Pembrolizumab Plus Chemotherapy Per PD-L1 Stratum In Patients With Metastatic Non-Small Cell Lung Cancer: Real-World Effectiveness Versus Trial Efficacy.

BACKGROUND: Clinical trial efficacy and real-world effectiveness of oncological treatments can differ. This study assessed the real-world survival outcomes of first-line pembrolizumab plus chemotherapy per PD-L1 stratum in patients with metastatic non-small cell lung cancer (mNSCLC) and compared them to clinical trial results. PATIENTS AND METHODS: All patients with nonsquamous and squamous mNSCLC who received first-line pembrolizumab plus chemotherapy in 7 Dutch teaching hospitals between January 1, 2019 and December 31, 2021 were included. Hazard ratios (HR) with confidence intervals (95% CI) for overall survival (OS) and progression-free survival (PFS) were estimated to determine the efficacy-effectiveness gap (EE gap) between real-world and clinical trial, stratified by PD-L1 stratum. RESULTS: The nonsquamous cohort (n = 486) consisted of 269 patients with PD-L1 < 1%, 158 with PD-L1 1% to 49%, and 59 with PD-L1 ≥ 50%. The squamous cohort (n = 117) consisted of 70 patients with PD-L1 < 1% and 47 with PD-L1 ≥ 1%. For OS, an EE gap was observed in nonsquamous patients with PD-L1 < 1% (HR 1.38 (95% CI 1.06-1.78; median OS 10 vs. 17.2 months) and HRs consistently >1 in all other nonsquamous and squamous PD-L1 strata, although not statistically significant. No EE-gap for PFS was observed in any stratum. CONCLUSION: No significant EE gap was found for pembrolizumab plus chemotherapy, except in the stratum nonsquamous mNSCLC with <1% PD-L1 tumor expression. In these patients, the survival in real-world was considerably shorter compared to the clinical trial results. Further studies are needed to determine which patient, treatment and or context factors contribute to this disparity.

Medication-Related Readmissions: Documentation of the Medication Involved and Communication in the Care Continuum.

Background: Of all readmissions, 21% are medication-related readmissions (MRRs). However, it is unknown whether MRRs are recognized at the time of readmission and are communicated in the care continuum. Objectives: To identify the prevalence of MRRs that contain a documentation on the medication involved (and therefore are regarded as recognized), and the proportion of communicated MRRs. Setting: The study was performed in a teaching hospital. Methods: In a previous study, a multidisciplinary team of physicians and pharmacists assessed the medication-relatedness, the medication involved and preventability of unplanned readmissions from seven departments. In the current cross-sectional study, two pharmacy team members evaluated the patient records independently. An MRR was regarded as recognized when the medication involved was documented in patient records. An MRR was regarded as communicated to the patient and/or the next healthcare provider when the medication involved or a description was mentioned in discharge letters or discharge prescriptions. The relationship between documented MRRs and whether the MRR was preventable as well as the relationship between (un)documented MRRs and the length of stay (LOS) were assessed. Descriptive data analysis was used. Results: Of 181 included MRRs, 72 (40%) were deemed preventable by the multidisciplinary team. For 159 of 181 MRRs (88%), a documentation on the medication involved was present. Of 159 documented MRRs, 93 (58%) were communicated to patients and/or caregivers, 137 (86%) to the general practitioner, and 4 (3%) to the community pharmacy. The medication involved was documented less often for potentially preventable MRRs than for non-preventable MRRs (78 vs. 95%; p = 0.002). The LOS was longer for MRRs where the medication involved was undocumented (median 8 vs. 5 days; p = 0.062). Conclusion: The results of this study imply that MRRs are not always recognized, which could impact patients' well-being. In this study an increased LOS was observed with unrecognized MRRs. Communication of MRRs to the patients and/or the next healthcare providers should be improved.

Implementation of a pharmacist-led transitional pharmaceutical care programme: Process evaluation of Medication Actions to Reduce hospital admissions through a collaboration between Community and Hospital pharmacists (MARCH).

