Psychotherapy Dropout: Using the Adolescent Psychotherapy Q-Set to Explore the Early In-Session Process of Short-Term Psychodynamic Psychotherapy

Research suggests that short-term psychodynamic psychotherapy (STPP) is an effective treatment for depression in adolescence, yet treatment dropout is a major concern and what leads to dropout is poorly understood. Whilst studies have begun to explore the role of patient and therapist variables, there is a dearth of research on the actual therapy process and investigation of the interaction between patient and therapist. This study aims to address this paucity through the utilisation of the Adolescent Psychotherapy Q-set (APQ) to examine the early treatment period. The sample includes 69 adolescents aged 16–18 years with major depressive disorder receiving STPP as part of the First Experimental Study of Transference Work–in Teenagers (FEST-IT) trial. Of these, 21 were identified as dropouts and were compared to completers on pre-treatment patient characteristics, symptomatology, functioning, and working alliance. APQ ratings available for an early session from 16 of these drop out cases were analysed to explore the patient-therapist interaction structure. Results from the Q-factor analysis revealed three distinct interaction structures that explained 54.3% of the total variance. The first described a process of mutual trust and collaboration, the second was characterised by patient resistance and emotional detachment, the third by a mismatch and incongruence between therapist and adolescent. Comparison between the three revealed interesting differences which taken together provide further evidence that the reasons why adolescents drop out of therapy vary and are multidimensional in nature.

High Solubilization and Controlled Release of Paclitaxel Using Thermosponge Nanoparticles for Effective Cancer Therapy

Cancer, which is a leading cause of death, contributes significantly to reducing life expectancy worldwide. Even though paclitaxel (PTX) is known as one of the main anticancer drugs, it has several limitations, including low solubility in aqueous solutions, a limited dosage range, an insufficient release amount, and patient resistance. To overcome these limitations, we suggest the development of PTX-loaded thermosponge nanoparticles (PTX@TNP), which result in improved anticancer effects, via a simple nanoprecipitation method, which allows the preparation of PTX@TNPs with hydrophobic interactions without any chemical conjugation. Further, to improve the drug content and yield of the prepared complex, the co-organic solvent ratio was optimized. Thus, it was observed that the drug release rate increased as the drug capacity of PTX@TNPs increased. Furthermore, increasing PTX loading led to considerable anticancer activity against multidrug resistance (MDR)-related colorectal cancer cells (HCT 15), implying a synergistic anticancer effect. These results suggest that the solubilization of high drug amounts and the controlled release of poorly water-soluble PTX using TNPs could significantly improve its anticancer therapy, particularly in the treatment of MDR-p-glycoprotein-overexpressing cancers.

New Angiogenic Regulators Produced by TAMs: Perspective for Targeting Tumor Angiogenesis

Angiogenesis is crucial to the supply of a growing tumor with nutrition and oxygen. Inhibition of angiogenesis is one of the main treatment strategies for colorectal, lung, breast, renal, and other solid cancers. However, currently applied drugs that target VEGF or receptor tyrosine kinases have limited efficiency, which raises a question concerning the mechanism of patient resistance to the already developed drugs. Tumor-associated macrophages (TAMs) were identified in the animal tumor models as a key inducer of the angiogenic switch. TAMs represent a potent source not only for VEGF, but also for a number of other pro-angiogenic factors. Our review provides information about the activity of secreted regulators of angiogenesis produced by TAMs. They include members of SEMA and S100A families, chitinase-like proteins, osteopontin, and SPARC. The COX-2, Tie2, and other factors that control the pro-angiogenic activity of TAMs are also discussed. We highlight how these recent findings explain the limitations in the efficiency of current anti-angiogenic therapy. Additionally, we describe genetic and posttranscriptional mechanisms that control the expression of factors regulating angiogenesis. Finally, we present prospects for the complex targeting of the pro-angiogenic activity of TAMs.

The Barriers and Facilitators of Different Stakeholders When Deprescribing Benzodiazepine Receptor Agonists in Older Patients—A Systematic Review

Treatment of older patients with benzodiazepines and Z-drugs (BZRA) is associated with an increased risk of side effects. However, this treatment is still used among these patients. Deprescribing can be a tool to reduce inappropriate medication. This review aims to identify and compare barriers and facilitators of stakeholders involved in BZRA deprescribing in older patients and uncover potential gaps in the research field. The search was conducted in PubMed, EMBASE, PsycINFO, and Cochrane Library. Ten articles based on qualitative data on BZRA deprescribing in older patients (≥65 years) published between 2005–2020 were included. Six articles referred to patients as stakeholders, two referred to physicians, and one to nurses and caregivers, respectively, indicating a need for more studies in the field. More barriers than facilitators were identified. Important findings were the patient willingness to deprescribe BZRA compared to physicians, who did not mention deprescribing to patients due to barriers such as expected patient resistance. Nurses mentioned barriers like lack of knowledge and the feeling that their options were not valued by physicians; education was found to be a shared deprescribing facilitator among the stakeholders. Being aware of deprescribing barriers and facilitators can be helpful in future successful deprescribing interventions.

