Frequency of missed doses and its effects on the regulation of glucose levels in patients with type 2 diabetes: A retrospective analysis.

This study aimed to investigate the association between medication adherence to oral hypoglycemic agents (OHAs) and HbA1c levels in patients with type 2 diabetes mellitus (T2DM) for more than 48 weeks, as well as the factors affecting long-term adherence to OHAs. This retrospective study included 83 patients who had been receiving OHAs for T2DM for ≥48 weeks. Medication adherence values (MAVs) were calculated using the following formula: (total prescription days - prescription days of OHAs brought at admission)/(days from the initiation of OHAs to hospitalization). We assessed the association between HbA1c and MAVs using the Jonckheere-Terpstra test. Furthermore, we examined the association between patient- and medication-related factors and MAVs affecting HbA1c levels. Based on the results, MAVs were categorized as MAV ≤0.86 and MAV >0.86, and factors affecting MAVs were analyzed. Logistic regression analysis revealed that the total number of medications, the number of nonhypoglycemic agents, and a family history of diabetes were independent determinants of MAV ≤0.86 (P < .05). Multiple regression analyses indicated that the number of dosages per day and the timing of OHA administration at lunch were independent determinants of lower MAVs (P < .05). Our findings suggest that poor medication adherence is associated with elevated HbA1c levels in T2DM patients. Independent factors contributing to poor adherence include a lower number of prescribed medications, fewer nonhypoglycemic agents, no family history, a higher daily dosage frequency, and the administration of OHAs at lunch.

A case-control study showing low creatinine clearance and high magnesium intake as risk factors for hypermagnesemia in older individuals.

According to epidemiological studies, constipation has a negative effect on life expectancy, necessitating appropriate treatment. According to the Pharmaceuticals and Medical Devices Agency (PMDA), patients who have been taking magnesium oxide (MgO) for constipation over a prolonged period, especially those with impaired renal function and older individuals, are at high risk of hypermagnesemia. Therefore, serum Mg levels, which are often not checked in clinical practice, should be monitored in these patients. Thus, to predict elevated serum Mg levels and prevent the development of hypermagnesemia, we aimed to identify the risk factors of hypermagnesemia, especially in the older population. Our study included patients who were prescribed MgO at our hospital between January 1, 2014, and March 31, 2016. Patients who did not meet the inclusion criteria were excluded and matched to adjust for background factors; finally, 35 patients in the hypermagnesemia arm and 140 patients in the non-hypermagnesemia arm were included in the analysis. Multivariate analysis identified estimated creatinine clearance (eCcr) ≤ 28.2 mL/min as a statistically significant risk factor. In addition, MgO dose ≥ 900 mg/day was identified as a risk factor for clinical consideration, although not statistically significant. Furthermore, the incidence of hypermagnesemia was shown to increase to 11.6% for those with MgO dose ≥ 900 mg/day, 27.0% for those with eCcr ≤ 28.2 mL/min, and 53.1% for those with both. Hypermagnesemia may occur in older patients with eCcr ≤ 28.2 mL/min who take more than 900 mg/day of MgO.

Risk analysis of COVID-19 hospitalization and critical care by race and region in the United States: a cohort study.

