A real-world multicentre evaluation of atezolizumab plus platinum-etoposide chemotherapy as first-line treatment in patients with extensive-stage small cell lung cancer in Italy.

INTRODUCTION: The aim of this study was to analyze real-life data from a cohort of adult patients receiving atezolizumab in combination with carboplatin and etoposide for first-line treatment of ES-SCLC, in order to assess relative dose intensity (RDI), time-to-treatment discontinuation (TTD), time-to-treatment failure (TTF), progression-free survival (PFS), overall survival (OS) of treatments as well as the correlation between these outcomes. METHODS: An observational retrospective study was conducted. All patients treated with atezolizumab combined with carboplatin and etoposide for first-line treatment of ES-SCLC were included. Median TTD, TTF, PFS and OS were calculated in our cohort of patient by the Kaplan Meier method. RESULTS: The curves obtained with the Kaplan Meier method of TTF and TTD are substantially similar, indicating a good concordance of the information extracted by the two different data sources. This tendency was confirmed also when the TTD versus PFS curves were compared. The median OS registered was 11.8 months. Patients with no liver metastases showed a longer median time of OS than patients with liver metastases. The mean value of RDI for the entire cohort was 87.4%. CONCLUSIONS: Our study showed that TTD, calculated from the administration data is a useful proxy of TTF as registered in the clinical chart. TTD is a real-world outcome that can be used to demonstrate the efficacy of drugs used for administered therapies. It can be used as an end point for RWE studies, where the evaluation is less structured and standardized.

Results of EAHP's 2023 shortages survey.

AIMS AND OBJECTIVE: The aim of the European Association of Hospital Pharmacists (EAHP)'s 2023 shortages survey was to collect data on causes and mitigation strategies of shortages of medicines and medical devices and their impact on patient care. The survey targeted hospital pharmacists (HPs), physicians (PHYs), nurses (NRS) and other healthcare professionals (OHCPs). A separate set of questions addressed patients (PTNs). METHODS: A 49-question survey was carried out by a team at EAHP, collecting information from European HPs, PTNs, NRS, PHYs and OTHCs on shortages of medicines and medical devices in their respective countries. The survey ran from 27 February to 19 May 2023. The results were analysed by EAHP. RESULTS: There were 1497 HP responses to the 2023 survey. While 95% (n=1429) of HPs and 86% (n=127) of OHCPs consider medicine shortages an ongoing problem, 84% (n=48) of PHYs and 68% (n=15) of NRS also agreed. Shortages of active pharmaceutical ingredients (77%, n=1148), manufacturing (67%, n=1007) and supply chain problems (50%, n=752) are major causes of shortages according to HPs as well as NRS and OHCPs; PHYs (49%, n=18) consider pricing to be the driver. More than 60% (n=765) of HPs, 55% (n=11) of NRS, 57% (n=30) of PHYs and 46% (n=56) of OHCPs experienced shortages of medical devices in 2022. Antimicrobials were most affected, according to all respondent groups, followed by analgesics, anaesthetics, cardiovascular and paediatric medicines. HPs (59%, n=269), NRS (57%, n=4), OHCPs (56%, n=37) and PHYs (54%, n=14) consider delays in care as the main consequence of medication shortages. CONCLUSIONS: Shortages of medicines and medical devices affect healthcare services and patient care. Increased transparency and access to information regarding ongoing and emerging shortages as well as better preparedness of healthcare professionals is crucial to their effective management.

The lack of head-to-head randomised trials and the consequences for patients and national health service: The case of non-small cell lung cancer.

