Current Status of Outpatient Oral Antimicrobial Prescription and the Influence of Antimicrobial Stewardship for Inpatients: A Repeated Cross-Sectional Study at a Japanese Community Hospital.

This study aimed to clarify the details of outpatient oral antimicrobial use (AMU) at a Japanese community hospital and investigate the influence of the current inpatient-based antimicrobial stewardship (AS) on outpatients. A repeated cross-sectional study was conducted in Komaki City Hospital. Data on patients, physicians, and oral antibiotics were collected in October 2013, 2016, and 2019, and appropriateness of treatment and surgical antimicrobial prophylaxis (SAP) was evaluated. The percentage of patients receiving oral antibiotics increased significantly from 4.7% in 2013 (345/7338) to 5.9% in 2019 (365/6146), and the overall number of antimicrobial prescriptions per 1000 outpatients increased from 51.8 in 2013 to 68.0 in 2019. Prescriptions for third-generation cephalosporins per 1000 outpatients decreased (from 21.4 to 6.3), whereas the number of prescriptions for penicillin (from 3.8 to 15.3), fluoroquinolones (from 7.0 to 13.2), and co-trimoxazole (from 5.0 to 15.8) increased from 2013 to 2019. The appropriate AMU for overall infections significantly increased (from 68.4% in 2013 to 83.7% in 2019). The choice and duration of AMU significantly improved for SAP. However, even in 2019, only 29.3% of patients received antibiotics before surgery. The improved selection of antibiotics on outpatient prescription may be due to the influence of AS-which is focused on inpatients-while prescriptions for fluoroquinolones and prophylactics also increased. The challenges of antimicrobial administration after surgeries were also highlighted.

[Utility of the Predictive Score for Cisplatin-Induced Nephrotoxicity in Patients with Chemotherapy for Lung Cancer].

BACKGROUND: Cisplatin(CDDP)-induced nephrotoxicity(CIN)is a critical complication of chemotherapy. Among patients undergoing chemotherapy with CDDP, short-hydration, and magnesium supplementation for lung cancer, this study was conducted to evaluate the frequency of CIN and utility of the predictive score. METHODS: Patients who underwent chemotherapy with CDDP for lung cancer were retrospectively investigated. A multiple logistic regression analysis to detect the risk factors for CIN and receiver operating characteristic analysis to examine the discrimination of the predictive score were performed. RESULTS: A total of 111 patients were included, with a total count of chemotherapy courses of 402 and a median count of chemotherapy courses of 4. CIN occurred in 9.9% of the patients, with grade 2 and higher in 7.2% and 87% of the CIN cases detected in the initial course, respectively. The significantly independent risk factors for CIN included the number of chemotherapy courses, female gender, and predictive score. The discriminative power of the predictive score was moderate. CONCLUSION: The predictive score for CIN was simple and useful in patients undergoing chemotherapy for lung cancer with CDDP, short-hydration, and magnesium supplementation, even in late courses.

Comparison between stereotactic radiosurgery and whole-brain radiotherapy for 10-20 brain metastases from non-small cell lung cancer.

The efficacy and safety of stereotactic radiosurgery (SRS) in comparison with whole brain radiotherapy (WBRT) for brain metastases (BMs) remains unclear. The present study retrospectively reviewed 44 patients who received SRS or WBRT as an initial treatment for 10-20 BMs from non-small cell lung cancer between 2009 and 2016. Of the patients, 24 (54.5%) were treated with SRS and 20 (45.5%) were treated with WBRT. Overall survival (OS), time to intracranial progression (TTIP), neurological survival (NS), and prognostic factors were examined. OS did not significantly differ between the two groups: 7.3 months in the SRS group vs. 7.2 months in the WBRT group (P=0.502). Median TTIP was significantly shorter in the SRS group than in the WBRT group (7.1 vs. 19.1 months, P=0.009). In contrast, there were no significant differences in NS between the two groups (14.5 months in the SRS group vs. 12.9 months in the WBRT group, P=0.346). Univariate and multivariate analysis revealed that the type of initial treatment for BMs (WBRT or SRS) was not a significant prognostic factor (hazard ratio=0.80, 95% confidence interval: 0.42-1.52, P=0.502). However, histology, performance status, subsequent molecular targeted drugs, subsequent chemotherapy and salvage treatment were independent prognostic factors. There were no significant differences in OS and NS between treatment with SRS and treatment with WBRT in patients with 10-20 BMs, although TTIP was improved with WBRT. As an upfront treatment for 10-20 BMs, SRS may delay WBRT and the adverse events associated with WBRT.

