Reorganising and improving quality of care for hyperemesis gravidarum in a Danish hospital: a quality improvement project

Background Hyperemesis gravidarum (HG) is a pregnancy complication comprising severe nausea and vomiting in pregnancy. It is associated with adverse outcomes for both mother and child. Treatment consists primarily of antiemetics and intravenous fluids; however, support from healthcare professionals is also important.Local problem At the department of obstetrics at Nordsjællands Hospital, an increasing workload caused challenges regarding patient care and organisation for patients with HG, and exploring possibilities of reorganising HG care to release midwife resources was warranted.Methods Through input from staff and patients, possible improvements were identified. Plan–do–study–act cycles were conducted with staff and patients, resulting in adjustments in care and organisation and thus use of resources. The specific, measurable, attainable, realistic and timely aims included patient satisfaction and number of follow-ups conducted via phone.Interventions HG care was relocated to the department of gynaecology, where it was managed primarily by nurses. Staff and patients were actively involved in the process.Results HG care was successfully relocated without compromising patient satisfaction. Additionally, an option of patient-administered home treatment for selected patients was established.Conclusion This quality improvement project describes the relocation and set-up of hospital care provided to patients with HG, resulting in high patient satisfaction. This project might serve as an inspiration to other departments of obstetrics and gynaecology

Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

Personalized cancer immunotherapy based on infusion of T cells holds the promise to specifically target a patient’s individual tumor. Accumulating evidence indicates that the T cells mediating these tumor regressions after cancer immunotherapies may primarily target patient-specific mutations expressed by the patients’ tumors and that the presence of these “neo-antigen” specific T-cells may be related to a high number of mutations in the tumor. In melanoma, treatment with autologous tumor-infiltrating lymphocytes (TILs) can mediate durable complete responses. Previous trials investigating TIL therapy in solid tumors other than melanoma have shown limited success, however none of these early trials used current preparative chemotherapy regimens, and the methods for in vitro lymphocyte expansion have changed considerably. New advances and understandings in T cell based immunotherapies have stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe the major advances in the characterization and application of TIL therapy for patients with RCC and OC

PD-1 + polyfunctional T cells dominate the periphery after tumor-infiltrating lymphocyte therapy for cancer

Purpose: Infusion of highly heterogeneous populations of autologous tumor-infiltrating lymphocytes (TILs) can result in tumor regression of exceptional duration. Initial tumor regression has been associated with persistence of tumor-specific TILs one month after infusion, but mechanisms leading to long-lived memory responses are currently unknown. Here we studied the dynamics of bulk tumor-reactive CD8+ T cell populations in patients with metastatic melanoma following treatment with TILs. Experimental Design: We analyzed the function and phenotype of tumor-reactive CD8+ T cells contained in serial blood samples of sixteen patients treated with TILs Results: Polyfunctional tumor-reactive CD8+ T cells accumulated over time in the peripheral lymphocyte pool. Combinatorial analysis of multiple surface markers (CD57, CD27, CD45RO, PD- 1 and LAG-3) showed a unique differentiation pattern of polyfunctional tumor-reactive CD8+ T cells, with highly specific PD-1 upregulation early after infusion. The differentiation and functional status appeared largely stable for up to 1 year post-infusion. Despite some degree of clonal diversification occurring in vivo within the bulk tumor-reactive CD8+ T cells, further analyses showed that CD8+ T cells specific for defined tumor-antigens had similar differentiation status. Conclusions: We demonstrated that tumor-reactive CD8+ T cell subsets which persist after TIL therapy are mostly polyfunctional, display a stable partially differentiated phenotype and express high levels of PD-1. These partially differentiated PD-1 + polyfunctional TILs have a high capacity for persistence and may be susceptible to PD-L1/PD-L2-mediated inhibition

Mirtazapine exposure in pregnancy and fetal safety:A nationwide cohort study

OBJECTIVE: To investigate the association between mirtazapine exposure in pregnancy and risk of specific adverse pregnancy outcomes. METHODS: A register‐based nationwide cohort study was conducted including all registered pregnancies in Denmark from 1997 to 2016. Mirtazapine‐exposed pregnancies were compared with mirtazapine unexposed pregnancies in a 1:4 ratio matched according to propensity scores. Outcomes were major congenital malformations analyzed using log binomial models, and spontaneous abortion, stillbirth and neonatal death analyzed using Cox proportional hazard regression. RESULTS: From a source population of 1,650,649 pregnancies, the propensity score‐matched cohort included 4475 pregnancies (895 mirtazapine exposed) in the analysis of major congenital malformations. The analyses of spontaneous abortion included 9 500 pregnancies (1900 mirtazapine exposed), and for the analyses of stillbirths and neonatal deaths 9725 (1 945 mirtazapine‐exposed) and 4485 pregnancies (897 mirtazapine‐exposed) were included, respectively. Thirty‐one (3.5%) children were diagnosed with major congenital malformation among the mirtazapine exposed compared with 152 (4.3%) among the unexposed pregnancies (OR=0.81, 95% CI 0.55–1.20). Spontaneous abortion occurred in 237 (12.5%) of the mirtazapine exposed compared with 931 (12.3%) of the unexposed pregnancies (HR = 1.04%, 95% CI 0.91–1.20). The analyses revealed no increased risk of stillbirth (HR = 0.88%, 95% CI 0.34–2.29) or neonatal death (HR = 0.60%, 95% CI 0.18–2.02). CONCLUSIONS: In this nationwide Danish register study, mirtazapine exposure in pregnancy was not associated with major congenital malformations, spontaneous abortion, stillbirth, or neonatal death. Clinicians and patients can be reassured that mirtazapine is safe in pregnancy