The Efficacy of Transdiagnostic Cognitive Behavioral Therapy on Migraine Headache: A Randomized Clinical Trial

Introduction: Psychological interventions are shown to be effective in migraine, but not utilized routinely yet. We aimed to evaluate the efficacy of transdiagnostic cognitive behavioral therapy (TCBT) on people with migraine (PwM). Method: This study was conducted on 40 PwM aged 20-50 years. We randomly assigned participants to two groups of intervention, receiving 10 sessions of TCBT, and control. Days with headache, headache severity, migraine-related disability and effects on daily life, number of pain-relivers taken for headache, depression, and anxiety were assessed pre-intervention, post-intervention (three-month follow-up), and one-month after TCBT termination (four-month follow-up).Results: Thirty-five participants suffering moderate to severe migraine completed the study (16 and 19 in TCBT and control groups, respectively). TCBT improved all measured items between study time-points (p<0.05) in the intervention group, while such an improvement was not observed in the control group. Between group comparisons revealed superiority of TCBT group compared to the control group in most measured items at three- and four-month follow-ups (p<0.05).Conclusion: Ten sessions of TCBT improved migraine severity, associated disability, anxiety, and depression in PwM, with persistent effects after one month of therapy termination. TCBT is an affordable, practical, and feasible intervention to be utilized for PwM.Protocol registration: The study protocol was registered in clinicaltrial.gov (NCT03701477) prior to enrollment.

Microneedle-mediated intratumoral delivery of anti-CTLA-4 promotes cDC1-dependent eradication of oral squamous cell carcinoma with limited irAEs

Head and neck squamous cell carcinoma (HNSCC) ranks 6th in cancer incidence worldwide and has a five-year survival rate of only 63%. Immunotherapies – principally immune checkpoint inhibitors (ICI), such as anti-PD-1 and anti-CTLA-4 antibodies that restore endogenous antitumor T-cell immunity – offer the greatest promise for HNSCC treatment. Anti-PD-1 has been recently approved for first line treatment of recurrent and metastatic HNSCC; however less than 20% of patients show clinical benefit and durable responses. In addition, the clinical application of ICI has been limited by immune-related adverse events (irAEs) consequent to compromised peripheral immune tolerance. Although irAEs are often reversible, they can become severe, prompting premature therapy termination or becoming life-threatening. To address the irAEs inherent to systemic ICI therapy, we developed a novel, local delivery strategy based upon an array of soluble microneedles (MN). Using our recently reported syngeneic, tobacco-signature murine HNSCC model, we found that both systemic and local-MN anti-CTLA-4 therapy lead to >90% tumor response, which is dependent on CD8 T cells and conventional dendritic cell type 1 (cDC1). However, local-MN delivery limited the distribution of anti-CTLA-4 antibody from areas distal to draining lymphatic basins. Employing Foxp3-GFPDTR transgenic mice to interrogate irAEs in vivo, we found that local-MN delivery of anti-CTLA-4 protects animals from irAEs observed with systemic therapy. Taken together, our findings support the exploration of MN-intratumoral ICI delivery as a viable strategy for HNSCC treatment with reduced irAEs, and the opportunity to target cDC1s as part of multimodal treatment options to boost ICI therapy.

Perimortem changes in clinical parameters in patients undergoing maintenance hemodialysis

Background End-of-life medical care for patients receiving maintenance hemodialysis (HD) therapy has become an increasingly important issue worldwide. Thus far, no clear indicators and/or biomarkers exist regarding the timing of HD therapy withdrawal. Methods To clarify the perimortem circumstances, we examined temporal changes in multiple clinical parameters during the last 10 serial HD sessions of 65 terminal patients with end-stage renal disease who had undergone maintenance HD and died in our hospital. Results The results showed that, while most of the laboratory data were unaltered, the physical parameters, such as systolic blood pressure and consciousness levels, gradually and significantly deteriorated toward the last HD session prior to death. The frequency of the use of vasopressors and O2 inhalation tended to increase. The accumulation of such severe conditions was observed at the last HD session. Of interest, the accumulation of severe conditions at the last HD session in patients with malignancies was significantly less than those with cardiovascular diseases or infectious diseases. The accumulation of severe conditions at the last HD session did not differ between patients who withdrew HD versus those who continued HD. Conclusion The results of the present study suggest that predicting the timing of maintenance HD therapy withdrawal is likely to be difficult and that the timing of maintenance HD therapy termination may differ among patient groups with distinct comorbid conditions.