BACKGROUND: This study aimed to identify the current risk factors for coronavirus disease 2019 severity and examine its association with medication use. METHODS: We used data from a large United States electronic health record database to conduct an anonymized cohort study of 171,491 patients with coronavirus disease 2019. The study was conducted from January 1, 2020, to August 27, 2021. Data on age, race, sex, history of diseases, and history of medication prescriptions were analyzed using the Cox proportional hazards model analysis to calculate hazard ratios for hospitalization and severe risk. RESULTS: Factors that increased the risk of hospitalization and critical care were age ≥ 65 years, male sex, type 2 diabetes, hypertension, interstitial pneumonia, and cardiovascular disease. In particular, age ≥ 65 years significantly increased the risk of hospitalization (hazard ratio, 2.81 [95% confidence interval, 2.58-3.07]; P < 0.001) and critical care (hazard ratio, 3.45 [2.88-4.14]; P < 0.001). In contrast, patients with hyperlipidemia had a reduced risk. However, patients with hyperlipidemia who were not taking statins had a significantly increased risk of hospitalization (hazard ratio, 1.24 [1.16-1.34]; P < 0.001). Sodium-glucose cotransporter-2 inhibitors, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, glucocorticoids, and statins significantly reduced the risk of hospitalization and critical care. The risk of hospitalization and critical care increased in patients of all ethnicities with type 2 diabetes. The factors that significantly increased the risk of hospitalization in all regions were older age, hypertension, chronic obstructive pulmonary disease, and cardiovascular disease. CONCLUSION: This study identified factors that increase or reduce the risk of severe coronavirus disease. The provision of appropriate drug treatment and modification of lifestyle-related risk factors may reduce coronavirus disease severity.

[Two Cases at Community Pharmacies of Mercaptopurine Removal from a Disk-type Powder-packaging Machine by Wiping It with Water].

"Leukerin® powder 10%" containing mercaptopurine (6-MP) is an oral anticancer drug that requires careful handling. As a powder formulation, there are risks of exposure due to scattering during dispensing and possible 6-MP contamination to other drugs due to adhesion to the packaging machine. We previously reported that wiping with an alcohol-containing towel is useful for removing scattered powder after dispensing. However, it is recommended to wipe disk-type powder-packaging machines with water instead of cleaning with the alcohol-containing towel. Hence, we scattered 6-MP powder 100 mg (total amount of 6-MP: 10 mg), and then wiped with water three times using different types of cloth each time. We confirmed that third time wiping cloth did not have any 6-MP. Furthermore, we confirmed that the adhering 6-MP could be removed by wipe-cleaning (water-wiping twice and dry-wiping once) after dispensing 6-MP powder at two pharmacies that routinely dispensed 6-MP powder using a disk-type powder-packaging machine. In addition, we confirmed the adhesion of 6-MP in parts of the machine not cleaned by wipe-cleaning and also in parts that were washed only with water, in both the pharmacies. Based on the above observations, we recommend the following steps for cleaning disk-type powder-packaging machines after dispensing 6-MP powder: (1) wipe-cleaning that includes water-wiping twice and then dry-wiping once, (2) cleaning all areas of the packaging machine, and (3) wipe-cleaning with water before washing with water.

Mixture of clopidogrel bisulfate and magnesium oxide tablets reduces clopidogrel dose administered through a feeding tube.

BACKGROUND: In clinical practice, a mixed suspension of clopidogrel bisulfate and magnesium oxide (MgO) tablets is administered frequently via a feeding tube. However, there is no report on the changes occurring when suspensions of these two drugs are combined, including the effects or potential decrease in dose following tube administration. Thus, the purpose of our study was to investigate the (i) changes caused by mixing clopidogrel bisulfate (ion form) and MgO tablets and (ii) effects on the administered clopidogrel dose after passing through a feeding tube. METHODS: The molecular structure of clopidogrel generated in a mixture of clopidogrel bisulfate and a basic compound, such as sodium bicarbonate or MgO tablet, was determined by 1H-NMR after extraction and purification. The suspension of clopidogrel bisulfate tablet alone and the mixed suspension of clopidogrel bisulfate tablet and MgO tablet were passed through a feeding tube. We compared the yield of the molecular form of clopidogrel from each passed fraction. RESULTS: The substance obtained from the mixture of clopidogrel bisulfate tablet and sodium bicarbonate or MgO tablet was identified as the molecular form of clopidogrel, and chemical degradation did not occur under these conditions. In the tube passage test, the yield of clopidogrel (molecular form) from the mixture of clopidogrel bisulfate and MgO tablets was lower than that from the suspension of clopidogrel bisulfate tablet alone. CONCLUSIONS: The mixture of clopidogrel bisulfate and MgO tablets caused a considerable reduction in the administered dose passed through the feeding tube. Therefore, it is recommended to administer the suspensions of clopidogrel bisulfate and MgO tablets separately for safe and effective pharmacotherapy.

