Kenji Tsuda

Inotuzumab Ozogamicin for Acute Lymphoblastic Leukemia.

n engl j med 375;21 nejm.org November 24, 2016 2100 is not metabolized in this manner. Therefore, we find it unlikely that different mechanisms of action and metabolism between these two medications would have resulted in such similar increases in symptoms as compared with placebo. In the Results section of our article, we reported that “no interaction was detected between asthmacontroller therapy and treatment group (P = 0.91),” indicating that there was no differential response in children receiving montelukast.

A Feasibility Study of Virtual Reality Exercise in Elderly Patients with Hematologic Malignancies Receiving Chemotherapy.

OBJECTIVE Adherence to rehabilitation exercise is much lower in patients with hematologic malignancies (22.5-45.8%) than in patients with solid tumors (60-85%) due to the administration of more intensive chemotherapeutic regimens in the former. Virtual reality exercise can be performed even in a biological clean room and it may improve the adherence rates in elderly patients with hematologic malignancies. Thus, in this pilot study, we aimed to investigate the feasibility and safety of virtual reality exercise intervention using Nintendo Wii Fit in patients with hematologic malignancies receiving chemotherapy. METHODS In this feasibility study, 16 hospitalized patients with hematologic malignancies aged ≥60 years performed virtual reality exercise for 20 minutes using the Nintendo Wii Fit once a day, five times a week, from the start of chemotherapy until hospital discharge. The adherence rate, safety, and physical and psychological performances were assessed. RESULTS The adherence rate for all 16 patients was 66.5%. Nine patients completed the virtual reality exercise intervention with 88 sessions, and the adherence rate was 62.0%. No intervention-related adverse effects >Grade 2, according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0, were observed. We noted maintenance of the physical performance (e.g., Barthel index, handgrip strength, knee extension strength, one-leg standing time, and the scores of timed up and go test and Instrumental Activities of Daily Living) and psychosocial performance (e.g., score of hospital anxiety and depression scale). CONCLUSION Virtual reality exercise using the Wii Fit may be feasible, safe and efficacious, as demonstrated in our preliminary results, for patients with hematologic malignancies receiving chemotherapy.

Treatment for high-risk smoldering myeloma.

n engl j med 369;18 nejm.org october 31, 2013 1762 menting environmental cleaning, and excluding nonessential staff as well as visitors. The epidemiologic investigation and phylogenetic analyses indicate that the most likely form of transmission during the outbreak was personto-person transmission, either through respiratory droplets or through direct or indirect contact. The applied infection-control measures appeared to have been effective in averting the outbreak. The CDC continues to recommend the use of airborne-infection isolation rooms for patients with SARS and MERS-CoV.1,2 Cohorting of patients in one floor or unit is a viable strategy to devote resources and staff to the care of patients.1 The infection-control measures applied in the Al-Hasa outbreak probably contributed to the control of the outbreak and were consistent with the World Health Organization’s interim infection-control guidance, which is based on the available scientific evidence.3 Ziad A. Memish, M.D.

Lenalidomide plus Rituximab for Mantle-Cell Lymphoma.

n engl j med 374;8 nejm.org February 25, 2016 792 ever, because randomization provides protection against confounding in a trial of this size. We agree with Zhang and Giovannucci that most of our participants are not at great risk for colorectal cancer. However, this does not argue against adenomas as biomarkers of colorectal carcinogenesis: the risk of colorectal cancer in patients after polypectomy presumably is reduced by the polypectomy. There is additional evidence that adenomas are valid biomarkers for colorectal carcinogenesis: adenomas contain genetic and epigenetic changes similar to — but less severe than — those in colorectal cancer characterized by chromosomal instability,2 and the epidemiologic risk factors for adenomas closely resemble those for colorectal cancer itself.3 Trials such as ours do focus on the early-tomid-adenoma stages of carcinogenesis and may miss effects at other stages (e.g., the transition to invasive cancer). Lesions missed at baseline may indeed be found during follow-up. However, in the study by Laiyemo et al.,4 the proportion of participants with adenomas at 1 year (called “missed” adenomas) and at 4 years (in participants without an examination at 1 year) implies that the real proportion of missed lesions is relatively small or that these lesions grow very slowly. In any case, the bottom line for adenoma trials is that in a trial with positive results, a difference in adenoma burden reflects a difference in carcinogenic activity. Whether this difference is due to the prevention of new adenomas or to an inhibition or regression of lesions not excised at baseline is a secondary mechanistic question. John A. Baron, M.D. University of North Carolina at Chapel Hill Chapel Hill, NC jabaron@ med . unc . edu

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

Abstract 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.

