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BMJ Open Apr 2024Postoperative pain after thoracic surgery impairs patients' quality of life and increases the incidence of respiratory complications. Optimised analgesia strategies...
INTRODUCTION
Postoperative pain after thoracic surgery impairs patients' quality of life and increases the incidence of respiratory complications. Optimised analgesia strategies include minimally invasive incisions, regional analgesia and early chest tube removal. However, little is known about the optimal analgesic regimen for uniportal video-assisted thoracoscopic surgery (uVATS).
METHODS AND ANALYSIS
We will conduct a single-centre, prospective, single-blind, randomised trial. The effects of postoperative analgesia will be tested using thoracic paravertebral block (PVB) in combination with patient-controlled intravenous analgesia (PVB+PCIA), erector spinae plane block (ESPB) in combination with patient-controlled intravenous analgesia (ESPB+PCIA) or PCIA alone; 102 patients undergoing uVATS will be enrolled in this study. Patients will be randomly assigned to the PVB group (30 mL of 0.33% ropivacaine with dexamethasone), ESPB group (40 mL of 0.25% ropivacaine with dexamethasone) or control groups. PCIA with sufentanil will be administered to all patients after surgery. The primary outcome will be total opioid consumption after surgery. Secondary outcomes include postoperative pain score; postoperative chronic pain at rest and during coughing; sensations of touch and pain in the chest wall, non-opioid analgesic consumption; length of stay; ambulation time, the total cost of hospitalisation and long-term postoperative analgesia. Adverse reactions to analgesics and adverse events related to the regional blocks will also be recorded. The statisticians will be blinded to the group allocation. Comparison of the continuous data among the three groups will be performed using a one-way analysis of variance to assess differences among the means.
ETHICS AND DISSEMINATION
The results will be published in patient education courses, academic conferences and peer-reviewed journals.
TRIAL REGISTRATION NUMBER
NCT06016777.
Topics: Humans; Ropivacaine; Thoracic Surgery, Video-Assisted; Prospective Studies; Quality of Life; Single-Blind Method; Analgesics; Pain, Postoperative; Analgesics, Opioid; Analgesia, Patient-Controlled; Dexamethasone; Randomized Controlled Trials as Topic
PubMed: 38569709
DOI: 10.1136/bmjopen-2023-079434 -
BioRxiv : the Preprint Server For... Mar 2024The ascending somatosensory pathways convey crucial information about pain, touch, itch, and body part movement from peripheral organs to the central nervous system....
The ascending somatosensory pathways convey crucial information about pain, touch, itch, and body part movement from peripheral organs to the central nervous system. Despite a significant need for effective therapeutics modulating pain and other somatosensory modalities, clinical translation remains challenging, which is likely related to species-specific features and the lack of in vitro models to directly probe and manipulate this polysynaptic pathway. Here, we established human ascending somatosensory assembloids (hASA)- a four-part assembloid completely generated from human pluripotent stem cells that integrates somatosensory, spinal, diencephalic, and cortical organoids to model the human ascending spinothalamic pathway. Transcriptomic profiling confirmed the presence of key cell types in this circuit. Rabies tracing and calcium imaging showed that sensory neurons connected with dorsal spinal cord projection neurons, which ascending axons further connected to thalamic neurons. Following noxious chemical stimulation, single neuron calcium imaging of intact hASA demonstrated coordinated response, while four-part concomitant extracellular recordings and calcium imaging revealed synchronized activity across the assembloid. Loss of the sodium channel SCN9A, which causes pain insensitivity in humans, disrupted synchrony across the four-part hASA. Taken together, these experiments demonstrate the ability to functionally assemble the essential components of the human sensory pathway. These findings could both accelerate our understanding of human sensory circuits and facilitate therapeutic development.
PubMed: 38559133
DOI: 10.1101/2024.03.11.584539 -
Lung Cancer (Amsterdam, Netherlands) May 2024Lorlatinib is a brain-penetrant, third-generation tyrosine kinase inhibitor (TKI) indicated for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic... (Review)
Review
Lorlatinib is a brain-penetrant, third-generation tyrosine kinase inhibitor (TKI) indicated for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC). In clinical trials, lorlatinib has shown durable efficacy and a manageable safety profile in treatment-naive patients and in those who have experienced progression while receiving first- and/or second-generation ALK TKIs. Lorlatinib has a distinct safety profile from other ALK TKIs, including hyperlipidemia and central nervous system effects. Clinical trial data showed that most adverse events (AEs) can be managed effectively or reversed with dose modifications (such as dose interruptions or reductions) or with concomitant medications without compromising clinical efficacy or quality of life for patients. A pragmatic approach to managing AEs related to lorlatinib is required. We present patient-focused recommendations for the evaluation and management of select AEs associated with lorlatinib developed by clinicians and nurses with extensive lorlatinib expertise in routine clinical practice. The recommendations follow the general framework of "prepare, monitor, manage, reassess" to streamline AE management and assist in practical, actionable, and personalized patient care.