A propensity score-matched comparison of the efficacies of OK-432 and talc slurry for pleurodesis for malignant pleural effusion induced by lung adenocarcinoma.

BACKGROUND: The choice of an optimal sclerosant for pleurodesis for malignant pleural effusion remains controversial. This retrospective clinical study compared the efficacy and safety of two sclerosants; talc slurry (talc-s) and OK-432. METHODS: We compared the characteristics, 30/90-day success rates, and adverse events in patients with lung adenocarcinoma who underwent pleurodesis by using either OK-432 or talc-s. Propensity score matching was used to compare the two scelrosants. RESULTS: Ninety-four patients (mean age=71.6±9.6 years) were included in this retrospective study, of whom 64 received OK-432 and 30 received talc-s. Seventy-three patients (77.6%) were initially diagnosed with clinical stage IV lung cancer, with a 28.7% epidermal growth factor receptor mutation frequency. The propensity score-matched cohort included 26 patients from each group. The 30-day success rates for OK-432 and talc-s were 80.7% and 76.9%, respectively (odds ratio: 1.26, 95% confidence interval: 0.33-4.77, p=0.73). Neither the overall incidence of adverse events nor the 90-day success rates differed significantly. Multivariate logistic regression revealed that the predictors of 30-day success were lower drainage volume on the previous day, particularly <250mL/day, the presence of full lung expansion, and pre-therapy with an epidermal growth factor receptor-tyrosine kinase inhibitor. The median post-pleurodesis survival time was 6.9 months, which was not significantly different between the study groups. CONCLUSIONS: Propensity score-matched analyses showed that pleurodesis using OK-432 and talc-s demonstrated comparable efficacy and safety profiles in patients with lung adenocarcinoma. This indicated that OK-432 could be a viable alternative to talc-s in this procedure.

[A Case of Acute Arterial Occlusion of the Lower Limb during Chemotherapy for Lung Cancer].

A 69-year-old man visited a clinic for left leg weakness. With suspicions of lung cancer and a metastatic brain tumor, he was referred to our hospital and was diagnosed with large cell neuroendocrine carcinoma, cT1bN0M1b (BRA), stage IV. After stereotactic radiosurgery for his brain metastasis, he was treated with chemotherapy containing cisplatin and irinotecan. A week after initiating chemotherapy, he suddenly developed severe right leg pain and adynamia. A computed tomography angiogram revealed occlusion of the right common femoral artery, and percutaneous thrombectomy was performed. The symptoms resolved completely, and he was discharged without any sequelae or recurrence. Acute arterial occlusion of the limbs during chemotherapy is uncommon and requires prompt diagnosis and treatment; hence, caution should be paid when it is clinically suspected.

Predictors and impact of time to clinical stability in community-acquired pneumococcal pneumonia.