[Safe Handling Method for Splitting Azathioprine Tablets].

The immunosuppressant azathioprine (AZA) is classified as a hazardous drug. AZA contamination during tablet-splitting increases exposure risk. However, there is no study on contamination and exposure during AZA tablet splitting and dispensing. AZA tablet splitting and dispensing methods were classified based on whether tweezers are used during splitting and packaging. In Dispensing Method (1), no tweezers were used in either step. In Dispensing Method (2), no tweezers were used during tablet splitting, but were used during packaging. In Dispensing Method (3), tweezers were used in both steps. After AZA half-tablet split-dispensing, we quantified the adherent AZA removed from the tools, packaging machines, and dispensing counters by three consecutive wipings with water-dampened polypropylene cloths. A large amount of AZA adhered to the gloves used in Dispensing Methods (1) and (2), wherein tablets were placed with gloved hands, compared with Dispensing Method (3), wherein tablets were held with tweezers. Thus, the gloves must be replaced before touching the packaging paper during the final step. After three consecutive wipings, AZA was not detected at most of the sites in the third round. Thus, we recommend that (1) AZA tablet splitting should be performed while wearing gloves, (2) the gloves should be changed before packaging the half tablets, and (3) the tools, packaging machines, and dispensing counters should be wiped twice or thrice with a water-dampened cloth after dispensing.

Evaluation of Measures against Exposure during Administration of Hazardous Drugs through a Feeding Tube.

Hazardous drugs (HD), which need to be handled with care, may be administered through a feeding tube using the simple suspension method. However, instrument contamination during HD administration with the simple suspension method remains unclear. Therefore, to minimize such contamination during the simple suspension method using an injector, we propose the following exposure countermeasures method: (1) Wear two layers of gloves. (2) Prepare injectors for administration and flushing. (3) Use caps. (4) Replace outer gloves after the removal of tablets from the press-through package (PTP) sheet. (5) Handle drugs on a tray. (6) Inject while wrapping the connection site between the injector for administration and the tube with gauze. (7) Wrap the connection site between the injector and tube with gauze. (8) Do not point the injector downward. To establish whether these countermeasures method are effective, 16 ward nurses who routinely administer drugs via a feeding tube were enrolled as subjects. By visual evaluation, we compared differences in instrument contamination between a suspension using a medicine cup and administration via a feeding tube (the conventional method) and the exposure countermeasures method. Exposure with the countermeasures method under our instruction was markedly lower than that with the conventional method. Furthermore, after implementing the exposure countermeasures method, most nurses noted that caution and awareness of exposure countermeasures increased. Thus, to minimize exposure, we recommend the implementation of the exposure countermeasures method and increasing knowledge and awareness of measures against exposure.

Clinical Pharmacy Education in Japan: Using Simulated Patients in Laboratory-Based Communication-Skills Training before Clinical Practice.

The Japanese pharmaceutical curriculum was extended from four to six years in 2006. Students now receive practical communication-skills training in their fourth year, before progressing to train in hospital and community pharmacies in their fifth year. Kitasato University School of Pharmacy, Tokyo, had established a program to meet these aims before the 2006 guidance. In the present study, we discuss and evaluate the features of this communication-skills training program. This study enrolled 242 fourth-year pharmacy students at Kitasato University. Students filled out a questionnaire survey after completing the laboratory element of their undergraduate education. As part of training, students were asked to obtain patient data from a model medical chart, before performing simulated patient interviews covering hospital admission and patient counseling. These simulations were repeated in a small group, and feedback was provided to students by both the simulated patient and the faculty after each presentation. It was found that students were able to develop their communication skills through this approach. Thus, an effective system of gradual and continuous training has been developed, which allows students to acquire clinical and practical communication skills.

Primary pulmonary glomus tumor of uncertain malignant potential: A case report with literature review focusing on current concepts of malignancy grade estimation.

