Potentially inappropriate medication (PIM) use and severe drug interactions (SDIs) in older adults with cancer.

BACKGROUND: Older adults with cancer frequently have other co-morbidities requiring prescription pharmacotherapy. The objectives of this study were to identify the prevalence of potentially inappropriate medications (PIMs), severe drug interactions (SDIs) and associated risk factors in these patients. MATERIALS AND METHODS: This twelve-month prospective observation study was conducted at an Irish Hospital. PIMs were identified in older adults (≥65 years) using STOPP and OncPal criteria; potential SDIs using Stockley's interaction checker. RESULTS: We enrolled 186 patients; mean age 72.5(SD5.7) years, 46.2% female, mean co-morbidities 7.5(SD3.4), median medications 7(IQR4-9). Polypharmacy (≥6 medications) and major polypharmacy (≥11 medications) were identified in 60.8% and 17.7% respectively. STOPP PIMs were observed in 73.1%; median 2(IQR1-3). The most common PIM identified was any drug prescribed beyond the recommended duration (46.5%). For each additional prescription, the odds of receiving a STOPP PIM increased by 79.2% (OR 1.792, 95% CI 1.459-2.02). Potential SDIs were identified in 50.5% participants. The most common were beta-blocker/alpha-blocker (6.5%), selective-serotonin re-uptake inhibitor (SSRI)/proton pump inhibitor (PPI) (5.9%) and SSRI/Aspirin (4.8%). For each additional prescription, the odds of an SDI increased by 50.8% (OR 1.508, 95% CI 1.288-1.764). Seventy-seven (41.4%) participants died within six months of enrolment. OncPal PIMs were observed in 81.8% of this cohort, median 2(IQR1-3). The most common OncPal PIM was statin therapy (38%). For each additional prescription, the odds of receiving an OncPal PIM increased by 38.2%, (OR 1.382, 95% CI 1.080-1.767). CONCLUSIONS: PIMs and SDIs are common in this population. Comprehensive specialist evaluation of medications by a geriatrician may identify PIMs thereby reducing related adverse outcomes such as SDIs.

Reducing inappropriate prescribing for older adults with advanced frailty: A review based on a survey of practice in four countries.

The management of medications in persons with frailty presents challenges. There is evidence of inappropriate prescribing and a lack of consensus among healthcare professionals on the judicious use of medications, particularly for patients with more severe frailty. This study reviews the evidence on the use of commonly prescribed pharmacological treatments in advanced frailty based on a questionnaire of prescribing practices and attitudes of healthcare professionals at different stages in their careers, in different countries. A convenience sample of those attending hospital grand rounds in Ireland, Canada and Australia/New Zealand (ANZ) were surveyed on the management of 18 medications in advanced frailty using a clinical vignette (man with severe dementia, Clinical Frailty Scale 7/9). Choices were to continue or discontinue (stop now or later) medications. In total, 298 respondents from Ireland (n = 124), Canada (n = 110), and ANZ (n = 64) completed the questionnaire, response rate 97%, including 81 consultants, 40 non-consultant hospital doctors, 134 general practitioners and 43 others (nurses, pharmacists, and medical students). Most felt that statins (88%), bisphosphonates (77%) and cholinesterase inhibitors (76%) should be discontinued. Thyroid replacement (88%), laxatives (83%) and paracetamol (81%) were most often continued. Respondents with experience in geriatric, palliative and dementia care were significantly more likely to discontinue medications. Age, gender and experience working in nursing homes did not contribute to the decision. Reflecting the current literature, there was no clear consensus on inappropriate prescribing, although respondents preferentially discontinued medications for secondary prevention. Experience significantly predicted the number and type discontinued, suggesting that education is important in reducing inappropriate prescribing for people in advanced states of frailty.

Adverse Drug Reactions in an Oncological Population: Prevalence, Predictability, and Preventability.

