Investigating the effect of prescribing status and patient characteristics on the therapeutic outcomes in patients with diabetes using a leftover drug adjustment protocol.

Treatment for diabetes includes anti-diabetic medication in addition to lifestyle improvements through diet and exercise. In Japan, protocol-based pharmacotherapy management allows drug treatment to be provided through cooperation between physicians and pharmacists, based on a protocol that is prepared and agreed upon in advance. However, there are no studies to clarify the relationship between patient characteristics and therapeutic effects after pharmacist intervention in protocol-based pharmacotherapy management for patients with diabetes. Therefore, this study aimed to use protocol-based reports from pharmacies to understand the status of outpatient diabetes medication compliance. We classified patients with diabetes on the basis of patient characteristics that can be collected in pharmacies and investigated the characteristics that impacted diabetes treatment. Patients were prescribed oral anti-diabetic drugs at outpatient clinics of Hitachinaka General Hospital, Hitachi, Ltd., from April 2016 to March 2021. Survey items included patient characteristics (sex, age, number of drugs used, observed number of years of anti-diabetic drug prescription, number of anti-diabetic drug prescription days, and presence or absence of leftover anti-diabetic drugs) and HbA1c levels. Graphical analyses indicated the relationship between each categorised patient characteristic using multiple correspondence analyses. Subsequently, the patients were clustered using K-means cluster analysis based on the coordinates obtained for each patient. Patient characteristics and HbA1c values were compared between the groups for each cluster. A total of 1,910 patients were included and classified into three clusters, with clusters 1, 2, and 3 containing 625, 703, and 582 patients, respectively. Patient characteristics strongly associated with Cluster 1 were ages between 65 and 74 years, use of three or more anti-diabetic drugs, use of 3 years or more of anti-diabetic drugs, and leftover anti-diabetic drugs. Furthermore, Cluster 1 had the highest number of patients with worsening HbA1c levels compared with other clusters. Using the leftover drug adjustment protocol, we clarified the patient characteristics that affected the treatment course. We anticipate that through targeted interventions in patients exhibiting these characteristics, we can identify those who are irresponsibly continuing with drug treatment, are not responding well to therapy, or both. This could substantially improve the efficacy of their anti-diabetic care.

Anticholinergic Load Is Associated with Swallowing Dysfunction in Convalescent Older Patients after a Stroke.

This study aimed to establish whether anticholinergic load affects the swallowing function of geriatric stroke patients in convalescent stages, as no proven association between the anticholinergic load-based Anticholinergic Risk Scale and the swallowing dysfunction in Japanese patients was known. A retrospective cohort study was conducted on hospitalized older patients undergoing rehabilitation after stroke. The study outcomes included evaluating the patients at hospital discharge using the Functional Oral Intake Scale. To evaluate the effects of an increased anticholinergic load, we used a multivariate analysis to examine whether the change in the Anticholinergic Risk Scale during hospitalization was associated with the outcome. Of 542 enrolled patients, 345 (63.7%) presented with cerebral infarction, 148 (27.3%) with intracerebral hemorrhage, and 49 (9%) with subarachnoid hemorrhage. The change in the Anticholinergic Risk Scale was independently associated with the Functional Oral Intake Scale (ß = -0.118, p = 0.0164) at discharge. Among anticholinergics, the use of chlorpromazine, hydroxyzine, haloperidol, metoclopramide, risperidone, etc., increased significantly from admission to discharge. An increased anticholinergic load was associated with swallowing dysfunction in older patients undergoing stroke rehabilitation.

Report on investigation of ISO 10993-12 extraction conditions.

The international standard ISO 10993-12 describes extraction conditions for generating extracts of medical devices to be used in testing of biological safety. Questions about the adequacy of the extraction conditions (and their variations) for hazard identification drove the development and execution of a round robin study. Four relevant device materials were each evaluated by four laboratories following an established protocol that specified multiple options of extraction solvent, temperature, duration, and ratio of solvent volume to quantity of test article. The resulting samples were analysed by three instrumental methods to identify and quantify extracted organic and elemental substances; however, quantification was not achieved due to lab resource constraints, and only numbers of compounds were reported. Results showed an increased number of volatile organic compounds extracted with organic solvents; however, no clear effect of varying the other extraction parameters could be discerned. Quantification of a small subset of analytes showed sensitivity that may be adequate for hazard identification. An unplanned post hoc comparison of results across labs showed differing numbers of compounds detected; however, fundamental differences in sample preparation and specific analysis methods as well as lack of quantification render the results poorly suited to either exonerate or indict the adequacy of chemical characterization as practiced by the participating laboratories.