Topics: Humans; Lactams; Aminopyridines; Carcinoma, Non-Small-Cell Lung; Pyrazoles; Lung Neoplasms; Protein Kinase Inhibitors; Lactams, Macrocyclic; Anaplastic Lymphoma Kinase; Drug-Related Side Effects and Adverse Reactions; Antineoplastic Agents; Disease Management
PubMed: 38554546
DOI: 10.1016/j.lungcan.2024.107535 -
Clinical Oral Investigations Mar 2024To compare the effectiveness of using a 0.454% stannous fluoride-containing dentifrice twice daily in relieving dentinal hypersensitivity (DH) in a Chinese population. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To compare the effectiveness of using a 0.454% stannous fluoride-containing dentifrice twice daily in relieving dentinal hypersensitivity (DH) in a Chinese population.
MATERIALS AND METHODS
This was a single-centre, randomized, controlled, examiner-blind, three-treatment-arm, parallel-group study in participants with clinically diagnosed DH. Subjects who met inclusion criteria (n = 197) were randomly allocated into 3 groups: test group (n = 66)-using a 0.454% stannous fluoride-containing dentifrice twice daily; positive control group (n = 64)-using a 5.0% calcium sodium phosphosilicate-containing dentifrice twice daily; negative control group (n = 67)-using a 1150 ppm of NaF dentifrice twice daily. Status of DH was assessed at week 4 and week 8 by the same independent examiner. Changes from baseline in Schiff sensitivity score, tactile threshold and Dentine Hypersensitivity Experience Questionnaire (DHEQ) score were analysed using analysis of covariance models. The DHEQ evaluated subject-perceived oral health-related quality of life (OHRQoL).
RESULTS
Statistically significant improvements in mean Schiff scores (p < 0.0001 for all products at Weeks 4 and 8), tactile threshold (p < 0.0001 for test and negative control at Weeks 4 and 8: Week 4 p = 0.0040 and Week 8 p < 0.0001 for positive control) and all DHEQ scores (p < 0.01 for all groups) were observed. No statistically significant differences were observed in the adjusted mean between all dentifrices at both timepoints, potentially driven by a placebo effect. Forty-two treatment-emergent adverse events (TEAEs) were reported (n = 32 subjects), with 2 serious AEs (n = 1) in the test group. TEAEs were not considered treatment-related.
CONCLUSIONS
All groups demonstrated statistically significant improvements in Schiff score, tactile threshold and OHRQoL. However, due to a possible placebo effect in the negative control, there were no statistically significant differences between the dentifrices.
CLINICAL RELEVANCE
This study adds to the growing research exploring why the placebo effect is a common phenomenon in DH studies.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04950465.
Topics: Humans; Tin Fluorides; Dentifrices; Sodium Fluoride; Quality of Life; Treatment Outcome; Dentin Sensitivity; Phosphates; Dentin Desensitizing Agents; Double-Blind Method; Touch; China; Fluorides
PubMed: 38530474
DOI: 10.1007/s00784-024-05610-9 -
Targeted Oncology Mar 2024Patients with non-small cell lung cancer harbouring mesenchymal-epithelial transition exon 14 (METex14) skipping typically demonstrate poorer prognosis than overall...
Modelling the Effectiveness of Tepotinib in Comparison to Standard-of-Care Treatments in Patients with Advanced Non-small Cell Lung Cancer (NSCLC) Harbouring METex14 Skipping in the UK.
BACKGROUND
Patients with non-small cell lung cancer harbouring mesenchymal-epithelial transition exon 14 (METex14) skipping typically demonstrate poorer prognosis than overall non-small cell lung cancer. Until recently, no targeted treatments were available for patients with non-small cell lung cancer harbouring METex14 skipping in the UK, with limited treatments available.
OBJECTIVE
This study estimates the long-term survival and quality-adjusted life-year benefit of MET inhibitor tepotinib versus current standard of care from a UK perspective.
METHODS
A partitioned-survival model assessed the survival and quality-adjusted life-year benefits of tepotinib versus immunotherapy ± chemotherapy and chemotherapy for untreated and previously treated patients, respectively, using evidence from the single-arm VISION trial (NCT02864992). Two approaches were used to inform an indirect treatment comparison: (1) published clinical trials in overall non-small cell lung cancer and (2) real-world evidence in the METex14 skipping population. Results are presented as median and total quality-adjusted life-year gain and survival for progression-free survival and overall survival. Survival curves were validated against the external literature and uncertainty assessed using a probabilistic sensitivity analysis.
