Treatment Response Rates Research Articles

Examination of clinical variables affecting resurgence: A reanalysis of 46 applications.

Despite the efficacy of behavioral interventions, resurgence of challenging behavior (e.g., aggression, self-injury) following successful treatment can still occur. Applied work has focused on identifying treatment-related variables thought to affect the occurrence and magnitude of resurgence. The current study describes the relation between several variables (i.e., phase duration, response rates in baseline and treatment, obtained rates of reinforcement, downshift in reinforcement step size) and resurgence in a retrospective consecutive controlled case series of 46 treatment applications for challenging behavior conducted in an inpatient setting. Only the downshift in reinforcement (e.g., schedule-thinning) step size was correlated with the magnitude of resurgence. These results are consistent with recent findings suggesting that treatment duration and other factors have inconsistent effects on resurgence of challenging behavior.

Regorafenib in patients with pretreated advanced melanoma: a single-center case series.

Melanoma patients failing all approved treatment options have a poor prognosis. The antimelanoma activity of regorafenib (REGO), a multitargeted kinase inhibitor, has not been investigated in this patient population. The objective response rate and safety of REGO treatment in advanced melanoma patients was investigated retrospectively. Twenty-seven patients received REGO treatment. All patients had progressed on anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibition and BRAF/MEK inhibitors (in case of a BRAF V600 mutation). REGO was administered in continuous dosing and combined (upfront or sequentially) with nivolumab ( n = 5), trametinib ( n = 8), binimetinib ( n = 2), encorafenib ( n = 1), dabrafenib/trametinib ( n = 9), or encorafenib/binimetinib ( n = 7). The best overall response was partial response (PR) in five patients (18.5%) and stable disease in three patients (11.1%). Three of seven (42.8%) BRAF V600mut patients treated with REGO in combination with BRAF/MEK inhibitors obtained a PR (including regression of brain metastases in all three patients). In addition, PR was documented in a BRAF V600mut patient treated with REGO plus anti-PD-1, and a NRASQ61mut patient treated with REGO plus a MEK inhibitor. Common grade 3-4 treatment-related adverse events included arterial hypertension ( n = 7), elevated transaminase levels ( n = 5), abdominal pain ( n = 3), colitis ( n = 2), anorexia ( n = 1), diarrhea ( n = 1), fever ( n = 1), duodenal perforation ( n = 1), and colonic bleeding ( n = 1). Median progression-free survival was 11.0 weeks (95% confidence interval, 7.1-14.9); median overall survival was 23.1 weeks (95% confidence interval, 13.0-33.3). REGO has a manageable safety profile in advanced melanoma patients, in monotherapy as well as combined with BRAF/MEK inhibitors or PD-1 blocking monoclonal antibodies. The triplet combination of REGO with BRAF/MEK inhibitors appears most active, particularly in the BRAF V600mut patients.

Efficacy of acupuncture treatment for breast cancer-related insomnia: study protocol for a multicenter randomized controlled trial

BackgroundInsomnia is one of the most common symptoms among breast cancer patients, which can be present throughout all stages of breast cancer. As a non-pharmacological alternative treatment, acupuncture has been suggested to improve sleep situations in patients with cancer suffering from insomnia. However, there is a lack of well-designed, high-quality clinical evidence regarding the efficacy of acupuncture in the treatment of breast cancer-related insomnia. This study is conducted to evaluate the efficacy and safety of acupuncture treatment for breast cancer-related insomnia.MethodsThis study was designed as a multicenter, randomized, sham-controlled clinical trial. A total of 264 eligible patients with breast cancer-related insomnia will be randomized into an acupuncture group and a sham acupuncture group in a 1:1 ratio. In the trial, patients in the acupuncture and sham acupuncture groups will receive 12 sessions over a consecutive 4-week period. The primary outcome will be the treatment response rate of Insomnia Severity Index (ISI) at week 4; secondary outcomes include treatment remission rate of ISI, Sleep Efficiency (SE) obtained by the use of Sleep diary, treatment response rate of ISI at 8th and 16th weeks of follow-up, the mean changes of ISI, Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Quality of Life Questionnaire - Core 30 (QLQ-C30), sleep parameters recorded in Actigraphy and weekly usage of remedial drugs. Adverse events will be recorded throughout the study. All analyses will be based on the ITT principle and performed with SAS 9.4 statistical software.DiscussionThis trial will evaluate the clinical efficacy and safety of acupuncture for breast cancer-related insomnia. If proven effective, acupuncture will provide an effective option for patients with breast cancer-related insomnia, which will play a positive role in helping patients reduce their use of sleeping medications.Clinical trial registrationClinicalTrials.gov, identifier NCT05510700.