INTRODUCTION: To introduce a drug to the market, it's not mandatory for it to be more effective and safer than the current treatment for the same condition. Consequently, head-to-head studies between the two best treatments for the same condition are not required, and this could result in a lack of information for patients, clinicians, and decision-makers. This study aims to evaluate the presence of head-to-head studies among the drugs used for the treatment of non-small cell lung cancer (NSCLC). METHODS: Taking into account the National Comprehensive Cancer Network (NCCN) guidelines updated to 2022, which list all available treatments for each NSCLC subtype, the search engine Pubmed and the platform clinicaltrials.gov were consulted to find all completed and ongoing head-to-head studies among various treatments for NSCLC. RESULTS: Among the anti-EGFR (epidermal growth factor receptor) drugs, 7 studies were found, with 6 completed and 5 registrational for drug commercialisation. No completed study to date has compared osimertinib and afatinib. For anti-ALK (anaplastic lymphoma kinase) drugs, 7 studies were found, with 5 completed. Alectinib, brigatinib, and lorlatinib have no completed comparison studies, but all were compared with crizotinib. Among various immunotherapy-based regimens, 5 studies were found, with only 1 completed. Therapeutic regimens based on pembrolizumab, atezolizumab, or the combination of nivolumab/ipilimumab have not been compared in studies published to date. CONCLUSION: There are few head-to-head studies comparing treatments for NSCLC; there are no such studies between the latest generation of drugs. Consequently, ambiguous areas exist due to the lack of comparative studies among the available evidence, preventing the clinician's choice of the most effective treatment and risking the patient receiving suboptimal therapy. Simultaneously, the price of the drug cannot be determined correctly, relying only on indirect evaluations from different trials. To dispel this uncertainty, it would be desirable to initiate a process that brings together the demands derived from clinical practice and clinical research to provide clinicians and patients with the best possible evidence.

Developing and piloting a communication assessment tool assessing patient perspectives on communication with pharmacists (CAT-Pharm).

BACKGROUND: Effective communication strategies in health care help to enhance patient empowerment and improve clinical outcomes. OBJECTIVE: Adapt the original Communication Assessment (CAT) instrument for the pharmacist profession (CAT-Pharm) and to test its validity and reliability in two different settings. SETTING: Five hospital pharmacies in Italy and five community pharmacies in Malta. METHOD: Pilot study involving a standardized multi-step process adhering to internationally accepted and recommended guidelines. Corrections and adjustments to the translation addressed linguistic factors and cultural components. CAT-Pharm, compared to the original CAT, maintained 10 out of the 14 items: one was slightly modified; three were changed to better fit the pharmacist role; one was added. MAIN OUTCOME MEASURES: CAT-Pharm development and testing its practicality to assess patient perceptions of pharmacists' interpersonal and communication skills. RESULTS: CAT-Pharm was tested on 97 patients in the Italian setting and 150 patients in the Maltese setting to assess the practicality of the tool and its usefulness in investigating gaps and priorities for improving pharmacist-patient communication. Results Show reliability and internal validity of the CAT-Pharm tool. The analysis of patient perceptions of communication with the pharmacist in Italy indicated differences from that in Malta. The different settings provided insight into the utility of CAT-Pharm. CONCLUSION: This study provided a valid and reliable tool that could be applied to assess patient perception of the pharmacist's communication abilities.

Managing antibiotic shortages: lessons from EAHP and ECDC surveys.

AIMS AND OBJECTIVE: To compare antibiotic shortages in Europe between 2013 and 2020 and the views of hospital pharmacists on overcoming shortages via antimicrobial stewardship. METHODS: A series of European Association of Hospital Pharmacists (EAHP) surveys on medicine shortages, including a survey on the future crisis preparedness of hospital pharmacies, conducted between 2013 and 2020 were compared for the type of antibiotic shortages and respective mitigation strategy. These were analysed taking into account hospital pharmacists' views on antibiotics provided in the European Centre for Disease Prevention and Control (ECDC) survey on healthcare professionals' knowledge, attitudes and behaviours about antibiotics, antibiotic use and antibiotic resistance from 2018. RESULTS: Since 2013 there has frequently been a shortage of antibiotics in European hospitals. In 2014, 67% (347/521) of hospital pharmacists experienced shortages of antimicrobials compared with 77% (1032/1348) in 2018, 63% (1158/1837) in 2019 and 37% (539/1466) in 2020. More than 80% of hospital pharmacists managed antibiotic shortages through substitution in 2014 (284/336) and 2018 (786/946), while this percentage was 40% (63/158) and 42% (620/1466) in 2019 and 2020, respectively. Although 72% (870/1204) of hospital pharmacists received information on how to avoid inappropriate antibiotic prescribing, dispensing and administration, only 37% (450/1204) changed their views and 28% (338/1204) changed their practice in steering antimicrobial treatment. CONCLUSION: Antibiotic shortages affect proper antimicrobial stewardship because of limited appropriate alternatives, taking into account patients' clinical condition and type of infection. While substitution remains a leading mitigating tool for antibiotic shortages, it carries numerous risks and the potential for antimicrobial resistance and suboptimal health outcomes.