We report a 38-year-old woman with a left lung tumor presenting as obstructive pneumonia. Bronchoscopic examination revealed a polypoid tumor filling the left main bronchus. The tumor was partially resected by a snaring procedure for diagnostic purposes. Microscopic examination revealed a submucosal tumor located underneath normal bronchial epithelium. The tumor was composed of sheets of uniform oval to cuboidal cells encompassing numerous blood vessels. Immunohistochemically, the tumor cells exhibited smooth muscle markers, but were negative for neuroendocrine markers. The diagnosis of primary pulmonary glomus tumor was therefore made. Subsequent bronchoscopic intervention allowed us to pin-point the origin of the tumor: superior segmental B6a/b. She underwent a left lower lobe superior segmental resection successfully. Glomus tumors are relatively rare soft tissue tumors, and those of bronchopulmonary origin are exceedingly rare clinical condition. Among primary lung tumors, the carcinoid tumor is a mimic of the glomus tumor, and differentiating these tumors is known to be difficult, especially using small biopsy samples. In the present case, a large tissue sample obtained by bronchoscopic snaring was quite useful for the correct preoperative diagnosis. Because of the disease rarity, malignancy grade estimation of visceral glomus tumors has not been clearly addressed. Recently, the histopathological diagnostic criteria for malignant glomus tumors was defined in the WHO classification of soft tissue and bone tumors 4th edition. Here we also reviewed the literature on primary bronchopulmonary glomus tumors with special attention to the current concept of malignancy grade estimation.

[Corrigendum] Aberrant methylation of CXCL12 in non-small cell lung cancer is associated with an unfavorable prognosis.

The PCR panels presented in Figs. 1 and 2 are incorrect. The authors provide the correct figures below. These changes do not affect the interpretation or conclusions of this work. The authors regret this error. [the original article was published in the International Journal of Oncology 33: 113-119, 2008 DOI: 10.3892/ijo.33.1.113]

Successful treatment of lung cancer by multimodal endobronchial interventions.

The innovation of thoracic interventions, such as endobronchial ultrasound and photodynamic ablation, has changed the interventional management of lung cancer. In this case report, we discuss the case of a successful treatment of endobronchial squamous cell carcinoma occluding the left upper lobe bronchus by a minimally invasive transbronchial approach. This case was initially planned for a sleeve left upper lobectomy. The careful assessment of radiological and ultrasonographic imaging concluded that the tumor was early-stage lung cancer. Multimodal endobronchial treatment cured the lung cancer without a thoracotomy. Pulmonary function was well preserved and no recurrence was found for more than 5 years. Even in the presence of a bulky endobronchial tumor, if there is no clear evidence of extraluminal invasion by computed tomography scan, a local bronchoscopic staging of the disease is mandatory.

Pleuroperitoneal shunt for refractory chylothorax accompanied with a mediastinal lymphangioma: a case report.

A 21-month-old Japanese boy was admitted with cough and hypoxemia. Chest X-ray showed massive right pleural effusion, which consisted of chyle. Computed tomography showed poor contrast area at superior and anterior mediastinum. Magnetic resonance imaging showed granular T2-low area at the same area. Lymphangioscintigraphy revealed a hot spot at superior mediastinum. These findings lead us to diagnose as mediastinal lymphangioma accompanied with chylothorax. Noninvasive treatments including total parenteral nutrition, administration of octreotide and sclerotherapy were tried, but all of them proved to be ineffective. Transfusions of blood products were frequently needed during these therapies. On the 48th hospital day, the mediastinal tumor and the thymus were excised through a median sternotomy. A leakage point of lymph into the intrathoracic space was not found, in spite of preoperative administration of milk with dye. Since the pleural effusion had continued to be drained, pleuroperitoneal shunt was placed on the 90th hospital day. The shunting amount continued to decline soon after the shunting, and had been under 10 ml/day since the 142nd day. The shunt was removed on the 148th day. There has been no reaccumulation of the pleural effusion and no recurrence of the mediastinal tumor for 1 year of observation.