Sintilimab (anti-PD-1 antibody) plus chidamide (histone deacetylase inhibitor) in relapsed or refractory extranodal natural killer T-cell lymphoma (SCENT): a phase Ib/II study.

Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma (RR-ENKTL), however, the complete response (CR) rate and the duration of response (DOR) need to be improved. This phase 1b/2 study investigated the safety and efficacy of sintilimab, a fully human anti-PD-1 antibody, plus chidamide, an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL. Expected objective response rate (ORR) of combination treatment was 80%. Patients received escalating doses of chidamide, administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 months. No dose-limiting events were observed, RP2D of chidamide was 30 mg twice a week. Twenty-nine patients were enrolled in phase 2. In the intention-to-treat population (n = 37), overall response rate was 59.5% with a complete remission rate of 48.6%. The median DOR, progression-free survival (PFS), and overall survival (OS) were 25.3, 23.2, and 32.9 months, respectively. The most common grade 3 or higher treatment-emergent adverse events (AEs) were neutropenia (28.9%) and thrombocytopenia (10.5%), immune-related AEs were reported in 18 (47.3%) patients. Exploratory biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic role. STAT3 mutation shows an unfavorable prognosis. Although outcome of anticipate ORR was not achieved, sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first time. It is a promising therapeutic option for this population.

Early Response, Long-Term Seizure Outcome, and Very-Low-Dose Adrenocorticotrophic Hormone Therapy for Infantile Epileptic Spasms Syndrome With Down Syndrome

BackgroundInfantile epileptic spasms syndrome (IESS) with Down syndrome has good treatment response and good seizure outcomes with high-dose adrenocorticotrophic hormone (ACTH) therapy. We investigated the early treatment response of epileptic spasms (ES), long-term seizure outcome, and efficacy of very-low-dose ACTH therapy for IESS with Down syndrome. MethodsWe retrospectively investigated patients with Down syndrome and IESS between April 1983 and January 2023. We defined response to treatment as clinical remission and electrographic resolution of hypsarrhythmia after treatment for more than one month and early treatment as any treatment for ES within three months of initiation of treatment. Long-term seizure outcomes were determined by the presence of any type of seizure within one year of the last visit. We investigated the dosage and efficacy of very-low-dose ACTH therapy. ResultsThirty patients were enrolled with a median follow-up period of 7.7 years (range: 1.3 to 19.1). The response and relapse rates in the early treatment were 83.3% and 16.0%, respectively. The seizure-free rate of long-term seizure outcomes was 80.0%. Long-term seizure outcomes correlated with early treatment response to ES. The response rate of very-low-dose ACTH therapy was 59.3%. The efficacy of ACTH therapy tended to be dose-dependent (P = 0.055). ConclusionsEarly treatment response to ES may be useful in predicting long-term seizure outcomes of IESS with Down syndrome. Very-low-dose ACTH therapy was the most effective treatment for ES and could exhibit dose-dependent efficacy. Depending on the IESS etiology, the ACTH dose could be reduced to minimize its side effects.

Exploring the Impact of Cytogenetic Abnormalities on Treatment Responses and Survival Outcomes in Multiple Myeloma: A Single-Centre Experience of 13 Years of Follow-Up.

(1) Background: The introduction of novel therapies has led to a considerable evolution in the management of Multiple Myeloma, and chromosomal abnormalities predict the success of treatment. We aimed to characterize cytogenetic abnormalities for risk stratification in the patient population and to evaluate the predictive and prognostic value of the specified abnormalities in distinct treatment modalities. (2) Methods: This study included patients with Multiple Myeloma who applied to the Internal Medicine Clinic of the Cukurova University Faculty of Medicine. Between 2010 and 2023, 98 cases with cytogenetic abnormality data were identified. We analysed the effects of cytogenetic abnormalities on survival and response rates to first chemotherapies. (3) Results: P53 del was the most prevalent abnormality, and t(11;14) was the most common translocation. There was no significant difference in the mean survival and treatment response rates for specific cytogenetic abnormalities. When chemotherapies based on lenalidomide were initiated, patients' life-death statuses differed significantly from those of treatments without lenalidomide. Regardless of the type of chromosomal aberration, lenalidomide-based treatments independently enhanced average survival 14-fold, while there was no significant difference in overall survival among treatments. (4) Conclusions: In individuals with cytogenetic abnormalities, lenalidomide-based treatments should be started regardless of the chemotherapy to be used for the condition.

