A mixed-method study evaluating an innovative care model for rural patients undergoing outpatient breast surgery.

BACKGROUND: The Delta Oasis program was launched in New Brunswick in 2006 to offer patients from rural areas who were undergoing breast cancer surgery and their families 1 night of free accommodations and a postoperative consultation with an extramural nurse. We sought to investigate patient experiences with this program. METHODS: This mixed-method retrospective study took place from 2020 to 2022 and compared the preoperative anxiety and quality of recovery of program participants and control patients who were discharged home over 100 km from hospital. We conducted 2 × 2 analysis of variance to evaluate the effects of intervention group and surgery type. We conducted semistructured interviews with intervention participants, which we then thematically analyzed. Two patient partners were engaged during data synthesis to support the interpretation of results. RESULTS: We included 34 patients who participated in the program and 18 control patients. No statistically significant differences were found between treatment groups in preoperative anxiety and quality of recovery, regardless of surgery type. Thematic analysis of interviews with 17 intervention participants revealed that they were highly satisfied with the program and that the experience helped reduce stress and discomfort related to their surgery. INTERPRETATION: The Delta Oasis program is a cost-effective alternative to inpatient care after breast cancer surgery and is highly regarded by rural patients; expansion to other regions with the inclusion of additional low-risk surgeries could help address hospital capacity issues. This study contributes to our understanding of the patient experience with the Delta Oasis program and informs the development of similar programs elsewhere.

How should multiple myeloma research change in a patient-oriented world? Findings and lessons from the pan-Canadian myeloma priority setting partnership.

BACKGROUND: Over the last decade there has been considerable research into the treatment, management, and quality of life of people living with multiple myeloma. However, there has been limited investigation into topics deemed important to patients and caregivers within this community. We conducted a James Lind Alliance Priority Setting Partnership to establish the 'Top 10 Priorities for Myeloma Research', informed by patient and public partners. METHODS: A research team and steering group were established in 2019 to conduct the myeloma priority setting partnership. Steering group members included patients, caregivers, and healthcare providers who advised the research team and oversaw the scope of the project, grounded on their lived experience. Following the James Lind Alliance guidelines for identification and ranking of research questions, we used surveys and a virtual workshop to collect and prioritize questions posed by myeloma patients, caregivers, and healthcare providers across Canada. RESULTS: The Top 10 list of priorities for myeloma research was finalized at the consensus-building workshop and encompassed questions related to diagnosis, treatment, management, and living well with myeloma. A final participant evaluation survey elicited a positive response. INTERPRETATION: The myeloma priority setting partnership identified the research priorities of people living with myeloma, caregivers, and healthcare providers to inform clinical research on this disease going forward. This project underscores the importance of patient and public engagement in the identification of research questions, highlighting the concerns of people affected by myeloma to ultimately improve the lives of people living with this disease.

Research on multiple myeloma, a rare blood cancer, rarely focuses on topics that are personally important to people living with myeloma, their caregivers, and their healthcare providers. The purpose of this study was to complete a priority setting partnership, following guidelines from the James Lind Alliance, to identify unanswered research questions from people directly affected by myeloma. The project was guided by a steering group of people living with myeloma, their caregivers, and healthcare providers who informed all stages of this process including two questionnaires to collect and rank questions and a priority setting workshop. The workshop brought together representatives from each group to form the final 'Top 10 Priorities for Myeloma Research', which included questions related to diagnosis, treatment, management, and living well with myeloma. This process allowed us to identify the research priorities of the myeloma community and highlighted the importance of including patients and the public as team members in the research process. We encourage other myeloma researchers to do the same to ensure research is meaningful and relevant to the communities who rely on it.

Use of Bayesian decision analysis to maximize value in patient-centered randomized clinical trials in Parkinson's disease.