The impact of decreasing potentially inappropriate medications on activities of daily living in a convalescent rehabilitation setting.

Background Polypharmacy or potentially inappropriate medications negatively affect the functional recovery of rehabilitation. However, limited research exists regarding the effect of decreasing in potentially inappropriate medications use on functional improvement of rehabilitation in geriatric Japanese patients. Objective To elucidate whether decreasing PIM during hospitalization could be a predictor of rehabilitation outcomes among geriatric patients in a convalescent rehabilitation setting. Setting This study was conducted at the convalescent rehabilitation ward in the Hitachinaka General Hospital in Japan. Methods This retrospective observational cohort study included consecutive geriatric patients admitted at the convalescent rehabilitation ward between 2010 and 2018. Participants were divided based on presence or absence of decreasing in potentially inappropriate medications use during hospitalization. A multiple linear regression analysis was performed to analyze whether decreasing potentially inappropriate medications use during hospitalization could be a predictor of Functional Independence Measure-Motor at discharge. Main outcome measures The primary outcome was the Functional Independence Measure-Motor at discharge. Results In total, 569 participants (interquartile range 73-85 years; 33.6% men) were included in the present study. A multiple linear regression analysis of Functional Independence Measure-Motor at discharge, adjusting for confounding factors, revealed that decreasing in potentially inappropriate medications use was independently correlated with Functional Independence Measure-Motor at discharge. In particular, the use of first-generation antihistamines, antipsychotics, benzodiazepines, and non-steroidal anti-inflammatory drugs among potentially inappropriate medications decreased significantly during hospitalization. Conclusion Decreased potentially inappropriate medications use during hospitalization may be a predictor of improvement of rehabilitation outcomes in geriatric patients.

Change in number of potentially inappropriate medications impacts on the nutritional status in a convalescent rehabilitation setting.

AIM: The association between potentially inappropriate medications (PIM) use and nutritional status is unclear in Japan. The aim of the present study was to establish whether PIM use during hospitalization affects the nutritional status among geriatric patients in the convalescing stage. METHODS: This retrospective longitudinal cohort study included consecutive geriatric patients admitted and discharged from convalescent rehabilitation wards between 2010 and 2016. Participants were divided based on the presence or absence of increased PIM from admission to discharge. Demographic data, laboratory data and the Functional Independence Measure were analyzed between groups. We used the 2015 American Geriatrics Society Beers Criteria to screen for PIM, and the primary outcome was the Geriatric Nutritional Risk Index at discharge. A multiple linear regression analysis was used to examine whether Geriatric Nutritional Risk Index at discharge was independently associated with increased PIM. RESULTS: In total, 643 participants (220 men, 423 women; interquartile range 73-85 years) were included in the present study. Multiple linear regression analysis for increased PIM, adjusting for confounding factors, showed that PIM use was independently and negatively correlated with Geriatric Nutritional Risk Index at discharge. In particular, first-generation antihistamine, antipsychotic, benzodiazepine, proton pump inhibitor and non-steroidal anti- inflammatory drug use increased significantly from admission to discharge. CONCLUSIONS: Increased PIM might be a predictor of nutritional status in geriatric patients. Geriatr Gerontol Int 2019; 19: 44-50.

Psychotropic drug use and cognitive rehabilitation practice for elderly patients.

