Relationship between Medication-Related Osteonecrosis of the Jaw and CDK4/6 Inhibitors in Breast Cancer.

OBJECTIVE: We aimed to evaluate the use of CDK4/6 inhibitors as a risk factor for medication-related osteonecrosis of the jaw (MRONJ) in a cohort of patients with metastatic breast cancer treated with denosumab. METHODS: This was a multicentre, retrospective, observational study. All patients with breast cancer treated with denosumab (January 2011-December 2022) were included. The relationship between CDK4/6 inhibitors and MRONJ was analysed. RESULTS: A total of 243 patients were included, ninety-five (44.2%) of whom used a CDK4/6 inhibitor. There were 21 patients with MRONJ. In patients treated with denosumab without CDK4/6 inhibitors, the incidence of MRONJ and mean time to the occurrence of MRONJ were 6.6% (8/120) and 16.8 months (SD 7.8), respectively; in patients treated with denosumab and CDK4/6 inhibitor, these values were 13.7% (13/95) and 15.4 months (SD 8.7), respectively. The difference in the incidence was not significant (p = 0.085). Among the 19 patients who used abemaciclib, the probability of MRONJ occurrence was significantly higher compared to patients not using CDK4/6 inhibitors (p = 0.0178). CONCLUSIONS: These results suggest that the incidence of MRONJ in patients with metastatic breast cancer treated with denosumab is higher, and the onset of MRONJ occurs earlier in the presence of CDK4/6 inhibitors. The differences were statistically significant in the patients who used abemaciclib. Given that the use of this combination is very common in routine clinical practice, it would be advisable to carry out larger prospective studies to clarify the risk of this association.

Analysis of neutropenia as a predictive factor of the efficacy of trifluridine-tipiracil treatment.

OBJECTIVES: Trifluridine-tipiracil (TAS-102), an oral cytotoxic agent used in adult patients with refractory metastatic colorectal cancer (mCRC), has been associated with neutropenia (chemotherapy-induced neutropenia) (CIN)). MATERIALS AND METHODS: We evaluated the efficacy and safety of TAS-102 in a group of 45 mCRC patients (median age 66 years) in Huelva province, Spain, in a retrospective, multicenter observational study. RESULTS: We showed that the association between TAS-102 and CIN can be used as a predictor of efficacy. 20% (9/45) of patients with an Eastern Cooperative Oncology Group (ECOG) score of 2 had received at least one previous chemotherapy treatment. Overall, 75.5% (34/45) and 28.9% (13/45) had received anti-VEGF and anti-EGFR monoclonal antibodies, respectively. Additionally, 80% (36/45) of patients had received third-line treatment. The mean treatment period, duration of overall survival (OS), and duration of progression-free survival (PFS) were 3.4, 12, and 4 months, respectively. A partial response was seen in 2 patients (4.3%), and disease stabilization was observed in 10 patients (21.3%). Neutropenia was the most frequent grade 3 - 4 toxicity (46.7%; 21/45). Other findings were anemia (77.8%; 35/45), all grades of neutropenia (73.3%; 33/45), and gastrointestinal toxicity (53.3%; 24/45). The dose of TAS-102 needed to be reduced in 68.9% (31/45) of patients, whereas treatment needed to be interrupted in 80% (36/45) of patients. Grade 3 - 4 neutropenia was a positive prognostic factor for OS (p = 0.023). CONCLUSION: A retrospective evaluation shows that grade 3 - 4 neutropenia is an independent predictor of treatment response and survival in patients undergoing routine treatment for mCRC, but this finding needs confirmation in a prospective study.

Results of the Protocolization of a Telepharmacy Program: Patient Selection and Dispensation Interruption Criteria.

