Prevalence and Preventability of Adverse Medicine Events in a Sample of Australian Aged-Care Residents: A Secondary Analysis of Data from the ReMInDAR Trial.

BACKGROUND: Aged care residents are vulnerable to the harmful effects of medicines; however, data on the prevalence and preventability of adverse medicine events in aged care residents are scarce. AIM: To determine the prevalence and preventability of adverse medicine events in Australian aged care residents. METHODS: A secondary analysis of data from the Reducing Medicine-Induced Deterioration and Adverse Reactions (ReMInDAR) trial was conducted. Potential adverse medicine events were identified and independently screened by two research pharmacists to produce a short-list of potential adverse medicine events. An expert clinical panel reviewed each potential adverse medicine to determine the likelihood that the event was medicine related (based on the Naranjo Probability Scale criteria). The clinical panel assessed preventability of medicine-related events using Schumock-Thornton criteria. RESULTS: There were 583 adverse events due to medicines, involving 154 residents (62% of the 248 study participants). There was a median of three medication-related adverse events (interquartile range [IQR] 1-5) per resident over the 12-month follow-up period. The most common medication-related adverse events were falls (56%), bleeding (18%) and bruising (9%). There were 482 (83%) medication-related adverse events that were preventable, most commonly falls (66% of preventable adverse medicine events), bleeding (12%) and dizziness (8%). Of the 248 residents, 133 (54% of the cohort) had at least one preventable adverse medicine event, with a median of 2 (IQR 1-4) preventable adverse medicine events per resident. CONCLUSION: In total, 62% of aged care residents in our study had an adverse medicine event and 54% had a preventable adverse medicine event in a 12-month period.

Preventing Adverse Drug Reactions After Hospital Discharge (PADR-AD): Protocol for a randomised-controlled trial in older people.

BACKGROUND: Adverse drug reactions (ADRs) and adverse drug events (ADEs) in older people contribute to a significant proportion of hospital admissions and are common following discharge. Effective interventions are therefore required to combat the growing burden of preventable ADRs. The Prediction of Hospitalisation due to Adverse Drug Reactions in Elderly Community Dwelling Patients (PADR-EC) score is a validated risk score developed to assess the risk of ADRs in people aged 65 years and older and has the potential to be utilised as part of an intervention to reduce ADRs. OBJECTIVES: This trial was designed to investigate the effectiveness of an intervention to reduce ADR incidence in older people and to obtain further information about ADRs and ADEs in the 12-24 months following hospital discharge. METHODS: The study is an open-label randomised-controlled trial to be conducted at the Royal Hobart Hospital, a 500-bed public hospital in Tasmania, Australia. Community-dwelling patients aged 65 years and older with an unplanned overnight admission to a general medical ward will be recruited. Following admission, the PADR-EC ADR score will be calculated by a research pharmacist, with the risk communicated to clinicians and discussed with participants. Following discharge, nominated general practitioners and community pharmacists will receive the risk score and related medication management advice to guide their ongoing care of the patient. Follow-up with participants will occur at 3 and 12 and 18 and 24 months to identify ADRs and ADEs. The primary outcome is moderate-severe ADRs at 12 months post-discharge, and will be analysed using the cumulative incidence proportion, survival analysis and Poisson regression. SUMMARY: It is hypothesised that the trial will reduce ADRs and ADEs in the intervention population. The study will also provide valuable data on post-discharge ADRs and ADEs up to 24 months post-discharge.

