. Eligible patients had relapsed or refractory CD22-positive B-NHL without major organ dysfunction. Inotuzumab ozogamicin was administered intravenously once every 28 days (dose escalation: 1.3 and 1.8 mg/m(2)). All 13 patients had follicular lymphoma, were previously treated with > or =1 rituximab-alone or rituximab-containing chemotherapy, and were enrolled into two dose cohorts (1.3 mg/m(2), three patients; 1.8 mg/m(2), 10 patients). No patient had dose-limiting toxicities, and the maximum tolerated dose, previously determined in non-Japanese patients (1.8 mg/m(2)), was confirmed. Drug-related adverse events (AEs) included thrombocytopenia (100%), leukopenia (92%), lymphopenia (85%), neutropenia (85%), elevated AST (85%), anorexia (85%), and nausea (77%). Grade 3/4 drug-related AEs in > or =15% patients were thrombocytopenia (54%), lymphopenia (31%), neutropenia (31%), and leukopenia (15%). The AUC and C(max) of inotuzumab ozogamicin increased dose-dependently with pharmacokinetic profiles similar to non-Japanese. Seven patients had complete response (CR, 54%) including unconfirmed CR, four patients had partial response (31%), and two patients had stable disease (15%). The overall response rate was 85% (11/13). Inotuzumab ozogamicin was well tolerated at doses up to 1.8 mg/m(2) and showed preliminary evidence of activity in relapsed or refractory follicular lymphoma pretreated with rituximab-containing therapy, warranting further investigations. This trial was registered in ClinicalTrials.gov (NCT00717925).

This is the first report on effective leukocytapheresis (LCAP) in an acquired infliximab (IFM) resistant patient with rheumatoid arthritis (RA). A 44-year-old Japanese woman with RA was treated with prednisolone, cyclosporine A, and methotrexate, which failed to stabilize the disease. Infliximab was then administered and the disease activity was controlled on December 2003. However, RA became active again on June 2004 so that LCAP was administered weekly for 5 weeks. After the LCAP treatment, the ACR20% response was obtained again and IFM has regained its efficacy.

An increasing incidence of Pneumocystis jiroveci pneumonia (PCP) in patients with B-cell non-Hodgkin lymphoma (B-NHL) receiving rituximab treatment has been reported. We reviewed patients with B-NHL who underwent chemotherapy from 2004 to 2008 at our institution to identify risk factors for PCP development during and after chemotherapy. Among 297 patients with B-NHL, six developed PCP. Of 121 patients (41%) who received PCP prophylaxis with sulfamethoxazole–trimethoprim during chemotherapy, none developed PCP (0%), while among 176 patients (59%) who had no prophylaxis, six (3.4%) developed PCP at a median of 2 months (range: 1–3 months) after starting chemotherapy. Patients with CD4+ lymphocyte counts ≤200/mm3 before chemotherapy had a higher risk of developing PCP (p=0.045), while a history of rituximab treatment was not related to PCP. CD4+ lymphocyte counts ≤200/mm3 during and after chemotherapy were observed in 18.9% of patients.

The feasibility and efficacy of cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL (intermediate DLBCL/BL) have never been reported. The effects of adding rituximab to CODOX-M/IVAC have not been published either. Fifteen consecutive patients with a median age of 39 years were treated with modified CODOX-M/IVAC regimen (particularly, reducing the dose of methotrexate to 3 g/m(2)) with or without rituximab at our institution. Although all patients developed grade 4 neutropenia and grade 3/4 thrombocytopenia/anemia, 93% had febrile neutropenia, 60% showed transaminase elevation, and 40% had mucositis/stomatitis (all grade 3), there were no treatment-related deaths. Two of nine patients treated with rituximab developed biphasic late-onset neutropenia. Thirteen patients (87%) showed complete responses. The remaining two patients had refractory disease; one had presented with peritoneal dissemination and complex chromosomal abnormalities, while the other had double IGH-MYC and IGH-BCL2 translocations. The estimated 5-year overall and progression-free survival were 87% each, with a median follow-up of 74 months. In conclusion, our modified CODOX-M/IVAC regimen is well tolerated and highly effective in Japanese adult patients with BL and intermediate DLBCL/BL, warranting a larger study for confirmation.

Antiphospholipid antibodies (aPL) have been reported to occur in numerous viral infections. We report a 24-year-old Japanese woman, who developed multiple venous thrombosis associated with the elevation of anticardiolipin IgM after acute viral infection presenting a mononucleosis-like illness. Two months later, aPL and thromboses disappeared. In this case both parvovirus B19 and cytomegalovirus antibodies IgM were elevated, which indicated the possibility of cross-reaction.