Role of the hospital pharmacist in an Italian antimicrobial stewardship programme.

The inappropriate use of antimicrobial agents is contributing to an increasing phenomenon of bacterial resistance. For this reason, there is a growing interest in 'antimicrobial stewardship', a series of coordinated and multidisciplinary interventions aimed to promote the safe and appropriate use of antimicrobials in which the pharmacist's contribution is necessary for the optimal choice of drug, dose, duration of therapy and the implementation of cost containment strategies. AIM OF THE STUDY: We wanted to create a reference model and a specific training manual on antibiotic stewardship to introduce the role of the department pharmacist with specific infection disease skills in the Italian health system hospitals. METHODS: This study was conducted in six Italian hospitals for 24 months. It was divided into three phases: definition of indicators (as defined daily doses/100 days of hospitalisation, switches from intravenous (IV) to oral and from empirical to targeted therapies, etc) elaboration of research protocol; sharing, application and detection of the indicators and selection of centres involved; analysis and sharing of results and subsequent drafting and distribution of the training manual.Statistical analysis focused on possible differences between the frequencies of the aforementioned switches. Differences were analysed comparing the values recorded in the first quarter with those of the third quarter trough a χ² test. Statistical significance was set at p<0.05. RESULTS: The pharmacist's work showed a statistically significant increase in the conversion from IV to oral antibiotic therapy (χ² (1.496)=9112 ; p=0.0025; df=1). It was also detected a 5% improvement in appropriate dosing, 34% reduction in drug stocks, 4% increase in allergy reports and 275% increase in the number of adverse drug reactions reported. CONCLUSIONS: In this study, the interventions of the antibiotic stewardship pharmacist led to an improvement in quality of care, resource efficiency and healthcare professional awareness.

Lessons learnt from the COVID-19 pandemic: results of EAHP survey on the future crisis preparedness of hospital pharmacies.

AIM: The present survey aimed to collect information on the lessons learnt from the COVID-19 pandemic by hospital pharmacists. It focused on the shortages of health goods and the experiences of hospitals during the first phase of the crisis. METHODS: A 17-question survey was conducted by EAHP, looking at the experiences of hospital pharmacists during the COVD-19 pandemic. The survey ran from 16 September to 23 December 2020. Statistical analysis included backward stepwise logistic regression (BSLR), Pearson's χ2 test, t-test and one-way ANOVA, as appropriate; p≤0.05 was considered statistically significant. RESULTS: 1466 hospital pharmacists answered the survey fully. 58%, 63% and 69% of them experienced shortages in medicines, disinfectants and personal protective equipment (PPE), respectively. BSLR showed that being a COVID-19 dedicated hospital increased the risk of medicine shortages (OR 1.63, 95% CI 1.15 to 2.31) but the shortages of disinfectants and PPE were lower (OR 0.62, 95% CI 0.44 to 0.88; OR 0.60, 95% CI 0.42 to 0.85). Being a specialised hospital reduced the odds of medicine shortages (OR 0.59, 95% CI 0.40 to 0.88), while countries with a greater percentage of the population infected had increased odds for all three types of shortages (OR 1.16, 95% CI 1.01 to 1.23; OR 1.34, 95% CI 1.19 to 1.50; OR 1.21, 95% CI 1.09 to 1.35). The odds were also higher in answers submitted in September compared with December. The classes of medicines with highest reported shortages were anaesthetics, antibiotics and muscle relaxants. The main entities that provided support were the national competent authorities and manufacturers. CONCLUSION: Medicine shortages affected the work of hospital pharmacists during the early stages of the pandemic. The features of the crisis and the feedback described in this survey can provide interesting insights for a more resilient healthcare framework in the future.

The European COVID-19 drugs calculation tool: an aid for the estimation of the drugs needed during the SARS-CoV 2 pandemic.