Background Psychotropic drugs were associated with greater risks of adverse drug reactions, including lower the level of consciousness, cause cognitive dysfunction, relax muscles, cause hypotension and others. However, the effect of psychotropic drug use on rehabilitation outcomes is poorly documented in Japan. Objective To assess the association of increased psychotropic drugs during hospitalization with activities of daily living among elderly patients. Setting This study was conducted at the convalescent rehabilitation ward in the Hitachinaka General Hospital in Japan. Method This retrospective longitudinal cohort study included consecutive patients aged ≥ 65 years between 2010 and 2016. Participants were divided based on presence or absence of increased psychotropic drugs including benzodiazepines, antidepressants, antipsychotics, and antiepileptic drugs during hospitalization. Functional recovery was assessed by the Functional Independence Measure (FIM). Multivariate analyses were performed, adjusting for confounding factors. Main outcome measures Cognitive gain in the Functional Independence Measure. Results We included 631 participants (227 males, 404 females) with a median age of 78 years (interquartile range 73-84 years). Multiple regression analysis revealed that change in psychotropic drug use, cognitive FIM at admission, and age were independently and negatively correlated with cognitive FIM gain. Multiple logistic regression analysis indicated that the "Comprehension" and "Memory" items of the cognitive FIM gain were independently and negatively associated with increased psychotropic drug use. Conclusion Increased psychotropic drug use during hospitalization may predict limited the improvement of cognitive activities of daily living in geriatric patients.

Anticholinergic drugs use and risk of hip fracture in geriatric patients.

AIM: Limited research exists regarding the effect of anticholinergic drugs on fracture in geriatric Japanese patients. The aim of the present study was to establish whether anticholinergic load affects hip fracture and to clarify the risk based on the Anticholinergic Risk Scale score among geriatric patients in a convalescent rehabilitation setting. METHODS: The present nested case-control study included consecutive geriatric patients admitted and discharged from the convalescent rehabilitation ward between 2010 and 2016. Participants were divided based on the presence or absence of hip fracture during hospitalization. Demographic data, laboratory data and the Functional Independence Measure were analyzed between groups. The primary outcome was the presence of hip fracture. Multiple logistic regression analysis was carried out to analyze the relationship between anticholinergic drug use and hip fracture. RESULTS: In total, 601 participants (210 men, 391 women; interquartile range 73-85 years) were included in the present study. Multiple logistic regression analysis of hip fracture, adjusting for confounding factors, showed that anticholinergic drug use was independently and positively correlated with hip fracture. In particular, an increase in the Anticholinergic Risk Scale score by 2 points correlates with a 2.86-fold greater risk for hip fracture, and an increase of ≥3 points results in a 4.21-fold greater risk, both being statistically significant results. CONCLUSION: Increased anticholinergic load during hospitalization might be a predictor of increased hip fracture in geriatric patients. Geriatr Gerontol Int 2018; 18: 1340-1344.

Assessment of aspiration pneumonia using the Anticholinergic Risk Scale.

AIM: The association between anticholinergic drug use and aspiration pneumonia (AP) based on the Anticholinergic Risk Scale (ARS) or clinical study reports on AP risks using the ARS are unclear in Japan. The aim of the present study was to establish whether anticholinergic load affects AP, and to clarify the risk based on the ARS score among geriatric patients in the convalescing stage. METHODS: This retrospective longitudinal cohort study included consecutive geriatric patients admitted and discharged from convalescent rehabilitation wards between 2010 and 2016. Participants were divided based on the presence or absence of an increased anticholinergic load from admission to discharge. Demographic data, laboratory data and the Functional Independence Measure were analyzed between groups. The primary outcome was the presence of AP. Multiple logistic regression analysis was carried out to analyze the relationship between anticholinergic drug use and AP. RESULTS: In total, 618 participants (220 men, 398 women; interquartile range 73-84 years) were included in the present study. Multiple logistic regression analysis of AP, adjusting for confounding factors, showed that anticholinergic drug use was independently and positively correlated with AP. In particular, an increase in ARS score by 2 points correlates with a 1.92-fold greater risk for AP, and an increase of ≥3 points results in a 3.25-fold greater risk, both being statistically significant results. CONCLUSION: Increased anticholinergic load during hospitalization might be a predictor of increased AP in geriatric patients. Geriatr Gerontol Int 2018; 18: 1230-1235.

The association of increased drugs use with activities of daily living and discharge outcome among elderly stroke patients.