Objective: To analyze the impact of applying criteria for patient selection and interruption of dispensation in a telepharmacy program. Secondary objective: to conduct a socioeconomic analysis of requests for telepharmacy after applying the criteria. Methods: A retrospective observational study was conducted. We applied the criteria from September 1, 2021 to December 31, 2021 and reviewed the impact of their application by comparing the prior period (October 14, 2020-August 31, 2021) with the period when the criteria were applied. We analyzed the evolution of applications over time, the number of users, the evolution over time of rejected applications, and the associated reasons. Finally, we studied how the average income and distance to hospital are related to the number of requests. This study was reviewed by the authors' institutional ethics committee and was considered exempted from further review. Results: We applied the criteria to 2,379 patients. Dispensations by telepharmacy increased progressively. We provided telepharmacy services to 41.7% of all outpatients and rejected 962 applications (65% after the criteria were applied). The main pre- and postcriteria reasons for rejecting applications were refusal without express reason and the patient having sufficient medication, respectively. All patients corrected the situation that caused rejection. Telepharmacy requests and distance to hospital were not related, although the number of requests and average income were related. Conclusions: We provided pharmaceutical care with this protocol and encouraged patients to correct the reasons for interrupted dispensations. The new criteria render telepharmacy available to all patients, regardless of where they live or their purchasing power. Lower-income individuals use telepharmacy more often.

Inotersen and severe thrombocytopenia: 2 case reports and review.

Hereditary transthyretin amyloidosis (hATTR) is an ultra-rare illness. Inotersen is a 2'-O-methoxyethyl (2'MOE)-modified antisense oligonucleotides (ASO) approved in 2018 as a polyneuropathy treatment for adults with hereditary transthyretin amyloidosis stages 1 or 2. Inotersen can produce grade 4 thrombocytopenia as a severe adverse reaction that can lead to potentially fatal hemorrhage complications. We describe our experience in the management of severe thrombocytopenia with inotersen. The onset of the thrombocytopenia and the incidences described in the cases in our hospital are different from that described in the literature. Also, recovery of platelet levels was faster in our patient who was administered human immunoglobulin G, which suggests that there is an immunological component.

Adaptación transcultural a la versión española del cuestionario “Structured History of Medication Use” para la conciliación de la medicación al ingreso / Cross-cultural adaptation to the Spanish version of the “Structured HIstory of Medication Use” questionnaire for medication reconciliation at admission

Antecedentes y objetivoEl cuestionario “Structured HIstory of Medication use” (SHIM) es una herramienta diseñada para obtener una visión completa de la medicación del paciente antes del ingreso mediante una entrevista estructurada, y ha demostrado su potencial para prevenir errores de conciliación. El objetivo de este estudio fue adaptar transculturalmente el cuestionario SHIM al español.Pacientes y métodosTraducción directa e inversa seguidas de una síntesis y adaptación, que contó con la participación de un panel de expertos, para garantizar la equivalencia entre el cuestionario original y su versión española. Posteriormente se realizó un análisis de la comprensibilidad de la versión española del cuestionario mediante entrevistas cognitivas en una muestra de pacientes polimedicados en seguimiento por el Servicio de Medicina Interna.ResultadosSe obtuvo la versión española del cuestionario SHIM (SHIM-e). El grado de dificultad asignado por los traductores a la traducción directa e inversa fue bajo. Durante la fase de síntesis y adaptación se resolvieron tres discrepancias y se decidió emplear, en la versión del cuestionario adaptada al español, algunos términos de uso común en la entrevista clínica. El análisis de la comprensibilidad, realizado en una muestra de 10 pacientes polimedicados e ingresados en la Unidad de Cirugía General y de Aparato Digestivo, mostró una comprensibilidad del 100% para todos los ítems, excepto para el número 13 que fue del 90%.ConclusionesEste trabajo presenta la primera adaptación transcultural al español del cuestionario SHIM. Los procesos de traducción directa e inversa han presentado una dificultad baja y los resultados de las entrevistas cognitivas muestran un nivel alto de comprensibilidad para la versión española de esta herramienta.

Cross-cultural adaptation to the Spanish version of the "Structured HIstory of Medication Use" questionnaire for medication reconciliation at admission. / Adaptación transcultural a la versión española del cuestionario "Structured HIstory of Medication Use" para la conciliación de la medicación al ingreso.

