Lung injury associated with bortezomib therapy in relapsed/refractory multiple myeloma in Japan: a questionnaire-based report from the "Lung Injury by Bortezomib" Joint Committee of the Japanese Society of Hematology and the Japanese Society of Clinical Hematology

Bortezomib is a proteasome inhibitor that can be effective in the treatment of refractory and relapsed multiple myeloma. Recently, severe pulmonary complications associated with bortezomib therapy have been reported in Japan. Because bortezomib has not yet been approved for general use in Japan and is imported by attending physicians on the request of patients, The Japanese Society of Hematology and The Japanese Society of Clinical Hematology sent urgent questionnaires to the councilors of both societies in order to explore the situation and details of pulmonary complications associated with bortezomib therapy. Clinical details were available for 46 patients who had been treated with personally imported bortezomib in Japan. Seven patients (15.2%), including 3 who died from respiratory failure, showed complications definitely or probably caused by bortezomib. Of the 7 patients, 6 had a prior history of stem cell transplantation (SCT), whereas only 14 of 39 patients without lung injury had received SCT treatment (p = 0.033 by Fischer's exact test). Multivariate analysis revealed that the concomitant use of corticosteroids might reduce the risk of lung injury (p = 0.024; odds ratio = 0.055) and that a previous SCT might increase the risk (p = 0.042; odds ratio = 13.140). We summarized these data from questionnaires for a limited Japanese cohort and therefore do not know the precise incidence of lung injury linked to fatal progression. Thus, future verification concerning these matters is warranted after the approval of bortezomib for use in Japan. Clinicians should be aware of the possibility of severe pulmonary complications associated with bortezomib therapy. Note that this report has the same contents as the article appeared in the International Journal of Hematology (vol. 84, p406-412, 2006) by permission of both the editorials of the Japanese Society of Hematology and the Japanese Society of Clinical Hematology, and should be considered as the Japanese translation of the article.     

Cardiac Output,Stroke Volume,and Pacing Rate: A Review of the Literature and a Proposed Technique for Selection of the Optimum Pacing Rate for an Exercise Responsive Pacemaker

Cardiac Output and Pacing Rate. Introduction : The purpose of this report is to determine the optimal pacing rate for an exercising patient. Methods and Results : From a review of the literature and from our own animal studies, the relationship between cardiac output and pacing rate and that between stroke volume and pacing rate are examined in resting and exercising animal and human subjects. With an adequately wide range of pacing rates, there exists a three-phase relationship between cardiac output and pacing rate. Starting with a low pacing pacing rate, an increase in pacing results in an increase in cardaac output (phase 1), then little change in cardiac output (phase 2), after which there is a decrease in cardiac output (phase 3). However, the relationship between stroke volume and pacing rate does not typically exhibit characteristics that allow identification of the three phases. In resting subjects with impaired ventricles and in exercising subjects, phase 2 is narrow or absent, the cardiac output increasing, then decreasing with an increase in pacing rate. From the experimental data reviewed herein, a technique is proposed for identifying the starting point in selecting the best pacing rate for resting and exercising subjects. The technique relies on identification of the transitions in the three-phase relationship between cardiac output and pacing rate. Conclusion : The best resting pacing rate is at the lower end of phase 2. A tentative first-choice exercise rate is at the middle of the resting phase 2 region. However, a change in cardiac output with a change in pacing rate will allow refinement of this first-choice exercise pacing rate.     

Multicenter survey on the validity of the CD-ROM guideline for antiarrhythmic drug therapy produced by the Japanese Circulation Society and the Japanese Society on Electrocardiology: preliminary report of the survey of the Japanese guideline for Arrhythmia Management By Individual Therapy (J-GAMBIT).

BACKGROUND: A multicenter investigational survey (Japanese Guideline for Arrhythmia Management By Individual Therapy) was conducted to evaluate the validity of using CD-ROM guidelines vs physician choice for the selection of antiarrhythmic drugs. METHODS AND RESULTS: Patients with paroxysmal atrial fibrillation (PAF, n=274) or premature ventricular contractions (PVC, n=216) were enrolled. The rate of concordance for drug selection between the treating physician and the CD-ROM was 216 of 274 patients (78.8%) with PAF. Of these, 168 (61.3%) were concordant for first-line agents and the remaining 48 (17.5%) were concordant for second-line agents. The concordance for the treatment of PVC was 154/216 cases (71.3%). Of these, 106 (49.1%) were concordant for first-line agents and the remaining 48 (22.2%) were concordant for second-line agents. Nonconcordance for PAF therapy was more likely to occur for patients with underlying heart disease (p<0.05), depressed cardiac function (p<0.001), and with more frequent ECG abnormalities and renal dysfunction. These differences were not seen in patients with PVC. CONCLUSION: The CD-ROM guidelines appear to be valid in the selection of antiarrhythmic drugs for both PAF and PVC, but their usefulness is influenced by the patient's clinical characteristics.     