Internet-Delivered Exposure and Response Prevention for Pediatric Tourette Syndrome

Behavior therapy is a recommended intervention for Tourette syndrome (TS) and chronic tic disorder (CTD), but availability is limited and long-term effects are uncertain. To investigate the long-term efficacy and cost-effectiveness of therapist-supported, internet-delivered exposure and response prevention (ERP) vs psychoeducation for youths with TS or CTD. This 12-month controlled follow-up of a parallel group, superiority randomized clinical trial was conducted at a research clinic in Stockholm, Sweden, with nationwide recruitment. In total, 221 participants aged 9 to 17 years with TS or CTD were enrolled between April 26, 2019, and April 9, 2021, of whom 208 (94%) provided 12-month follow-up data. Final follow-up data were collected on June 29, 2022. Outcome assessors were masked to treatment allocation throughout the study. A total of 111 participants were originally randomly allocated to 10 weeks of therapist-supported, internet-delivered ERP and 110 participants to therapist-supported, internet-delivered psychoeducation. The primary outcome was within-group change in tic severity, measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS), from the 3-month follow-up to the 12-month follow-up. Treatment response was defined as 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement scale. Analyses were intention-to-treat and followed the plan prespecified in the published study protocol. A health economic evaluation was performed from 3 perspectives: health care organization (including direct costs for treatment provided in the study), health care sector (additionally including health care resource use outside of the study), and societal (additionally including costs beyond health care [eg, parent's absenteeism from work]). In total, 221 participants were recruited (mean [SD] age, 12.1 [2.3] years; 152 [69%] male). According to the YGTSS-TTSS, there were no statistically significant changes in tic severity from the 3-month to the 12-month follow-up in either group (ERP coefficient, -0.52 [95% CI, -1.26 to 0.21]; P = .16; psychoeducation coefficient, 0.00 [95% CI, -0.78 to 0.78]; P > .99). A secondary analysis including all assessment points (baseline to 12-month follow-up) showed no statistically significant between-group difference in tic severity from baseline to the 12-month follow-up (coefficient, -0.38 [95% CI, -1.11 to 0.35]; P = .30). Treatment response rates were similar in both groups (55% in ERP and 50% in psychoeducation; odds ratio, 1.25 [95% CI, 0.73-2.16]; P = .42) at the 12-month follow-up. The health economic evaluation showed that, from a health care sector perspective, ERP produced more quality-adjusted life years (0.01 [95% CI, -0.01 to 0.03]) and lower costs (adjusted mean difference -$84.48 [95% CI, -$440.20 to $977.60]) than psychoeducation at the 12-month follow-up. From the health care organization and societal perspectives, ERP produced more quality-adjusted life years at higher costs, with 65% to 78% probability of ERP being cost-effective compared with psychoeducation when using a willingness-to-pay threshold of US $79 000. There were no statistically significant changes in tic severity from the 3-month through to the 12-month follow-up in either group. The ERP intervention was not superior to psychoeducation at any time point. While ERP was not superior to psychoeducation alone in reducing tic severity at the end of the follow-up period, ERP is recommended for clinical implementation due to its likely cost-effectiveness and support from previous literature. ClinicalTrials.gov Identifier: NCT03916055.

Abstract PO1-15-07: Subtyping-directed precision treatment refines traditional one-size-fits-all therapy in HR+/HER2- breast cancer: a sub-study of the MULAN umbrella trial

