Pharmacist-led screening for mental illness: A systematic review.

BACKGROUND: Early identification and treatment of mental illnesses is imperative for optimal patient outcomes. Pharmacists may play an important role in mental healthcare through the provision of screening services for mental illnesses. OBJECTIVE: (s): To systematically review the impact of pharmacist-led mental illness screening on clinical or patient-reported outcomes and identify and report any follow-up or referral systems used in pharmacist-led screening interventions for mental illnesses. METHODS: A systematic review was conducted by searching MEDLINE, CINAHL, Embase and APA PsycInfo via EBSCOhost from inception to 9 March 2023 to identify studies involving pharmacist-led screening interventions for mental illnesses. Data was collected on the mental illness in question, setting and population characteristics, screening tools used, clinical or patient-reported outcomes, and follow-up and referral systems reported. RESULTS: Twenty six studies were identified that related to screening for mental illnesses, such as depressive disorders and substance use disorders. There were a variety of study designs, including uncontrolled studies (n = 23), pre-post studies (n = 2) and randomised controlled trials (n = 1). Screening was conducted in different settings, with most studies conducted in community pharmacies (n = 21/26, 87.8 %) and focusing on depression screening (n = 12/26, 46.1 %). A range of follow-up and referral methods to other healthcare professionals were reported, including verbal (n = 3/26, 11.5 %), both written and verbal (n = 3/26, 11.5 %), communications via electronic health record (n = 2/26, 7.7 %) and written (n = 1/26, 3.8 %). CONCLUSIONS: Pharmacists provide screening for a variety of mental illnesses in different settings. Various referral methods and follow-up pathways may be utilised for post-screening patient care. However, current evidence is insufficient to establish improvements in early detection, treatment, or outcomes. Further large, well-designed studies are required to support the role of pharmacists in mental illness screening, provide evidence on the impact of pharmacist-led mental illness screening services and inform the most effective follow up and referral methods.

Community pharmacists' acceptability of pharmacist-delivered depression screening for older adults: a qualitative study.

BACKGROUND: Late-life depression often goes underdiagnosed and undertreated, affecting the quality of life of older adults. Pharmacists are well-placed to identify older adults who may be at risk of depression by using appropriate screening tools. AIM: To explore community pharmacists' acceptability of performing late-life depression screening in Australian community pharmacies. METHOD: Semi-structured interviews with community pharmacists were conducted to gauge their perceptions regarding delivering depression screening services for older adults. Data analysis was conducted using an iterative, inductive approach. Key themes were identified, which were further explored and divided into subthemes. Subthemes were categorised as either barriers or facilitators. Each subtheme was mapped to the Capability, Opportunity, Motivation-Behaviour model by classifying whether they impacted pharmacists' capability, opportunity, or motivation regarding depression screening. RESULTS: Fifteen pharmacists were interviewed, 12 of whom were female and 11 of whom practised in a metropolitan area. Four key themes were identified including: training needs, environmental factors, pharmacists' roles, and organisational support, which were further divided into 13 subthemes. Three subthemes were mapped to Capability, seven to Opportunity and three to Motivation. Barriers included lack of resources and lack of remuneration, while facilitators included training, pharmacists' accessibility, and rapport with consumers. CONCLUSION: The findings of this study demonstrate that while community pharmacists found depression screening for older adults in community pharmacies to be an acceptable service, there remains a need for the development of funding schemes and standardised guidelines for pharmacist-delivered depression screening for older adults.

PD-L1 blockade restores CAR T cell activity through IFN-γ-regulation of CD163+ M2 macrophages.

BACKGROUND: The immune suppressive tumor microenvironment (TME) that inhibits T cell infiltration, survival, and antitumor activity has posed a major challenge for developing effective immunotherapies for solid tumors. Chimeric antigen receptor (CAR)-engineered T cell therapy has shown unprecedented clinical response in treating patients with hematological malignancies, and intense investigation is underway to achieve similar responses with solid tumors. Immunologically cold tumors, including prostate cancers, are often infiltrated with abundant tumor-associated macrophages (TAMs), and infiltration of CD163+ M2 macrophages correlates with tumor progression and poor responses to immunotherapy. However, the impact of TAMs on CAR T cell activity alone and in combination with TME immunomodulators is unclear. METHODS: To model this in vitro, we utilized a novel co-culture system with tumor cells, CAR T cells, and polarized M1 or M2 macrophages from CD14+ peripheral blood mononuclear cells collected from healthy human donors. Tumor cell killing, T cell activation and proliferation, and macrophage phenotypes were evaluated by flow cytometry, cytokine production, RNA sequencing, and functional blockade of signaling pathways using antibodies and small molecule inhibitors. We also evaluated the TME in humanized mice following CAR T cell therapy for validation of our in vitro findings. RESULTS: We observed inhibition of CAR T cell activity with the presence of M2 macrophages, but not M1 macrophages, coinciding with a robust induction of programmed death ligand-1 (PD-L1) in M2 macrophages. We observed similar PD-L1 expression in TAMs following CAR T cell therapy in the TME of humanized mice. PD-L1, but not programmed cell death protein-1, blockade in combination with CAR T cell therapy altered phenotypes to more M1-like subsets and led to loss of CD163+ M2 macrophages via interferon-γ signaling, resulting in improved antitumor activity of CAR T cells. CONCLUSION: This study reveals an alternative mechanism by which the combination of CAR T cells and immune checkpoint blockade modulates the immune landscape of solid tumors to enhance therapeutic efficacy of CAR T cells.