Background Few systematic studies have evaluated the association between drugs and functional recovery for geriatric patients after strokes in the convalescent stage. Objective To assess the association of increased drugs during hospitalization with activities of daily living and outcome among geriatric stroke patients. Setting This study was conducted at the convalescent rehabilitation ward in the Hitachinaka General Hospital in Japan. Methods This retrospective cohort study included consecutive patients aged ≥ 65 years who had experienced stroke between 2010 and 2016. The participants were classified into two groups according to their discharge destination: home discharge group and non-home discharge group. Multiple linear regression analysis and multiple logistic regression analysis were used to examine the association of increased drugs with FIM gain and home discharge, respectively. MAIN OUTCOME MEASURES: The main outcome measures were Functional Independence Measure (FIM) gain and home discharge. Results In total, 417 participants (165 males and 252 females; mean age, 78.8 years) were assessed and classified into home discharge (n = 226) and non-home discharge (n = 191) groups. The median FIM score was 77 (interquartile range 57-96). Multiple linear regression analysis revealed that increased use of drugs during hospitalization negatively correlated with FIM gain. Multiple logistic regression analysis showed that increased use of drugs was independently associated with a low possibility of home discharge. Conclusion The increased use of drugs during hospitalization was negatively associated with both functional recovery and possibility of home discharge among geriatric stroke patients in a convalescent rehabilitation ward.

Clinical factors affecting potentially inappropriate medications at discharge in older stroke patients.

INTRODUCTION: Factors for increased in potentially inappropriate medications (PIMs) are poorly documented in a rehabilitation setting. The goal of this study is to identify clinical factors that are strongly associated with increased PIMs in stroke patients. METHODS: This retrospective cohort study included consecutive geriatric stroke patients in convalescent rehabilitation wards between 2010 and 2016. We investigated functional independence measure (FIM) and the characteristics of patients with and without PIMs at discharge. We used the 2015 American Geriatrics Society Beers Criteria to screen for PIMs. Multiple linear regression analysis was performed to analyze the relationship between PIM use and functional recovery. RESULTS: In total, 418 participants (171 males, 247 females; median age 78 years; interquartile range 72-84 years) were included in the present study. Multiple linear regression analysis of PIMs use at discharge adjusting for potential confounders showed that gender, cardiac disease, diabetes mellitus, number of drugs at discharge, FIM-cognitive gain, and age are independent factors associated with PIMs prescribed at discharge (R2 = 0.384; p < 0.0001). CONCLUSION: Potentially inappropriate medications use at discharge is negatively correlated with cognitive recovery of activities of daily living. This suggests that PIMs increase might have caused cognitive deterioration.

Role of potentially inappropriate medication use in rehabilitation outcomes for geriatric patients after strokes.

AIM: The effect of the use of potentially inappropriate medications (PIM) on mortality and functional outcome after strokes is unclear in Japan. The aim of the present study was to establish whether treatment with PIM affects functional improvements among geriatric patients convalescing after strokes. METHODS: This retrospective longitudinal study included consecutive geriatric patients admitted and discharged from convalescent rehabilitation wards for stroke between 2010 and 2016. Demographic data, laboratory data and the Functional Independence Measure (FIM) were analyzed. We used the 2015 American Geriatrics Society Beers Criteria to screen for PIM, and the primary outcome was motor FIM gain. Multivariate regression analysis was carried out to analyze the relationship between PIM use and functional recovery. RESULTS: In total, 272 participants (102 men, 170 women; median age 79 years, interquartile range 72-85 years) were included in the present study. Multivariate regression analysis of motor FIM gain, adjusting for confounding factors, showed that PIM use was independently and negatively correlated with motor FIM gain. In particular, anticholinergic drugs (such as antipsychotics, antidepressants and first-generation antihistamines) were significantly increased from admission to discharge. CONCLUSION: Increased PIM use during hospitalization might be a predictor of reduced functional improvement in geriatric patients after strokes. Geriatr Gerontol Int 2018; 18: 321-328.

Anti-centromere antibody is an independent risk factor for chronic kidney disease in patients with primary biliary cirrhosis.