Exploration of Barriers and Facilitators for Deprescribing Opioids and Benzodiazepines to Reduce Older Adult Falls

As part of a randomized control trial for deprescribing opioids and benzodiazepines (BZD) to reduce falls (funded by Centers for Disease Control), we conducted a virtual focus group and surveys to evaluate opioid and BZD prescribing practices among healthcare providers in four primary care clinics in North Carolina. Survey and focus group questions measured providers’ confidence in their abilities to weigh benefits and harms of opioids and/or BZDs in older adults; determine alternative interventions; create a safe dosing plan; and incorporate patient preferences. A validated pre-intervention survey, adapted from a survey by the Canadian Deprescribing Network, was administered to providers in control and intervention clinics (n=29). Providers expressed high confidence in their abilities to weigh risks and benefits of deprescribing opioids and BZDs, but low confidence in deprescribing under impeding circumstances (e.g. when not the original prescriber or when there is no evidence to inform them). Results were similar across opioids and BZDs. A focus group was conducted among seven providers from the two intervention clinics. Barriers to deprescribing identified included patient resistance, lack of knowledge of deprescribing best practices, and lack of time to discuss deprescribing during regular clinic visits. Providers also expressed concerns about deprescribing medications initiated by or managed by other prescribers. Key facilitators of deprescribing included patient trust in physician, patients being agreeable to reduce medications, and use of gradual tapering rather than abrupt discontinuation. Barriers and facilitators were subsequently used to optimize training and provider resources for the deprescribing intervention, which is currently being implemented.

Cumulative mechanism of several major imatinib-resistant mutations in Abl kinase

Despite the outstanding success of the cancer drug imatinib, one obstacle in prolonged treatment is the emergence of resistance mutations within the kinase domain of its target, Abl. We noticed that many patient-resistance mutations occur in the dynamic hot spots recently identified to be responsible for imatinib’s high selectivity toward Abl. In this study, we provide an experimental analysis of the mechanism underlying drug resistance for three major resistance mutations (G250E, Y253F, and F317L). Our data settle controversies, revealing unexpected resistance mechanisms. The mutations alter the energy landscape of Abl in complex ways: increased kinase activity, altered affinity, and cooperativity for the substrates, and, surprisingly, only a modestly decreased imatinib affinity. Only under cellular adenosine triphosphate (ATP) concentrations, these changes cumulate in an order of magnitude increase in imatinib’s half-maximal inhibitory concentration (IC50). These results highlight the importance of characterizing energy landscapes of targets and its changes by drug binding and by resistance mutations developed by patients.

Local anesthetic resistance in a Crohn’s patient undergoing cesarean delivery

IntroductionPatient resistance to local anesthetics is rarely considered as the cause of regional anesthesia failure.Case reportWe report a case of resistance to local anesthetics in a patient with Crohn’s disease who underwent cesarean section under continuous spinal anesthesia.DiscussionResistance to local anesthetics may be more common than we think, especially among patients with chronic pain. Providers should consider local anesthetic resistance when regional anesthesia is unsuccessful. Further research is needed to determine if skin wheal tests and/or a different local anesthetic could improve results.

Medical Authority under Siege: How Clinicians Transform Patient Resistance into Acceptance

Over the past decades, professional medical authority has been transformed due to internal and external pressures, including weakened institutional support and patient-centered care. Today’s patients are more likely to resist treatment recommendations. We examine how patient resistance to treatment recommendations indexes the strength of contemporary professional authority. Using conversation analytic methods, we analyze 39 video recordings of patient-clinician encounters involving pediatric epilepsy patients in which parents resist recommended treatments. We identify three distinct grounds for parental resistance to treatments: preference-, fear-, and experience-based resistance. Clinicians meet these grounds with three corresponding persuasion strategies ranging from pressuring, to coaxing, to accommodating. Rather than giving parents what they want, physicians preserve their professional authority, adjusting responses based on whether the resistance threatens their prerogative to prescribe. While physicians are able to convert most resistance into acceptance, resistance has the potential to change the treatment recommendation and may lead to changed communication styles.

Home medicines reviews: a qualitative study of GPs' experiences

This qualitative study explored GPs’ experiences with pharmacist-led home medicines reviews (HMRs) and the barriers and facilitators to GPs using HMRs to optimise medicines for older people. Semi-structured interviews were conducted with 32 GPs Australia-wide. Purposeful sampling was undertaken to obtain a representative group in terms of age, gender and location. Data were analysed using framework analysis. Overall, GPs found HMRs useful for educating patients about their medicines, improving adherence and understanding the patient’s home environment. Barriers to effective use of HMRs included patient resistance to having medicines reviewed and limited access to HMRs in regional or rural areas. GPs differed in the extent and way they use HMRs. One group found HMRs very useful, wanted more access to HMRs and reported frequent interactions with pharmacists. A second group was ambivalent, and perceived HMRs could be useful but had limitations in what they can achieve. A third group was sceptical, and reported HMRs rarely provide new insights, and recommendations were not clinically relevant to patients. Understanding GPs’ expectations and preferences through interprofessional communication and partnerships are ways to address these barriers. Future improvements to the HMR program may include incentives and resources that promote collaboration between GPs and pharmacists.