Trends of Media Coverage on Human Papillomavirus Vaccination in Japanese Newspapers.

A sensational newspaper article concerning a possible adverse reaction to the human papillomavirus (HPV) vaccine was published in March 2013 in Japan. In June 2013, the Japanese government suspended their proactive recommendation for vaccination, despite the lack of proof for a causal relationship. We searched Nikkei Telecom 21, the largest newspaper database in Japan, for articles published from January 2011 to December 2015 to evaluate the characteristics of newspaper publications about human papillomavirus vaccination. We identified 1138 HPV vaccine-related articles. Compared with those published before March 2013, articles concerning human papillomavirus vaccination after March 2013 were more likely to include adverse reaction-related and authority-related keywords; articles that included efficacy-related keywords decreased significantly. Negative-negative and negative-neutral articles became more frequent, and positive-positive and positive-neutral articles were less frequent. A sensational case report shaped the tone of negative media coverage as a catalyst, regardless of scientific statements from health authorities.

Cord Blood Transplantation for Multiple Myeloma: A Study from the Multiple Myeloma Working Group of the Japan Society for Hematopoietic Cell Transplantation.

Cord blood has been investigated as an alternative source for hematopoietic stem cell transplantation, but information about its use for multiple myeloma is limited. The purpose of this study was to evaluate the feasibility of cord blood transplantation (CBT) for patients with multiple myeloma. Eighty-six patients with multiple myeloma who underwent a first CBT between 2001 and 2011 were included in this retrospective study. Sixty-two of them had received other types of stem cell transplantation before CBT. The cumulative incidences of neutrophil engraftment at day 50, grade II to IV acute graft-versus-host disease (GVHD), and chronic GVHD were 81.4%, 39.0%, and 19.5%, respectively. The incidence of nonrelapse mortality at 2 years was 39.0%, but it was only 6.2% in patients who underwent planned tandem autologous/reduced-intensity conditioning CBT (auto/RIC-CBT). Progression-free survival (PFS) and overall survival (OS) at 6 years were 13.0% and 15.2%, respectively. Less than a partial response before CBT and lack of prior transplantation were independent significant adverse factors for PFS, whereas the presence of prior transplantation and planned tandem transplantation were associated with better OS. OS at 6 years in patients who underwent auto/RIC-CBT was 45.9%. In addition, the development of chronic GVHD was associated with superior PFS. In conclusion, we demonstrated that cord blood is feasible as an alternative graft source for myeloma patients. Although CBT provided long-term survival for a fraction of patients, optimal use of this graft requires further clinical studies.

[Current clinical practice in the treatment of febrile neutropenia (FN)].

Because of the refractory and recurrent nature of febrile neutropenia (FN), definite diagnosis and early empiric treatment with antibiotics are important for FN patients. With this background, guidelines for FN treatment have been published in Japan and overseas, although a treatment method appropriate for clinical practice in Japan has not yet been established. Therefore, we conducted a survey of actual practice, including trends in prescription of antibiotics for FN, in the hope that it would help establish a definitive treatment for FN in Japan. The survey results confirmed that FN patients under care of hematology departments accounted for the largest proportion, followed by pediatrics (hematology), pulmonary medicine, medical oncology, and respiratory surgery, and the proportions of patients diagnosed with FN and those receiving antibiotics in hematology departments are larger than in other departments. Across all departments, cefepime (CFPM) is most frequently used as the initial treatment of choice, accounting for 35.9% of prescriptions, followed by meropenem (MEPM) (24.3%). These drugs are selected because they exhibit high potency and wide coverage against organisms that are presumed to cause FN, and their costs are covered by insurance, while the existence of insurance coverage is the major determining factor for treatment in Japan. Among second-line drugs, MEPM is most frequently used, accounting for 46.3% of prescriptions. The guidelines are commonly used as the basis for treatment, accounting for 52.0% of all departments, especially the guidelines established by the Japan Febrile Neutropenia Study Group. On the other hand, the percentage of departments that have introduced a hospital protocol and clinical path is only 13.0% in total. To provide appropriate treatment for FN patients, insurance coverage and introduction of a hospital protocol and clinical path based on guidelines and evidence are essential. The current situation, in which these are not implemented, is not desirable. The survey results show that the guidelines need to be revised to more closely reflect the actual situation in Japan and hospital protocols and clinical paths need to be introduced.

