International Journal of Clinical Pharmacy最新文献

Background: Inclisiran, the newest lipid-lowering drug, has not shown significant safety problems in major clinical studies. However, its recent market introduction and limited clinical use have produced few reports of adverse reactions, leaving a comprehensive understanding of its long-term safety yet to be established.

Aim: The aim of the study was to conduct a signal detection analysis of adverse events (AEs) associated with inclisiran using FDA Adverse Event Reporting System (FAERS) datasets.

Method: Data on AEs associated with inclisiran were collected from the FAERS database from 2021 to 2023. Signal detection was conducted using the reporting odds ratio (ROR) and the information component (IC). The analysis was standardized using the Medical Dictionary for Regulatory Activities (MedDRA) and focused on System Organ Classes (SOCs) and Preferred Terms.

Results: Of 17,307,196 AE reports, 2976 were relevant to inclisiran. The male-to-female ratio of these events was 0.74:1, predominantly in patients aged 45 to 74 years. A total of 102 AE signals associated with inclisiran were identified in 15 SOCs. Among these, 86 involved muscle injuries, liver injuries, diabetes, neurocognitive dysfunction, and other events not listed on the drug label.

Conclusion: The findings confirm all AEs documented on the drug label and in current clinical trials while also revealing new AEs such as muscle pain, elevated liver enzymes, increased blood glucose levels, and neurocognitive dysfunction. This study contributes to real-world research data, providing valuable references for rational drug use.

Background: QTc interval prolongation can result in potentially lethal arrhythmias. One risk factor is QTc-prolonging drugs, including some antifungals often used in hemato-oncology patients. Screening tools for patients at risk have not yet been investigated in this patient population.

Aim: Our aim was to evaluate the sensitivity and specificity of five QTc risk scores in hemato-oncology patients receiving systemic antifungal therapy.

Method: Data were retrieved from an internal study database including adult hemato-oncology patients prescribed systemic antifungal therapy. Data on QTc-prolonging medication, risk factors for QTc prolongation, and electrocardiograms (ECG) were collected retrospectively for a period of 12 months. The QTc risk scores according to Tisdale, Vandael, Berger, Bindraban, and Aboujaoude as well as their sensitivity and specificity were calculated.

Results: During the evaluated period, 77 patients were prescribed systemic antifungals resulting in 187 therapy episodes. Regarding therapy episodes, median age was 56 years (IQR 44-68), 41% (77) were female, and a median of 3 QTc-prolonging drugs were prescribed (range 0-6). ECGs were available for 45 (24%) of the therapy episodes 3-11 days after initiation of the antifungal therapy, 22 of which showed QTc prolongation. Regarding these 45 therapy episodes, sensitivity and specificity of the risk scores were calculated as follows: Tisdale 86%/22%, Vandael 91%/35%, Berger 32%/83%, Bindraban 50%/78%, Aboujaoude 14%/87%.

Conclusion: The QTc risk scores according to Tisdale and Vandael showed sufficient sensitivity for risk stratification in the studied patient population. In contrast, risk scores according to Berger, Bindraban, and Aboujaoude cannot be considered suitable due to poor sensitivity.

Background: The process of identifying drug-related hospitalisations is subjective and time-consuming. Assessment tool for identifying hospital admissions related to medications (AT-HARM10) was developed to simplify and objectify this process. AT-HARM10 has not previously been externally validated, thus the predictive precision of the tool is uncertain.

Aim: To externally validate AT-HARM10 in adult patients admitted to the emergency department (ED).

Method: This retrospective cross-sectional study investigated 402 patients admitted to the ED, Diakonhjemmet Hospital, Oslo, Norway. A trained 5th-year pharmacy student used AT-HARM10 to assess all patients and to classify their ED visits as possibly or unlikely drug-related. Assessment of the same patients by an interdisciplinary expert panel acted as the gold standard. The external validation was conducted by comparing AT-HARM10 classifications with the gold standard.

Results: According to AT-HARM10 assessments, 169 (42%) patients had a possible drug-related ED visit. Calculated sensitivity and specificity values were 95% and 71%, respectively. Further, positive and negative predictive values were 46% and 98%, respectively. Adverse effects/over-treatment and suboptimal treatment were the issues most frequently overestimated by AT-HARM10 compared with the gold standard.

Conclusion: AT-HARM10 identifies drug-related ED visits with high sensitivity. However, the low positive predictive value indicates that further review of ED visits classified as possible drug-related by AT-HARM10 is necessary. AT-HARM10 can serve as a useful first-step screening that efficiently identifies unlikely drug-related ED visits, thus only a smaller proportion of the patients need to be reviewed by an interdisciplinary expert panel.

Medicine shortages are an increasing issue, with broad public health implications for patients, health professionals and institutions. Despite national notification mechanisms involving sponsors and national regulators (e.g. Australian Therapeutic Goods Administration), shortages continue to be a significant workload in hospitals, particularly for pharmacy staff. In this article, we describe the implications of medicine shortages and a team approach to their management in an Australian public hospital. The medicine shortages team comprises senior pharmacists, a pharmacy technician, and a purchasing officer, in consultation with medical staff. A 10 week audit recorded 34 medicine shortages and/or discontinuations, comprising 49 usually stocked products. Shortages were more quickly identified by the purchasing officer using established relationships with suppliers, rather than relying on sponsor or government communication. Having a team systematically dealing with these shortages enables expertise in supply chains, finances, therapeutics, and medicine safety to be shared, to identify optimal interventions to mitigate patient risk.