Video-assisted thoracoscopic surgery extended thymectomy for myasthenia gravis using manual manipulators: the radius surgical system.

A 32-year-old woman with ocular-typed myasthenia gravis (MG) without thymoma was admitted to the hospital to undergo surgical treatment. Video-assisted thoracoscopic surgery (VATS) extended thymectomy was successfully performed with three small ports using manual manipulators, the Radius Surgical System (RSS). The device may facilitate many degrees of freedom to general thoracic surgery.

Pleomorphic carcinoma of the lung producing granulocyte colony-stimulating factor: report of a case.

We herein report a case of acute respiratory distress syndrome (ARDS) that appeared to be related to a granulocyte colony-stimulating factor (G-CSF)-producing lung cancer. A 77-year-old man with arterial sclerotic obstruction (ASO) underwent reconstructive surgery of the left femoral artery. He developed ARDS on the 5th postoperative day, which resolved following mechanical ventilation with steroid pulse treatment. Four months later, he was admitted with a fever and right arm pain. Chest computed tomography showed a malignant lesion in the right apical lung, and percutaneous needle biopsy demonstrated adenocarcinoma. Laboratory data revealed neutrophilia with elevated serum G-CSF levels. He underwent a right upper lobectomy with chest wall resection, and administration of sivelestat sodium to treat his postoperative pre-acute lung injury state. Pathology revealed a G-CSF-producing pleomorphic carcinoma. Retrospectively, a tumor shadow was noted on chest X-ray at the time of ARDS just after ASO surgery. The relationship between an abnormal G-CSF level and ARDS was considered, and the implications are herein discussed.

Risk of acute exacerbation of interstitial pneumonia after pulmonary resection for lung cancer in patients with idiopathic pulmonary fibrosis based on preoperative high-resolution computed tomography.

PURPOSE: In patients with lung cancer accompanied by idiopathic pulmonary fibrosis (IPF), acute exacerbation of the IPF often occurs after pulmonary resection; however, few studies have been done to identify its preexisting risk factors. METHODS: We analyzed the high-resolution computed tomography (HRCT) findings of IPF to identify the radiological characteristics of IPF susceptible to acute exacerbation after lung cancer surgery. We reviewed retrospectively 28 lung cancer patients with IPF who underwent pulmonary resection. Clinical data, respiratory function, HRCT findings, and historical features were compared between the acute exacerbation (n = 9) and nonexacerbation (n = 19) groups. The classification of radiological findings of IPF on HRCT was done using a scoring system of seven factors related to the interstitial shadow, including fibrosis, ground-glass opacity, and low-attenuation area. RESULTS: There were no significant differences in clinical background, respiratory function, composite physiologic index, or pathological features between the groups; however, the degree of fibrosis on preoperative HRCT was significantly higher in the exacerbation group (P < 0.003). The fibrosis score was higher on the opposite side to the lung cancer in the exacerbation group (P < 0.05). CONCLUSION: Although it is difficult to predict postoperative acute IPF exacerbation, the degree and laterality of co-existing fibrosis seem to be predictors.

Progress toward optical biopsy: bringing the microscope to the patient.

The investigation of many lung diseases currently requires bronchoscopic or surgical histopathological tissue biopsy. This creates risks for patients and entails processing costs and delays in diagnosis. However, several mainly probe-based biophotonic techniques that can image solitary lesions and diffuse lung diseases are fuelling a paradigm shift toward real-time in vivo diagnosis. Optical coherence tomography (OCT) uses near-infrared light in a process analogous to ultrasonography to image the mucosal and submucosal tissue boundaries of the bronchial tree. With 15-µm resolution, early work suggests it can differentiate between neoplasia, carcinoma in situ, dysplasia, and metaplasia based around epithelial thickness and breaches in the basement membrane. Probe-based confocal laser endomicroscopy (pCLE) has superior resolution but less penetration than OCT and employs blue argon laser light to fluoresce the endogenous elastin of (1) the acinar scaffold of the peripheral lung and (2) the basement membrane lying under bronchial mucosa. Initial studies suggest that the regular fibre arrangement of the basement membrane is altered in the presence of overlying malignant epithelium. pCLE produces detailed representations of the alveolar septal walls, microvessels, and some inflammatory cells. A third device, the endocytoscope, is a contact microscope requiring contrast agent to provide subcellular resolution of bronchial mucosa. Further development of these "optical biopsy" techniques and evaluation of diagnostic sensitivity and specificity of the acquired images are needed before they can be considered effective methods for eliminating the need for, and thus risks of, pinch biopsy to enable real-time diagnosis to streamline management.