Abstract Background: The standard approach of using one-size-fits-all endocrine therapy for hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancers has faced significant challenges due to variations in treatment response among individuals. Consequently, there is still an urgent need to understand the molecular biology of HR+/HER2- breast cancer and explore precision treatment strategy. Methods: We established a multiomics cohort (n = 351), multicenter real-world clinical cohorts (n = 643), a prospective clinical cohort (MULAN trial), and a drug-testing platform containing patient-derived organoids (n = 126) and patient-derived tumor fragments (n = 49) of HR+/HER2- breast cancers. Integrating "bench" and “bedside” data, we conducted comprehensive preclinical and clinical translational research on precision strategies in HR+/HER2- breast cancer. Results: We implemented a comprehensive classification system for HR+/HER2- breast cancer, comprising four distinct subtypes. We further demonstrated the efficacy and mechanisms of subtyping-directed precision treatment strategies through clinical cohort studies, omics analysis and functional assays: endocrine therapy alone for the canonical luminal subtype; the addition of CDK4/6 inhibitor and PARP inhibitor for the proliferative subtype; the immunotherapy for the immunogenic subtype; and tyrosine kinase inhibitors for the receptor tyrosine kinase-driven subtype. Using clinically applicable subtyping methods, we validated that matched precision treatment strategies outperformed unmatched approaches in a real-world cohort, almost doubling the median progression-free survival time for patients with refractory advanced HR+/HER2- breast cancer (9.83 months [95% CI, 5.74-13.93] vs 4.77 months [95% CI, 3.35-6.18]; hazard ratio 0.64 [95% CI, 0.41-0.99]). Importantly, the first-stage analysis of the MULAN phase II umbrella clinical trial (NCT04355858) verified the higher objective response rate (88.9%, 95%CI: 51.7%-99.7%) of the subtyping-directed precision treatment. Conclusion: Our study emphasizes the superiority of subtyping-directed precision treatment strategies for HR+/HER2- breast cancer, refines traditional “one-size-fits-all” therapy, and facilitates the translation of precision treatment strategies from bench to bedside. Overall study design Part 1 Subtype Molecular Characteristics: Molecular features of the four subtypes of HR+/HER2- breast cancer. Part 2 Multidimensional Efficacy Validation: Integrating data from a multiomics cohort, real-world study, drug testing platform and prospective clinical research to validate the subtyping-directed precision treatment strategy in HR+/HER2- breast cancer. Part 3 Subtyping-directed Precision Treatment Strategy: Integrating clinical cohort studies, omics analysis and functional assays revealed the heterogeneity of treatment response in HR+/HER2- breast cancer, and proposed a subtyping-directed precision treatment strategy. CIN, chromosomal instability; RTK, receptor tyrosine kinase; CNA, copy-number alteration; ER, estrogen receptor; HR, hormone receptor; HER2, human epidermal growth factor receptor 2. Citation Format: Xiu-Zhi Zhu, Xi Jin, Hu-Yun-Long Zhang, Xiyu Liu, Yi-Fan Zhou, Yi-Yu Chen, Tong Fu, Ming-Liang Jin, Ya-Xin Zhao, Yi-Fan Xie, Ruo-Xi Wang, Zhong-Hua Wang, Lei Fan, Yi-Zhou Jiang, Zhi-Ming Shao. Subtyping-directed precision treatment refines traditional one-size-fits-all therapy in HR+/HER2- breast cancer: a sub-study of the MULAN umbrella trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-07.

Gene mutation profiling in microsatellite instability colorectal cancer and its association with the efficacy of immunotherapy: A retrospective study.

Microsatellite instability-high (MSI-H) colorectal cancer (CRC) is known for its heightened responsiveness to immunotherapy. However, establishing robust predictive markers for immunotherapy efficacy remains imperative. This retrospective study aimed to elucidate the genetic landscape of MSI-H CRC and correlate these genetic alterations with immunotherapy outcomes in a cohort of 121 patients. We analyzed clinical and molecular data from 121 patients with MSI-H CRC. We conducted a thorough genetic analysis of MSI-H CRC patients, with a specific emphasis on the APC, TP53, RAS, and MMR genes. We further analyzed the relationship between gene mutations and immunotherapy efficacy. The primary endpoints analyzed were objective response rate (ORR) and progression-free survival (PFS). All statistical analysis was conducted using SPSS26.0 and R 4.2.0 software. Our findings underscored the complexity of the genetic landscape in MSI-H CRC, shedding light on the intricate interplay of these genes in CRC development. Notably, mutations in MMR genes exhibited a distinctive pattern, providing insights into the underlying mechanisms of MSI-H. Furthermore, our results revealed correlations between specific genetic alterations and immunotherapy outcomes, with a particular focus on treatment response rates and progression-free survival. This study represents a significant step toward unraveling the genetic nuances of MSI-H CRC. The distinctive pattern of MMR gene mutations not only adds depth to our understanding of MSI-H CRC but also hints at potential avenues for targeted therapies. This research sets the stage for future investigations aimed at refining therapeutic strategies and improving outcomes for patients with MSI-H CRC.