A fixed one-sided significance level of 5% is commonly used to interpret the statistical significance of randomized clinical trial (RCT) outcomes. While it is necessary to reduce the false positive rate, the threshold used could be chosen quantitatively and transparently to specifically reflect patient preferences regarding benefit-risk tradeoffs as well as other considerations. How can patient preferences be explicitly incorporated into RCTs in Parkinson's disease (PD), and what is the impact on statistical thresholds for device approval? In this analysis, we apply Bayesian decision analysis (BDA) to PD patient preference scores elicited from survey data. BDA allows us to choose a sample size (n) and significance level (α) that maximizes the overall expected value to patients of a balanced two-arm fixed-sample RCT, where the expected value is computed under both null and alternative hypotheses. For PD patients who had previously received deep brain stimulation (DBS) treatment, the BDA-optimal significance levels fell between 4.0% and 10.0%, similar to or greater than the traditional value of 5%. Conversely, for patients who had never received DBS, the optimal significance level ranged from 0.2% to 4.4%. In both of these populations, the optimal significance level increased with the severity of the patients' cognitive and motor function symptoms. By explicitly incorporating patient preferences into clinical trial designs and the regulatory decision-making process, BDA provides a quantitative and transparent approach to combine clinical and statistical significance. For PD patients who have never received DBS treatment, a 5% significance threshold may not be conservative enough to reflect their risk-aversion level. However, this study shows that patients who previously received DBS treatment present a higher tolerance to accept therapeutic risks in exchange for improved efficacy which is reflected in a higher statistical threshold.

Patient-Centered Identification of Meaningful Regulatory Endpoints for Medical Devices to Treat Parkinson's Disease.

Introduction. A growing literature has developed on identifying outcomes that matter to patients. This study demonstrates an approach involving patient and regulatory perspectives to identify outcomes that are meaningful in the context of medical devices for Parkinson's disease (PD). Methods. A systematic process was used for specifying relevant regulatory endpoints by synthesizing inputs of various sources and stakeholders. First, a literature review was conducted to identify important benefits, risks, and other considerations for medical devices to treat PD; patient discussion groups (n = 6) were conducted to refine the list of considerations, followed by a survey (n = 29) to prioritize them; and patient and Food and Drug Administration (FDA) reviewers informed specification of the final endpoints. Two FDA clinicians gave clinical and regulatory perspectives at each step. Results. Movement symptoms were ranked as most important (ranked 1 or 2 by 72% of participants) and psychological and cognitive symptoms as the next most important (ranked 1 or 2 by 52% of participants). Within movement symptoms, falls, impaired movement, bradykinesia, resting tremor, stiffness, and rigidity were ranked highly. Overall, nine attributes were identified and prioritized as patient-centric for use in clinical trial design and quantitative patient preference studies. These attributes were benefits and risks related to therapeutics for PD as well as other considerations, including time until a medical device is available for patient use. Discussion. This prospective approach identified meaningful and relevant benefits, risks, and other considerations that may be used for clinical trial design and quantitative patient preference studies. Although PD was the focus of this study, the approach can be used to study patient perspectives about other disease or treatment areas.

Parkinson's Patients' Tolerance for Risk and Willingness to Wait for Potential Benefits of Novel Neurostimulation Devices: A Patient-Centered Threshold Technique Study.

Background. Parkinson's disease (PD) is neurodegenerative, causing motor, cognitive, psychological, somatic, and autonomic symptoms. Understanding PD patients' preferences for novel neurostimulation devices may help ensure that devices are delivered in a timely manner with the appropriate level of evidence. Our objective was to elicit preferences and willingness-to-wait for novel neurostimulation devices among PD patients to inform a model of optimal trial design. Methods. We developed and administered a survey to PD patients to quantify the maximum levels of risks that patients would accept to achieve potential benefits of a neurostimulation device. Threshold technique was used to quantify patients' risk thresholds for new or worsening depression or anxiety, brain bleed, or death in exchange for improvements in "on-time," motor symptoms, pain, cognition, and pill burden. The survey elicited patients' willingness to wait to receive treatment benefit. Patients were recruited through Fox Insight, an online PD observational study. Results. A total of 2740 patients were included and a majority were White (94.6%) and had a 4-year college degree (69.8%). Risk thresholds increased as benefits increased. Threshold for depression or anxiety was substantially higher than threshold for brain bleed or death. Patient age, ambulation, and prior neurostimulation experience influenced risk tolerance. Patients were willing to wait an average of 4 to 13 years for devices that provide different levels of benefit. Conclusions. PD patients are willing to accept substantial risks to improve symptoms. Preferences are heterogeneous and depend on treatment benefit and patient characteristics. The results of this study may be useful in informing review of device applications and other regulatory decisions and will be input into a model of optimal trial design for neurostimulation devices.