A Concise Overview on Recent Advances in Pharmaceutical Aerosols and Their Commercial Applications

Background: Localized drug delivery to the respiratory system has become an increasingly successful and essential treatment strategy for several pulmonary diseases, including asthma, chronic abstractive disease, pneumonia, bronchitis, and cystic fibrosis. The rising incidence of respiratory diseases is a significant factor driving the worldwide market for respiratory inhaler devices. Objective: The objective of this article is to present various aspects of pharmaceutical aerosols, including their types, components, fundamentals, in-process and finished product quality control tests based on pharmacopeial standards and specifications, and commercial utility considering the pharmaceutical aerosol dosage forms that have been patented from 2000 to 2020, along with a list of marketed pharmaceutical products. Method: Aerosol, collectively referred to as a pressurized device, operates by triggering an appropriate valve system with a continuous or metered dosage of tiny mist spray. It is used not only in the treatment of asthma and chronic obstructive pulmonary disease but also in the treatment of cancer, diabetes, migraine, angina pectoris, acute lung injury, bone disorders, tuberculosis, and many more. A multitude of different variables, including types and properties of propellants, active substances, containers, valves, actuators, spray patterns, valve crimping efficiency, and particle size of the aerosols, influence the therapeutic effectiveness of pharmaceutical aerosols. Conclusion: Based on the current findings, distinct characteristics such as the elimination of firstpass metabolism, quick drug absorption, ease of therapy termination, as well as a larger surface area have attributed to the success of pharmaceutical aerosols.

Prognostic Impact of Muscle Quantity and Quality and Fat Distribution in Diffuse Large B-Cell Lymphoma Patients

Baseline CT scans of 116 patients (48% female, median 64 years) with diffuse large B-cell lymphoma (DLBCL) were retrospectively reviewed to investigate the prognostic role of sarcopenia and fat compartment distributions on overall survival (OS), progression-free survival (PFS), and early therapy termination. Skeletal muscle index (SMI), skeletal muscle density (SMD), and intermuscular adipose tissue (IMAT) were quantified at the level of the third lumbar vertebra (L3) and proximal thigh (PT). Low L3-SMD, but not low L3-SMI, was associated with early therapy termination (p = 0.028), shorter OS (HR = 6.29; 95% CI = 2.17–18.26; p &lt; 0.001), and shorter PFS (HR = 2.42; 95% CI = 1.26–4.65; p = 0.008). After correction for sex, International Prognostic Index (IPI), BMI, and R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), low L3-SMD remained associated with poor OS (HR = 3.54; 95% CI = 1.10–11.40; p = 0.034) but not with PFS. Increased PT-IMAT was prognostic for poor OS and PFS after correction for sex, IPI, BMI, and R-CHOP therapy (HR = 1.35; CI = 1.03–1.7; p = 0.03, and HR = 1.30; CI = 1.04–1.64; p = 0.024, respectively). Reduced muscle quality (SMD) and increased intermuscular fat (IMAT), rather than low muscle quantity (SMI), are associated with poor prognosis in DLBCL, when measured at the L3 level, and particularly at the level of the proximal thigh. The proximal thigh represents a novel radiological landmark to study body composition.

THE ASSIMILATION PROCESS OF PROBLEMATIC EXPERIENCES AND LONG-TERM OUTCOMES IN PSYCHOTHERAPY FOR DEPRESSION: COMPARING A RELAPSED AND A NON-RELAPSED CASE

"Over the years, research has demonstrated that psychotherapy is an effective treatment in different psychopathological conditions. However, which are the mechanisms or processes involved in therapeutic change that could explain its efficacy are not yet clear. The Assimilation of Problematic Experiences Model describes change in therapy as a process that occurs through the gradual assimilation of problematic experiences in the self – higher levels of assimilation seem to be associated with a better outcome at the end of therapy. However, little is known about the contribution of this process to the maintenance of therapeutic gains after the end of therapy. In the current study we aimed to explore how the level of assimilation achieved throughout therapy is associated with relapse prevention after treatment. We analyzed two good outcome cases of Emotion-Focused Therapy, previously diagnosed with depression: one case that remained asymptomatic and another that relapsed one year and a half after the end of therapy. The Assimilation of Problematic Experiences (APES) was used to assess the assimilation levels achieved and the Beck Depression Inventory-II (BDI-II) was used to assess the intensity of depressive symptoms. Five therapeutic sessions and three follow-up sessions were rated using the APES. The results showed that higher APES levels were associated with lower intensity of symptoms at the end and after therapy termination, being associated with relapse prevention in depression. These results suggest that a complete assimilation of the problematic experiences may help clients to maintain therapeutic gains reducing the probability of relapsing in depression."