Epigenetics of Fear, Anxiety and Stress - Focus on Histone Modifications.

Fear-, anxiety- and stress-related disorders are among the most frequent mental disorders. Given substantial rates of insufficient treatment response and often a chronic course, a better understanding of the pathomechanisms of fear-, anxiety- and stress-related disorders is urgently warranted. Epigenetic mechanisms such as histone modifications - positioned at the interface between the biological and the environmental level in the complex pathogenesis of mental disorders - might be highly informative in this context. The current state of knowledge on histone modifications, chromatin-related pharmacology and animal models modified for genes involved in the histone-related epigenetic machinery will be reviewed with respect to fear-, anxiety- and stress-related states. Relevant studies, published until 30th June 2022, were identified using a multi-step systematic literature search of the Pub- Med and Web of Science databases. Animal studies point towards histone modifications (e.g., H3K4me3, H3K9me1/2/3, H3K27me2/3, H3K9ac, H3K14ac and H4K5ac) to be dynamically and mostly brain region-, task- and time-dependently altered on a genome-wide level or gene-specifically (e.g., Bdnf) in models of fear conditioning, retrieval and extinction, acute and (sub-)chronic stress. Singular and underpowered studies on histone modifications in human fear-, anxiety- or stress-related phenotypes are currently restricted to the phenotype of PTSD. Provided consistent validation in human phenotypes, epigenetic biomarkers might ultimately inform indicated preventive interventions as well as personalized treatment approaches, and could inspire future innovative pharmacological treatment options targeting the epigenetic machinery improving treatment response in fear-, anxiety- and stressrelated disorders.

Results of a study examining the use of onabotulinumtoxinA in pediatric patients with overactive bladder

There is a lack of approved treatments for pediatric patients with overactive bladder (OAB) with inadequate response to anticholinergic therapy. OnabotulinumtoxinA 100U is approved to treat OAB in adults based on data from randomized, pivotal trials. To investigate the efficacy and safety of onabotulinumtoxinA treatment of OAB in children aged 12-17 years who were not adequately managed with anticholinergics. In this multinational, multicenter, randomized, double-blind, parallel-group, multiple-dose study (NCT02097121), pediatric patients with OAB were randomized 1:1:1 to receive onabotulinumtoxinA 25U, 50U, or 100U (≤6U/kg). Patients could request retreatment starting at week 12. The primary endpoint was change from baseline to week 12 after treatment 1 in daily frequency of daytime urinary incontinence (UI) episodes. Safety assessments evaluated treatment-emergent adverse events (TEAEs). Of 68 screened patients, 55 received ≥1 treatment. Mean age was 14 years; 85.5% of patients were female. At week 12 after treatment 1, least squares mean change from baseline in daily frequency of daytime UI episodes showed a numerically greater reduction in the 100U arm (-2.4) versus the 25U arm (-1.4; P=0.38), with a significant within-group change from baseline in the 100U arm (P=0.0027). Achievement of treatment response was significantly greater with onabotulinumtoxinA 100U vs 25U (Figure). Median time to request retreatment was ≥16 weeks in all groups. The most frequently reported TEAEs were nasopharyngitis (10.9%) and urinary tract infection (UTI; 10.9%). Urinary retention was observed in 1 patient during treatment cycle 2; there were no serious TEAEs of UTI or urinary retention. Throughout 2 additional treatment cycles continued efficacy for the 100U dose arm was observed along with a consistent safety profile. Change in daily frequency of UI episodes at week 12 in treatment cycle 1 was not significantly different between arms. However, ≥50% response rate was significantly higher with onabotulinumtoxinA 100U versus 25U. Enrollment challenges that lowered the sample size could have reduced statistical power. Also, the lack of a placebo arm and the observed benefit with the 25U comparator limited interpretation. OnabotulinumtoxinA injections were well tolerated in children with OAB at all doses studied. Although the primary endpoint was not met, the significantly greater treatment response rate observed with onabotulinumtoxinA 100U versus 25U suggests additional benefit of the higher dose, without additional safety concerns.