Background: Provision of take-home naloxone (THN) and overdose education reduces opioid-related mortality. In Australia, from July 2022, all Australian community pharmacies were eligible to supply naloxone for free through the national THN Program.

Aim: This study aimed to identify naloxone stocking rates and correlates of stocking naloxone across Australian pharmacies.

Method: Data were collected from a representative sample of Australian pharmacists in Victoria, New South Wales, Queensland and Western Australia via an online survey. Data collected included pharmacy and pharmacist characteristics and services offered within the pharmacy, including needle and syringe programs, opioid agonist treatment (OAT) and stocking naloxone. Binary probit regression analysis was used to identify correlates of stocking naloxone after controlling for key covariates.

Results: Data from 530 pharmacists were analysed. In total, 321 pharmacies (60.6%) reported stocking naloxone. Chain pharmacies and pharmacies that provided OAT had a greater probability of stocking naloxone (B = 0.307, 95%CI: [0.057, 0.556], and B = 0.543, 95%CI: [0.308, 0.777] respectively). Most (61.7%) pharmacists felt comfortable discussing overdose prevention with patients who use prescription opioids, and this comfort was associated with a higher probability of stocking naloxone (B = 0.392, 95%CI: 0.128, 0.655). Comfort discussing overdose prevention with people who use illicit opioids was lower (49.4%) and was not associated with stocking naloxone.

Conclusion: There is scope to increase stocking of naloxone and comfort with overdose prevention, particularly through addressing comfort working with higher risk groups such as people who use illicit opioids.

Background: Remimazolam tosilate is a new type of benzodiazepine currently used for gastrointestinal endoscopy and can be combined with alfentanil.

Aim: This trial compared the effectiveness and safety of remimazolam with alfentanil to propofol with alfentanil in patients undergoing gastrointestinal endoscopy.

Method: One hundred and sixty-six patients were randomly divided into propofol-alfentanil anaesthesia (Group P) and remimazolam-alfentanil anaesthesia (Group R). The primary outcomes were perioperative haemodynamic variables, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and oxygen saturation (SpO₂) preoperatively (T0); after anaesthesia induction (T1); when the gastroscope passed through the oropharynx (T2); 3 min (T3), 5 min (T4) and 7 min (T5) after T2; at the end of surgery (T6); and when patients successfully awakened (T7). The secondary outcomes included induction and awakening time, patient satisfaction, operator satisfaction, and adverse event occurrences.

Results: Compared with those in Group P, the SBP in Group R was significantly higher at T1, T2, T3, and T6 (P < 0.05); the DBP and MAP were significantly higher at T1, T2, T3, T5, and T6 (P < 0.05); the HR was significantly faster at T1 to T6 (P < 0.05); the SpO₂ was significantly higher at T1 to T4 (P < 0.05); the incidences of hypoxemia, hypotension, and drug injection pain were significantly lower in Group R (P < 0.05); the incidence of hiccups was higher (P < 0.05); the awakening time was shorter in Group R (P < 0.05); and the operator satisfaction score was high (P < 0.05).

Conclusion: Compared to propofol with alfentanil, remimazolam with alfentanil can be used safely and effectively for sedation in patients undergoing gastrointestinal endoscopy, with less impact on the patient's circulatory and respiratory systems and a lower incidence of adverse events.

Trial registration: This trial protocol was registered in the Chinese Clinical Trial Registry (ChiCR2300077252, date: 2023-11-02).

Background: Community pharmacy practice is rarely considered in ethical research, although various ethical conflicts are known for this setting. Data on the actual frequency and perceived burden of ethical conflicts occurring in the community pharmacy setting are required.

Aim: The survey aimed at investigating the frequency and perceived burden of ethical conflicts, reasons for the perceived burden and influences on decision-making in ethical conflicts in German community pharmacists.

Method: An online survey was conducted among community pharmacists. It contained 15 ethical conflicts in which the ethically required action conflicts with another principle (e.g. law). Basing on these conflicting principles, 12 considerations relevant for decision-making were defined (e.g. solidarity principle). Participants were asked to rate the ethical conflicts in terms of frequency and perceived burden and to rate the influence on decision-making for the considerations. Results were analysed descriptively.

Results: Five hundred and thirty-five questionnaires were evaluated. The participant's median age was 39 (min-max: 20-78) years, 378 (71%) were female. Seven of the 15 predefined ethical conflicts were rated as occurring predominantly at least once a week. "Generic drug is not most suitable" was rated as the most frequent. Three ethical conflicts were rated mainly with a (very) strong burden. "Concerns for an unborn child" was rated as the most burdensome. Three of the 12 predefined decision-making considerations: pharmaceutical knowledge, legal requirements and personal values were rated primarily as having a very strong influence on decision-making.

