Locoregional CAR T Cells for the Treatment of CNS Tumors in Children: Investigational Drug Service Pharmacy Activities.

BACKGROUND: A major obstacle in translating the therapeutic potential of chimeric antigen receptor (CAR) T cells to children with central nervous system (CNS) tumors is the blood-brain barrier. To overcome this limitation, preclinical and clinical studies have supported the use of repeated, locoregional intracranial CAR T-cell delivery. However, there is limited literature available describing the process for the involvement of an investigational drug service (IDS) pharmacy, particularly in the setting of a children's hospital with outpatient dosing for CNS tumors. OBJECTIVES: To describe Seattle Children's Hospital's experience in clinically producing CAR T cells and the implementation of IDS pharmacy practices used to deliver more than 300 intracranial CAR T-cell doses to children, as well as to share how we refined the processing techniques from CAR T-cell generation to the thawing of fractionated doses for intracranial delivery. METHODS: Autologous CD4+ and CD8+ T cells were collected and transduced to express HER2, EGFR, or B7-H3-specific CAR T cells. Cryopreserved CAR T cells were thawed by the IDS pharmacy before intracranial delivery to patients with recurrent/refractory CNS tumors or with diffuse intrinsic pontine glioma/diffuse midline glioma. RESULTS: The use of a thaw-and-dilute procedure for cryopreserved individual CAR T-cell doses provides reliable viability and is more efficient than typical thaw-and-wash protocols. Cell viability with the thaw-and-dilute protocol was approximately 75% and was always within 10% of the viability assessed at cryopreservation. Cell viability was preserved through 6 hours after thawing, which exceeded the 1-hour time frame from thawing to infusion. CONCLUSION: As the field of adoptive immunotherapy grows and continues to bring hope to patients with fatal CNS malignancies, it is critical to focus on improving the preparatory steps for CAR T-cell delivery.

[Validation of the French version of the Assessment Tool for Hospital Admissions Related to Medications (AT-HARM10) to detect drug-related hospitalizations]. / Validation d'une version française de l'outil AT-HARM10 pour la détection des hospitalisations liées au médicament.

Admissions of the elderly related to medication errors are frequent in hospital, more than half would be avoidable, but there is currently no validated method in French to identify them. The objective of this work was to validate the French version of the AT-HARM10 tool in order to use it for patients admitted in our healthcare facilities. The tool has 10 questions. A positive response to any of the first 3 questions identify admissions that are unlikely to be drug-related. A positive response to one of the following 7 questions identify possible medication-related admissions. For semantic and linguistic validation, we performed cross-validation with forward-backward translation. To clinically validate the method, we conducted a retrospective study including patients over 65 admitted to short-stay units (UHCD) and to orthopedic surgery units in two French hospitals. Two hundred and sixty-six (266) patients were included ; 166 patients admitted to UHCD (mean age 86.0±5.7 years; sex ratio 0.66; mean number of drugs prescribed 7.7±3.8) and 100 patients admitted to orthopedic units (mean age 85.2±6.1 years; sex ratio 0.43; mean number of prescribed drugs 6.4±3.6). We identified 55 % of admissions probably related to medication in UHCD and 76 % in orthopedic units (p<0.05). The most represented item was P5 in both groups (Might [side] effects of the medications the patient was taking [prescribed or not prescribed] prior to hospitalization have caused the admission [including over-treatment] ? The validated AT-HARM10 tool is now integrated into our clinical pharmacy practices and medication reviews are offered as a priority to patients admitted for iatrogenic reasons.

Practices, barriers and facilitators to the delivery of pretravel health services by community pharmacists: A scoping review using the theoretical domains framework.

BACKGROUND: The involvement of community pharmacists (CPs) in the provision of pretravel health services is increasing due to the increase in international travelers, the increased risk of travel-related diseases, and the expansion of pharmacists' scope of practice in some countries. In order to improve the quality and effectiveness of pretravel health care provided by CPs, a greater understanding of the practices, barriers, and facilitators is required. OBJECTIVE: This scoping review aimed to identify and describe existing studies on pretravel health services provided by CPs, and the barriers, and facilitators. METHODS: The PubMed, Science Direct, Scopus, and Web of Science databases were searched for pertinent studies from their inception to February 2023. A manual search was also conducted of prominent travel medicine journals, Google Scholar, and the reference lists of the included studies. Potential barriers and facilitators were mapped to the 14 domains of the Theoretical Domains Framework (TDF). RESULTS: There were twelve studies included in the review. Pretravel health advice was the most prevalent form of pretravel health services. Within ten domains of the TDF, various factors that either facilitate or impede the provision of pretravel health services by CPs were identified. CONCLUSION: The provision of pretravel health services by CPs may be affected by a number of practitioner and organizational factors. The provision of pretravel health services can be facilitated by informational resources, training and education in travel medicine, and collaboration amongst healthcare providers.

Public views of community pharmacy services during the COVID-19 pandemic: a national survey.