A Real-Life 208 Week Single-Centred, Register-Based Retrospective Study Assessing Secukinumab Survival and Long-Term Efficacy and Safety Among Greek Patients with Moderate to Severe Plaque Psoriasis, Including Difficult-to-Treat Manifestations Such as Genitals and Scalp.

Psoriasis is a chronic inflammatory disease with multiple skin manifestations, and in case of lesions affecting the genital area, sexual health impairment and psychological distress can furthermore impair the patients quality of life. Secukinumab is a fully humanized immunoglobulin G1 kappa antagonist of IL-17A and is indicated for the treatment of moderate-to-severe psoriasis, since it shows a significant efficacy in clinical outcomes, with rapid onset of remission, prolonged treatment response rate, advantageous safety profile and a valuable improvement of the patients quality of life. This study was conducted in order to gather retrospective real-world data regarding the efficacy of secukinumab in treating patients with moderate-to-severe plaque psoriasis in Greece. To fill the relevant literature gap, we included difficult-to-treat manifestations in our analysis, specifically regarding the efficacy in the genital area and on the skin folds where relevant data are missing both from the drug clinical program as well as from the real-world setting. All adult patients receiving 300 mg secukinumab and attending follow-up visits on a regular basis, according to routine medical practice were included. The timeline of the study was from 2015 to 2020. Primary endpoint of the study was the percentage of patients who achieved a psoriasis area and severity index (PASI) 75 response rate at week 16 and week 52 post baseline. Secondary endpoints were the evaluation at baseline (week 0), week 4 (±1), week 16 (±1), week52 (±1), and week 104 (±1), week 156 (±1), week 208 (±1) of clinical outcomes, incidence of adverse events and potential predictive variables influencing response rate. Ninety-nine patients were included in the study population, from whom sixty six patients (66.67%) were bio-naive, whereas 33 patients had never received systemic treatment. Regarding difficult-to-treat manifestations, we recorded scalp involvement in 74.74% (74/99) of our patients, genital psoriasis in 27.27% (27/99) and skin folds involvement (psoriasis inversa) in 17% (17/99). At week 16, PASI75/PASI90/PASI100 were observed in 87.5%/69.8%/49%, respectively. At week 4 lesions affecting the genital area and patients with skin fold involvement experienced a rapid regression and 84.1% of patients achieved sPGA 0/1 (Physician Global Assessment). Treatment with secukinumab during the 208 weeks of observation did not reveal any major adverse event or systemic infection and generally it was well tolerated. According to our outcomes secukinumab is an effective treatment choice for treating chronic plaque psoriasis, but, additionally, it can be efficacious in the subgroups of patients with difficult-to-treat manifestations, as our patients experienced great improvement starting even 5 weeks after treatment initiation. This real-life study offers information about clinical efficacy, retention and safety profile of secukinumab in patients from everyday clinical practice over a long-term, 4-year, follow-up period in Greece.

Curative effect of motherwort combined with ethinylestradiol-cyproterone acetate on dysfunctional uterine bleeding

ABSTRACT Objective This study aimed to investigate the curative effect of motherwort combined with ethinylestradiol-cyproterone acetate (EE/CPA) on dysfunctional uterine bleeding (DUB). Methods Atotal of 68 patients with DUB were divided into a single medication group (treated with EE/CPA) and a combination medication group(treated with motherwort and EE/CPA). The clinical efficacy, uterine hemodynamic parameters, sex hormone levels, coagulation index levels, blood routine test levels, and adverse reactions of patients were evaluated. Results After three months of treatment, total treatment response rate of the combination medication group was significantly higher than that of the single medication group. Decreased uterine volume, endometrial thickness and resistance index (RI), increased pulsatility index(PI), average flow rate, and uterine artery blood flow, as well asreduced follicle-stimulating hormone (FSH), luteinizing hormone (LH),estradiol (E2), progesterone (P), activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen (FIB), thrombin time(TT), platelet count (PLT), red blood cell (RBC), and hemoglobin (Hb)levels were witnessed in patients of the two groups. In thecombination medication group, there exhibited reduced uterine volume, endometrial thickness and RI, elevated PI, average flow rate, and uterine artery blood flow, reduced P, E2, FSH, LH, aPTT, PT, FIB, TT,PLT, RBC, and Hb levels in comparison to the single medication group. Conclusion The combination of motherwort and EE/CPA is clinically effective in the treatment of DUB.