BACKGROUND: A clinical stability (CS) evaluation is thought to be important in community-acquired pneumonia (CAP) treatment, but evidence concerning the time to CS (TCS) remains lacking. METHODS: Among consecutive patients hospitalized with pneumococcal pneumonia, relationships between TCS and other clinical outcomes were examined, and predictors and a predictive TCS score were derived from patient characteristics on admission. RESULTS: A total of 144 patients were enrolled, including 46% and 27% with moderate and severe pneumonia, respectively, defined by the pneumonia severity index (PSI). The median TCS was 2 days, and was significantly correlated with the length of hospital stay (r = 0.595); a longer TCS was significantly associated with the more presence of poor clinical outcomes and ICU stays (adjusted odds ratios: 1.359 and 1.366, respectively). A multivariate Cox proportional hazard model revealed an absence of bilateral pneumonia (hazard rate (HR): 2.107) or bacteremia (HR: 2.520), and mild or moderate pneumonia (HR: 2.798 and 2.515, respectively, versus severe) as predictors of CS. A predictive score had moderate discriminating power for the prolonged TCS (area under the curve: 0.76), and provided similar predictive values for poor clinical outcomes and ICU stays. A score of 3 or more points indicated the prolonged TCS, with a sensitivity and specificity of 73.3% and 70.9%, respectively. CONCLUSIONS: Because TCS has a significant relationship with other clinical outcomes of pneumococcal CAP, the prediction of TCS might lead to the prevention of complications or an earlier transition to oral therapy. Future studies are warranted to validate these results.

Distinct features of distant metastasis and lymph node stage in lung adenocarcinoma patients with epidermal growth factor receptor gene mutations.

BACKGROUND: The influence of epidermal growth factor receptor (EGFR) mutation status on distant and lymph node metastasis is not fully understood. METHODS: Ninety-five consecutive patients with stage IV lung adenocarcinoma, who had been examined for the EGFR mutation status, were retrospectively analyzed with regard to numbers of distant metastasis and clinical stage of lymph node metastasis at the time of diagnosis. RESULTS: While EGFR mutation status did not influence the presence or absence of distant metastasis in the lung, brain, or liver, patients with EGFR mutations demonstrated a significantly greater number of metastatic lesions in the lung (median: 85 vs. 4, P=0.01) and the brain (11 vs. 3.5, P=0.04). On the other hand, patients with EGFR mutations showed a significantly lower lymph node staging (P<0.01). CONCLUSION: The presence of EGFR mutations in patients with lung adenocarcinoma correlates with lower lymph node stage and a greater number of metastatic lesions in the lung and brain.

Re-expansion pulmonary edema: evaluation of risk factors in 173 episodes of spontaneous pneumothorax.

BACKGROUND: The precise incidence and clinical features of re-expansion pulmonary edema (RPE) are unclear, and they vary among reports. In this study, we assessed the incidence, risk factors, and outcomes of patients with RPE over a 3-yr period in a general hospital, with the goal of proposing a primary intervention for pneumothorax. METHODS: We retrospectively reviewed records of inpatients with spontaneous pneumothorax treated by tube thoracostomy between October 2007 and December 2010. RESULTS: A total of 173 episodes of spontaneous pneumothorax occurred in 156 patients. The incidence of RPE was 27/173 (15.6%). Symptom duration and pneumothorax size were significant risk factors for RPE, and the occurrence of RPE was independent of primary treatment of spontaneous pneumothorax. Among the patients with RPE, 18 (67%) were symptomatic. Five patients (18.5%) were treated with temporary oxygen, however, 21 patients (78%) did not need any treatment. All patients survived and none required mechanical ventilation. The occurrence of RPE did not influence the clinical outcome. CONCLUSIONS: The risk of developing RPE increases with an increased duration or size of pneumothorax. Our results suggest that the methods of primary intervention, including prompt suction, do not affect the onset of RPE. Close observation is always required regardless of the intervention because of the potentially fatal complications.

Diagnostic management of patients with suspected ocular sarcoidosis.

BACKGROUND: Ophthalmologists often refer patients with suspected ocular sarcoidosis to pulmonologists for diagnostic examination of sarcoidosis. However, no recommendation has been proposed for managing such patients. This study aims to prospectively evaluate the diagnostic values of examinations and propose the management of patients with suspected ocular sarcoidosis. METHODS: Consecutive patients with suspected ocular sarcoidosis were prospectively investigated according to type of ocular lesions, measurement of serum ACE, and findings of chest radiography, chest CT, bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB). Diagnostic values were calculated on the basis of pathological results. RESULTS: Forty-two patients were included (female, 71.4%; mean age, 56.2±14.8 years), of whom 64.3% was diagnosed with sarcoidosis. Patient characteristics and ocular lesions did not differ significantly, regardless of the presence of sarcoidosis. Chest CT had low specificity and very high sensitivity for detecting sarcoidosis; in contrast, chest radiography and direct findings of bronchofiberscopy had high specificity and low sensitivity. Serum ACE and BAL did not have high diagnostic value. A flow chart was proposed to diagnose sarcoidosis, and this chart reduced the requirement of TBLB to 50% in our population. During the median follow-up of 51 months, 7 patients in the sarcoidosis group (25.9%) developed new lesions. CONCLUSIONS: Application of our flow chart appears to detect avoidable TBLB. Development of a more comprehensive flow chart including survey of ocular findings is warranted.