Lasting changes to circulating leukocytes in people with mild SARS-CoV-2 infections

Survivors of severe SARS-CoV-2 infections frequently suffer from a range of post-infection sequelae. Whether survivors of mild or asymptomatic infections can expect any long-term health consequences is not yet known. Herein we investigated lasting changes to soluble inflammatory factors and cellular immune phenotype and function in individuals who had recovered from mild SARS-CoV-2 infections (n=22) compared to those that had recovered from other mild respiratory infections (n=11). Individuals who had mild SARS-CoV-2 infections had elevated levels of C-reactive protein 1-3 months after symptom onset, and changes in phenotype and function of circulating T cells that were not apparent in individuals 6-9 months post-symptom onset. Markers of monocyte activation and expression of adherence and chemokine receptors indicative of altered migratory capacity were also higher at 1-3 months post-infection in individuals who had mild SARS-CoV-2, but these were no longer elevated by 6-9 months post-infection. Perhaps most surprisingly, polyclonal activation of T cells was higher in individuals who had recently experienced a mild SARS-CoV-2 infection compared to individuals with other recent respiratory infections. These data are indicative of prolonged immune activation and systemic inflammation that persists for up to three months after mild or asymptomatic SARS-CoV-2 infections.

Medication Regimen Complexity Index Prediction of Adverse Drug Reaction-Related Hospital Admissions.

BACKGROUND: The relationship between the medication regimen complexity index (MRCI) and adverse drug reaction (ADR)-related hospital admissions has not yet specifically been investigated. OBJECTIVE: To evaluate the MRCI and compare with medication count for prediction of ADR-related hospital admissions in older patients. METHODS: This was a retrospective analysis of a prospectively collected convenience sample of 768 unplanned medical admissions of Australians aged 65 years old and older. The sample consisted of 115 (15.0%) ADR-related unplanned hospital admissions and 653 (85.0%) non-ADR-related unplanned medical admissions. The MRCI score was calculated from the medical records and analyzed to predict ADR-related hospital admissions. RESULTS: The cohort had a median age of 81 years, 5 comorbidities, and 11 medications, with a slight majority of women. The MRCI score was not significantly different in patients who had ADR-related admissions compared with other medical admissions-38.5 versus 34.0, respectively; Wilcoxon Rank Sum test W = 33 522; P = 0.067. The medication count was significantly different between the ADR-related admissions compared with other medical admissions: 12 versus 10; W = 32 508; P = 0.021. However, the medication count was not a strong predictor of ADR-related admissions; unadjusted odds ratio = 1.044; 95% CI = 1.006-1.084. CONCLUSION AND RELEVANCE: The MRCI score did not discriminate between ADR-related admissions and other medical admissions despite taking time to calculate with potential for inconsistent application. Medication count is more readily applicable with marginally greater relevance in this cohort; however, both measures do not appear to be useful when used alone for clinicians to identify patients at risk of ADRs.

Sputum Inflammometry to Manage Chronic Obstructive Pulmonary Disease Exacerbations: Beyond Guidelines / 결핵및호흡기질환

Quantitative sputum cytometry facilitates in assessing the nature of bronchitis associated with exacerbations of chronic obstructive pulmonary disease (COPD). This is not assessed in most clinical trials that evaluate the effectiveness of strategies to prevent or to treat exacerbations. While up to a quarter of exacerbations may be associated with raised eosinophil numbers, the vast majority of exacerbations are associated with neutrophilic bronchitis that may indicate airway infections. While eosinophilia may be a predictor of response to corticosteroids (oral and inhaled), the limited efficacy of anti–interleukin 5 therapies would suggest that eosinophils may not directly contribute to those exacerbations. However, they may contribute to airspace enlargement in patients with COPD through various mechanisms involving the interleukin 13 and matrix metalloprotease pathways. The absence of eosinophils may facilitate in limiting the unnecessary use of corticosteroids. The presence of neutrophiia could prompt an investigation for the specific pathogens in the airway. Additionally, sputum measurements may also provide insight into the mechanisms of susceptibility to airway infections. Iron within sputum macrophages, identified by hemosiderin staining (and by more direct quantification) may impair macrophage functions while the low levels of immunoglobulins in sputum may also contribute to airway infections. The assessment of sputum at the time of exacerbations thus would facilitate in customizing treatment and treat current exacerbations and reduce future risk of exacerbations.

Prospective identification versus administrative coding of adverse drug reaction-related hospitalizations in the elderly: A comparative analysis.