Efficacy and mechanism of acupuncture for functional constipation in older adults: study protocol for a randomized controlled trial.

Functional constipation (FC) is a common functional gastrointestinal disorder in clinical practice, with the prevalence of which increasing with age. With the increasing aging of the population worldwide, this problem is bound to become more prominent. Acupuncture is effective and recommended for the treatment of FC. However, little is known about how acupuncture affects the gut microbiota and inflammatory cytokines and thus improves gut function. Meanwhile, there are few high-quality clinical trials specifically focusing on acupuncture in treating FC in older people. The objective of this study is to assess the efficacy and safety of acupuncture in treating FC in older people. Additionally, the research aims to explore the mechanism of action of acupuncture in treating FC in older people by affecting intestinal microbiota and inflammation cytokines. This study is designed as a single-center, randomized, sham-controlled clinical trial. A total of 98 eligible FC patients will be randomized in a 1:1 ratio into an acupuncture group and a sham acupuncture group. Both groups will receive 24 treatments over 8 weeks with a 12-week follow-up. The primary outcome of the study is the treatment response rate, which is the proportion of participants with ≥3 mean weekly Complete Spontaneous Bowel Movements (CSBMs) over weeks 3-8. The secondary outcomes will include the proportion of participants with ≥3 mean weekly CSBMs during other assessment periods; the percentage of patients with ≥1 increase in mean weekly CSBMs from baseline; the average changes in CSBMs; Patient Assessment of Constipation-Symptoms (PAC-SYM), Bristol Stool Scale, Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) and weekly usage of emergency bowel medications. Adverse events will be recorded throughout the study. Data for the outcomes will be collected at Week 0 (baseline), Week 4 (the intervention period), Week 8 (the post-treatment), Week 12 (the follow-up period) and Week 20 (the follow-up period). In addition, changes in intestinal microbiota will be analyzed using 16S rRNA high-throughput detection, and the concentration of relevant inflammatory cytokines in serum will be measured by ELISA based on blood samples. The intention-to-treat analysis will be performed in this study.Clinical trial registration: [https://www.chictr.org.cn/], identifier [ChiCTR2300070735].

Pharmacogenetic intervention improves treatment outcomes in Chinese adult men with schizophrenia

To investigate the clinical application value of pharmacogenetic testing in individualized drug therapy for adult male patients with schizophrenia. A total of 186 adult patients with schizophrenia were enrolled and randomised into the pharmacogenetic (PGx) intervention group and the standard care group. In the PGx intervention group, PGx testing was performed, and the medication regimen was adjusted according to the results of the pharmacogenomic analysis. In contrast, in the standard care group, patients were treated according to the physician's medication experience. Differences in the primary indicator of schizophrenia, the Positive and Negative Symptom Scale (PANSS), and the secondary efficacy measures, the Clinical Global Impressions–Severity of Illness scale (CGI-SI) and Clinical Global Impressions–Global Improvement (CGI-GI) scale, were compared between the intervention and standard care groups. At baseline, the PGx intervention group consisted of 109 individuals, while the standard care group had 77 participants. After 12 weeks of treatment, 49 individuals withdrew from the PGx group (a dropout rate of 45.0%), and 34 withdrew from the standard care group (a dropout rate of 44.2%), with no significant difference in dropout rates between the two groups. The PANSS score reduction rate in the PGx intervention group significantly exceeded that of the standard care group during weeks 3, 6, and 12 of follow-up (P < 0.05). At the 12th week, the PGx intervention group achieved a treatment response rate of 81.7%, significantly surpassing the 48.8% of the standard care group (odds ratio of 4.67, 95% confidence interval of 1.96–11.41; P = 0.001). Furthermore, the PGx intervention was significantly more effective than standard care regardless of whether the patient had a first episode or a relapse (P < 0.05). Furthermore, the Global Assessment of Functioning (GAF) scores and the Personal and Social Performance Scale (PSP) score changes in the PGx intervention group were both significantly different from those in the standard care group (P < 0.05). It is noteworthy that the PGx intervention similarly improves the prognostic outcomes for patients with and without a family history of mental disorders.In conclusion, the application of a PGx intervention treatment model based on PGx testing can significantly improve medication efficacy and shorten the time to achieve the effects of medication in schizophrenia.

A preliminary study of optimal treatment response rates in patients undergoing hepatic arterial infusion chemotherapy combined with molecular targeting and immunotherapy.