Intensive speech and language therapy after stroke

1 Breitenstein C, Grewe T, Flöel A, et al. Intensive speech and language therapy in patients with chronic aphasia after stroke: a randomised, open-label, blinded-endpoint, controlled trial in a health-care setting. Lancet 2017; 389: 1528–38. 2 Kang JH, Kwon JH, Hui D, Yennurajalingam S, Bruera E. Changes in symptom intensity among cancer patients receiving outpatient palliative care. J Pain Symptom Manage 2013; 46: 652–60. 3 Blomert L, Kean ML, Koster C, Schokker J. Amsterdam–Nijmegen everyday language test: construction, reliability and validity. Aphasiology 1994; 8: 381–407. communication in people aged 70 years or younger with chronic aphasia after stroke. The primary outcome measure was assessed using the AmsterdamNijmegen Everyday Language Test (ANELT) A-scale, and the mean difference of the ANELT A-scale score improved 2·61 (SD 4·94) points from baseline to after intensive speech and language therapy, but not from baseline to after treatment deferral. Although Breitenstein and colleagues state that even a 1-point increase in verbal effectiveness in daily life situations is important, we speculate that the minimal clinically important difference of the ANELT A-scale score has not yet been established. The ANELT A-scale score can range from a minimum of 10 to a maximum of 50. In the field of pain management, a study showed that patients with worse baseline symptoms were more likely to report a greater improvement. Therefore, a patient with a lower baseline ANELT A-scale score might have greater improvement after treatment compared to a patient with a higher baseline score. Therefore, the degree of improved score might have different significance in each patient depending on his or her baseline score. Additionally, as the ANELT A-scale assesses verbal communication in aphasia, the effectiveness in aphasia subtypes, such as Global and Wernicke, might have been under-represented compared with a stroke subtype solely involving motor speech areas. It would be helpful to interpret the study results in depth if more detailed information is available concerning the influence of baseline score in each patient, the association between characteristics of each patient, and the change in ANELT A-scale score.

Rituximab and autologous stem-cell transplantation for high-risk diffuse large B-cell lymphoma

In The Lancet Oncology, Annalisa Chiappella and colleagues reported that abbreviated rituximab-dosedense chemotherapy followed by R-MAD (rituximab plus high-dose cytarabine plus mitoxantrone plus dexamethasone) and high-dose BEAM chemotherapy (carmustine, etoposide, cytarabine, and melphalan) plus autologous stem-cell transplantation reduced the risk of treatment failure compared with full course rituximabdose-dense chemotherapy (2-year failure-free survival 71% [95% CI 64–77] vs 62% [55–68]; hazard ratio [HR] 0·65, 95% CI 0·47–0·91, stratified logrank test p=0·012), but resulted in no difference in 5-year overall survival in young patients with diffuse large B-cell lymphoma (78% [95% CI 71–83] vs 77% [71–83]; HR 0·98, 95% CI 0·65–1·48, stratified log-rank test p=0·91). To be eligible for the study, patients were required to have an intermediate-high risk or high risk score of 2–3 in the ageadjusted International Prognostic Index (aa-IPI) based on three parameters: Eastern Cooperative Oncology Group performance status, concentration of serum lactate dehydrogenase, and Ann Arbor staging. However, it should be noted that aa-IPI was developed before the rituximab-era, and some researchers suggest that the presence of more than one extranodal site of disease, as compared with no extranodal sites or one extranodal site, was associated with significantly inferior overall and progression-free survival even in patients younger than 60 years, and the standard IPI might be more suitable than the aa-IPI for selecting high-risk younger patients with diffuse large B-cell lymphoma in the rituximab era. Because more than 30% of patients had more than one extranodal involvement in each group, we are concerned whether there were any differences in treatment response and survival results in patients with or without such features. We are grateful if the authors could provide further analyses on this matter.

Temporal Changes in Subsequent Malignancies Among Childhood Cancer Survivors

the increase in noncalcified plaque volume was confined to the fibrous component. Changes in that component did reach statistical significance, but changes in the other noncalcified plaque components were also greater in the testosterone group, although they did not reach statistical significance (P values of .11 and .14). Thus, the results for all 3 components were consistent. Dhindsa and colleagues also ask whether results were driven by large changes in plaque volume in a few men in the testosterone group. This was not the case. The proportion of men in the testosterone group whose noncalcified plaque volume increased during the 1 year of the trial was 70%, compared with 54% of men in the placebo group, whereas the proportions showing a decrease in noncalcified plaque volume were 27% in the testosterone group and 45% in the placebo group. Only 2 men in the testosterone group had larger changes than the largest change in the placebo group, and those changes were not markedly larger. Reanalysis of plaque volume as a percentage of vessel volume is an interesting idea but was not a prespecified analysis. We agree that a larger and longer-term trial to evaluate clinical cardiovascular events is needed.

Zoledronic Acid Dosing Interval for Metastatic Cancer

Concept and design: Bollen, van Smaalen, ten Hoopen, van Heurn, Ysebaert. Acquisition, analysis, or interpretation of data: Bollen, van Smaalen, Ysebaert, Van Mook. Drafting of the manuscript: Bollen, van Smaalen. Critical revision of the manuscript for important intellectual content: van Smaalen, ten Hoopen, van Heurn, Ysebaert, Van Mook. Statistical analysis: Bollen, van Smaalen. Administrative, technical, or material support: Bollen. Supervision: ten Hoopen, van Heurn, Ysebaert, Van Mook.

Evidence Required for Drugs Granted Accelerated Approval

Azithromycin and Survival After Hematopoietic Stem Cell Transplant To the Editor Dr Bergeron and colleagues prospectively assessed the effect of azithromycin on airflow decline–free survival after allogeneic hematopoietic stem cell transplantation.1 In the azithromycin group, azithromycin was administered at a dose of 250 mg orally 3 times a week for 2 years. Unexpectedly, the azithromycin group had increased mortality mainly due to an increased incidence of relapse. In the Discussion, the authors described possible mechanisms to explain the results. However, they did not mention the possible drug-drug interaction of azithromycin through the inhibition of cytochrome P450 enzymes.2 Azithromycin can elevate the level of calcineurin inhibitors (CNIs) (ie, cyclosporine).3,4 If the concentration of CNIs was elevated in the azithromycin group, it might suppress graftvs-leukemia–lymphoma effects. In terms of drug-drug interaction between azithromycin and CNIs, data are limited. Therefore, it would be interesting if the authors could provide data about the comparison of dose and concentration of CNIs between the 2 groups.