Sphingolipids inhibit endosomal recycling of nutrient transporters by inactivating ARF6.

Endogenous sphingolipids (ceramide) and related synthetic molecules (FTY720, SH-BC-893) reduce nutrient access by decreasing cell surface expression of a subset of nutrient transporter proteins. Here, we report that these sphingolipids disrupt endocytic recycling by inactivating the small GTPase ARF6. Consistent with reported roles for ARF6 in maintaining the tubular recycling endosome, MICAL-L1-positive tubules were lost from sphingolipid-treated cells. We propose that ARF6 inactivation may occur downstream of PP2A activation since: (1) sphingolipids that fail to activate PP2A did not reduce ARF6-GTP levels; (2) a structurally unrelated PP2A activator disrupted tubular recycling endosome morphology and transporter localization; and (3) overexpression of a phosphomimetic mutant of the ARF6 GEF GRP1 prevented nutrient transporter loss. ARF6 inhibition alone was not toxic; however, the ARF6 inhibitors SecinH3 and NAV2729 dramatically enhanced the killing of cancer cells by SH-BC-893 without increasing toxicity to peripheral blood mononuclear cells, suggesting that ARF6 inactivation contributes to the anti-neoplastic actions of sphingolipids. Taken together, these studies provide mechanistic insight into how ceramide and sphingolipid-like molecules limit nutrient access and suppress tumor cell growth and survival.

Microfluidic-based manufacture of siRNA-lipid nanoparticles for therapeutic applications.

A simple, efficient, and scalable manufacturing technique is required for developing siRNA-lipid nanoparticles (siRNA-LNP) for therapeutic applications. In this chapter we describe a novel microfluidic-based manufacturing process for the rapid manufacture of siRNA-LNP, together with protocols for characterizing the size, polydispersity, RNA encapsulation efficiency, RNA concentration, and total lipid concentration of the resultant nanoparticles.

CONTROLLED DELIVERY OF ANTIANGIOGENIC DRUG TO HUMAN EYE TISSUE USING A MEMS DEVICE.

We demonstrate an implantable MEMS drug delivery device to conduct controlled and on-demand, ex vivo drug transport to human eye tissue. Remotely operated drug delivery to human post-mortem eyes was performed via a MEMS device. The developed curved packaging cover conforms to the eyeball thereby preventing the eye tissue from contacting the actuating membrane. By pulsed operation of the device, using an externally applied magnetic field, the drug released from the device accumulates in a cavity adjacent to the tissue. As such, docetaxel (DTX), an antiangiogenic drug, diffuses through the eye tissue, from sclera and choroid to retina. DTX uptake by sclera and choroid were measured to be 1.93±0.66 and 7.24±0.37 µg/g tissue, respectively, after two hours in pulsed operation mode (10 s on/off cycles) at 23°C. During this period, a total amount of 192 ng DTX diffused into the exposed tissue. This MEMS device shows great potential for the treatment of ocular posterior segment diseases such as diabetic retinopathy by introducing a novel way of drug administration to the eye.

Microspheres as resistive elements in a check valve for low pressure and low flow rate conditions.

In this paper we describe a microsphere-based check valve integrated with a micropump. The check valve uses Ø20 µm polystyrene microspheres to rectify flow in low pressure and low flow rate applications (Re < 1). The microspheres form a porous medium in the check valve increasing fluidic resistance based on the direction of flow. Three check valve designs were fabricated and characterized to study the microspheres' effectiveness as resistive elements. A maximum diodicity (ratio of flow in the forward and reverse direction) of 18 was achieved. The pumping system can deliver a minimum flow volume of 0.25 µL and a maximum flow volume of 1.26 µL under an applied pressure of 0.2 kPa and 1 kPa, respectively. A proof-of-concept study was conducted using a pharmaceutical agent, docetaxel (DTX), as a sample drug showing the microsphere check valve's ability to limit diffusion from the micropump. The proposed check valve and pumping concept shows strong potential for implantable drug delivery applications with low flow rate requirements.