EBV/LMP-specific T cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation.

Autologous T cells targeting Epstein-Barr virus (EBV) latent membrane proteins (LMPs) have shown safety and efficacy in the treatment of patients with type 2 latency EBV-associated lymphomas for whom standard therapies have failed, including high-dose chemotherapy followed by autologous stem-cell rescue. However, the safety and efficacy of allogeneic donor-derived LMP-specific T cells (LMP-Ts) have not been established for patients who have undergone allogeneic hematopoietic stem-cell transplantation (HSCT). Therefore, we evaluated the safety and efficacy of donor-derived LMP-Ts in 26 patients who had undergone allogeneic HSCT for EBV-associated natural killer/T-cell or B-cell lymphomas. Seven patients received LMP-Ts as therapy for active disease, and 19 were treated with adjuvant therapy for high-risk disease. There were no immediate infusion-related toxicities, and only 1 dose-limiting toxicity potentially related to T-cell infusion was seen. The 2-year overall survival (OS) was 68%. Additionally, patients who received T-cell therapy while in complete remission after allogeneic HSCT had a 78% OS at 2 years. Patients treated for B-cell disease (n = 10) had a 2-year OS of 80%. Patients with T-cell disease had a 2-year OS of 60%, which suggests an improvement compared with published posttransplantation 2-year OS rates of 30% to 50%. Hence, this study shows that donor-derived LMP-Ts are a safe and effective therapy to prevent relapse after transplantation in patients with B cell- or T cell-derived EBV-associated lymphoma or lymphoproliferative disorder and supports the infusion of LMP-Ts as adjuvant therapy to improve outcomes in the posttransplantation setting. These trials were registered at www.clinicaltrials.gov as #NCT00062868 and #NCT01956084.

Adoptive T Cell Therapy for Epstein-Barr Virus Complications in Patients With Primary Immunodeficiency Disorders.

Patients with primary immunodeficiency disorders (PID) have an increased risk from acute and chronic Epstein-Barr Virus (EBV) viral infections and EBV-associated malignancies. Hematopoietic stem cell transplantation (HSCT) is a curative strategy for many patients with PID, but EBV-related complications are common in the immediate post-transplant period due to delayed reconstitution of T cell immunity. Adoptive T cell therapy with EBV-specific T cells is a promising therapeutic strategy for patients with PID both before and after HSCT. Here we review the methods used to manufacture EBV-specific T cells, the clinical outcomes, and the ongoing challenges for future development of the strategy.

Clinical presentation and management of arterial thoracic outlet syndrome.