BACKGROUND AND OBJECTIVE: The "Structured HIstory of Medication use" (SHIM) questionnaire is a tool developed to obtain an accurate pre-admission overview of medications, involving a structured interview with patients, and has demonstrated its potential to prevent reconciliation errors. The objective of this study was to cross-culturally adapt the SHIM questionnaire to Spanish. PATIENTS AND METHODS: Forward and blind-back translations followed by a synthesis and adaptation, with the participation of an expert panel, to guarantee the equivalence between the original questionnaire and the Spanish version. Subsequently, pilot testing of the Spanish version was carried out through cognitive interviews in a sample of polymedicated patients under follow-up by the Department of Internal Medicine. RESULTS: The Spanish version of the SHIM questionnaire (SHIM-e) was obtained. Scores for difficulty assigned by translators involved in forward and back translations were low. During the synthesis and adaptation phase, three discrepancies were resolved, and the expert panel decided to include some terms commonly used for clinical interviews in the Spanish version of the questionnaire. The pilot testing, which was performed in a sample of 10 polymedicated patients admitted to the Department of General and Digestive Surgery, showed 100% comprehensibility for all items, except for number 13, which was 90%. CONCLUSIONS: This work presents the first cross-cultural adaptation to Spanish of the SHIM questionnaire. The forward and blind-back translations presented low difficulty and the results of the pilot testing showed a high level of comprehensibility for the Spanish version of this tool.

Concordance Among 10 Different Anticholinergic Burden Scales in At-Risk Older Populations.

OBJECTIVE: The aim of the study was to evaluate the concordance among 10 anticholinergic scales for the measurement of anticholinergic drug exposure in at-risk elderly complex chronic patients in primary care. METHODS: An 8-month cross-sectional, multicenter study was carried out in a cohort of complex chronic patients older than 65 years in treatment with at least 1 drug with anticholinergic activity. Demographic, pharmacological, and clinical data were collected. Anticholinergic burden and risk were detected using the 10 scales included on the anticholinergic burden calculator (http://www.anticholinergicscales.es/). We used κ statistics to evaluated the concordance 2 to 2 (according to risk: high, medium, low or without risk) among the included scales. RESULTS: Four hundred seventy-three patients were recruited (60.3% female, median age of 84 years [interquartile range = 10]). Eighty was the total number of anticholinergic drugs with any scale (1197 prescriptions), with a median of 2 drugs with anticholinergic activity per patient (interquartile range = 2). The κ statistics comparing all the 10 scales ranged from -0.175 (Drug Burden Index versus Chew Scale) to 0.708 (Anticholinergic Activity Scale [AAS] versus Chew Scale). The best concordance was obtained between AAS and Chew Scale (κ = 0.708), followed by Clinician-Rated Anticholinergic Scale and Duran Scale (κ = 0.632) and AAS and Anticholinergic Cognitive Burden Scale (κ = 0.618), being considered substantial strengths of concordance. CONCLUSIONS: The agreement among the 10 scales in elderly patients with complex chronic conditions was highly variable. Great care should be taken when assessing anticholinergic drug exposure using existing scales because of the wide variability among them. The only scales that showed agreement were the AAS-Chew, Clinician-Rated Anticholinergic Scale-Duran, and AAS-Anticholinergic Cognitive Burden Scale pairs. In the rest of the cases, the scales are not interchangeable.

Estimating the annual economic burden for the management of patients with transthyretin amyloid polyneuropathy in Spain.

Background: Transthyretin amyloid polyneuropathy (ATTR-PN) is a fatal disease associated with substantial burden of illness. Three therapies are approved by the European Medicines Agency for the management of this rare disease. The aim of this study was to compare the total annual treatment specific cost per-patient associated with ATTR-PN in Spain.Methods: An Excel-based patient burden and cost estimator tool was developed to itemize direct and indirect costs related to treatment with inotersen, patisiran, and tafamidis in the context of ATTR-PN. The product labels and feedback from five Spanish ATTR-PN experts were used to inform resource use and cost inputs.Results: Marked differences in costs were observed between the three therapies. The need for patisiran- and inotersen-treated patients to visit hospitals for pre-treatment, administration, and monitoring was associated with increased patient burden and costs compared to those treated with tafamidis. Drug acquisition costs per-patient per-year were 291,076€ (inotersen), 427,250€ (patisiran) and 129,737€ (tafamidis) and accounted for the majority of total costs. Overall, the total annual per-patient costs were lowest for patients treated with tafamidis (137,954€), followed by inotersen (308,358€), and patisiran (458,771€).Conclusions: Treating patients with tafamidis leads to substantially lower costs and patient burden than with inotersen or patisiran.

Utility of a trigger tool (TRIGGER-CHRON) to detect adverse events associated with high-alert medications in patients with multimorbidity.