BACKGROUND: Our goal was to determine (a) the prevalence of multimorbidity and polypharmacy in patients with cancer and (b) the prevalence, predictability, and preventability of adverse drug reactions (ADRs) causing/contributing to hospitalization. MATERIALS AND METHODS: We conducted a 12-month prospective observational study of patients aged ≥16 years admitted to an oncology center. Older adults were aged ≥70 years. RESULTS: We enrolled 350 patients: 52.3% (n = 183) female, mean age 63.6 years (SD 12.1), 36.6% (n = 121) aged ≥70 years. Multimorbidity (≥2 conditions) was identified in 96.9%; 68% had ≥5 conditions. The median number of medications was 6 (interquartile range [IQR] 4-8); 47% were prescribed ≥6 medications and 11.4% ≥11 medications. Older adults had higher numbers of comorbid conditions (7 [IQR 5-10] vs. 5 [IQR 3-7]) and were prescribed more medications (median 7 [IQR 4-9] vs. 4 [IQR 2-7]). ADRs caused/contributed to hospitalization in 21.5% (n = 75): 35.8% (n = 72) of emergency admissions and 4.7% (n = 3) of elective admissions. The most common ADRs were neutropenia with infection (25.3%), dyspepsia/nausea/vomiting (20%), and constipation (20%). Causative medications included systemic anticancer therapies (SACTs; 53.3%), opioids (17.3%), corticosteroids (6.7%), and nonsteroidal anti-inflammatory drugs (5.3%). ADR prevalence was similar in older and younger adults secondary to SACTs (8.3% vs. 13.1%), non-cancer medications (10.7% vs. 8.3%), and both (0% vs. 1.3%). ADRs were predictable in 89.3% (n = 67), definitely avoidable in 29.3% (n = 22), and possibly avoidable in 33.3% (n = 25). No association was identified between ADRs and age, gender, daily medication number, length of stay, or death. No ADR predictor variables were identified by logistic regression. CONCLUSION: More than 21% of admissions to an oncology service are ADR-related. ADRs are caused by both SACTs and non-cancer-specific medications. The majority are predictable; ≥60% may be preventable. Patients with cancer have high levels of multimorbidity and polypharmacy, which require vigilance for related adverse outcomes. IMPLICATIONS FOR PRACTICE: A diagnosis of cancer often occurs in patients with multimorbidity and polypharmacy. Cancer can cause an altered physiological environment, placing patients at risk of drug-drug interactions, drug-disease interactions, and adverse drug reactions (ADRs). This study identified that ADRs caused or contributed to one in five hospital admissions of patients with cancer. ADRs were caused by systemic anticancer therapies (SACTs) in 53.3% of cases and non-cancer medications in 45.4% of cases, and a combination of both in 1.3%. ADRs occurred in similar frequencies in older and younger patients secondary to SACTs (8.3% vs. 13.1%, p = .295), non-SACTs (10.7% vs. 8.3%, p = .107), and a combination of both (0% vs. 1.3%, p = .240). The majority of ADRs were predictable (89.3%) and potentially preventable (62.6%). These findings support the need for increased awareness of medication-related adversity in patients with cancer and interventions to minimize their occurrence, thus supporting the American Society of Clinical Oncology guidelines that recommend adults ≥65 years of age receiving chemotherapy have geriatric assessment to identify medical and medication issues.

STOPPFrail (Screening Tool of Older Persons' Prescriptions in Frail adults with a limited life expectancy) criteria: application to a representative population awaiting long-term nursing care.