[Use of the critical path with the electronic chart system using meropenem, vancomycin, liposome amphotericin B for the febrile neutropenia].

Febrile neutropenia (FN) is a serious complication associated with morbidity and mortality. To manage infections in neutropenic patients, it is necessary to administer empirical antibiotic therapy in a timely and efficient manner. We developed an electronic critical pathway system for a computer-stored medical record system (EGMAIN-GX, Fujitsu), which matches FN patients to either: i) the first-line therapy with meropenem (3 g/day) alone, or ii) the second-line therapy with meropenem plus vancomycin (2 g/day). If patients do not respond to the first-line therapy within 72 hours, then they are provided with the second-line therapy. A total of 28 FN events were treated in 14 patients presenting with hematological malignancies. The mean and median neutrophil counts were 42 (0-300)/microl and 0/microl, respectively. The response rates with the first-line and second-line therapies were 57% and 93%, respectively. There were no serious adverse events. Meropenem is a highly effective treatment for FN. Use of an electronic critical pathway system could ensure that neutropenic patients receive this necessary empiric therapy in a timely manner so as to prevent the serious complications associated with FN.

Chronic graft-versus-host disease following umbilical cord blood transplantation: retrospective survey involving 1072 patients in Japan.

We have little information on chronic graft-versus-host disease (GVHD) after cord blood transplantation (CBT). We investigated its clinical features in 1072 Japanese patients with hematologic malignancies who received a transplant through the Japan Cord Blood Bank Network. The primary end point was to investigate the incidence of any chronic GVHD. Median age of the patients was 33 years (range, 0-79 years). The cumulative incidence of chronic GVHD 2 years after transplantation was 28%. Chronic GVHD was fatal in 29 patients. Multivariate analysis demonstrated that development of chronic GVHD was favorably associated with both overall survival and event-free survival. Multivariate analysis identified risk factors of chronic GVHD: higher patient body weight, higher number of mismatched antigens for GVHD direction, myeloablative preparative regimen, use of mycophenolate mofetil in GVHD prophylaxis, and development of grades II to IV acute GVHD. Although chronic GVHD is a significant problem after CBT, it is associated with improved survival, perhaps due to graft-versus-malignancy effects.

Physician Decision-Making Patterns and Family Presence: Cross-Sectional Online Survey Study in Japan.

BACKGROUND: Due to a low birth rate and an aging population, Japan faces an increase in the number of elderly people without children living in single households. These elderly without a spouse and/or children encounter a lack of caregivers because most sources of care for the elderly in Japan are not provided by private agencies but by family members. However, family caregivers not only help with daily living but are also key participants in treatment decision making. The effect of family absence on treatment decision making has not been elucidated, although more elderly people will not have family members to make surrogate decisions on their behalf. OBJECTIVE: The aim is to understand the influence of family absence on treatment decision making by physicians through a cross-sectional online survey with three hypothetical vignettes of patients. METHODS: We conducted a cross-sectional online survey among Japanese physicians using three hypothetical vignettes. The first vignette was about a 65-year-old man with alcoholic liver cirrhosis and the second was about a 78-year-old woman with dementia, both of whom developed pneumonia with consciousness disturbance. The third vignette was about a 70-year-old woman with necrosis of her lower limb. Participants were randomly assigned to either of the two versions of the questionnaires-with family or without family-but methods were identical otherwise. Participants chose yes or no responses to questions about whether they would perform the presented medical procedures. RESULTS: Among 1112 physicians, 454 (40.8%) completed the survey; there were no significant differences in the baseline characteristics between groups. Significantly fewer physicians had a willingness to perform dialysis (odds ratio [OR] 0.55, 95% CI 0.34-0.80; P=.002) and artificial ventilation (OR 0.51, 95% CI 0.35-0.75; P<.001) for a patient from vignette 1 without family. In vignette 2, fewer physicians were willing to perform artificial ventilation (OR 0.59, 95% CI 0.39-0.90; P=.02). In vignette 3, significantly fewer physicians showed willingness to perform wound treatment (OR 0.51, 95% CI 0.31-0.84; P=.007), surgery (OR 0.35, 95% CI 0.22-0.57; P<.001), blood transfusion (OR 0.45, 95% CI 0.31-0.66; P<.001), vasopressor (OR 0.49, 95% CI 0.34-0.72; P<.001), dialysis (OR 0.38, 95% CI 0.24-0.59; P<.001), artificial ventilation (OR 0.25, 95% CI 0.15-0.40; P<.001), and chest compression (OR 0.29, 95% CI 0.18-0.47; P<.001) for a patient without family. CONCLUSIONS: Elderly patients may have treatments withheld because of the absence of family, highlighting the potential importance of advance care planning in the era of an aging society with a declining birth rate.