OBJECTIVE: To create an informatics supportive tool, which can assist healthcare professionals in estimating potential requirements for essential drug supplies to respond to the current SARS-CoV-2 pandemic based on epidemiological forecasting. METHODS: The tool was based on a Susceptible-Infected-Removed (SIR) epidemiological model in which the population is divided into three compartments and transmission parameters are specified to define the rate at which people move between stages. Appropriate data entry was guaranteed by the creation of structured guided paths. The drugs needed for the forecasted patients were estimated according to a list of critical care drugs compiled by consulting previous published scientific works, national and international guidelines. For each drug, an estimation was made of the percentage average ICU uptake for each therapeutic group and active principle. RESULTS: The tool consists of a Microsoft Excel template that is based on the initial epidemiological situation, the non-pharmaceutical interventions applied, the risk of hospitalisation based on the population age distribution, and the hospital beds available. The tool provides a forecast of which patients with COVID-19 will need to be treated in a hospital setting. The number of patients is used to estimate the drugs needed based on the average daily dose and the treatment length of each drug. The possibility of editing the type of distribution (exponential or linear) of the number of patients at the beginning of the analysis, the percentage adherence with non-pharmaceutical interventions and their delayed effect, and all the key epidemiological parameters make the estimation tailorable to different clinical contexts and needs. CONCLUSIONS: This model might be an effective supporting tool that could be easily implemented within the workflow of health professionals. All the information reported in this paper could be useful in developing new strategies to tackle the COVID-19 pandemic.

[A prospective observational study on daily intake of drugs, supplements and herbal products and detection of adverse drug reactions in elderly patients.] / Studio osservazionale prospettico relativo all'assunzione giornaliera di farmaci, integratori e prodotti erboristici nei pazienti anziani e rilevazione delle reazioni avverse ai farmaci.

Polytherapy is a common condition in the elderly patient and represents a risk factor for the onset of adverse drug reactions (ADRs). The objectives of this prospective study were the verification of the compliance with implicit criteria (Lipton, MAI and POM) to geriatric prescriptions, the identification of ADRs and the estimatation of the intake of drugs, over-the-counter (OTC) drugs, supplements and herbal products through the administration of a questionnaire. A total of 400 elderly patients (average age 73 years) were analyzed between September 2018 and September 2019. 79.5% of them were in polytherapy (≥4 drugs). The most frequently prescribed drugs were antihypertensives (75%). The use of OTC drugs was reported for 12% patients; the use of supplements for 25% of patients and the use of herbal products only for 2% patients. The prescriptions analysed resulted in compliance with the implicit criteria in terms of dosage, therapeutic indications and the presence of any drug allergies. ADRs were reported for 10% of patients: those related to nintedanib (53%) and pirfenidone (34%) were the most frequent.

Systematic Review and Meta-analysis of Pirfenidone, Nintedanib, and Pamrevlumab for the Treatment of Idiopathic Pulmonary Fibrosis.

BACKGROUND: The comparative efficacy of pirfenidone, nintedanib, and pamrevlumab in slowing the rate of forced vital capacity (FVC) decline and mortality in patients with idiopathic pulmonary fibrosis (IPF) is unknown. OBJECTIVE: To perform a systematic review and meta-analysis (MA) of these drugs for IPF. METHODS: We searched CENTRAL, PubMed, EMBASE, ClincalTrials.gov, and the World Health Organization's registry databases up to March 2020. Phase II/III randomized controlled trials in adults with IPF were eligible. The random-effect model was implemented calculating the effect size and respective 95% CI as Cohen's d for change from baseline FVC (in percentage predicted and liters) and odds ratio (OR) for 10% reduction in FVC and all-cause mortality (ACM). RESULTS: Six studies were included in the MA. For change from baseline in percentage predicted FVC, the MA indicated that the 3 drugs were more effective than placebo (pirfenidone: d=3.30%, 95% CI=2.15-4.45; nintedanib: d=3.15%, 95% CI=2.35-3.95; pamrevlumab: d=4.30%, 95% CI=0.45-8.15). These results are superimposable to those relating to change from baseline FVC in liters (pirfenidone: d=0.09L, 95% CI=0.04-0.14; nintedanib: d=0.13L, 95% CI=0.10-0.16; pamrevlumab: d=0.20L, 95% CI=0.05-0.35). Each drug had a positive effect on 10% reduction in FVC (pirfenidone: OR=0.57, 95% CI=0.45-0.74; nintedanib: OR=0.66, 95% CI=0.51-0.85; pamrevlumab: OR=0.24, 95% CI=0.08-0.73), but only pirfenidone showed an effect on ACM (OR=0.50; 95% CI=0.31-0.83). CONCLUSION AND RELEVANCE: This MA provided encouraging results on pamrevlumab efficacy in slowing the decline in FVC compared with pirfenidone and nintedanib. Actually, in phase 3, it could become a potential IPF treatment.