Empirical antibiotic usage and bacterial superinfections in patients with COVID-19 in Japan: A nationwide survey by the Japanese Respiratory Society

An internet questionnaire survey for investigating empirical antibiotic usage and bacterial superinfections in patients with coronavirus disease-2019 (COVID-19) in Japan was conducted among the chief physicians of respiratory disease departments of 715 Japanese Respiratory Society-certified hospitals using Google Forms between January 28, 2021 and February 28, 2021. Responses to the questionnaire survey were obtained from 198 of 715 hospitals (27.6%). The survey revealed that the complication incidences of community-acquired pneumonia; hospital-acquired pneumonia, including ventilator-associated pneumonia; and sepsis were 2.86, 5.59, and 0.99%, respectively, among patients with moderate/severe and critical COVID-19. Bacterial co-infection and secondary infection rarely affected patients with COVID-19 in Japan, and the isolated pathogens were not specific to these patients. Moreover, the anti-inflammatory effects of macrolides for COVID-19 were not observed in several studies. These results might be useful in clinical practice for COVID-19.     

The current status of treatment‐related severe hypoglycemia in Japanese patients with diabetes mellitus: A report from the committee on a survey of severe hypoglycemia in the Japan Diabetes Society

Despite great strides in pharmacotherapy for diabetes, there is increasing concern over the risk of hypoglycemia in patients with diabetes receiving pharmacotherapy as they become increasingly older. This has prompted the Japan Diabetes Society (JDS) to initiate a survey on the current status of severe hypoglycemia in clinical settings. In July 2015, following approval from the JDS Scientific Survey/Research Ethics Committee, the JDS extended an invitation to executive educators, who represented a total of 631 healthcare facilities accredited by the JDS for diabetes education, to participate in the proposed survey. Of these, those who expressed their willingness to participate in the survey were sent an application form required for obtaining ethical approval at these healthcare facilities and were then asked, following approval, to enter relevant clinical data on an unlinked, anonymous basis in a web‐based registry. The current survey was fully funded by the JDS Scientific Survey/Research Committee. A case registry (clinical case database) was launched after facility‐specific information (healthcare facility database) was collected from all participating facilities and after informed consent was obtained from all participating patients. With severe hypoglycemia defined as the “presence of hypoglycemic symptoms requiring assistance from another person to treat and preferably venous plasma glucose levels at onset/diagnosis of disease or at presentation clearly less than 60 mg/dL (capillary whole blood glucose, less than 50 mg/dL)”, the current survey was conducted between April 1, 2014 and March 31, 2015, during which facility‐specific information was collected from a total of 193 facilities with a total of 798 case reports collected from 113 facilities. Of the 193 respondent facilities, 149 reported having an emergency department as well, with the median number of patients who required emergency transportation services to reach these facilities totaling 4,962 annually, of which those with severe hypoglycemia accounted for 0.34% (17). The respondent facilities accommodated a total of 2,237 patients with severe hypoglycemia annually, with the number of patients thus accommodated being 6.5 patients per site. A total of 1,171 patients were admitted for severe hypoglycemia, with the number of patients thus admitted being 4.0 per site, who accounted for 52.3% of all patients visiting annually for severe hypoglycemia. A review of the 798 case reports collected during the survey revealed that 240, 480 and 78 patients had type 1 diabetes, type 2 diabetes, and other types of diabetes, respectively; those with type 2 diabetes were shown to be significantly older (median [interquartile range], 77.0 [68.0–83.0]) than those with type 1 diabetes (54.0 [41.0–67.0]) (P < 0.001); and the BMI was shown to be significantly higher for those with type 2 diabetes (22.0 [19.5–24.8] kg/m²) than for those with type 1 diabetes (21.3 [18.9–24.0] kg/m²) (P = 0.003). It was also found that the median estimated glomerular filtration rate (eGFR) was significantly lower among those with type 2 diabetes (50.6 mL [31.8–71.1]/min/1.73 m²) than among those with type 1 diabetes (73.3 [53.5–91.1] mL/min/1.73 m²) (P < 0.001). Again, the median HbA1c value at onset of severe hypoglycemia was shown to be 7.0 (6.3–8.1)% among all patients examined, 7.5 (6.9–8.6)% among those with type 1 diabetes, and 6.8 (6.1–7.6)% among those with type 2 diabetes, with the HbA1c value at onset of hypoglycemia being significantly lower among those with type 2 diabetes (P < 0.001). Antecedent symptoms of severe hypoglycemia were shown to be present, absent and unknown in 35.5, 35.6, and 28.9% of all patients, respectively, with the incidence of symptomatic hypoglycemia being significantly lower among those with type 1 diabetes (41.0%) than among those with type 2 diabetes (56.9%). The antidiabetic agents used in those with type 2 diabetes were insulin preparations (292 patients including 29 receiving concomitant sulfonylureas [SUs]) (60.8%), SUs (159 insulin‐naïve patients) (33.1%), and no insulin preparations or SUs (29 patients) (6.0%). Of the 798 patients surveyed, 296 patients (37.2%) were shown to have required emergency transportation services for severe hypoglycemia before. Thus, the survey revealed, for the first time, the current status of treatment‐related severe hypoglycemia in Japan and clearly highlights the acute need for implementing preventive measures against hypoglycemia not only through education on hypoglycemia but through optimization of antidiabetic therapy for those at high risk of severe hypoglycemia or those with a history of severe hypoglycemia.     