Paradoxical infarct in tuberculous meningitis: a case report.

We describe a case of 78-year-old woman with a 1-week history of fever and left hemiparesis. Head magnetic resonance imaging showed a small infarct. After admission, she showed altered consciousness and another small infarct. She finally had diagnoses of miliary tuberculosis (miliary-TB) and tuberculous meningitis (TBM). She recovered after receiving anti-tuberculous therapy (ATT) with prednisolone. However, 5 weeks later, we found another infarct. This is a rare case of TBM with recurrent infarcts in atypical lesions in spite of ATT. We suggest the possibility that the new infarct after ATT was due to a paradoxical reaction.

Prospective evaluation of the relationship between acute exacerbations of COPD and gastroesophageal reflux disease diagnosed by questionnaire.

BACKGROUND: Little is known about the relationship between acute exacerbations of COPD (AECOPD) and gastroesophageal reflux disease (GERD). The aim of this study was to investigate the effects on AECOPD of GERD diagnosed by a questionnaire. METHODS: The subjects were 221 consecutive patients with stable COPD who were evaluated using the Frequency Scale for Symptoms of GERD (FSSG) and a prospective survey of AECOPD for one year. Patients taking drugs for acid suppression were excluded. The association between the frequency of AECOPD and the presence of GERD or FSSG score was examined. RESULTS: Based on the FSSG, the prevalence of GERD was 26.7%. AECOPD and hospitalization due to AECOPD were significantly more frequent in patients with GERD than in those without GERD, with crude relative risks of 3.42 and 3.66, respectively. Multivariate analyses showed that GERD and COPD stage IV were significant predictors of hospitalization due to AECOPD, independent of respiratory therapies or patient characteristics. The severity of GERD symptoms, as measured by the FSSG score, was significantly correlated with the frequencies of AECOPD and hospitalization due to AECOPD. Similar correlations were seen for the FSSG subscores for acid reflux and gastric dysmotility. CONCLUSIONS: This prospective cohort study showed that GERD appears to be a predictive factor for hospitalization due to AECOPD and that severer GERD symptoms may be associated with more frequent AECOPD. Thus, further studies are warranted to evaluate the preventive effect of the therapy for GERD on AECOPD.

[A case of six metachronous primary malignancies].

Recently, the early detection and the advances in therapy for malignant diseases have contributed to prolonged survival of patients, resulting in an increment of multiple primary malignancies. We describe a 55-year-old man, at the first presentation, with six malignancies over 14 years(malignant lymphoma, gastric cancer, ureteral cancer, small cell lung cancer, bladder cancer, and squamous cell lung cancer). A case of six primary malignancies is extremely rare and, as far as we know, this is the 16th case of its kind reported in Japan. The overlapping of many malignant diseases resulted in some difficulties with treatment. Whereas the ureteral cancer and small cell lung cancer were synchronous, considering the therapeutic duration of lung cancer, we proceeded with the operation for ureteral cancer and had to delay the start of chemotherapy for small cell lung cancer for more than one month. Moreover, dose intensity of the chemotherapy for the small cell lung cancer was limited by expectancy of augmented myelosuppression, due to the effect of prior chemotherapy for malignant lymphoma. However, a strong neutropenia-induced postoperative abdominal infection necessitated discontinuation of chemotherapy and treatment with radiotherapy alone. In addition, the therapies for the newly developed squamous cell lung cancer, the sixth malignancy, were also limited because of reduced lung function and myelopoiesis. In treatment or follow-up of patients with multiple primary malignancies, as opposed to those with a single malignant disease, the characteristics of other malignancies and the morbidities by preceding therapies must be considered.