PURPOSE: To compare prospective identification of adverse drug reaction (ADR)-related hospital admissions in the elderly with administrative coding using the International Classification of Diseases 10th Revision Australian Modification (ICD-10-AM) coding system. METHODS: We linked the records of 768 enrolled patients from an earlier study, where clinical pharmacists identified ADRs using prospective data collection, to hospital administrative data. We identified patients in the study whose admissions were coded as ADRs using ICD-10-AM codes. We then compared the prevalence and characteristics of ADR-related hospital admissions identified by the two approaches. RESULTS: According to ICD-10-AM coding, 2.7% of patients were admitted due to ADRs, while 15.0% of patients were deemed to have been admitted due to ADRs based on prospective identification by clinical pharmacists. Most (85.7%) patients coded as having an ADR-related hospital admission were also identified as such prospectively. Hematological (23.1%) and metabolic reactions (23.1%) were frequent causes of ADRs identified by coding, whereas cardiovascular ADRs (27.8%) were more common causes of ADRs identified prospectively by pharmacists. Antidepressants (16.7%) and cardiac glycosides (16.7%) were the most commonly implicated drug groups in ADRs identified by coding, whereas diuretics (28.8%) and renin-angiotensin system inhibitors (17.0%) were frequently implicated as causes of ADRs identified prospectively by pharmacists. CONCLUSIONS: Reliance on administrative coding potentially underestimates the extent of the problem of ADRs as a cause of hospitalization in the elderly, and more detailed prospective analysis of admissions provides additional targets for strategies to prevent ADRs. The types of ADRs identified also differ between the two approaches.

Autoimmune Responses in Severe Asthma

Asthma and autoimmune diseases both result from a dysregulated immune system, and have been conventionally considered to have mutually exclusive pathogenesis. Autoimmunity is believed to be an exaggerated Th1 response, while asthma with a Th2 underpinning is congruent with the well-accepted Th1/Th2 paradigm. The hypothesis of autoimmune involvement in asthma has received much recent interest, particularly in the adult late-onset non-atopic patients (the “intrinsic asthma”). Over the past decades, circulating autoantibodies against diverse self-targets (beta-2-adrenergic receptors, epithelial antigens, nuclear antigens, etc.) have been reported and subsequently dismissed to be epiphenomena resulting from a chronic inflammatory condition, primarily due to lack of evidence of causality/pathomechanism. Recent evidence of ‘granulomas’ in the lung biopsies of severe asthmatics, detection of pathogenic sputum autoantibodies against autologous eosinophil proteins (e.g., eosinophil peroxidase) and inadequate response to monoclonal antibody therapies (e.g., subcutaneous mepolizumab) in patients with evidence of airway autoantibodies suggest that the role of autoimmune mechanisms be revisited. In this review, we have gathered available reports of autoimmune responses in the lungs, reviewed the evidence in the context of immunogenic tissue-response and danger-associated molecular patterns, and constructed the possibility of an autoimmune-associated pathomechanism that may contribute to the severity of asthma.

Repeat Adverse Drug Reaction-Related Hospital Admissions in Elderly Australians: A Retrospective Study at the Royal Hobart Hospital.