Impact of coronavirus disease 2019 on respiratory care in Japan: A nationwide survey by the Japanese Respiratory Society

BackgroundCoronavirus disease 2019 (COVID-19) has spread worldwide since 2020, placing a huge burden on medical facilities. In the field of respiratory medicine, there has been a decrease in the number of patients. While many pulmonologists have been receiving patients with COVID-19, the actual effects on respiratory care have not been elucidated. Therefore, we conducted this study to clarify the effects of COVID-19 on medical care in the field of respiratory medicine.MethodsWe conducted a questionnaire survey among 749 hospitals belonging to the Board-Certified Member system of the Japanese Respiratory Society on the effects of COVID-19 from November 2021.ResultsResponses were obtained from 170 hospitals (23%), in approximately 70% of which the respiratory medicine department was the main department involved in managing COVID-19. The number of spirometry and bronchoscopy tests decreased by 25% and 15%, respectively, and the number of both outpatients and inpatients decreased in 93% of hospitals. Among respiratory diseases, the number of patients hospitalized for usual pneumonia, bronchial asthma, and chronic obstructive pulmonary disease decreased greatly by 30%–45%. In 62% of hospitals, the biggest effect of the COVID-19 pandemic was the greater burden in terms of the clinical workload due to COVID-19.ConclusionsAlthough the number of tests and non-COVID-19 outpatients and inpatients decreased in respiratory medicine departments during the COVID-19 pandemic, the workload increased due to COVID-19, resulting in a great increase in the clinical burden.     

The prevalence of comorbid respiratory disease among COVID-19 patients,and mortality during the first wave in Japan: A nationwide survey by the Japanese Respiratory Society

There is a concern that persons with underlying respiratory disease may have increased susceptibility to COVID-19 and/or increased severity/mortality if infected. However, information regarding such patients during the first wave of the epidemic is lacking in Japan. We surveyed chest physicians nationwide, and collected anonymous data concerning 1444 patients.Among COVID-19 patients, the prevalence of asthma, chronic obstructive pulmonary disease (COPD), and interstitial lung diseases (ILD) was 3.4%, 4.8%, and 1.5%, respectively. Among COVID-19 patients with these 3 comorbidities, exacerbation of the comorbidity occurred in 12.2%, 18.8%, and 36.4%, respectively, and mortality (6.2% overall) was 4.1%, 13.0%, and 31.8%, respectively.The prevalence of asthma among COVID-19 patients was not higher than that for the general population, and mortality in COVID-19 patients with asthma was not higher than mortality in COVID-19 patients without underlying respiratory disease. COVID-19 patients having COPD or ILD had relatively high mortality, especially for ILD.