A systematic review of interventions to improve medication adherence in adults with mental-physical multimorbidity in primary care.

BACKGROUND: Medication non-adherence is a significant contributor to healthcare inefficiency, resulting in poor medication management, impaired patient outcomes and ineffective symptom control. This review summarises interventions targeting medication adherence for adults with mental-physical multimorbidity, in primary healthcare settings. METHODS: A systematic review of literature was conducted using Medline, Embase, PsycInfo, Web of Science, Cochrane Library, and CINAHL were searched for relevant studies. Data were extracted and synthesized using narrative synthesis. The Cochrane Effective Practice and Organisation of Care (EPOC) was used to classify intervention types. Risk of bias was assessed using the National Heart, Lung, and Blood Institute (NHLBI) quality assessment tool. RESULTS: Eleven studies representing 2,279 patients were included. All interventions examined were classified into one EPOC domain, which was delivery arrangements. All included studies examined patients with a physical condition, alongside depression. Seven studies examining coordination of care and management of care processes interventions reported significant improvements in medication adherence attributed to the intervention. Four studies considering the use of information and communication technology observed no changes in medication adherence. CONCLUSION: Interventions that coordinate and manage healthcare processes may help improve how patients adhere to their medication regimes, particularly in patients with mental-physical multimorbidity. However, we still need to better understand how digital health technology can support patients in following their medication regimes. As we face the growing challenges of treating multimorbidity, everyone involved in health services - from providers to policymakers - must be receptive to a more integrated approach to the delivery of healthcare.

The effects of community interventions on unplanned healthcare use in patients with multimorbidity: a systematic review.

OBJECTIVES: To summarise the impact of community-based interventions for multimorbid patients on unplanned healthcare use. The prevalence of multimorbidity (co-existence of multiple chronic conditions) is rapidly increasing and affects one-third of the global population. Patients with multimorbidity have complex healthcare needs and greater unplanned healthcare usage. Community-based interventions allow for continued care of patients outside hospitals, but few studies have explored the effects of these interventions on unplanned healthcare usage. DESIGN: A systematic review was conducted. MEDLINE, EMBASE, PsychINFO and Cochrane Library online databases were searched. Studies were screened and underwent risk of bias assessment. Data were synthesised using narrative synthesis. SETTING: Community-based interventions. PARTICIPANTS: Patients with multimorbidity. MAIN OUTCOME MEASURES: Unplanned healthcare usage. RESULTS: Thirteen studies, including a total of 6148 participants, were included. All included studies came from high-income settings and had elderly populations. All studies measured emergency department attendances as their primary outcome. Risk of bias was generally low. Most community interventions were multifaceted with emphasis on education, self-monitoring of symptoms and regular follow-ups. Four studies looked at improved care coordination, advance care planning and palliative care. All 13 studies found a decrease in emergency department visits post-intervention with risk reduction ranging from 0 (95% confidencec interval [CI]: -0.37 to 0.37) to 0.735 (95% CI: 0.688-0.785). CONCLUSIONS: Community-based interventions have potential to reduce emergency department visits in patients with multimorbidity. Identification of specific successful components of interventions was challenging given the overlaps between interventions. Policymakers should recognise the importance of community interventions and aim to integrate aspects of these into existing healthcare structures. Future research should investigate the impact of such interventions with broader participant characteristics.

Association Between Lung Immune Prognostic Index and Durvalumab Consolidation Outcomes in Patients With Locally Advanced Non-Small-Cell Lung Cancer.

INTRODUCTION: The LIPI, based on pretreatment derived neutrophils/[leukocytes-neutrophils] ratio (dNLR) and LDH, is associated with immune checkpoint inhibitors (ICI) outcomes in advanced non-small-cell lung cancer (NSCLC). We aimed to assess baseline LIPI correlation with durvalumab consolidation outcomes in the locally advanced setting. MATERIAL AND METHODS: Multicentre retrospective study (330 patients) with stage III unresectable NSCLC treated with durvalumab after chemo-radiotherapy between April 2015 and December 2020; 65 patients treated with chemo-radiotherapy only. Baseline LIPI characterized 3 groups: good (dNLR≤3+LDH≤ULN), intermediate (dNLR>3/LDH>ULN) and poor (dNLR>3+LDH>ULN). Primary endpoint was overall survival (OS). RESULTS: In the durvalumab cohort, median age was 67 years, 95% smokers, 98% with a performance status of 0-1; 60% had nonsquamous histology and 16% a PD-L1 expression <1%. Radiotherapy was delivered concurrently in 81%. LIPI was evaluable in 216 patients: 66% good, 31% intermediate, 3% poor. LIPI significantly correlated with median OS (median follow-up: 19 months): 18.1 months vs. 47.0 months vs. not reached in poor, intermediate and good LIPI groups, respectively (P = .03). A trend between objective response rate and LIPI groups was observed: 0% vs. 41% vs. 45%, respectively (P = .05). The pooled intermediate/poor LIPI group was associated with shorter OS (HR 1.97; P = .03) and higher risk of progressive disease (OR 2.68; P = .047). Survivals and response were not influenced in the control cohort. CONCLUSION: Baseline LIPI correlated with outcomes in patients with locally advanced NSCLC treated with durvalumab consolidation, but not in those who only received chemo-radiotherapy, providing further evidence of its prognostic and potential predictive role of ICI benefit in NSCLC.