BACKGROUND: Anti-centromere antibody (ACA), a typical autoantibody of systemic sclerosis, is also detected in primary biliary cirrhosis (PBC). However, its pathogenic role is not fully understood. The aim of this study was to determine the association between ACA and kidney function in PBC. METHODS: A cohort of 37 patients diagnosed as having PBC from July 2001 to November 2011 at Yokosuka Kyosai Hospital was retrospectively analyzed for a follow-up period of 12 months. The annual rate of estimated glomerular filtration rate (eGFR) decline within 1 year after the diagnosis was evaluated. The factors associated with eGFR decline were evaluated by linear regression analysis and logistic regression analysis. RESULTS: Overall, 37 PBC patients were included, of whom 12 (32%) had ACA. The patients with ACA had a lower eGFR (65.9 ± 19.9 vs. 80.3 ± 12.1 mL/min/1.73 m(2), P = 0.01), a higher likelihood of chronic kidney disease (CKD) (58 vs. 4%, P = 0.0005), and a higher rate of annual eGFR decline (-4.3 ± 5.1 vs. 0.2 ± 4.6 mL/min/year, P = 0.01) than those without ACA. Univariate regression analysis and multivariate regression analysis adjusted for potential cofounders including age, eGFR, sex, diabetes mellitus, and hypertension showed that ACA was associated with eGFR decline (P = 0.011 and 0.017, respectively). Multivariate logistic regression analysis adjusted for these cofounders showed that ACA was associated with eGFR decline less than -4 mL/min/year (odds ratio 7.21, 95% confidence interval 0.93-56.1, P = 0.059). CONCLUSIONS: ACA is an independent risk factor for CKD in PBC. Evaluation of ACA and kidney function is necessary to prevent CKD progression in PBC patients.

Estimated glomerular filtration rate -a more stable indicator than creatinine clearance in peritoneal dialysis practice.

OBJECTIVE: The usefulness of estimated glomerular filtration rate may not be restricted to pre-dialysis patients, since we reported that estimated glomerular filtration rate was well correlated with measured total creatinine clearance in peritoneal dialysis patients. To clarify the clinical usefulness of estimated glomerular filtration rate as a parameter for peritoneal dialysis adequacy, we retrospectively surveyed estimated glomerular filtration rate and total creatinine clearance in peritoneal dialysis patients treated at JA Toride Medical Center. PATIENTS AND METHODS: A total of 114 data sets of estimated glomerular filtration rate and total creatinine clearance from 21 PD patients treated at JA Toride Medical Center were collected from November 2010 to October 2011. The patients consisted of 15 men and six women with an average age of 66.6 ± 12.6 years (46-95 years old). The average number of samples was 5.4 ± 1.5 (2 to 7) per patient. RESULTS: The collected data showed less correlation of estimated glomerular filtration rate and total creatinine clearance (r. = 0.435) than that of a previous cross-sectional study (r. = 0.836). As reported in pre-dialysis patients, the differences between estimated glomerular filtration rate and total creatinine clearance were correlated with total creatinine excretion in urine and PD effluent (r. = 0.821). The differences were also correlated with normalized protein catabolic rate, which was one of the main determinant factors for total creatinine excretion (r. = 0.636). A similar tendency was apparently observed in one patient with poor compliance to diet therapy and fluctuating dietary intake. From the analysis of these data, serum creatinine seemed to fluctuate less possibly due to compensatory capacity of the residual renal function in small solute clearance. CONCLUSIONS: Consequently, estimated glomerular filtration rate was turned out to be a more stable parameter than total creatinine clearance, which might be a desirable feature in long-term follow-up of peritoneal dialysis patients.

Vascular responses to a biodegradable polymer (polylactic acid) based biolimus A9-eluting stent in porcine models.

AIMS: The time-dependent changes in endothelial and healing properties of coronary arteries implanted with a biodegradable polymer-based biolimus A9-eluting stent (BioPol-BES) have not been investigated. We evaluated the short-term and the long-term in vivo response of BioPol-BES, as compared to a permanent polymer-based sirolimus-eluting stent (PermPol-SES), and a bare metal stent (BMS). METHODS AND RESULTS: Overlapping stents were placed in 33 swine (n=11 for BES, SES, and BMS, respectively) for two and four weeks and single stents in 30 miniature pigs (n=18 for BES, n=9 for SES, n=3 for BMS) for three, nine and 15-month evaluations. The vessel patency, arterial healing and endothelialisation were assessed by angiography, histopathology and scanning electron microscopy. At four weeks, the endothelialisation at overlapping stent regions was greater with BioPol-BES (87.8±3.7%) and BMSs (98.0±0.4%) than with PermPol-SES (66.4±3.2%). The inflammation score in vessels implanted with single BioPol-BES increased slightly from three to 15 months (0.00±0.00 to 0.28±0.14), while this increase was more pronounced with PermPol-SES (0.11±0.07 to 1.56±0.68). Compared to BMS moderate lymphocyte infiltration was seen with BioPol-BES, and marked granulomatous formation with PermPol-SES. CONCLUSIONS: The level of endothelial coverage in BioPol-BES was comparable to BMS at four weeks, with no significant increase of inflammatory reaction up to 15 months.