[A case of fulminant community-acquired Acinetobacter pneumonia in a healthy woman].

We describe a case of fulminant community-acquired Acinetobacter baumannii pneumonia. A 68-year-old woman, who had no past medical history, was admitted with septic shock and pneumonia of left lower lobe. Despite intensive treatment she died on day 3 after admission. To the best of our knowledge, this is the 4th report of community-acquired Acinetobacter pneumonia in Japan and the 1st report in a healthy patient. We report a case of Acinetobacter pneumonia and discuss the clinical characteristics of the community-acquired type compared with the hospital-acquired type.

Phase II study of S-1 monotherapy as a first-line treatment for elderly patients with advanced nonsmall-cell lung cancer: the Central Japan Lung Study Group trial 0404.

Although S-1 has been shown to have activity against advanced nonsmall-cell lung cancer (NSCLC), its efficacy for elderly patients remains unclear. This phase II study evaluated the efficacy and safety of S-1 as a first-line treatment for elderly patients. Chemotherapy-naïve patients aged 70 years or older with stages IIIB to IV or postoperative NSCLC and performance status 1 or lower were eligible. Patients received S-1 approximately equivalent to 80 mg/m/day for 2 weeks followed by a 1-week rest period every 3 weeks. The primary end point was the response rate. Secondary end points were toxicity, disease control rate, progression-free survival, and overall survival. Twenty-nine patients were eligible. The median age was 78 years (range, 70-85 years). The overall response rate and the disease control rate were 27.6 [95% confidence interval (CI), 11.3-43.9%] and 65.5% (95% CI: 48.2-82.8%), respectively. The median progression-free survival time was 4.0 months (95% CI: 4.0-9.8 months). The median overall survival was 12.1 months (95% CI: 13.8-25.5 months) and the 1-year survival rate was 53.6%. No grade 4 toxicities were observed. The only hematological toxicity of grade 3 was anemia in 6.9% of patients. The grade 3 nonhematological toxicities included hyponatremia, anorexia, nausea, oral mucositis, and diarrhea in 3.4% of patients and infection in 6.9% of patients. S-1 monotherapy was effective and well tolerated as a first-line treatment for elderly patients with advanced NSCLC. The results of this study warrant further investigations of this regimen, including a randomized controlled trial.

[Relationship between chronic obstructive pulmonary disease and gastroesophageal reflux disease defined by the Frequency Scale for the Symptoms of gastroesophageal reflux disease].

Little is known about gastroesophageal reflux disease (GERD) in chronic obstructive pulmonary disease (COPD) patients. The aim of this study was to investigate the prevalence, clinical characteristics and risk factors for GERD in COPD patients, based on the Frequency Scale for the Symptoms of GERD (FSSG). In 228 COPD patients, the prevalence of GERD was 26.7%, independent of COPD stage. Logistic regression multivariate analysis revealed significant risk factors for accompanying GERD were age (p = 0.009; odds ratio (OR), 0.933; 95% confidence interval (CI) 0.885 to 0.983) and number of COPD exacerbation within one year (p = 0.043; OR, 1.675; 95% CI, 1.075 to 2.764). The risk factors of COPD exacerbation were total FSSG score (p = 0.031; OR, 1.079; 95% CI, 1.007 to 1.156) and inhaled corticosteroid use (p = 0.003; OR, 3.238; 95% CI, 1.482 to 7.076). Moreover, the Spearman rank correlation test showed that FSSG score was weakly but significantly correlated with the number of COPD exacerbations (rs = 0.317, p < 0.001). In conclusion, the incidence of GERD in COPD patients is high, and the incidence of GERD is closely related to COPD exacerbation.

Spontaneous pneumomediastinum: an algorithm for diagnosis and management.