Cytokine Profile in Sweet's Syndrome under the Treatment of Pulmonary Toxoplasmosis Complicated with Myelodysplastic Syndrome.

We herein describe a case of Sweet's syndrome (SS) in a patient being treated for pulmonary toxoplasmosis complicated with myelodysplastic syndrome (MDS). The patient's SS developed after the pulmonary toxoplasmosis improved following treatment. We searched his cytokine profiles comprehensively using a bead-based immunoassay. The results showed no elevation of interleukin (IL)-2, interferon (IFN)-γ or IL-17A, and IL-6 was only observed to have increased at the onset of SS, suggesting that the pulmonary toxoplasmosis had been well controlled and that chronic inflammation may have been the cause of SS. Pulmonary toxoplasmosis is an extremely rare occurrence. The cytokine profile can help to clarify the pathological condition of SS and MDS complicated with severely invasive infectious diseases.

Patients' demographics of a convenient clinic located in a large railway station in metropolitan Tokyo area.

Hidden barriers to visit a medical facility especially for young busy workers have been neglected in the aging society. The aim of this cross-sectional study is to analyze demographics of patients who had visited the first known convenient clinic located inside a railway station, which is adjusted to the lifestyle of working generations.We analyzed de-identified data of patients who had visited the department of internal medicine of a clinic, which is located inside a railway station building and offers primary care with after-hours accessibility in Tokyo, between August 2013 and June 2016. Data were collected on patients' sex, age, time of visit, waiting time, presence or absence of an appointment, diagnosis, and patients' addresses using the electronic health and billing records.Overall, 28,001 patients visited 87,126 times. Number of visits increased in winter season compared with the other seasons. Sixty-one percent were women and the median age of all patients was 38 years (range, 0-102). The number of visits on Mondays was the highest in a week and the most frequent visiting time was between 6 and 7 p.m. The number of visits of working generations (from 15 to 65 years old) and men increased after 6 p.m. and on weekends. The 3 most common diagnoses were upper respiratory tract infection (22,457), allergic rhinitis (20,916), and hypertension (4869). The number of individuals who were referred to other medical institutions was 1022 (1.2%). The median waiting time was 748 seconds (range, 2-5344). The number of visits from within 2-, 5-, and 10-mile radius from our clinic was 41,696 (50.6%), 63,190 (76.7%), and 75,015 (91.1%), respectively, and patients' addresses were mainly located along the railway network.The locational and temporal convenience of our clinic has attracted the unmet medical demands especially for young workers who have difficulty in visiting conventional medical institutions.

Successful engraftment of mismatched unrelated cord blood transplantation following reduced intensity preparative regimen using fludarabine and busulfan.