Background We report a case of invasive sinus aspergillosis that extended to the orbital cavity and cavernous sinus and was improved by treatment with micafungin and itraconazole. Case report A 83-year-old woman was referred to our hospital because of headache and impaired of eye movement on the right side. Physical examination revealed impaired function of cranial nerves, II, II, IV, and VI on the right side. MRI showed evidence of inflammation of the right sphenoid sinus and ethmoidal sinus and an enhancing mass in the right cavernous sinus and orbit. Because a culture of a specimen from the right sphenoid sinus extracted during endoscopic sinus surgery, yielede Aspergillus fumigatus, a diagnosed of invasive sinus aspergillosis complicated by cavernous sinus symdrome and orbital apex symdrome was made. It was difficult to completely remove the mass in the sinuses surgically and drug therapy with micafungin was started and then itraconazole was added. The clinical manifestations and the impaired function of cranial nerves II, III, IV, and VI improved, and MRI showed regression of the mass in the sinuses temporary in response to drug therapy. Conclusion Invasive sinus aspergillosis often progresses rapidly in the absence of surgery. Our case is valuable, because invasive sinus aspergillosis was improved by drug therapy alone, and combined treatment with micafungin and itraconazole was effective.

a 64-year-old woman with a 4-year history of pruritic erythema was admitted to our hospital because of aggravation of the erythema that did not respond to 20 mg/ day oral prednisolone. The patient had had malignant thymoma and myasthenia gravis for 12 years, together with recurrent oral herpes infection for several years. In spite of thymectomy, chemotherapy, and radiation therapy, malignant thymoma was disseminated to the thoracic cavity and no more treatment options could be utilized on admission. The patient presented with erythema that was scaly, mildly keratotic, and distributed over the face, body trunk, and extremities (Fig. 1a). The patient reported severe pruritus. Biopsy specimen of the erythema revealed superficial perivascular dermatitis with parakeratosis, hypogranulosis, dyskeratosis with satellite cell necrosis, mild acanthosis, and vacuolar change in the epidermis, and moderate infiltration of lymphocytes in the upper dermis (Fig. 1b). Direct immunofluorescence was negative (data not shown). Immunohistochemistry revealed that there were more CD8+ T cells than CD4+ T cells infiltrated in the epidermis and dermis (Fig. 1c, d). Differential diagnoses included psoriasis, lichen planus, pityriasis rosea, lichenoid drug eruption, pityriasis lichenoides chronica, and thymoma-associated GVHD-like erythroderma. psoriasis was ruled out by the presence of dyskeratosis, and parakeratosis is not usually observed in lichen planus. The clinical course was too long for pityriasis rosea, and lichenoid drug eruption could be ruled out because of the absence of eosinophils in the dermis. Furthermore, pityriasis lichenoides chronica is not usually pruritic and the eruptions are more oval than those of our case. Based on the characteristic distribution and clinical features of the erythema and pathological findings, a diagnosis of thymoma-associated GVHD-like erythroderma was made. potent topical steroid (clobetasol propionate 0.05%), systemic steroid (prednisolone 2 mg/kg/day), and cyclosporine (5 mg/kg/day) were prescribed for 2 weeks, but did not control the erythema (Fig. s1; available from http://www.medicaljournals.se/acta/content/?d oi=10.2340/00015555-1577). Intriguingly, after the initiation of oral acyclovir (15 mg/kg/day) for exacerbated oral herpes infection, the erythema began to subside. acyclovir was then switched to valacyclovir hydrochloride (15 mg/kg/day). Incidentally, we detected a high level of CMV antigenemia of up to 1,564 cells/slide, although it was only 11 cells/slide 6 months previously. The patient did not report any symptoms of retinitis, pneumonia, or colitis, thus we administered ganciclovir (5 mg/kg/day) and discontinued valacyclovir. The erythema recurred when prednisolone was tapered to 0.75 mg/kg/day; therefore, prednisolone was increased up to 1 mg/kg/day, which was not successful. Next, broadband ultraviolet Reactivation of Herpes Simplex Virus and Cytomegalovirus in a Case of Thymoma-associated Graft-versus-host Disease-like Erythroderma