CPAP Therapy Termination Rates by OSA Phenotype: A French Nationwide Database Analysis

The nationwide claims data lake for sleep apnoea (ALASKA)—real-life data for understanding and increasing obstructive sleep apnea (OSA) quality of care study—investigated long-term continuous positive airway pressure (CPAP) termination rates, focusing on the contribution of comorbidities. The French national health insurance reimbursement system data for new CPAP users aged ≥18 years were analyzed. Innovative algorithms were used to determine the presence of specific comorbidities (hypertension, diabetes and chronic obstructive pulmonary disease (COPD)). Therapy termination was defined as cessation of CPAP reimbursements. A total of 480,000 patients were included (mean age 59.3 ± 13.6 years, 65.4% male). An amount of 50.7, 24.4 and 4.3% of patients, respectively, had hypertension, diabetes and COPD. Overall CPAP termination rates after 1, 2 and 3 years were 23.1, 37.1 and 47.7%, respectively. On multivariable analysis, age categories, female sex (1.09 (1.08–1.10) and COPD (1.12 (1.10–1.13)) and diabetes (1.18 (1.16–1.19)) were significantly associated with higher CPAP termination risk; patients with hypertension were more likely to continue using CPAP (hazard ratio 0.96 (95% confidence interval 0.95–0.97)). Therapy termination rates were highest in younger or older patients with ≥1 comorbidity. Comorbidities have an important influence on long-term CPAP continuation in patients with OSA.

The Synergistic Process of Improvement in Cognitive Behavioral Therapy for Major Depression

Background: There is a substantial lack of qualitative research concerning individual cognitive behavioral therapy (CBT) for patients with major depressive disorder (MDD). In the present study, we wanted to explore how patients suffering from MDD experience improvement in CBT. Method: Patients with MDD (N = 10) were interviewed at therapy termination with semi-structured qualitative interviews. The transcripts were analyzed using a thematic analysis approach. Results: We identified three elements that were relevant to the process of improvement for all patients: the therapeutic relationship, the therapeutic interventions and increased insight. There is a dynamic interrelationship and synergy between these elements that may explain why patients considered the same elements as helpful, but often in different ways and at different stages of therapy. Conclusions: Highlighting the synergies and interrelationship between the elements that patients experience as helpful, may help therapists to learn from and utilize these experiences. This is a reminder of the importance of always being attentive to the individual processes of patients.

Positive Airway Pressure Therapy Adherence with Mask Resupply: A Propensity-Matched Analysis

There are currently few data on the impact of mask resupply on longer-term adherence to positive airway pressure (PAP) therapy. This retrospective analysis investigated the effects of mask/mask cushion resupply on the adherence to PAP versus no resupply. Deidentified patient billing data for PAP supply items were merged with telemonitoring data from Cloud-connected AirSense 10/AirCurve 10 devices via AirViewTM (ResMed). Eligible patients started PAP between 1 July 2014 and 17 June 2016, had ≥360 days of PAP device data, and achieved initial U.S. Medicare adherence criteria. Patients who received a resupply of mask systems/cushions (resupply group) were propensity-score-matched with those not receiving any mask/cushion resupply (control group). A total of 100,370 patients were included. From days 91 to 360, the mean device usage was 5.6 and 4.5 h/night in the resupply and control groups, respectively (p < 0.0001). The proportion of patients with a mean device usage ≥4 h/night was significantly higher in the resupply group versus the control group (77% vs. 59%; p < 0.0001). The therapy termination rate was significantly lower in the resupply group versus the control group (14.7% vs. 31.9%; p < 0.0001); there was a trend toward lower therapy termination rates as the number of resupplies increased. The replacement of mask interface components was associated with better longer-term adherence to PAP therapy versus no resupply.