OBJECTIVE: Arterial thoracic outlet syndrome (TOS) is a rare condition characterized by subclavian artery pathology associated with a bony abnormality. This study assessed contemporary clinical management of arterial TOS at a high-volume referral center. METHODS: A prospectively maintained database was used to conduct a retrospective review of patients undergoing primary or reoperative treatment for arterial TOS during an 8-year period (2008 to 2016). Presenting characteristics, operative findings, and clinical and functional outcomes were evaluated. RESULTS: Forty patients underwent surgical treatment for arterial TOS, representing 3% of 1401 patients undergoing operations for all forms of TOS during the same interval. Patients were a mean age of 40.3 ± 2.2 years (range, 13-68 years), and 72% were women. More than half presented with upper extremity ischemia/emboli (n = 21) or posterior stroke (n = 2), including eight that had required urgent brachial artery thromboembolectomy. The presentation in 17 (42%) was nonvascular, with 11 having symptoms of neurogenic TOS and six having an asymptomatic neck mass or incidentally discovered subclavian artery dilatation. All patients underwent thoracic outlet decompression (25 supraclavicular, 15 paraclavicular), of which there were 30 (75%) with a cervical rib (24 complete, 6 partial), 5 with a first rib abnormality, 4 with a clavicle fracture, and 1 (reoperation) with no remaining bone abnormality. Subclavian artery reconstruction was performed in 70% (26 bypass grafts, 1 patch, 1 suture repair), and 30% had mild subclavian artery dilatation (<100%) requiring no arterial reconstruction. Mean postoperative length of stay was 5.4 ± 0.6 days. During a mean follow-up of 4.5 ± 0.4 years (range, 0.9-8.1 years), subclavian artery patency was 92%, none had further dilatation or embolism, and chronic symptoms were present in six (4 postischemic/vasospasm, 2 neurogenic). Functional outcomes measured by scores on the 11-item version of the Disability of the Arm, Shoulder and Hand Outcome Measure improved from 39.1 ± 3.8 to 19.2 ± 2.7 (P < .0001). CONCLUSIONS: This relatively large single-institution series demonstrates the diverse clinical presentation of arterial TOS coincident with a spectrum of bony and arterial pathology. Current surgical protocols can achieve excellent outcomes for this rare and often complicated condition.

Adoptive T Cell Immunotherapy for Patients with Primary Immunodeficiency Disorders.

Primary immunodeficiency disorders (PID) are a group of inborn errors of immunity with a broad range of clinical severity but often associated with recurrent and serious infections. While hematopoietic stem cell transplantation (HSCT) can be curative for some forms of PID, chronic and/or refractory viral infections remain a cause of morbidity and mortality both before and after HSCT. Although antiviral pharmacologic agents exist for many viral pathogens, these are associated with significant costs and toxicities and may not be effective for increasingly drug-resistant pathogens. Thus, the emergence of adoptive immunotherapy with virus-specific T lymphocytes (VSTs) is an attractive option for addressing the underlying impaired T cell immunity in many PID patients. VSTs have been utilized for PID patients following HSCT in many prior phase I trials, and may potentially be beneficial before HSCT in patients with chronic viral infections. We review the various methods of generating VSTs, clinical experience using VSTs for PID patients, and current limitations as well as potential ways to broaden the clinical applicability of adoptive immunotherapy for PID patients.

Management of post-transplant lymphoproliferative disorders.

PURPOSE OF REVIEW: Post-transplant lymphoproliferative disease (PTLD) is a major complication of hematopoietic stem cell and solid organ transplantation. The incidence of transplantation in childhood has been steadily rising, making PTLD the most common form of lymphoproliferation in childhood. The purpose of this review is to summarize the role of the Epstein-Barr virus (EBV) in the pathophysiology and discuss the management of PTLD. RECENT FINDINGS: More than 90% of pediatric PTLD is EBV-positive. In immunocompetent hosts, the virus is controlled by cytotoxic T-cells, the cells targeted by immunosuppression to avoid graft-versus-host disease and/or organ rejection in transplant patients. The majority of pediatric transplant candidates are EBV-negative prior to transplant increasing the risk of EBV-induced lymphoproliferation upon seroconversion after transplant. Treatment options include reduction of immunosuppression, anti-CD20 monoclonal antibodies, and/or chemotherapy. Advanced understanding of the importance of cellular immunity in controlling lymphoproliferation has led to the development of cellular therapies targeting virus-specific antigens. SUMMARY: PTLD is the most common form of lymphoproliferation in childhood due to the rising incidence of transplantation. EBV plays a pivotal role in the pathophysiology. Cellular therapies targeting viral antigens may replace chemotherapy in the treatment of PTLD in the near future.

Patient Perspectives on Deep Brain Stimulation Clinical Research in Early Stage Parkinson's Disease.