Evidence-based application of explicit criteria to assess the appropriateness of geriatric prescriptions at admission and hospital stay.

BACKGROUND: Inappropriate prescribing in the elderly is a critical issue in primary care, causing a higher risk of Adverse Drug Reactions (ADRs) and resulting in major patient safety concerns. At international level, many tools have been developed to identify Potentially Inappropriate Medications (PIMs). OBJECTIVE: The aim of this study was the application of Beers, Screening Tool of Older People's Prescriptions (STOPP)/Screening Tool to Alert to Right Treatment (START) and Improving Prescribing in the Elderly Tool (IPET) criteria as key tool to improve the quality of prescribing. METHODS: A retrospective study was conducted using the aforementioned criteria. Two different cohorts of elderly patients were enrolled between January 2015 and December 2016, 1800 at admission and 1466 at hospital stay. The index of each criterion divided by politherapy were correlated with comorbidities (Pearson correlation). A comparison was made between admission and hospital stay through a Student's t test of the average of the index. RESULTS: The Proton Pump Inhibitors (PPIs) were the most prescribed PIMs according Beers criteria in both patient cohorts (56%). The most detected drug-drug and drug-disease interactions at admission and at hospital stay were 3 or more drugs active on the Central Nervous System (CNS) as they can predispose to fall-risk. The most detected PIMs with STOPP criteria at admission were PPIs administered for more than 8 weeks. Inhaled ß2-agonists or antimuscarinics were the most prescribed Potential Prescription Omissions (PPOs) according to START criteria. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in patients with high blood pressure were the most detected PIMs according to IPET criteria during hospital stay. A significant correlation between the comorbidities and the all index at hospital stay, while at admission there was no significant correlation for Beers and IPET index. CONCLUSION: The prescriptive criteria were a useful tool for assessing the quality of prescriptions in the geriatric population and identifying their critical issues.

Results of EAHP's 2019 Medicines Shortages Survey.

AIMS AND OBJECTIVES: The aim of the 2019 EAHP Medicines Shortages Survey was to collect information on reasons and management strategies for medicines shortages as well as details on their impact on patients. The survey targeted hospital pharmacists (HPs), physicians (PHYs), nurses (NRS) and other healthcare professionals (OHCPs). A separate set of questions addressed patients (PTNs). METHODS: A 28-question survey was conducted by EAHP, collecting information from European HPs, PTNs, NRS, PHYs and OHCPs on the shortage situation in their respective countries. The survey ran from 7 November 2019 to 13 January 2020. The results were analysed by EAHP. RESULTS: There were 2136 HP responses to the 2019 survey compared with 1666 in 2018. While 95% of HPs and 89% of OHCPs consider medicine shortages a current problem, only 71% of PHYs and 62% of NRS state the same. Shortages of active pharmaceutical ingredients (72%), manufacturing (72%) and supply chain problems (49%) are leading causes of shortages according to HPs, while PHYs (40%) and NRS (37%) consider the pricing to be their driver. Antimicrobials and oncology medicines were most affected by shortages in 2019. Compared to 2018, the percentage of respondents who reported shortages of oncology medicines increased from 39% to 47% in 2019. HPs (42%), PHYs (36%) and OHCPs (38%) consider delays in care as the main consequence of medication shortages. The satisfaction with reporting systems for medicine shortages decreased from 56% in 2018 to 48% in 2019 for HPs, while they remain low for PHYs (36%). CONCLUSIONS: Medicines shortages affect patient care and healthcare professionals' everyday tasks. Better enforcing of the mandatory early notification of shortages and structured mitigation response is recognised by all respondents as best strategy to tackle shortages.

Covid-19 and drug therapy, what we learned.