Anti-centromere antibody-positive subjects presenting with hypertensive emergency and renal dysfunction in the absence of skin manifestations: a variant of systemic sclerosis or a novel entity?

Two patients with anti-centromere antibody (ACA), hypertensive emergency, and acute renal failure, mimicking scleroderma renal crisis, without Raynaud's phenomenon and typical skin manifestations of systemic sclerosis (SSc), are reported. A review of 26 ACA-positive patients between March 2003 and March 2011 in Yokosuka Kyosai Hospital identified four additional patients with similar manifestations. All patients were Japanese women between 41 and 84 years of age at presentation. Human leukocyte antigen (HLA) genotyping tests revealed the absence of the HLA-DQB1*0501 and DRB1*0101 alleles, which are associated with disease susceptibility to ACA-positive SSc among Japanese. These subjects' manifestations may represent a novel entity.

Recovery of renal function in a dialysis-dependent patient with microscopic polyangiitis and both myeloperoxidase anti-neutrophil cytoplasmic antibodies and anti-glomerular basement membrane antibodies.

A 40-year-old man with microscopic polyangiitis developed both myeloperoxidase anti-neutrophil cytoplasmic antibodies (90 EU) and anti-glomerular basement membrane antibodies (134 EU)-positive rapidly progressive glomerulonephritis and heparin-induced thrombocytopenia. Although the patient initially showed no signs of improvement, persistent therapy including 1 g/day intravenous methylprednisolone, 50 mg/day oral prednisolone, plasma exchange, and 900 mg/day intravenous cyclophosphamide resulted in the normalization of both titers, recovery of renal function, and discontinuation of dialysis. Though previous studies showed poor outcomes in such "double-positive" patients, aggressive immunosuppression in younger patients may result in the recovery of renal function, even in those with severe renal dysfunction.

Fluoride complexation of element 104, rutherfordium.

Fluoride complexation of element 104, rutherfordium (Rf), produced in the 248Cm(18O,5n)261Rf reaction has been studied by anion-exchange chromatography on an atom-at-a-time scale. The anion-exchange chromatographic behavior of Rf was investigated in 1.9-13.9 M hydrofluoric acid together with those of the group-4 elements Zr and Hf produced in the 18O-induced reactions on Ge and Gd targets, respectively. It was found that the adsorption behavior of Rf on anion-exchange resin is quite different from those of Zr and Hf, suggesting the influence of relativistic effects on the fluoride complexation of Rf.

Upper thoracic spinal cord injury without vertebral bony lesion: a report of two cases.

STUDY DESIGN: Case report. OBJECTIVES: To describe a rarely reported type of upper thoracic spinal cord injury without vertebral bony lesion in two cases with multiple trauma. SUMMARY OF BACKGROUND DATA: Because it is supported by the stiffness of the rib cage, the upper thoracic spine has greater stability than the cervical and lumbar regions, and thus its fracture or fracture dislocation is less frequent. Nevertheless, when fracture or fracture dislocation of upper thoracic spine occurs, spinal cord involvement and severe concomitant injuries are frequently associated. METHODS: Two cases who were suspected to have thoracic spinal cord injuries were referred to our emergency center: a 19-year-old girl presented with paraparesis after her motorcycle collided with a truck, and a 63-year-old male involved in an industrial accident presented with paraplegia. RESULTS: Radiograph and computed tomography scan showed no abnormality or dislocation in the vertebral bodies in these two cases, although the upper thoracic spinal cord injuries were suspected by clinical features. Magnetic resonance images detected abnormal signals, suggesting spinal cord injuries, and these signals each emanated from levels that coincided with the observed clinical features. CONCLUSIONS: Transient subluxation or displacement might have caused the upper thoracic spinal cord injuries after the support of the rib cages was temporarily lost on application of excessive force, although such findings could not be confirmed by imaging procedures.