We conducted a pilot study to evaluate the feasibility of reduced-intensity cord blood transplantation (RI-CBT) using a non-total body irradiation (TBI) regimen in adult patients with advanced hematologic malignancies. Seventeen patients with a median age of 58 years (range, 38-74) underwent RI-CBT at Tsukuba Memorial Hospital between April 2004 and November 2005. Preparative regimens were fludarabine 30 mg/m(2) for 6 days, and busulfan 4 mg/kg for 2 days. Tacrolimus was used for prophylaxis of graft-vs-host disease (GVHD). Median numbers of infused total nucleated were 2.6 x 10(7)/kg (range, 2.0-3.3). HLA disparity was found in 2/6 antigens (n=16) and 1/6 antigens (n=1). Underlying diseases progressed despite preparative regimens in four patients. Of the remaining 13 patients, nine patients achieved engraftment at a median of day 18 (range, 17-28). Six of the nine patients with engraftment achieved complete donor-type chimerism by day 100. Six patients were alive in remission at median follow-up of 13.1 months (range, 1.0-19.0). This study demonstrated the feasibility of RI-CBT using a non-TBI regimen in adults. When disease progression is controlled by the preparative regimen, RI-CBT carries a clinically significant graft-vs-tumor effect. Further studies are required to identify patients who benefit from this regimen.

Feasibility and obstacles in home chemotherapy for malignant lymphoma.

Home care has become a treatment option for cancer patients; however, medical practice at patients' homes has been expected mainly for terminal care in Japan. Most physicians believe that it is difficult to treat patients with hematologic malignancy at home because they frequently develop complications requiring urgent interventions. We herein report the case of an 80-year-old patient with advanced follicular lymphoma who safely received aggressive chemotherapy at home and finally died due to disease progression at the hospital. Home chemotherapy can be a feasible and potentially novel treatment option for some patients with hematologic malignancy, although the clinical course of the present patient suggested that patient selection is critical for the safe operation of home chemotherapy and that it is important to educate families on how to evaluate patients' conditions and how to cope with aggravation and admission arrangements in back-up hospitals.

Regulation of tubular recycling endosome biogenesis by the p53-MICALL1 pathway.

p53, one of the most frequently mutated genes in colon cancer, suppresses cancer development through transactivation of its targets. Herein, we conducted a comprehensive analysis of the p53 downstream pathway in colorectal cancer by using multi-omics analysis. Mass spectrometric analysis of HCT116 p53+/+ and HCT116 p53-/- cells treated with adriamycin identified 124 proteins increased by DNA damage in a p53-dependent manner. Further screening using a cDNA microarray and the TCGA database revealed MICALL1 as a novel p53 target, and we identified functional p53 binding motifs located approximately 3000 base pairs upstream of the MICALL1 gene. MICALL1 expression was significantly decreased in colorectal cancer tissues with p53 mutation compared with those without p53 mutation. In response to DNA damage, MICALL1 co-localized with RAB8A and CD2AP at tubular recycling endosomes, whereas these proteins hardly localized at tubular recycling endosomes when p53 or MICALL1 expression was inhibited by siRNA. Our findings show that p53 regulates tubular recycling endosome biogenesis via transcriptional regulation of MICALL1, whose expression is frequently suppressed in colorectal cancer tissues.

Impact of the automatic rounding-off function of the computerized physician order entry system on the ordering time and dose dispersion of chemotherapeutic drugs in regimens for hematologic malignancies.

INTRODUCTION: EGMAIN-GX is the computerized physician order entry system used in Japan. The automatic rounding-off of the calculated dose of chemotherapeutic drugs is an update in version 4, compared to version 2. We conducted a comparative study between EGMAIN-GX versions 2 and 4 to estimate the effect of the automatic rounding-off function on ordering time and dose dispersion. METHODS: Twelve hematologists ordered 5 predefined chemotherapeutic regimens most commonly used in treating hematologic malignancies, twice for each regimen. RESULTS: EGMAIN-GX version 4 significantly reduced ordering times compared to version 2 (635s vs. 259s, p<0.01). EGMAIN-GX version 4 also yielded a significantly higher ratio of actual to ideal doses of chemotherapeutic drugs than did version 2 (1.0097 and 0.9997, respectively; p<0.01) and a lower standard deviation (0.0275 and 0.0290, respectively). CONCLUSIONS: The automatic rounding-off function could decrease the ordering time and dose dispersion of chemotherapeutic drugs.