BACKGROUND: Adverse drug reactions are a major cause of hospital admissions in older individuals, with the majority potentially preventable. Despite the apparent magnitude of this problem, little is known about rates of repeat admission to hospital as a result of adverse drug reactions. OBJECTIVES: The objectives of this study were to investigate the occurrence of repeat adverse drug reaction-related hospital admissions in elderly patients within 12 months of an adverse drug reaction-related admission to a medical ward and whether a validated adverse drug reaction score could be useful in identifying patients at higher risk of a repeat adverse drug reaction-related hospitalisation. METHODS: This retrospective study followed elderly participants who were hospitalised with an adverse drug reaction from our earlier study [the PADR-EC (Prediction of Hospitalization due to Adverse Drug Reactions in Elderly Community-Dwelling Patients) study] to identify repeat adverse drug reaction-related hospital admissions within 12 months of discharge. The PADR-EC score is the sum of points assigned to five significant predictors of adverse drug reaction-related hospitalisation: antihypertensive use, renal failure, dementia, inappropriate anticholinergic use and drug changes in the preceding 3 months. The causality, preventability and severity of each adverse drug reaction-related repeat admission within the 12-month follow-up were assessed. RESULTS: Adverse drug reaction-related repeat admissions occurred after 13.4% (n = 15) of 112 adverse drug reaction-related index admissions. Patients with a repeat adverse drug reaction-related admission had significantly higher PADR-EC scores at discharge of their index admission (median PADR-EC score 7, interquartile range 7-9) than patients who were not readmitted (median PADR-EC score 7, interquartile range 5-7, p = 0.034). Most (73.3%) adverse drug reaction-related repeat admissions were considered 'preventable'. Adverse drug reaction severity was 'moderate' in all cases. Renal disorders (44.4%) represented the most common adverse drug reactions and the most frequently implicated drug classes were diuretics (44.8%). All adverse drug reaction-related repeat admissions were found to be 'probable'. CONCLUSIONS: One in eight elderly patients hospitalised because of an adverse drug reaction had a repeat admission for an adverse drug reaction within 12 months of discharge. The PADR-EC score could potentially be used at hospital discharge to prioritise patients for interventions to prevent subsequent adverse drug reaction-related hospital admissions.

Adverse Drug Reaction-Related Hospitalizations in Elderly Australians: A Prospective Cross-Sectional Study in Two Tasmanian Hospitals.

INTRODUCTION: Adverse drug reactions (ADRs) have been commonly cited as a major cause of hospital admissions in older individuals. However, despite the apparent magnitude of this problem, there are limited prospective data on ADRs as a cause of hospitalization in elderly medical patients. OBJECTIVES: The objective of this study was to evaluate the proportion, clinical characteristics, causality, severity, preventability, and outcome of ADR-related admissions in older patients admitted to two Tasmanian hospitals. METHODS: We conducted a prospective cross-sectional study at the Royal Hobart and Launceston General Hospitals in Tasmania, Australia. A convenience sample of patients, aged 65 years and older, undergoing unplanned overnight medical admissions was screened. ADR-related admissions were determined through expert consensus from detailed review of medical records and patient interviews. The causality, preventability and severity of each ADR-related admission were assessed. RESULTS: Of 1008 admissions, the proportion of potential ADR-related medical admissions was 18.9%. Most (88.5%) ADR-related admissions were considered preventable. Cardiovascular complaints (29.3%) represented the most common ADRs, followed by neuropsychiatric (20.0%) and renal and genitourinary disorders (15.2%). The most frequently implicated drug classes were diuretics (23.9%), agents acting on the renin angiotensin system (16.4%), ß-blocking agents (7.1%), antidepressants (6.9%), and antithrombotic agents (6.9%). Application of the Naranjo algorithm found 5.8% definite, 70.1% probable, and 24.1% possible ADRs. ADR severity was rated moderate and severe in 97.9% and 2.1% of admissions, respectively. For most (93.2%) ADR-related admissions the ADR resolved and the patient recovered. CONCLUSION: Hospitalization due to an ADR is a common occurrence in this older population. There is need for future studies to implement and evaluate interventions to reduce the risk of ADR-related admissions in elderly populations.

Prediction of Hospitalization due to Adverse Drug Reactions in Elderly Community-Dwelling Patients (The PADR-EC Score).