Oncology emergency refers to critical conditions among complications of cancer itself and adverse events by anti-cancer treatments. In my opinion, it can be divided into two categories including emergency in a narrow sense, which needs hasty correspondence within at least several hours, and urgency, which demands speedy one within not hours but one day. Even though they are the identical condition, certain oncologic emergencies can be assigned to different categories such as emergency, urgency and others in terms of their time course and severity. Furthermore, cancer diagnosis can be triggered by diagnosis of oncology emergency, and therefore considered to be an important theme for all of health care providers. In some sense, patients' history and physical examination are more essential than laboratory and imaging tests in order to adequately divide into three categories mentioned above and take care of patients with oncology emergency. As a general internist as well as a medical oncologist, I would like to share its importance with all of you through dynamics from diagnosis to treatment of spinal cord compression and hypercalcemia as representative of oncologic emergency.

A 61-year-old man with hypertension had developed exertional dyspnea for 2 years. His symptom got worse with fever and wet cough 4months prior to admission (PTA), and inspiratory pain on his right chest 3 months PTA. He was suspected of having an atypical pneumonia or a tuberculosis on CT. Enhanced chest CT showed large mural defects in right main pulmonary artery, clearly delineated by contrast medium.He was diagnosed as having a pulmonary embolism and received anticoagulation therapy with heparin followed by warfarin. Despite 1 week of warfarin therapy, he remained symptomatic with no change in the pulmonary artery filling defects on repeated enhanced CT.Pulmonary artery sarcoma, or a metastatic tumor were suspected of by its time course and accompanying symptoms and signs of fever, secondary anemia, and weight loss. Increased uptake of FDG in the affected pulmonary artery indicated that pulmonary artery sarcoma was most likely.Aspiration cytology and needle biopsy through pulmonary artery catheter revealed malignant cells with results of CD31(-), CD34(-), D2-40(+),α-Actin(-), and AE1/AE3(+), consistent with pulmonary artery sarcoma which was not able to be specified further.It was out of operative indication because of distant metastasis in his lungs. Therefore, he received weekly Paclitaxel(45mg/m2) + Carboplatin(AUC 2)concurrent with TRT 60Gy/30Fr in order to mainly control intra-arterial mass. However, we discontinued it at 6courses because of neutropenia(Gr3) and development and progression of non-tuberculosis mycobacterium infection. He was also intolerable to pazopanib due to many side effects of increasing in the liver enzymes(Gr1), hypertension(Gr3), anorexia(Gr3), diarrhea(Gr3), nausea(Gr3) and NTM exacerbation. On the other hand, his primary and metastatic lesions have a tendency to decrease in size in comparison with one before chemotherapy. We will report this case with literature review in terms of diagnostic difficulty of pulmonary artery sarcoma.

Background: There are few seminars with workshop style mainly consisting of group work in multidisciplinary care. We established in Nara prefecture a novel seminar called MAHOLOBA (Medical And HOListic Oncology Brush-up Academy) and reported 1st workshop in 2013. Objective: To clarify relevant issues on chemotherapy and ensure needs of participants for this sort of workshop. Participants: Physicians, nurses and pharmacists engaging in cancer chemotherapy. Method: Cross-sectional study. Primary outcome: Identify relevant issues on chemotherapy by K-J (Kawakita Jiro) method in 4groups and determine priority among them by two dimensions plotting of significance and emergency. Secondary outcome: Obtain information by means of questionnaires concerning satisfaction level of participants toward this workshop and their hope to it from now on. Results: Forty-six health care providers participated in the workshop and were divided into 4groups. Common relevant issues on chemotherapy among those groups were the followings: measures for adverse events(4/4), regimen management(4/4), measures for exposure(3/4), human resources(3/4) and equipment(3/4). Thirty-six participants, among whom 10 had qualification as an expert and 20 worked for core hospitals, answered the questionnaires with the results of high level of satisfaction(36/36) and wish(30/36) for participation in the next workshop. Many participants hoped to obtain the executable and sustainable contents at their own institute and share information among multicenter or multidiscipline. Conclusion: We identified those issues on chemotherapy including adverse events, regimen management and measures for exposure. We observed high level of satisfaction toward the workshop with multicenter and multidiscipline and ensured the need for it. COI: We received financial support to hold this workshop from Ono Pharmaceutical Co., LTD in Japan.