COVID-19, the disease associated in December 2019 with the novel coronavirus SARS-CoV-2, was observed for the first time in China and then spread worldwide becoming pandemic. Currently, there is still no licensed specific antiviral treatment for the human coronavirus disease and a vaccine will not be ready soon. However, based on experience from the use of other antiviral agents to treat similar virusses, some treatment options have been tried with some efficacy. Clinical trials for future therapies are still ongoing. In the meantime, prevention, control, active communication and investment in research are the only ways to overcome this challenge.

How can we optimise antifungal use in a solid organ transplant centre? Local epidemiology and antifungal stewardship implementation: A single-centre study.

PURPOSE: We aimed to implement and to assess the impact of the antifungal stewardship programme (AFSp) on prescription appropriateness of antifungals, management and outcomes of candidaemia patients, and antifungal consumption and costs at our solid organ transplant (SOT) institute. METHODS: Local epidemiology of invasive fungal infections (IFIs) from 2009 to 2017 was analysed in order to prepare an effective AFSp, implemented in January 2018. It included suspension of empirical antifungal prescriptions after 72 hours (antifungal time-out), automated alert and infectious disease (ID) consult for empirical prescriptions and for every patient with IFI, and indication for step-down to oral fluconazole when possible. We used process measures and results measures to assess the effects of the implemented programme. RESULTS: The ASFp led to significant improvements in selection of the appropriate antifungal (40.5% in pre-AFS vs 78.6% in post-AFS), correct dosing (51.2% vs 79.8%), correct length of treatment (55.9% vs 75%) and better management of patients with candidaemia. Analysis of prescribed empirical antifungal revealed that defined daily doses (DDDs) per 100 patient days decreased by 36.7% in 2018 compared to the average of pre-AFSp period, with important savings in costs. CONCLUSION: This AFSp led to a better use of antifungal drugs in terms of appropriateness and consumption, with stable clinical and microbiological outcomes in patients with IFI.

Prospective Risk Assessment of Medicine Shortages in Europe and Israel: Findings and Implications.

INTRODUCTION: While medicine shortages are complex, their mitigation is more of a challenge. Prospective risk assessment as a means to mitigate possible shortages, has yet to be applied equally across healthcare settings. The aims of this study have been to: 1) gain insight into risk-prevention against possible medicine shortages among healthcare experts; 2) review existing strategies for minimizing patient-health risks through applied risk assessment; and 3) learn from experiences related to application in practice. METHODOLOGY: A semi-structured questionnaire focusing on medicine shortages was distributed electronically to members of the European Cooperation in Science and Technology (COST) Action 15105 (28 member countries) and to hospital pharmacists of the European Association of Hospital Pharmacists (EAHP) (including associated healthcare professionals). Their answers were subjected to both qualitative and quantitative analysis (Microsoft Office Excel 2010 and IBM SPSS Statistics®) with descriptive statistics based on the distribution of responses. Their proportional difference was tested by the chi-square test and Fisher's exact test for independence. Differences in the observed ordinal variables were tested by the Mann-Whitney or Kruskal-Wallis test. The qualitative data were tabulated and recombined with the quantitative data to observe, uncover and interpret meanings and patterns. RESULTS: The participants (61.7%) are aware of the use of risk assessment procedures as a coping strategy for medicine shortages, and named the particular risk assessment procedure they are familiar with failure mode and effect analysis (FMEA) (26.4%), root cause analysis (RCA) (23.5%), the healthcare FMEA (HFMEA) (14.7%), and the hazard analysis and critical control point (HACCP) (14.7%). Only 29.4% report risk assessment as integrated into mitigation strategy protocols. Risk assessment is typically conducted within multidisciplinary teams (35.3%). Whereas 14.7% participants were aware of legislation stipulating risk assessment implementation in shortages, 88.2% claimed not to have reported their findings to their respective official institutions. 85.3% consider risk assessment a useful mitigation strategy. CONCLUSION: The study indicates a lack of systematically organized tools used to prospectively analyze clinical as well as operationalized risk stemming from medicine shortages in healthcare. There is also a lack of legal instruments and sufficient data confirming the necessity and usefulness of risk assessment in mitigating medicine shortages in Europe.