In vivo microscopic imaging of the bronchial mucosa using an endo-cytoscopy system.

OBJECTIVES: We investigated the capabilities of an endo-cytoscopy system (ECS) that enables microscopic imaging of the tracheobronchial tree during bronchoscopy, including normal bronchial epithelium, dysplastic mucosa and squamous cell carcinoma. METHODS: The newly developed ECS has a 3.2 mm diameter that can be passed through the 4.2 mm working channel of a mother endoscope for insertion of the ECS. It has a high magnification of 570× on a 17 in. video monitor. Twenty-two patients (7 squamous cell carcinoma, 11 squamous dysplasia and 4 after PDT therapies) were underwent white light, NBI light and AFI bronchoscopy. Both abnormal areas of interest and normal bronchial mucosa were stained with 0.5% methylene blue and examined with ECS at high magnification (570×). Histological examinations using haematoxylin and eosin staining were made of biopsied specimens. Analyzed ECS images were compared with the corresponding histological examinations. RESULTS: In normal bronchial mucosa, ciliated columnar epithelial cells were visible. In bronchial squamous dysplasia, superficial cells with abundant cytoplasm were arranged regularly. In squamous cell carcinoma, large, polymorphic tumor cells showed increased cellular densities with irregular stratified patterns. These ECS images corresponded well with the light-microscopic examination of conventional histology. CONCLUSION: ECS was useful for the discrimination between normal bronchial epithelial cells and dysplastic cells or malignant cells during bronchoscopy in real time. This novel technology has an excellent potential to provide in vivo diagnosis during bronchoscopic examinations.

Risk of lung cancer in patients with preinvasive bronchial lesions followed by autofluorescence bronchoscopy and chest computed tomography.

OBJECTIVES: To assess risk of lung cancer (LC) in patients with preinvasive bronchial lesions and to identify factors associated with higher risk. METHODS: 124 patients with one or more preinvasive bronchial lesions and normal chest computed tomography (CT) (mean age 66.7 years, 121 males and 3 females), followed-up by white light and autofluorescence bronchoscopy (AFB) every 4-6 mo and chest CT every 6-12 mo, end points were development of carcinoma in situ (CIS) or LC. RESULTS: Among 124 patients with 240 preinvasive bronchial lesions, 20 CIS or LC lesions were detected during follow-up in 20 (16%) patients, 7 were detected as new endobronchial lesions, 10 as new peripheral lesions and 3 as local progression from severe dysplasia to CIS. Median time to progression from the same site or development of CIS/LC elsewhere was 24 months (range: 6-54 mo). The Cumulative risk of development of CIS/LC was 7% at one year, 20% at three years and 44% at 5 years. Among detected lung cancers, 80% were stage 0 or stage I and underwent treatment with curative intent. Diagnosis of new SD during follow-up (p=0.0001), chronic obstructive pulmonary disease (COPD) (p=0.001) or smoking index >52 pack-year (p=0.042) was associated with higher risk. Even after controlling for other risk factors, COPD was associated with risk for lung cancer. Baseline lesion grade was not predictive of patient outcome (p=0.146). CONCLUSION: Patients with preinvasive bronchial lesions, especially those with new SD during follow-up, COPD or smoking >52 pack-year are at high risk of LC, AFB and CT follow-up facilitated early detection and treatment with curative intent.