The FDA has approved a multicenter, double-blind, Phase III, pivotal trial testing deep brain stimulation (DBS) in 280 people with very early stage Parkinson's disease (PD; IDE#G050016). In partnership with The Michael J. Fox Foundation for Parkinson's Research, we conducted a survey to investigate motivating factors, barriers, and gender differences among potentially eligible patients for participation in a trial testing DBS in early PD compared to standard medical treatment. The majority of survey respondents (72%) indicated they would consider learning more about participating. Early PD patients are therefore likely to consider enrolling in trials of invasive therapies that may slow symptom progression and help future patients.

EBV-Directed T Cell Therapeutics for EBV-Associated Lymphomas.

Epstein Barr virus (EBV) is a human gamma herpes virus that establishes latency in B cells after primary infection. EBV generally only causes a mild, self-limiting viral illness but is also associated with several malignancies including posttransplantation lymphoproliferative disorder in the immunosuppressed host as well as Hodgkin and non-Hodgkin lymphoma in the immune competent host. The expression of EBV antigens by lymphoma has important applications as targets for adoptive T cell therapy. However, as many lymphomas only express subdominant EBV antigens that are less immunogenic, novel strategies are needed to manufacture EBV-specific T cell products specific for Latent Membrane Protein 1 (LMP1) and LMP2, which are expressed in lymphomas with type II and III latency. While several techniques for manufacturing EBV-CTLs are described in the literature, this chapter focuses on one method for generating Good Manufacturing Practice (GMP)-compliant EBV-specific T cell products that are enriched with LMP1 and LMP2.

Human parainfluenza virus-3 can be targeted by rapidly ex vivo expanded T lymphocytes.

BACKGROUND AIMS: Human parainfluenza virus-3 (HPIV) is a common cause of respiratory infection in immunocompromised patients and currently has no effective therapies. Virus-specific T-cell therapy has been successful for the treatment or prevention of viral infections in immunocompromised patients but requires determination of T-cell antigens on targeted viruses. METHODS: HPIV3-specific T cells were expanded from peripheral blood of healthy donors using a rapid generation protocol targeting four HPIV3 proteins. Immunophenotyping was performed by flow cytometry. Viral specificity was determined by interferon (IFN)-γ ELISpot, intracellular cytokine staining and cytokine measurements from culture supernatants by Luminex assay. Cytotoxic activity was tested by 51Cr release and CD107a mobilization assays. Virus-specific T cells targeting six viruses were then produced by rapid protocol, and the phenotype of HPIV3-specific T cells was determined by immunomagnetic sorting for IFN-γ-producing cells. RESULTS: HPIV3-specific T cells were expanded from 13 healthy donors. HPIV3-specific T cells showed a CD4+ predominance (mean CD4:CD8 ratio 2.89) and demonstrated specificity for multiple HPIV3 antigens. The expanded T cells were polyfunctional based on cytokine production but only had a minor cytotoxic component. T cells targeting six viruses in a single product similarly showed HPIV3 specificity, with a predominant effector memory phenotype (CD3+/CD45RA-/CCR7-) in responder cells. DISCUSSION: HPIV3-specific T cells can be produced using a rapid ex vivo protocol from healthy donors and are predominantly CD4+ T cells with Th1 activity. HPIV3 epitopes can also be successfully targeted alongside multiple other viral epitopes in production of six-virus T cells, without loss of HPIV3 specificity. These products may be clinically beneficial to combat HPIV3 infections by adoptive T-cell therapy in immune-compromised patients.

Diagnosis and treatment of effort-induced thrombosis of the axillary subclavian vein due to venous thoracic outlet syndrome.