RESULTS
Using the indirect treatment comparison against the published literature, tepotinib is estimated to have a median progression-free survival gain versus pembrolizumab ± chemotherapy (11.0 and 9.2 months) in untreated patients, and docetaxel ± nintedanib (5.1 and 6.4 months) in previously treated patients. Across the populations, tepotinib is estimated to have a median survival gain of 15.4 and 9.2 months versus pembrolizumab ± chemotherapy in untreated patients and 12.8 and 5.1 months versus docetaxel ± nintedanib in previously treated patients. The total quality-adjusted life-year gain ranges between 0.56 and 1.17 across the untreated and previously treated populations. Results from the real-world evidence of indirect treatment comparisons are consistent with these findings.
CONCLUSIONS
Despite the limitations of the evidence base, the numerous analyses conducted have consistently indicated positive outcomes for tepotinib versus the current standard of care.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Docetaxel; Exons; United Kingdom; Piperidines; Pyridazines; Pyrimidines
PubMed: 38492157
DOI: 10.1007/s11523-024-01038-z -
PloS One 2024Therapeutic alliance is a relevant aspect of healthcare and may influence patient outcomes. So far, little is known about the therapeutic alliance in telerehabilitation.
INTRODUCTION
Therapeutic alliance is a relevant aspect of healthcare and may influence patient outcomes. So far, little is known about the therapeutic alliance in telerehabilitation.
PURPOSE
To identify and describe central elements of therapeutic alliance in the setting of telerehabilitation and compare it to those in conventional rehabilitation.
METHODS
In this qualitative study, a literature search and in-depth semi-structured interviews with rehabilitation and telerehabilitation experts were conducted from 15.5.-10.8.2020 on elements influencing the therapeutic alliance in rehabilitation and telerehabilitation. Using a combined deductive and inductive approach, qualitative content analysis was used to identify categories and derive central themes.
RESULTS
The elements bond, communication, agreement on goals and tasks and external factors were identified in the literature search and informed the development of the interview guide. Twelve purposively sampled experts from the fields of physiotherapy, occupational therapy, speech and language therapy, psychology, general medicine, sports science and telerehabilitation software development participated in the interviews. We identified three central themes: building effective communication; nurturing a mutual relationship of trust and respect; and agreement on goals and tasks and drivers of motivation.
CONCLUSIONS
In this qualitative study, key elements of therapeutic alliance in rehabilitation confirmed those reported in the literature, with additional elements in telerehabilitation comprising support from others for ensuring physical safety and technical connectedness, caregivers acting as co-therapists and applying professional touch, and promoting patient autonomy and motivation using specific strategies.
Topics: Humans; Therapeutic Alliance; Telerehabilitation; Qualitative Research; Physical Therapy Modalities; Occupational Therapy
PubMed: 38457374
DOI: 10.1371/journal.pone.0299909 -
PloS One 2024Although pain relief is a crucial component of modern obstetric care, it remains a poorly established service in sub-Saharan countries such as Kenya. Maternal health...
BACKGROUND
Although pain relief is a crucial component of modern obstetric care, it remains a poorly established service in sub-Saharan countries such as Kenya. Maternal health care providers have an extensive role to play in meeting the analgesic needs of women during childbirth. This study sought to examine the practice of labour pain relief among Kenyan maternal health care providers.
METHODS
This was an institution-based, cross-sectional, descriptive survey. The study included midwives, obstetricians, and anaesthesiologists (n = 120) working at the second-largest tertiary facility in Kenya. A structured, self-administered questionnaire was used. The labour pain relief practice, knowledge, attitude, and perceived barriers to labour pain management were described.
RESULTS
One hundred and seventeen respondents participated in the study representing a response rate of 97.5%. More than half of maternal health care providers routinely provided the service of labour pain relief (61.5%). Sixty-four (88.9%) respondents reported providing pharmacological and non-pharmacological methods, while 11.1% provided only pharmacological ones. The most common pharmacological method prescribed was non-opioids (12.8%). The most preferred non-pharmacological method of pain management was touch and massage (93.8%). Regional analgesia was provided by 3.4% of the respondents. More than half of the respondents (53%) had poor knowledge of labour pain relief methods. Almost all (94%) of the respondents had a positive attitude towards providing labour pain relief. Non-availability of drugs and equipment (58.1%), lack of clear protocols and guidelines (56.4%), and absence of adequate skilled personnel (55.6%) were reported as the health system factors that hinder the provision of labour analgesia.
CONCLUSIONS
More than half of maternal health care providers routinely relieve labour pain. Epidural analgesia is still relatively underutilized. There is a need to develop institutional labour pain management protocols to meet the analgesic needs of women during childbirth.
Topics: Pregnancy; Female; Humans; Pain Management; Kenya; Labor Pain; Cross-Sectional Studies; Analgesics; Surveys and Questionnaires; Health Personnel; Analgesia, Obstetrical
PubMed: 38452017
DOI: 10.1371/journal.pone.0299211 -
JMIR Diabetes Mar 2024Patients with type 2 diabetes mellitus (T2DM) experience multiple barriers to improving self-management. Evidence suggests that motivational interviewing (MI), a...