WHAT IS KNOWN AND OBJECTIVE: The recently conducted Medication Actions to Reduce hospital admissions through a collaboration between Community and Hospital pharmacists (MARCH) transitional care programme, which aimed to test the effectiveness of a transitional care programme on the occurrence of ADEs post-discharge, did not show a significant effect. To clarify whether this non-significant effect was due to poor implementation or due to ineffectiveness of the intervention as such, a process evaluation was conducted. The aim of the study was to gain more insight into the implementation fidelity of MARCH. METHODS: A mixed methods design and the modified Conceptual Framework for Implementation Fidelity was used. For evaluation, the implementation fidelity and moderating factors of four key MARCH intervention components (teach-back, the pharmaceutical discharge letter, the post-discharge home-visit and the transitional medication review) were assessed. Quantitative data were collected during and after the intervention. Qualitative data were collected using semi-structured interviews with MARCH healthcare professionals (community pharmacists, clinical pharmacists, pharmacy assistants and pharmaceutical consultants) and analysed using thematic analysis. RESULTS AND DISCUSSION: Not all key intervention components were implemented as intended. Teach-back was not always performed. Moreover, 63% of the pharmaceutical discharge letters, 35% of the post-discharge home-visits and 44% of the transitional medication reviews were not conducted within their planned time frames. Training sessions, structured manuals and protocols with detailed descriptions facilitated implementation. Intervention complexity, time constraints and the multidisciplinary coordination were identified as barriers for the implementation. WHAT IS NEW AND CONCLUSION: Overall, the implementation fidelity was considered to be moderate. Not all key intervention components were carried out as planned. Therefore, the non-significant results of the MARCH programme on ADEs may at least partly be explained by poor implementation of the programme. To successfully implement transitional care programmes, healthcare professionals require full integration of these programmes in the standard work-flow including IT improvements as well as compensation for the time investment.

The dynamics in applied COVID-19 pharmacotherapy and the influence of national guidance in The Netherlands: a quantitative and qualitative study.

OBJECTIVE: At the beginning of the COVID-19 pandemic in the Netherlands, the Dutch Working Party on Antibiotic Policy constructed an advisory document about off-label drug treatment options that was regularly updated with new scientific findings. The aim of this study is to describe the dynamics in applied COVID-19 pharmacotherapy during the first 100 days of the pandemic and to assess how the national advisory document influenced local hospital policies. METHODS: A multicentre observational cohort study was conducted in six hospitals in the Netherlands. Patients with confirmed COVID-19 admitted between 27 February and 7 June 2020 were studied. Drug prescription data were collected and percentages of patients receiving a specific treatment were calculated. These percentages were plotted together with release dates of the national advisory document. Semi-structured in-depth interviews with hospital pharmacists and infectious diseases specialists were conducted to gain insight into the development and implementation of pharmacotherapy treatment protocols in hospitals. RESULTS: Data from 1511 patients (60% men, mean age 66 years) were analysed. From mid-March (hydroxy)chloroquine was being prescribed in all six hospitals to approximately 70% of patients at admission. Frequencies of other off-label treatments were below 2%. In the week of 6 April 2020, the first hospital discontinued prescribing (hydroxy)chloroquine and the last hospital discontinued in the week of 4 May 2020 (total range -19 to +10 days after the national advisory document advised against its use (1 May 2020)). All interviewees (n=6) stated that the hospitals based their policies mainly on the national advisory document but also assessed scientific literature themselves. Order panels were constructed to support prescribing. CONCLUSION: Dutch hospitals opted en masse for (hydroxy)chloroquine as COVID-19 therapy at the start of the pandemic, although the time until the therapy was no longer prescribed differed by several weeks. The fact that hospitals defined pharmacotherapy regimens based on their own assessment of the scientific literature besides the national advisory document can explain this variation.

Application of intervention mapping to develop and evaluate a pharmaceutical discharge letter to improve information transfer between hospital and community pharmacists.

BACKGROUND: Insufficient information transfer is a major barrier in the transition from hospital to home. This study describes the systematic development and evaluation of an intervention to improve medication information transfer between hospital and community pharmacists. OBJECTIVE: To develop and evaluate an intervention to improve the medication information transfer between hospital and community pharmacists based on patients', community and hospital pharmacists' needs. METHODS: The intervention development and evaluation was guided by the six-step Intervention Mapping (IM) approach: (1) needs assessment to identify determinants of the problem, with a scoping review and focus groups with patients and healthcare providers, (2) formulation of intervention objectives with an expert group, (3) inventory of communication models to design the intervention, (4) using literature review and qualitative research with pharmacists and patients to develop the intervention (5) pilot-testing of the intervention in two hospitals, and (6) a qualitative evaluation of the intervention as part of a multicenter before-after study with hospital and community pharmacists. RESULTS: Barriers in the information transfer are mainly time and content related. The intervention was designed to target a complete, accurate and timely medication information transfer between hospital and community pharmacists. A pharmaceutical discharge letter was developed to improve medication information transfer. Hospital and community pharmacists were positive about the usability, content, and comprehensiveness of the pharmaceutical discharge letter, which gave community pharmacists sufficient knowledge about in-hospital medication changes. However, hospital pharmacists reported that it was time-consuming to draft the discharge letter and not always feasible to send it on time. The intervention showed that pharmacists are positive about the usability, content and comprehensiveness. CONCLUSION: This study developed an intervention systematically to improve medication information transfer, consisting of a discharge letter to be used by hospital and community pharmacists supporting continuity of care.