OBJECTIVE: To determine the utility of a tool (TRIGGER-CHRON) for identifying adverse drug events (ADEs) associated with the administration of high-alert medications in elderly patients with multimorbidity and to determine the medications most frequently implicated. METHODS: A retrospective observational study was conducted at 12 Spanish hospitals. A random sample of five medical records from each hospital was selected weekly for review over a 12-week period. We included patients aged 65 and over with multimorbidities, hospitalised for >48 hours. ADEs detected by the 32 TRIGGER-CHRON signals and caused by high-alert medications included on the Spanish HAMC list for chronic patients were selected for analysis. Triggers identified and ADEs detected were recorded. The severity and preventability of the ADEs were evaluated. The positive predictive value (PPV) of each trigger was calculated. RESULTS: On 720 charts reviewed, 908 positive triggers were identified that led to the detection of 158 ADEs caused by at least one high-alert medication on the HAMC list. These ADEs occurred in 139 patients (prevalence 19.3/100 admissions). The majority of ADEs were mild and 59.5% were deemed preventable. The drugs most frequently associated with ADEs were corticosteroids, loop diuretics, opioid analgesics and oral anticoagulants. Fifteen triggers had PPVs ≥20%. Six triggers (serum glucose >110 mg/dL, abrupt cessation of medication, oversedation/lethargy, hypotension, adverse reaction recorded and constipation) accounted for 69.8% of the ADEs identified. CONCLUSIONS: Applying the TRIGGER-CHRON to hospitalised patients with multimorbidity in 12 Spanish centres allowed detection of one adverse event caused by a high-alert drug for every four patients, which were preventable in a large proportion of patients. This confirms the need to establish interventions that reduce harm with these medications. We believe that TRIGGER-CHRON can be a useful tool to measure this harm and to determine the effects of medication safety improvement programmes as they are implemented.

Implementation of a novel home delivery service during pandemic.

INTRODUCTION: During the COVID-19 pandemic, measures have been put in place to adapt to patients' needs during home quarantine, such as "telehealthcare". With this service, hospital pharmacists develop a distinct role via the implementation of pharmacovigilance services and pharmaceutical care plans for patients with comorbidities, and for special populations as immunosuppressed patients.MethodsCross-sectional study involving hospital and community pharmacists actively practising during the COVID-19 pandemic. Patients who could not come to the hospital pharmacy department were provided with a delivery service to the community pharmacy of their choice. RESULTS: A total of 1186 patients requested this service. Erythropoiesis-stimulating agents were the most in-demand medication, followed by rheumatoid arthritis and antiretroviral drugs. 125 patients responded to the telephone survey, most of whom stated that they would use the delivery service again, and expressed their desire to continue doing so. DISCUSSION: Without a doubt, telepharmacy and medication delivery services have provided multiple benefits during home quarantine. The delivery service enabled us to provide drugs to patients in their immediate environment through a service that was free for both the patient and the hospital pharmacy service. However, at present, the available evidence of the impact of telepharmacy models is sparse. CONCLUSIONS: This medication delivery service has provided multiple benefits to patients during home quarantine. Although the users of this service seem to be satisfied with the current model, in the future, we should consider which patients would benefit most from this service and shape it to individual needs.

Prevalence of drug interactions in hospital healthcare.

AIM OF THE REVIEW: To study the prevalence of drug interactions in hospital healthcare by reviewing literature. METHOD: A review was carried out of studies written in Spanish and English on the prevalence of drug interactions in hospital care published in Pubmed between January 1990 and September 2008. The search strategy combined free text and MeSH terms, using the following keywords: "Drug interaction", "prevalence" and "hospital". For each article, we classified independent variables (pathology, age of population, whether patients were hospitalized or not, geographical location, etc.) and dependent variables (number of interactions per 100 patients studied, prevalence of patients with interactions, most common drug interactions, and others). RESULTS: The search generated 436 articles. Finally, 47 articles were selected for the study, 3 provided results about drug interactions with real clinical consequences, 42 about potential interactions, and 2 described both. The prevalence of patients with interactions was between 15 and 45 % and the number of interactions per 100 patients was between 37 and 106, depending on the group of studies analyzed. There was a considerable increase in these rates in patients with heart diseases and elderly persons. CONCLUSION: There is a large number of studies on the prevalence of drug interactions in hospitals but they report widely varying results. The prevalence is higher in patients with heart diseases and elderly people.