Venous thoracic outlet syndrome (VTOS) is uncommon but most frequently occurs in young, active, healthy patients. This condition typically presents as subclavian vein (SCV) effort thrombosis, also known as Paget-Schroetter syndrome. The pathophysiology underlying VTOS is chronic repetitive compression injury of the SCV in the costoclavicular space, resulting in progressive venous scarring, focal stenosis, and eventual thrombosis. Clinical evaluation includes a history and physical examination followed by catheter-based venography, for definitive confirmation of the diagnosis and initial treatment with pharmacomechanical thrombolysis. After restoration of SCV patency, patients are maintained with anticoagulation and surgical therapy is usually planned within 4 to 6 weeks. Surgical management of VTOS can be accomplished via different protocols involving either the transaxillary, infraclavicular or paraclavicular approaches to thoracic outlet decompression. The paraclavicular approach is emphasized in this review, because it affords the surgeon the ability to safely perform complete thoracic outlet decompression (complete anterior and middle scalenectomy, removal of the entire first rib, and resection of the subclavius muscle and costoclavicular ligament), along with definitive management of the damaged SCV (external venolysis, intraoperative venography, and direct vein reconstruction, if needed, using patch angioplasty or bypass grafting), in one operative setting. After surgical therapy, interval anticoagulation and a comprehensive physical therapy and rehabilitation program are important in achieving a return to full function. Current protocols on the basis of the paraclavicular surgical approach have thereby routinely provided patients with lasting symptomatic relief, freedom from indefinite anticoagulation, and the ability to return to unrestricted upper extremity activity.

Adoptive T-cell therapies for refractory/relapsed leukemia and lymphoma: current strategies and recent advances.

Despite significant advancements in the treatment and outcome of hematologic malignancies, prognosis remains poor for patients who have relapsed or refractory disease. Adoptive T-cell immunotherapy offers novel therapeutics that attempt to utilize the noted graft versus leukemia effect. While CD19 chimeric antigen receptor (CAR)-modified T cells have thus far been the most clinically successful application of adoptive T immunotherapy, further work with antigen specific T cells and CARs that recognize other targets have helped diversify the field to treat a broad spectrum of hematologic malignancies. This article will focus primarily on therapies currently in the clinical trial phase as well as current downfalls or limitations.

The supraclavius muscle is a novel muscular anomaly observed in two cases of thoracic outlet syndrome.

Various anomalous muscles and fibrofascial structures have been described in relation to the anatomy of thoracic outlet syndrome. We describe two patients with a previously undescribed muscle anomaly, which originated laterally near the trapezius muscle, coursed across the supraclavicular space deep to the scalene fat pad, and attached obliquely to the superior undersurface of the medial clavicle, which we have termed the "supraclavius" muscle. The significance of the supraclavius muscle is unknown, but its occurrence in patients with thoracic outlet syndrome indicates that it can be associated with narrowing of the anatomic space adjacent to the neurovascular structures.

Topical antimicrobial treatment of acne vulgaris: an evidence-based review.

Topical antimicrobial treatment is indicated for mild to moderate acne vulgaris. Our literature review includes searches of Ovid, MEDLINE, EMBASE, and the databases of the Cochrane Library. A detailed search strategy is included. All searches were limited to controlled trials and systematic reviews. No year limits were applied to the searches, but we focused on trials, guidelines, and reviews published since 2004, the year that the last review of topical antimicrobials was published in this journal. Several controlled trials demonstrate that benzoyl peroxide, topical antibiotics, and topical retinoids used in combination provide the greatest efficacy and safety profile for the treatment of mild to moderate acne, but there are few trials directly comparing different combinations of these topical therapies with one another. Additionally, robust studies comparing cost and efficacy of generic combinations of the above agents with proprietary fixed-dose combination therapies that may increase compliance are also lacking. Although they have not been extensively studied, alternative agents including dapsone, salicylic acid, azelaic acid, and zinc are safe and efficacious when combined with traditional therapies.

Introduction: US dermatologic health care needs assessment.

The health care needs assessment (HCNA) addressed in this issue of Dermatologic Clinics is designed to aid practitioners and policy makers by providing current, evidence-based research that can be used to guide United States' dermatologic care. The topics covered in this skin disease HCNA include those that are considered common dermatology care needs in society and those severe enough to create a burden on the medical system. Disease discussions address epidemiology, costs to society and patients, prevention, treatment, gaps in management, and future recommendations.