Conclusion: Pharmacists in community pharmacies are frequently affected by burdensome ethical conflicts in patient care situations.

Background: Despite developing a polypharmacy core outcome set (COS) in primary care, it is not clear how these outcomes should be measured.

Aim: To select outcome measurement instruments (OMIs) for a COS targeting appropriate polypharmacy in older patients in primary care.

Method: Following the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guideline, OMIs were identified from a Cochrane review focusing on appropriate polypharmacy. The quality of OMIs was assessed using a published checklist. Subsequently, two rounds of Delphi questionnaires were conducted via the SoGoSurvey^® platform, engaging stakeholders (researchers, clinicians and journal editors specialising in geriatric primary care) to achieve consensus on OMIs using a scale encompassing "agree", "disagree", or "unsure". Consensus was achieved if 70% or more participants chose "agree" and 15% or fewer chose "disagree."

Results: The quality of 20 OMIs identified from the Cochrane review was evaluated. Seven OMIs were selected based on meeting the COSMIN guideline's minimum requirements. Out of 188 potential participants, 57 (30.3%) consented to participate. Rounds 1 and 2 of Delphi exercises were completed by 50 respondents, achieving agreement on three OMIs: 'number of serious adverse drug reactions (ADRs)' (98%), 'number of deaths' (76%), and 'number of patients who fell' (70%) for measuring 'serious ADRs,' 'mortality,' and 'falls,' respectively. No agreement was reached for 'medication appropriateness,' 'medication side-effects,' 'quality of life,' and 'medication regimen complexity.'

Conclusion: OMIs were selected for a limited number of outcomes in the polypharmacy COS. Future research should identify suitable OMIs for the remaining four outcomes.

Background: Arylpropionic acid derivatives (APs) are the main triggers of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Data on clinical patterns and risk factors for AP hypersensitivity in children are quite limited.

Aim: To assess the clinical characteristics and potential risk factors for proven AP hypersensitivity in children.

Method: Patients with a history of AP hypersensitivity were retrospectively assessed using a standardized diagnostic algorithm. Children with confirmed hypersensitivity were defined as selective responders or cross-intolerants based on the result of drug provocation tests and further categorized according to the EAACI/ENDA classification. A multivariable logistic regression analysis was performed to analyze the potential risk factors for proven AP hypersensitivity.

Results: A total of 166 patients (51.2% male, median age of six years) with a history of AP hypersensitivity were included. Ibuprofen (89.2%) was the most frequently reported AP in the patients' histories. The reported hypersensitivity of 40 (22.4%) patients was confirmed by diagnostic testing: eight (13.6%) patients with a history of reaction only to APs and 32 (29.9%) patients with a history of reactions to multiple NSAIDs, including chemically unrelated NSAIDs in addition to APs. Five (12.5%) patients were classified as selective responders and 35 (87.5%) were cross-intolerants. Overall, five (12.5%) of the confirmed cases could not be categorized according to the EAACI/ENDA classification. Older age (aOR: 1.11, 95% CI 1.02-1.21, p = 0.015), chronic urticaria as an underlying disease (aOR: 2.87, 95% CI 1.09-7.54, p = 0.033) and a history of anaphylaxis (aOR: 7.84, 95% CI 1.86-33.04, p = 0.005) were related to confirmed AP hypersensitivity.

Conclusion: Almost a quarter of children and adolescents were confirmed to have AP hypersensitivity. Older age, the presence of chronic urticaria and a history of anaphylaxis were potential risk factors for proven AP hypersensitivity.

Background: Monoclonal antibodies targeting calcitonin gene-related peptide (anti-CGRP mAbs) have shown clinical effectiveness and safety in randomized clinical studies. However, long-term studies in clinical practice remain limited.

Aim: To assess the long-term effectiveness, clinical predictors and safety of three anti-CGRP mAbs (erenumab, galcanezumab, fremanezumab) in resistant migraine patients.

Method: A single-center retrospective study was conducted from December 2019 to June 2023 involving 120 resistant migraine patients who received at least a month of anti-CGRP mAbs treatment. Patients completed a headache diary that included monthly acute medication intake (MAM), monthly migraine days (MMD), adverse events as well as completed Patient-Reported Outcome questionnaires (MIDAS [Migraine Disability Assessment] and Headache Impact Test 6 [HIT-6]). The number of patients achieving a ≥ 50% reduction in monthly migraine days was determined and classified as ≥ 50% responders, and baseline parameters and logistic regression between responders and non-responders were analyzed to identify potential predictors of response. Adverse events were registered in every follow-up.

Results: Treatment with anti-CGRP mAbs led to reductions in MIDAS, HIT-6, MMD and MAM from baseline to 6-24 months. At 6-12 months, responders (61% and 57%, respectively) exhibited lower baseline MMD and MAM. Medication overuse  was associated with non-responders from 6 to 24 months and it was identified as a negative predictor of treatment effectiveness (OR 0.23, 95% CI 0.07-0.74; p = 0.014).

Conclusion: Anti-CGRP mAbs prove effectiveness and safety over a 24-month period in a RM population. Patients with no medication overuse and lower basal MMDs and MAM may respond better to anti-CGRP mAbs.