The effect of a transitional pharmaceutical care program on the occurrence of ADEs after discharge from hospital in patients with polypharmacy.

INTRODUCTION: Transitional care programs (i.e. interventions delivered both in hospital and in primary care), could increase continuity and consequently quality of care. However, limited studies on the effect of these programs on Adverse Drug Events (ADEs) post-discharge are available. Therefore, the aim of this study was to investigate the effect of a transitional pharmaceutical care program on the occurrence of ADEs 4 weeks post-discharge. METHODS: A multicentre prospective before-after study was performed in a general teaching hospital, a university hospital and 49 community pharmacies. The transitional pharmaceutical care program consisted of: teach-back to the patient at discharge, a pharmaceutical discharge letter, a home visit by a community pharmacist and a clinical medication review by both the community and the clinical pharmacist, on top of usual care. Usual care consisted of medication reconciliation at admission and discharge by pharmacy teams. The primary outcome was the proportion of patients who reported at least 1 ADE 4 weeks post-discharge. Multivariable logistic regression was used to adjust for potential confounders. RESULTS: In total, 369 patients were included (control: n = 195, intervention: n = 174). The proportion of patients with at least 1 ADE did not statistically significant differ between the intervention and control group (general teaching hospital: 59% vs. 67%, ORadj 0.70 [95% CI 0.38-1.31], university hospital: 63% vs 50%, OR adj 1.76 [95% CI 0.75-4.13]). CONCLUSION: The transitional pharmaceutical care program did not decrease the proportion of patients with ADEs after discharge. ADEs after discharge were common and more than 50% of patients reported at least 1 ADE. A process evaluation is needed to gain insight into how a transitional pharmaceutical care program could diminish those ADEs.

Clinical characteristics and risk factors of preventable hospital readmissions within 30 days.

Knowledge regarding preventable hospital readmissions is scarce. Our aim was to compare the clinical characteristics of potentially preventable readmissions (PPRs) with non-PPRs. Additionally, we aimed to identify risk factors for PPRs. Our study included readmissions within 30 days after discharge from 1 of 7 hospital departments. Preventability was assessed by multidisciplinary meetings. Characteristics of the readmissions were collected and 23 risk factors were analyzed. Of the 1120 readmissions, 125 (11%) were PPRs. PPRs occurred equally among different departments (p = 0.21). 29.6% of PPRs were readmitted by a practitioner of a different medical specialty than the initial admission (IA) specialist. The PPR group had more readmissions within 7 days (PPR 54% vs. non-PPR 44%, p = 0.03). The median LOS was 1 day longer for PPRs (p = 0.16). Factors associated with PPR were higher age (p = 0.004), higher socio-economic status (p = 0.049), fewer prior hospital admissions (p = 0.004), and no outpatient visit prior to readmission (p = 0.025). This study found that PPRs can occur at any department in the hospital. There is not a single type of patient that can easily be pinpointed to be at risk of a PPR, probably due to the multifactorial nature of PPRs.

Medication-Related Hospital Readmissions Within 30 Days of Discharge: Prevalence, Preventability, Type of Medication Errors and Risk Factors.