BACKGROUND: Adverse drug reactions (ADRs) are the major cause of medication-related hospital admissions in older patients living in the community. This study aimed to develop and validate a score to predict ADR-related hospitalization in people aged ≥65 years. METHODS: ADR-related hospitalization and its risk factors were determined using a prospective, cross-sectional study in patients aged ≥65 years admitted to two hospitals. A predictive model was developed in the derivation cohort (n = 768) and the model was applied in the validation cohort (n = 240). ADR-related hospital admission was determined through expert consensus from comprehensive reviews of medical records and patient interviews. The causality and preventability of the ADR were assessed based on the Naranjo algorithm and modified Schumock and Thornton criteria, respectively. RESULTS: In the derivation sample (mean [±SD] age, 80.1±7.7 years), 115 (15%) patients were admitted due to a definite or probable ADR; 92.2% of these admissions were deemed preventable. The number of antihypertensives was the strongest predictor of an ADR followed by presence of dementia, renal failure, drug changes in the preceding 3 months and use of anticholinergic medications; these variables were used to derive the ADR prediction score. The predictive ability of the score, assessed from calculation of the area under the receiver operator characteristic (ROC) curve, was 0.70 (95% confidence interval (CI) 0.65-0.75). In the validation sample (mean [±SD] age, 79.6±7.6 years), 30 (12.5%) patients' admissions were related to definite or probable ADRs; 80% of these admissions were deemed preventable. The area under the ROC curve in this sample was 0.67 (95% CI 0.56-0.78). CONCLUSIONS: This study proposes a practical and simple tool to identify elderly patients who are at an increased risk of preventable ADR-related hospital admission. Further refinement and testing of this tool is necessary to implement the score in clinical practice.

Hospitalization in older patients due to adverse drug reactions -the need for a prediction tool.

Adverse drug reactions (ADRs) represent a major burden on society, resulting in significant morbidity, mortality, and health care costs. Older patients living in the community are particularly susceptible to ADRs, and are at an increased risk of ADR-related hospitalization. This review summarizes the available evidence on ADR-related hospital admission in older patients living in the community, with a particular focus on risk factors for ADRs leading to hospital admission and the need for a prediction tool for risk of ADR-related hospitalization in these individuals. The reported proportion of hospital admissions due to ADRs has ranged from 6% to 12% of all admissions in older patients. The main risk factors or predictors for ADR-related admissions were advanced age, polypharmacy, comorbidity, and potentially inappropriate medications. There is a clear need to design intervention strategies to prevent ADR-related hospitalization in older patients. To ensure the cost-effectiveness of such strategies, it would be necessary to target them to those older individuals who are at highest risk of ADR-related hospitalization. Currently, there are no validated tools to assess the risk of ADRs in primary care. There is a clear need to investigate the utility of tools to identify high-risk patients to target appropriate interventions toward prevention of ADR-related hospital admissions.

Unstable hemiarthroplasty of the hip-treated with a simple technique of acetabular augmentation.

Hemiarthroplasty of the hip is one of the most frequently performed orthopedic procedures for trauma in the elderly. Dislocation is one of its well-recognized complications and ranges from 1% to 16% (Acta Orthop Scand. 2003;74:45-48) in different series. Often, dislocation can be recurrent when the morbidity is even higher. Suggested methods of treatment for this difficult problem range from closed/open reduction followed by conservative management to Girdlestone excision arthroplasty. We report a unique, simple, and effective method of managing this problem, particularly in those elderly patients who are medically unfit to undergo a total hip arthroplasty or a major revision hip surgery at a later date for a dislocated hemiarthroplasty. Nine patients have been treated with our technique, and none of these patients had a further dislocation over a 6-month to 9-year follow-up.

Bonding agent is a decisive factor in determining the marginal leakage of dental composites subjected to thermal cycling: an in vitro study.

The marginal leakage at the dentine/composite interface in Class II composite restorations subjected to thermal cycling has been effectively evaluated using the silver staining technique. The presence of a bonding agent at the dentine/composite interface is found to improve adhesion. Scanning electron and optical microscopic observations of sectioned specimens reveal that applying a second coat of bonding agent on the dentinal surface helps in reducing microleakage compared to a single coat application, in all three radiopaque composite/bonding agent systems studied (Z100/Single Bond, Spectrum TPH/Prime & Bond 2.1 and Chitra/Chitrabond 1.0). Thermal cycling during in vitro studies was found to provide a more appropriate representation of the adhesive behaviour of the composite in clinical situations.