Acceptability of Mobile App-Based Motivational Interviewing and Preferences for App Features to Support Self-Management in Patients With Type 2 Diabetes: Qualitative Study.
BACKGROUND
Patients with type 2 diabetes mellitus (T2DM) experience multiple barriers to improving self-management. Evidence suggests that motivational interviewing (MI), a patient-centered communication method, can address patient barriers and promote healthy behavior. Despite the value of MI, existing MI studies predominantly used face-to-face or phone-based interventions. With the growing adoption of smartphones, automated MI techniques powered by artificial intelligence on mobile devices may offer effective motivational support to patients with T2DM.
OBJECTIVE
This study aimed to explore the perspectives of patients with T2DM on the acceptability of app-based MI in routine health care and collect their feedback on specific MI module features to inform our future intervention.
METHODS
We conducted semistructured interviews with patients with T2DM, recruited from public primary care clinics. All interviews were audio recorded and transcribed verbatim. Thematic analysis was conducted using NVivo.
RESULTS
In total, 33 patients with T2DM participated in the study. Participants saw MI as a mental reminder to increase motivation and a complementary care model conducive to self-reflection and behavior change. Yet, there was a sense of reluctance, mainly stemming from potential compromise of autonomy in self-care by the introduction of MI. Some participants felt confident in their ability to manage conditions independently, while others reported already making changes and preferred self-management at their own pace. Compared with in-person MI, app-based MI was viewed as offering a more relaxed atmosphere for open sharing without being judged by health care providers. However, participants questioned the lack of human touch, which could potentially undermine a patient-provider therapeutic relationship. To sustain motivation, participants suggested more features of an ongoing supportive nature such as the visualization of milestones, gamified challenges and incremental rewards according to achievements, tailored multimedia resources based on goals, and conversational tools that are interactive and empathic.
CONCLUSIONS
Our findings suggest the need for a hybrid model of intervention involving both app-based automated MI and human coaching. Patient feedback on specific app features will be incorporated into the module development and tested in a randomized controlled trial.
PubMed: 38446526
DOI: 10.2196/48310 -
Lung Cancer (Amsterdam, Netherlands) Apr 2024First-line pembrolizumab plus chemotherapy has shown clinical benefit in patients with metastatic non-small cell lung cancer (NSCLC) regardless of tissue tumor...
BACKGROUND
First-line pembrolizumab plus chemotherapy has shown clinical benefit in patients with metastatic non-small cell lung cancer (NSCLC) regardless of tissue tumor mutational burden (tTMB) status. Blood tumor mutational burden (bTMB), assessed using plasma-derived circulating tumor DNA (ctDNA), may be a surrogate for tTMB. The KEYNOTE-782 study evaluated the correlation of bTMB with the efficacy of first-line pembrolizumab plus chemotherapy in NSCLC.
METHODS
Previously untreated patients with stage IV nonsquamous NSCLC received pembrolizumab 200 mg plus pemetrexed 500 mg/m and investigator's choice of carboplatin area under the curve 5 mg/mL/min or cisplatin 75 mg/m for 4 cycles, then pembrolizumab plus pemetrexed for ≤31 additional cycles every 3 weeks. Study objectives were to evaluate the association of baseline bTMB with objective response rate (ORR) (RECIST v1.1 by investigator assessment; primary), progression-free survival (PFS; RECIST v1.1 by investigator assessment), overall survival (OS), and adverse events (AEs; all secondary). A next-generation sequencing assay (GRAIL LLC) with a ctDNA panel that included lung cancer-associated and immune gene targets was used to measure bTMB.
RESULTS
117 patients were enrolled; median time from first dose to data cutoff was 19.3 months (range, 1.0-35.5). ORR was 40.2 % (95 % CI 31.2-49.6 %), median PFS was 7.2 months (95 % CI 5.6-9.8) and median OS was 18.1 months (95 % CI 13.5-25.6). Treatment-related AEs occurred in 113 patients (96.6 %; grade 3-5, n = 56 [47.9 %]). Of patients with evaluable bTMB (n = 101), the area under the receiver operating characteristics curve for continuous bTMB to discriminate response was 0.47 (95 % CI 0.36-0.59). Baseline bTMB was not associated with PFS or OS (posterior probabilities of positive association: 16.8 % and 7.8 %, respectively).
CONCLUSIONS
AEs were consistent with the established safety profile of first-line pembrolizumab plus chemotherapy in NSCLC. Baseline bTMB did not show evidence of an association with efficacy.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Pemetrexed; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38422883
DOI: 10.1016/j.lungcan.2024.107506