PURPOSE: STOPPFrail criteria highlight instances of potentially inappropriate medications (PIMs) in frailer older adults with poor 1-year survival prognosis. The objectives of this study were to (i) determine the proportion of older adults requiring long-term nursing care in whom STOPPFrail criteria are applicable, (ii) measure the prevalence of STOPPFrail PIMs, and (iii) identify risk factors for PIMs in this cohort. METHODS: We retrospectively reviewed applications for long-term nursing care to nursing homes in the Cork area over a 6-month period. We recorded diagnoses, medications, functional status, cognitive ability, frailty status, and applied STOPPFrail criteria as appropriate. RESULTS: We reviewed 464 applications; 38 were excluded due to incomplete information and 274 patients (64.3%) met STOPPFrail eligibility criteria (median age 83 years (IQR 77.25-88); 233 (54.7%) female). Those STOPPFrail eligible were prescribed 2194 medications (mean 8, (SD 4)), of which 828 (37.7%) were PIMs. At least one PIM was identified in 250 eligible patients (91.2%). The median number of PIMs was 3 (IQR 2-4), the most common being (i) medications without clear indication identified in 47.0% (n = 129) of patients, (ii) long-term high-dose proton pump inhibitors in 31.4% (n = 86), and (iii) statins in 29.6% (n = 81). For every additional medication prescribed, the odds of identifying a PIM increased by 58% (odds ratio 1.58, 95% CI 1.32-1.89, p < 0.001). CONCLUSION: Almost 65% of patients awaiting long-term care are eligible for the application of STOPPFrail criteria with over 90% prescribed at least one PIM. Transition to nursing home care represents an opportunity to review therapeutic appropriateness and goals of prescribed medications.

Inter-rater reliability of STOPPFrail [Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy] criteria amongst 12 physicians.

PURPOSE: STOPPFrail is an explicit tool, developed by Delphi consensus, to assist physicians with deprescribing medications in frail older adults with poor survival prognosis. This study aimed to determine the inter-rater reliability (IRR), amongst physicians, of STOPPFrail application. METHODS: Twenty clinical cases were collated to represent frail older patients. Eighteen cases met STOPPFrail inclusion criteria. They had a mean age of 79.5 (SD6) years and a median of 7 (IQR6-8.25) comorbidities and were prescribed a median of 9 (IQR7.75-11.25) medications. Two of the STOPPFrail originators reached complete agreement (gold standard) in determining 91 of 165 medications (55.2%) as inappropriate. Twelve physicians (6 geriatricians, 3 general practitioners and 3 palliative care physicians) independently applied STOPPFrail criteria. IRR between physicians and gold standard (GS) assessment was determined using Cohen's kappa statistic. RESULTS: Eighteen of the 20 cases that met STOPPFrail inclusion criteria were correctly identified by 9 of 12 physicians (75%). The average time taken per clinical case was 2.7 (SD0.94) minutes. The kappa co-efficient between physicians and GS assessment ranged from 0.71 (substantial) to 0.86 (good), with a mean kappa value of 0.758 (SD0.059). The Fleiss kappa coefficients between GS assessment and geriatricians, GPs and palliative care physicians were 0.80 (SD0.6), 0.77 (SD0.9) and 0.75 (SD0.1), respectively. No significant difference was noted, between groups or between participants within groups, as determined by one-way ANOVA, (df (2, 9) = 0.712, p = 0.516). CONCLUSIONS: IRR of STOPPFrail criteria between physicians, practising in different specialties, is substantial, despite no prior knowledge of the criteria.

STOPPFrail (Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy): consensus validation.