Background: Hospital readmission rates are increasingly used as a measure of healthcare quality. Medicines are the most common therapeutic intervention but estimating the contribution of adverse drug events as a cause of readmissions is difficult. Objectives: To assess the prevalence and preventability of medication-related readmissions within 30 days after hospital discharge and to describe the risk factors, type of medication errors and types of medication involved in these preventable readmissions. Design: A cross-sectional observational study. Setting: The study took place across the cardiology, gastroenterology, internal medicine, neurology, psychiatry, pulmonology and general surgery departments in the OLVG teaching hospital, Netherlands. Participants: Patients with an unplanned readmission within 30 days after discharge from an earlier hospitalization (index hospitalization: IH) were reviewed. Measurements: The prevalence and preventability of medication-related readmissions were assessed by residents in multidisciplinary meetings. A senior internist and hospital pharmacist reassessed the prevalence and preventability of identified cases. Generalized estimating equation with logistic regression was performed to identify risk factors of potentially preventable medication-related readmissions. Results: Of 1,111 included readmissions, 181 (16%) were medication-related, of which 72 (40%) were potentially preventable. The number of medication changes at IH (Adjusted odds ratio [ORadj]: 1.14; 95% CI: 1.05-1.24) and having ≥3 hospitalizations 6 months before IH (ORadj: 2.11; 95% CI: 1.12-3.98) were risk factors of a preventable medication-related readmission. Of these preventable readmissions, 35% were due to prescribing errors, 35% by non-adherence and 30% by transition errors. Medications most frequently involved were diuretics and antidiabetics. Conclusion: This study shows that 16% of readmissions are medication-related, of which 40% are potentially preventable. If the results are confirmed in larger multicentre studies, this may indicate that more attention should be paid to medication-related harm in order to lower the overall readmission rates.

Preventability of unplanned readmissions within 30 days of discharge. A cross-sectional, single-center study.

OBJECTIVES: To identify the preventability, determinants and causes of unplanned hospital readmissions within 30 days of discharge using a multidisciplinary approach and including patients' perspectives. DESIGN: A prospective cross-sectional single-center study. SETTING: Urban teaching hospital in Amsterdam, the Netherlands. PARTICIPANTS: 430 patients were included. Inclusion criteria were: age ≥ 18 years, discharged from one of seven participating clinical departments and an unplanned readmission within 30 days. METHODS: Residents from the participating departments individually assessed whether the readmission was caused by healthcare, the preventability and possible causes of readmissions using a tool. Thereafter, the preventability of the cases was discussed in a multidisciplinary meeting with residents of all participating departments and clinical pharmacists. The primary outcome was the proportion of readmissions that were potentially preventable. Secondary outcomes were the determinants for a readmission, causes for preventable readmissions, the change in the final decision on preventability after the multidisciplinary meeting and the value of patient interviews in assessing preventability. Differences in characteristics of potentially preventable readmissions (PPRs) and non-PPRs were analyzed using multivariable logistic regression. RESULTS: Of 430 readmissions, 56 (13%) were assessed as PPRs. Age was significantly associated with a PPR (adjusted OR: 2.42; 95%, CI 1.23-4.74; p = 0.01). The main causes for PPRs were diagnostic (30%), medication (27%) and management problems (27%). During the multidisciplinary meeting, the final decision on preventability changed in 11% of the cases. When a patient interview was available, it was used as a source of information to assess preventability in 26% of readmissions. In 7% of cases, the patient interview was mentioned as the most important source. CONCLUSION AND IMPLICATIONS: 13% of readmissions were potentially preventable with diagnostic, medication or management problems being main causes. A multidisciplinary review approach and including the patient's perspective could contribute to a better understanding of the complexity of readmissions and possible improvements.

Patients' and providers' perspectives on medication relatedness and potential preventability of hospital readmissions within 30 days of discharge.

BACKGROUND: Hospital readmissions are increasingly used as an indicator of quality in health care. One potential risk factor of readmissions is polypharmacy. No studies have explored the patients' perspectives on the medication relatedness and potential preventability of their readmissions. OBJECTIVE: To compare the patients' perspectives on the medication relatedness and potential preventability of their readmissions with the providers' perspectives. METHODS: Patients unplanned readmitted within 30 days after discharge at one of the participating departments of OLVG Hospital in Amsterdam were interviewed during their readmission. Patients' perspectives regarding medication relatedness of their readmissions, the potential preventability, possible preventable interventions, and satisfaction with medication information were examined. Health-care providers also reviewed files of these readmitted patients. Primary outcome was the percentage of medication-related and potentially preventable readmissions according to the patient vs the provider. Descriptive data analysis was used. RESULTS: According to patients, 36 of 172 (21%) readmissions were medication-related, and of these, 21 (58%) were potentially preventable. According to providers, 26 (15%) readmissions were medication-related and 6 (23%) of these were potentially preventable. Patients and providers agreed on the medication relatedness in 11 of the 172 readmissions, and in two of these, agreement on the potential preventability existed. According to patients, preventive interventions belonged mostly to the hospital level, followed by the primary care level and patient level. CONCLUSION: Patients and providers differ substantially on their perspectives regarding the medication relatedness and preventability of readmissions. Patients were more likely to view medication-related readmissions as preventable.

