Development and validation of a risk score (Delay-7) to predict the occurrence of a treatment delay following cycle 1 chemotherapy.

BACKGROUND: The risk of toxicity-related dose delays, with cancer treatment, should be included as part of pretreatment education and be considered by clinicians upon prescribing chemotherapy. An objective measure of individual risk could influence clinical decisions, such as escalation of standard supportive care and stratification of some patients, to receive proactive toxicity monitoring. PATIENTS AND METHODS: We developed a logistic regression prediction model (Delay-7) to assess the overall risk of a chemotherapy dose delay of 7 days for patients receiving first-line treatments for breast, colorectal and diffuse large B-cell lymphoma. Delay-7 included hospital treated, age at the start of chemotherapy, gender, ethnicity, body mass index, cancer diagnosis, chemotherapy regimen, colony stimulating factor use, first cycle dose modifications and baseline blood values. Baseline blood values included neutrophils, platelets, haemoglobin, creatinine and bilirubin. Shrinkage was used to adjust for overoptimism of predictor effects. For internal validation (of the full models in the development data) we computed the ability of the models to discriminate between those with and without poor outcomes (c-statistic), and the agreement between predicted and observed risk (calibration slope). Net benefit was used to understand the risk thresholds where the model would perform better than the 'treat all' or 'treat none' strategies. RESULTS: A total of 4604 patients were included in our study of whom 628 (13.6%) incurred a 7-day delay to the second cycle of chemotherapy. Delay-7 showed good discrimination and calibration, with c-statistic of 0.68 (95% confidence interval 0.66-0.7), following internal validation and calibration-in-the-large of -0.006. CONCLUSIONS: Delay-7 predicts a patient's individualised risk of a treatment-related delay at cycle two of treatment. The score can be used to stratify interventions to reduce the occurrence of treatment-related toxicity.

Antihypertensive Agents and Incident Alzheimer's Disease: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Hypertension is a recognized risk factor for dementia. However, evidence for using antihypertensive agents to reduce the risk of Alzheimer's disease in people with hypertension is inconclusive. OBJECTIVE: To examine the association between antihypertensive agents and the incidence of Alzheimer's disease in adults with hypertension and normal cognition. DESIGN: We conducted a systemic review and performed meta-analyses using Ovid MEDLINE, Ovid Embase, Ovid PsycINFO, Web of science and Scopus, from inception to 18th February 2022. SETTING: Cohort and case-control studies. PARTICIPANTS: Adults ≥ 40 years with hypertension and normal cognition. INTERVENTION: Antihypertensive agents. MEASUREMENTS: We performed two separate meta-analyses, pooling the adjusted relative risk (RR) of non-antihypertensive comparator and antihypertensive comparator study design. RESULTS: We included nine studies, totalling 1,527,410 individuals. Meta-analysis of non-antihypertensive user comparator studies found that the use of antihypertensive agents is associated with a reduced risk of incident Alzheimer's disease (RR= 0.94, 95% CI 0.90-0.99; p=0.01). Meta-analysis of antihypertensive comparator studies found evidence that angiotensin II receptor blocker users are associated with a reduction in the risk of Alzheimer's disease compared to other antihypertensive agents (RR= 0.78, 95% CI 0.68-0.88; p< 0.001). CONCLUSION: Our review provides evidence that the use of antihypertensive agents is associated with a lower incidence of Alzheimer's disease. The use of angiotensin II receptor blockers may provide the most benefit among antihypertensive agents. Lowering raised blood pressure may not be the only mechanism for cognitive protection and further investigation of the effects of angiotensin II on cognition is indicated.

Pharmacist's review and outcomes: Treatment-enhancing contributions tallied, evaluated, and documented (PROTECTED-UK).

PURPOSE: The purpose was to describe clinical pharmacist interventions across a range of critical care units (CCUs) throughout the United Kingdom, to identify CCU medication error rate and prescription optimization, and to identify the type and impact of each intervention in the prevention of harm and improvement of patient therapy. MATERIALS AND METHODS: A prospective observational study was undertaken in 21 UK CCUs from November 5 to 18, 2012. A data collection web portal was designed where the specialist critical care pharmacist reported all interventions at their site. Each intervention was classified as medication error, optimization, or consult. In addition, a clinical impact scale was used to code the interventions. Interventions were scored as low impact, moderate impact, high impact, and life saving. The final coding was moderated by blinded independent multidisciplinary trialists. RESULTS: A total of 20517 prescriptions were reviewed with 3294 interventions recorded during the weekdays. This resulted in an overall intervention rate of 16.1%: 6.8% were classified as medication errors, 8.3% optimizations, and 1.0% consults. The interventions were classified as low impact (34.0%), moderate impact (46.7%), and high impact (19.3%); and 1 case was life saving. Almost three quarters of interventions were to optimize the effectiveness of and improve safety of pharmacotherapy. CONCLUSIONS: This observational study demonstrated that both medication error resolution and pharmacist-led optimization rates were substantial. Almost 1 in 6 prescriptions required an intervention from the clinical pharmacist. The error rate was slightly lower than an earlier UK prescribing error study (EQUIP). Two thirds of the interventions were of moderate to high impact.

Neurological complications of 5-fluorouracil chemotherapy: case report and review of the literature.

Neurological complications of 5-fluorouracil (5-FU) chemotherapy are uncommon events. The two patients presented demonstrate two manifestations of 5-FU neurotoxicity, namely a cerebellar syndrome in association with global motor weakness and bulbar palsy, and a bilateral third cranial (oculomotor) nerve palsy. Both highlight the rapid onset and severity of these unusual side effects but also emphasize that, unlike paraneoplastic syndromes or central nervous system involvement by tumour, complete spontaneous recovery is a potential outcome.