Objective: to validate STOPPFrail, a list of explicit criteria for potentially inappropriate medication (PIM) use in frail older adults with limited life expectancy. Design: a Delphi consensus survey of an expert panel comprising academic geriatricians, clinical pharmacologists, palliative care physicians, old age psychiatrists, general practitioners and clinical pharmacists. Setting: Ireland. Subjects: seventeen panellists. Methods: STOPPFrail criteria were initially created by the authors based on clinical experience and literature appraisal. Criteria were organised according to the physiological system; each criterion accompanied by an explanation. Using Delphi consensus methodology, panellists ranked their agreement with each criterion on a 5-point Likert scale and provided written feedback. Criteria with a median Likert response of 4/5 (agree/strongly agree) and a 25th centile of ≥4 were included in the final list. Results: all panellists completed three Delphi rounds. Thirty criteria were proposed, 27 were accepted. The first two criteria suggest deprescribing medications without indication or where compliance is poor. The remaining 25 criteria include lipid-lowering therapies, alpha-blockers for hypertension, anti-platelets, neuroleptics, memantine, proton-pump inhibitors, H2-receptor antagonists, anti-spasmodic agents, theophylline, leukotriene antagonists, calcium supplements, bone anti-resorptive therapy, selective oestrogen receptor modulators, non-steroidal anti-inflammatories, corticosteroids, 5-alpha-reductase inhibitors, alpha-1-selective blockers, muscarinic antagonists, oral diabetic agents, ACE-inhibitors, angiotensin receptor blockers, systemic oestrogens, multivitamins, nutritional supplements and prophylactic antibiotics. Consensus could not be reached on the inclusion of acetylcholinesterase inhibitors. Full consensus was reached on the exclusion of anticoagulants and antidepressants from the list. Conclusion: STOPPFrail comprises 27 criteria relating to medications that are potentially inappropriate in frail older patients with limited life expectancy. STOPPFrail may assist physicians in deprescribing medications in these patients.

Predicting risk of adverse drug reactions in older adults.

Adverse drug reactions (ADRs) are common in older adults, with falls, orthostatic hypotension, delirium, renal failure, gastrointestinal and intracranial bleeding being amongst the most common clinical manifestations. ADR risk increases with age-related changes in pharmacokinetics and pharmacodynamics, increasing burden of comorbidity, polypharmacy, inappropriate prescribing and suboptimal monitoring of drugs. ADRs are a preventable cause of harm to patients and an unnecessary waste of healthcare resources. Several ADR risk tools exist but none has sufficient predictive value for clinical practice. Good clinical practice for detecting and predicting ADRs in vulnerable patients includes detailed documentation and regular review of prescribed and over-the-counter medications through standardized medication reconciliation. New medications should be prescribed cautiously with clear therapeutic goals and recognition of the impact a drug can have on multiple organ systems. Prescribers should regularly review medication efficacy and be vigilant for ADRs and their contributory risk factors. Deprescribing should occur at an individual level when drugs are no longer efficacious or beneficial or when safer alternatives exist. Inappropriate prescribing and unnecessary polypharmacy should be minimized. Comprehensive geriatric assessment and the use of explicit prescribing criteria can be useful in this regard.

Streptococcus agalactiae endocarditis presenting as acalculous cholecystitis in a previously well woman.

This case report describes the unusual presentation of a previously very well woman with Streptococcus agalactiae endocarditis in the emergency department. History, examination and preliminary laboratory and radiological investigations supported a diagnosis of acalculous cholecystitis, for which she was given intravenous broad spectrum antimicrobial therapy. One day following admission, the patient deteriorated and became unresponsive. Subsequent MRI of the brain revealed multiple bihemispheric cerebral emboli and a large, mobile mitral valve thrombus was visualised on her transoesophageal echocardiogram. S agalactiae was cultured from venous blood samples and her antimicrobial cover was adjusted accordingly. Despite her presumed guarded prognosis, this patient made a remarkable recovery. To our knowledge, the association of S agalactiae endocarditis with acalculous cholecystitis has not been previously described.

Interventional treatment for acute ischaemic stroke in an 86-year-old.

An 86-year-old lady presented to the accident and emergency department with a 90 min history of receptive and expressive dysphasia. There were no motor symptoms or visual symptoms reported. A partial anterior circulation stroke was diagnosed. On examination, she had a National Institutes of Health Stroke Scale of 6. CT angiography showed an occlusive thrombus within the left internal carotid artery extending into the left M1 segment of the middle cerebral artery and the proximal A1 segment of the anterior cerebral artery. Intra-arterial thrombectomy was preformed. Full recovery was achieved.