Validity of a nationwide medication record system in the Netherlands.

Background In the Netherlands, a nationwide Medication Record System based on pharmacy dispensing data is used to obtain information about patients' actual medication use. However, it is not clear to what extent the information of the Nationwide Medication Record System corresponds to the medication information obtained with the Best Possible Medication History. Objective To examine the validity of medication dispensing records collected from the Nationwide Medication Record System by comparing them to the Best Possible Medication History. Method An observational study was performed. Patients from several hospital departments were included at admission. To obtain the Best Possible Medication History, pharmacy technicians performed medication reconciliation at admission, using dispensing records from the Nationwide Medication Record System and information from the patient himself. Primary outcome is percentage of patients with no discrepancies between the Nationwide Medication Record System and the Best Possible Medication History. Descriptive analysis was used. Results Eighty-two patients were approached and 66 (80%) were included, with in total 478 medicines in the Best Possible Medication History. Seventeen percent of the patients had no discrepancies and 33% (n = 156) of the medication records contained a discrepancy between the Nationwide Medication Record System and the Best Possible Medication History. Most common type of discrepancy was omission (44%). Conclusion Even with a Nationwide Medication Record System medication reconciliation with the patient remains essential to obtain complete information about patient's actual medication use.

Prevalence and Preventability of Drug-Related Hospital Readmissions: A Systematic Review.

OBJECTIVES: To summarize the evidence on the prevalence and preventability of drug-related hospital readmissions. DESIGN: A systematic review was performed of studies that examined drug-related hospital readmissions. PubMed, EMBASE, and the Cochrane Library were searched from inception through August 2016. Reference lists and a citation analysis on Web of Science and Scopus were also consulted. Two reviewers extracted study data with dual assessment of risk of bias. Prevalence and preventability of readmission due to drugs were calculated. Data were qualitatively summarized according to outcome. RESULTS: Nineteen studies met the eligibility criteria. Nine measured readmissions due to drug-related problems, seven due to adverse drug reactions, two due to adverse drug events, and one due to drug-drug interactions. Rates of readmissions due to drugs varied from 3% to 64% (median 21%, interquartile range (IQR) 14-23%). Readmissions were deemed preventable in 5% to 87% of cases (median 69%, IQR 19-84%). Evidence regarding the risk factors for drug-related readmissions and drugs causing these readmissions was inconsistent. CONCLUSION: Although studies show high variability in prevalence and preventability of drug-related hospital readmissions, readmissions due to drugs seem to occur often, especially in older adults. Further research is needed to specify the causes of preventable readmissions and implement effective interventions to reduce medication-related hospital admissions.

Completeness of medication-related information in discharge letters and post-discharge general practitioner overviews.

BACKGROUND: Communication and documentation of medication-related information are needed to improve continuity of care. OBJECTIVE: To assess the completeness of medication-related information in discharge letters and post-discharge general practitioner (GP)-overviews. SETTING: A general teaching hospital in Amsterdam, the Netherlands. METHOD: An observational study was performed. Patients from several departments were included after medication reconciliation at hospital discharge. In liaison with the resident and patient, a pharmacy team prepared a Transitional Pharmaceutical Care (TPC)-overview of current medications, including changes and allergies. The resident was instructed to download the TPC-overview into the discharge letter instead of typing a self-made medication list. Medication overviews were gathered from the GP 2 weeks after the handover of the discharge letter. The TPC-overview (gold standard) was compared with the information in the discharge letter and post-discharge GP-overviews regarding correct medications and allergies. Descriptive data analysis was used. MAIN OUTCOME MEASURE: The number and percentage of complete medication-related information in the discharge letter and the GP-overview were compared to the TPC-overview. RESULTS: Ninety-nine patients were included. Medication-related information was complete in 62 (63 %) of 99 discharge letters. Sixteen of 99 GP-overviews (16 %) were complete. Communication of medication-related information increased documentation by the GP, but the medication history could still be incomplete, mainly regarding medication changes and allergies. CONCLUSIONS: Medication-related information is lost in discharge letters and GP-overviews post-discharge despite in-hospital medication reconciliation. This could result in discontinuity of care.