Spontaneous pneumomediastinum (SPM) is a rare disorder most often affecting young males which is generally self-limiting. Despite the benign prognosis with few complications and little morbidity, it frequently confuses clinicians in primary settings, who may have difficulty differentiating SPM from other serious organ ruptures, especially oesophageal rupture (the so-called Boerhaave syndrome), which may lead to mediastinitis and may be fatal, even with appropriate interventions. An overview of adult SPM is provided, reviewing 17 studies (414 patients), including our clinical experience, and finally an algorithm for diagnosis and management of SPM is proposed, based on the characteristics of SPM.

[Predictors of survival in patients with chronic hypercapnic respiratory failure receiving domiciliary NPPV].

Fifty-four cases (36 men) with chronic hypercapnic respiratory failure were prescribed domiciliary NPPV during 9 years. COPD (26 patients) and sequelae of tuberclosis (16 patients) were the major primary diseases. At the initiation of NPPV, the age was 71.2 +/- 7.3 years-old (mean +/- standard deviation) and PaCO2 was 76.7 +/- 16.2Torr. Overall, the 1-year and 5-year survival rates were 63.8% and 26.0%, respectively. Multivariate analysis identified BMI (body mass index) (hazzard ratio : 0.837, p = 0.020) and the number of days of hospitalization during 1 year before NPPV (hazzard ratio: 1.013, p = 0.016) as predictors of survival. Patients with frequent hospitalization for exacerbation or with malnutrition had poor prognosis, so comprehensive supports aimed to improve general status are needed for patients with chronic respiratory failure received domiciliary NPPV.

Management of spontaneous pneumomediastinum based on clinical experience of 25 cases.

STUDY OBJECTIVES: Spontaneous pneumomediastinum (SPM) is a rare disorder that usually occurs in young individuals and has a self-limiting course and no recurrence in most cases. But actually in many cases, patients are undergo some examinations or some limitations. The purpose of this study was to evaluate the clinical characteristics and recommend appropriate management of SPM. DESIGN: Retrospective research of clinical records of a single institution. RESULTS: Over 11 years, we diagnosed 25 patients (18 males) with SPM. Their average age was 20.1 years (range 13-28 years). Chest pain or neck symptoms were most frequent, and 17 patients (68%) had subcutaneous emphysema. In all cases, blood counts and C-reactive protein (CRP) were measured, and their mean values were 10,100+/-4600/mm(3) and 1.0+/-1.5 mg/dL, respectively. In 20 patients (80%), either leucocytosis or elevated CRP was observed. Twenty-four patients (96%) were admitted (average 7.8+/-4.1 days) and 20 of them were prescribed antibiotics or limited oral intake. The symptoms were self-limiting in all cases and disappeared on average 1.8+/-0.9 days after diagnosis. No recurrence was noted in the approximately 2 years follow-up period. CONCLUSION: SPM is a self-limiting disease with mild inflammatory signs. For patients suspicious of SPM, shortened hospitalization for about 2 days with observation alone may be feasible, if their symptoms improve gradually. Otherwise, less invasive procedures, such as esophagram, should be performed immediately. Long-term follow-up is usually unnecessary. We propose a new algorithm for management of SPM based on clinical experience.

[Purpura fulminans due to pneumococcal pneumonia in a healthy adult: a case report].

We report a case of infectious purpura fulminans due to pneumococcal pneumonia in a 61-year-old man presenting multiple organ failure and pneumococcal bacteremia secondary to pneumonia on admission. His lower limbs showed rapidly progressive purpura and symmetrical dry gangrene. He had no history of or apparent immunodeficiency, including asplenia, in abdominal ultrasonography. Despite of therapy, he died on day 15 after admission. Infectious purpura fulminans involves skin lesions with severe infection often accompanied by disseminated intravascular coagulation and septic shock. Although it occurs mainly in childhood, especially as a complication of Neisseria meningitis or Varicella virus infection, it has also been reported in adult, as a rare complication of invasive pneumococcal infection. Most had immunodeficiency such as asplenia or postsplenectomy. Purpura fulminans in a previously healthy adult is very rare and this is insofar as we know, the first report in Japan detailing the development from pneumococcal pneumonia.