Maintained complete response to talazoparib in a BRCA-2 mutated metastatic luminal breast cancer: case report and review of literature.

PARP inhibitors are progressively becoming a part of our therapeutic arsenal against BRCA-defective tumors, because of their capacity to induce synthetic lethality in cells with a deficiency in the homologous recombination repair system. Olaparib and talazoparib have been approved for metastatic breast cancer in carriers of germline BRCA mutations, which are found in approximately 6% of patients with breast cancer. We report the case of a patient with metastatic breast cancer, carrier of a germline mutation in BRCA2, with a complete response to first-line treatment with talazoparib, maintained after 6 years. To the best of our knowledge, this is the longest response reported with a PARP inhibitor in a BRCA-mutated tumor. We have made a review of literature, regarding the rationale for PARP inhibitors in carriers of BRCA mutations and their clinical relevance in the management of advanced breast cancer, as well as their emerging role in early stage disease, alone and in combination with other systemic therapies.

A Systematic Review of Interventions that Use Multidisciplinary Team Meetings to Manage Multimorbidity in Primary Care.

Introduction: Multidisciplinary team (MDT) meetings could facilitate coordination of care for individuals living with multimorbidity, yet there is limited evidence on their effectiveness. We hence explored the common characteristics of MDT meetings in primary care and assessed the effectiveness of interventions that include such meetings, designed to improve outcomes for adults living with multimorbidity. Methods: A systematic review of literature was conducted using MEDLINE and EMBASE. A narrative synthesis was performed, extracting study and MDT meeting characteristics, in addition to any outcomes reported. Results: Four randomised controlled trials that were conducted in the United States of America were identified as eligible, recruiting a total of 3,509 adults living with multimorbidity. Common MDT meeting themes include regular frequency of discussion, the absence of patient involvement and the participation of three or four multiprofessionals. Significant improvements were observed in response to interventions with an MDT component across most measures, yet this trend did not extend to physical health outcomes. Discussion: It is unclear if the results in this review are sufficient to support the widespread implementation of MDT meetings in primary care, for adults living with multimorbidity. Due to the paucity of studies collated, further research is required to inform widespread implementation.

Durvalumab consolidation in patients with unresectable stage III non-small cell lung cancer with driver genomic alterations.

INTRODUCTION: Durvalumab is the standard-of-care as consolidation therapy after chemo-radiotherapy in stage III unresectable non-small cell lung cancer (NSCLC); however, its activity across patients with NSCLC harbouring driver genomic alterations (dGA) is poorly characterised. MATERIAL AND METHODS: Multicentre retrospective study including patients with stage III unresectable NSCLC treated with durvalumab after chemo-radiotherapy between April 2015 and October 2020 at 26 centres in Europe and America. Clinical and biological data were collected; dGA included: EGFR/BRAF/KRAS mutations (m) and ALK/ROS1 rearrangements (r). We evaluated progression-free survival (PFS) and overall survival (OS) based on dGA. RESULTS: Out of 323 patients included, 43 patients had one dGA: KRASm (n = 26; 8 G12C), EGFRm (n = 8; 6 del19/ex21), BRAFm (n = 5; 4 V600E) and ALKr (n = 4). The median age was 66 years [39-84], gender ratio 1:1, with 98% performance status (PS) 0-1 and 19% non-smokers; 88% had adenocarcinoma. PD-L1 was positive in 85% (n = 4 missing). In the whole cohort, the median PFS was 17.5 months (mo.) (95% CI, 13.2-24.9) and median OS 47 mo (95%CI, 47-not reached [NR]). No statistically significant differences in terms of the median PFS were observed between patients with dGA vs. non-dGA: 14.9 mo (95% CI, 8.1-NR) vs. 18 mo. (95% CI, 13.4-28.3) (P = 1.0); however, when analysed separately: the median PFS was NR (11.3-NR) in the KRASm G12C vs. 8.1 mo (5.8-NR) in the EGFRm del19/ex21 vs. 7.8 mo (7.7-NR) in the BRAFm V600E/ALKr (P = 0.02). CONCLUSIONS: We observed limited activity of durvalumab consolidation in patients with stage III unresectable NSCLC with EGFR/BRAFm and ALKr but not for those harbouring KRASm. Larger prospective studies are needed to confirm these findings.