OBJECTIVE: To assess public opinion about community pharmacy services in Lebanon during the COVID-19 pandemic. METHOD: A cross-sectional study using an online questionnaire was conducted between April and August of 2021. A link was shared randomly among the Lebanese population using WhatsApp and Facebook. Public perceptions were explored within 3 different indicators: general services (B) dispensing (C), and storage (D). Chi-square, Student's test and ANOVA tests were used. p < 0.05 was considered statistically significant. RESULTS: Out of 491 responses, only 9.6% scored above the 75th percentile (19.3% for the general services, 2.4% for dispensing indicator and 12.6% for storage indicator). The main concerns focused on lack of medication and reduced opening hours; however, 67.1% of respondents preferred consulting the community pharmacist instead of visiting primary health care centers, doctor's private clinic and hospitals. Higher mean values of indicators B, C and in the overall indicator were significantly found in the presence of a pharmacist compared to the support pharmacy workforce. CONCLUSION: The overall public perception was inadequate. Significant difference in terms of quality of services was detected in the presence and absence of a community pharmacist during the crisis. It is recommended that the Order of Pharmacist of Lebanon (OPL) and the Ministry of Public Health (MOPH) undergo further steps mainly to enforce the laws concerning dispensing and storage indicators, improve the services in terms of extending the opening hours, ensure the availability of medicines and increase public awareness.

Inter-rater reliability and validity of good pharmacy practices measures in inspection of public sector health facility pharmacies in Uganda.

BACKGROUND: The National Drug Authority (NDA) inspects and certifies private and public sector pharmacies in Uganda using an indicator-based inspection tool that measures adherence to good pharmacy practices (GPP). 67 measures identify the situation in the domains of premises, dispensing quality, stores management, and operating requirements. Although the GPP measures are well-recognized and used internationally, little is known about their validity and reliability. The study aimed to assess validity, which measures agreement of GPP measures between a gold standard inspector and NDA inspector and inter-rater reliability (IRR), which measures agreement among NDA inspectors, of GPP measures. METHODS: We assessed validity and IRR by four teams of inspectors in eight government health facilities that represent three levels of care. Each team inspected two facilities, resulting in 24 total inspections. Each team comprised one central-level inspector, one district-level inspector, and one gold-standard inspector (i.e., a very experienced central-level inspector). We calculated median validity and IRR for each GPP measure, overall, indicator categorized as either critical, major, or minor, by domains, by the inspection decision (i.e., certified or not certified) and by adequatevalidity and IRR score (i.e., score ≥ 75%). RESULTS: The median validity for all GPP measures was 69%, with 29 (43%) measures having an adequate validity of ≥75%. The median IRR for all GPP measures was 71%, with 31 (46%) having an adequate IRR measure of ≥75%. Validity did not differ significantly by indicator category, domain or level of care. Adequate IRR and validity score (≥75%) was lowest for critical measures, which are key determinants of the certification decision, scoring 20 and 40% respectively. District inspectors had lower median validity for critical indicators and premises and higher validity for store management. Compared to central inspectors, the validity of district inspectors'certification decisions was lower; in the eight facilities, three district inspectors agreed with gold standard inspector vs. all eight central inspectors. CONCLUSIONS: Our findings question the validity and reliability of many GPP inspection measures, particularly critical measures that greatly impact certification decision. This study demonstrates the need for assessments of, and interventions to improve, validity and reproducibility of GPP measures and inspections.

First regulatory inspections measuring adherence to Good Pharmacy Practices in the public sector in Uganda: a cross-sectional comparison of performance between supervised and unsupervised facilities.

BACKGROUND: Since its inception, the Uganda National Drug Authority (NDA) has regularly inspected private sector pharmacies to monitor adherence to Good Pharmacy Practices (GPP). This study reports findings from the first public facility inspections following an intervention (SPARS: Supervision, Performance Assessment, and Recognition Strategy) to build GPP and medicines management capacity in the public sector. METHODS: The study includes 455 public facilities: 417 facilities were inspected after at least four SPARS visits by trained managerial district staff (SPARS group), 38 before any exposure to SPARS. NDA inspectors measured 10 critical, 20 major, and 37 minor GPP indicators in every facility and only accredited facilities that passed all 10 critical and failed no more than 7 major indicators. Lack of compliance for a given indicator was defined as less than 75 % facilities passing that indicator. We assessed factors associated with certification using logistic regression analysis and compared number of failed indicators between the SPARS and comparative groups using two sample t-tests with equal or unequal variance. RESULTS: 57.4 % of inspected facilities obtained GPP certification: 57.1 % in the SPARS and 60.5 % in the comparative group (Adj. OR = 0.91, 95 % CI 0.45-1.85, p = 0.802). Overall, facilities failed an average of 10 indicators. SPARS facilities performed better than comparative facilities (9 (SD 6.1) vs. 13 (SD 7.7) failed indicators respectively; p = 0.017), and SPARS supported facilities scored better on indicators covered by SPARS. For all indicators but one minor, performance in the SPARS group was equal to or significantly better than in unsupervised facilities. Within the SPARS (intervention) group, certified facilities had < 75 % compliance on 7 indicators (all minor), and uncertified facilities on 19 (4 critical, 2 major, and 13 minor) indicators. CONCLUSIONS: Half of the Ugandan population obtains medicines from the public sector. Yet, we found only 3/5 of inspected public health facilities meet GPP standards. SPARS facilities tended to perform better than unsupervised facilities, substantiating the value of supporting supervision interventions in GPP areas that need strengthening. None compliant indicators can be improved through practices and behavioral changes; some require infrastructure investments. We conclude that regular NDA inspections of public sector pharmacies in conjunction with interventions to improve GPP adherence can revolutionize patient care in Uganda.