We present three cases of intracranial hemorrhage with metastasis of gastric cancer to the bone/bone marrow. Case1: A 62-year-old man with history of distal gastrectomy 15 years ago was pointed out to have elevated ALP level and diffuse increased uptake of bone scintigraphy, which turned out to be a recurrence of diffuse metastases to bone and bone marrow confirmed by bone marrow biopsy. After partially successful treatment of chemotherapy with 6 cycles of TS-1 + CDDP, he developed an acute subdural hematoma, complicated by DIC. Craniotomy for removal of hematoma was performed. However, he was died of brain bleeding 12 months after diagnosis of recurrence. Case2: A 60-year-old man underwent subtotal gastrectomy 9 years ago. Similarly, diffuse bone and bone marrow metastasis was confirmed by bone marrow biopsy with trigger of elevated ALP level and diffuse increased uptake of bone scintigraphy. After chemotherapy with TS-1 + CDDP as 1st line and DTX as 2nd line was performed, he also developed and died of subdural hematoma with DIC 22months after diagnosis of recurrence. Case3: A 65-year-old woman with rheumatoid arthritis was pointed out to have low platelet and elevation of LDH and ALP in her regular visits. Endoscope examinations and imaging studies showed gastric cancer with multiple metastases to bone and bone marrow complicated by DIC. Although chemotherapy with TS-1 and blood transfusion was performed, she developed an acute subdural hematoma and received craniotomy for removal of hematoma. However she died of brain rebleeding 4 months after initial diagnosis. The following things are quite interesting in these 3 cases. 1) The former 2cases recurred with bone and bone marrow metastasis after long interval. 2) All cases developed bone and bone marrow metastasis complicated by fatal intracranial hemorrhage without obvious bleeding tendencies in other parts of body. We will discuss those issues with literature review.

Background Although corticosteroid treatment is essential in the management of rheumatic diseases, adverse events of corticosteroids pose serious problems. Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) frequently requires higher corticosteroids doses than does rheumatoid arthritis, and such high doses may cause severe adverse events such as infectious diseases. Few studies have investigated the relationship between the steroid dose and adverse effects in AAV. Objectives This study aimed to analyze the relationship between readmission of patients with AAV and their corticosteroid dose and to estimate the dose that poses a risk of readmission. Methods Study Design: A retrospective cohort study with 2-year follow-up after the initiation of corticosteroid therapy. Setting: Tenri hospital, Tenri, Japan. Participants: Patients with AAV who were discharged after the initial corticosteroid therapy from 1990 to 2012. Outcomes: (1) Readmission because of an infectious disease after the initial corticosteroid therapy. 2) Cumulative corticosteroid doses that may cause the readmission because of an infection. Analysis: We performed survival analysis using Kaplan–Meier estimates and the multivariate Cox regression model to calculate the readmission rate related to infectious diseases. In order to define corticosteroid categories (high-dose/low-dose), we drew a boundary using an accumulation model with median corticosteroid doses on each day until readmission or the end of follow-up. We described the cumulative corticosteroid doses in the readmission group with infectious disease. Results We enrolled 78 participants [mean age (SD): 68.2 (11.8) years]. During the 2-year follow-up, 41 (52%) participants were readmitted because of infectious disease (n=16), relapse (n=10), fracture (n=5), or other reasons (n=10). Of the 16 patients with infections, 9 had bacterial infections (mainly respiratory tract infections), 5 had viral infections, and 2 had fungal infections. The adjusted hazard ratio for readmission due to infectious disease was 1.91 [95% CI: 0.63–5.62] for the high-dose group. The cumulative median steroid dose for readmission because of infection was 4,896 mg (range: 1,370–14,285 mg) as a prednisone equivalent. The median interval from corticosteroid initiation to readmission was 189 days (range: 57–729 days). Conclusions Among patients with AAV, the high-dose corticosteroid group is more likely to be readmitted than the low-dose group. Readmission due to infectious disease was limited to participants whose cumulative steroid dose was >1370 mg (approximately 2 months after the initiation). Thus, such patients should be carefully monitored for signs and symptoms of infection. References Hoes JN, Jacobs JWG, Boers M, Boumpas D, Buttegereit F, Caeyers N, Choy EH, Cutolo M, Da Silva JAP, Esselens G, Guillevin L, Hafstrom I, Kirwan JR, Rovensky J, Russell A, Saag KG, Svensson B, Westhovens R, Zeidler H, Bijlsma JWJ. EULAR evidence-based recommendation on the management of systemic glucocorticoid therapy in rheumatic disease. Ann Rheum Dis. 2007; 66: 1560-7. Acknowledgements This study was supported by a grant-in-aid by Ministry of Health, Labor and Welfare in Japan, “Development of Clinical Research Fellowship” (Grant no: H21-007) Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1586