This study aimed to examine the effectiveness of the best response rate (BRR) as a surrogate for overall survival (OS), using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), in patients with unresectable hepatocellular carcinoma (HCC) undergoing hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) combined with molecular targeting and immunotherapy. This study enrolled 111 consecutive patients who had complete imaging data. The median age of patients was 58 years (IQR 50.5-65.0). Among the patients, those with Barcelona Clinic Liver Cancer (BCLC) stage A, BCLC stage B, and BCLC stage C comprised 6.4%, 19.1%, and 73.6%, respectively. The optimal threshold of BRR can be determined using restricted cubic splines (RCS) and the rank sum statistics of maximum selection. Survival curves of patients in the high rating and low rating groups were plotted. We then used the change-in-estimate (CIE) method to filter out confounders and the inverse probability of treatment weighting (IPTW) to balance confounders between the two groups to assess the robustness of the results. The median frequency of the combination treatment regimens administered in the overall population was 3 times (IQR 2.0-3.0). The optimal BRR truncation value calculated was -0.2. Based on this value, 77 patients were categorized as the low rating group and 34 as the high rating group. The differences in the OS between the high and low rating groups were statistically significant (7 months [95%CI 6.0-14.0] vs. 30 months [95%CI 30.0-]; p< 0.001). Using the absolute 10% cut-off value, the CIE method was used to screen out the following confounding factors affecting prognosis: successful conversion surgery, baseline tumor size, BCLC stage, serum total bilirubin level, number of interventional treatments, alpha-fetoprotein level, presence of inferior vena cava tumor thrombus, and partial thrombin activation time. The survival curve was then plotted again using IPTW for confounding factors, and it was found that the low rating group continued to have better OS than the high rating group. Finally, the relationship between BRR and baseline factors was analyzed, and inferior vena cava tumor thrombus and baseline tumor size correlated significantly with BRR. BRR can be used as a surrogate endpoint for OS in unresectable HCC patients undergoing FOLFOX-HAIC in combination with molecular targeting and immunotherapy. Thus, by calculating the BRR, the prognosis of HCC patients after combination therapy can be predicted. Inferior vena cava tumor thrombus and baseline tumor size were closely associated with the BRR.

Comparative Outcomes of Levetiracetam and Phenobarbital Usage in the Treatment of Neonatal Seizures: A Retrospective Analysis.

The primary aim of this study was to conduct a comparative analysis of the safety and efficacy of levetiracetam (LEV) and phenobarbital (PB) as first-line treatments for neonatal seizure management. This study was designed to measure and compare the incidence of adverse effects and to determine the discharge and mortality rates associated with the use of these antiseizure medications (ASMs). Through this comparison, this research sought to provide insights to optimise care for neonates experiencing seizures. This retrospective cohort study evaluated 104 neonates treated for seizures at Zeynep Kamil Hospital from 2015 to 2020 after excluding those on non-PB/LEV antiseizure medications. Seizures were characterised using electroencephalogram (EEG) and categorised according to aetiology and frequency. Treatment efficacy was gauged by seizure cessation, as confirmed using EEG. Adverse effects and demographic data were recorded. Statistical analyses were conducted using SPSS, employing the Shapiro-Wilk, independent t-test, Mann-Whitney U test, and chi-square test, with a significance threshold of p < 0.05. Overall, 104 neonates treated with first-line ASM were evaluated for efficacy; PB was administered in 68.26% of the cases, while LEV was utilised in 31.74%. The total complete response rate was 40.38%, with no significant difference between the PB and LEV groups (p = 0.309). The incidence rate ratios (IRRs) demonstrated that seizure frequency profoundly influenced treatment effectiveness, with IRRs of 2.09 for rare seizures, 3.25 for frequent seizures, and 4.01 for status epilepticus, indicating a higher treatment response rate with increasing seizure frequency. For second-line treatment, among a subset of 62 patients, PB had a slight, non-significant advantage over LEV, with an odds ratio of 1.09, suggesting a marginally better response to LEV. Adverse events were significantly more frequent in the PB group, affecting 19 of 67 neonates (28.36%), compared to only 2 of 71 neonates (2.82%) in the LEV group (p < 0.001). No significant difference was observed in the discharge rates between the two groups (PB, 67.61%; LEV, 75.76%; p = 0.674). Interestingly, the mortality rate was significantly higher in the LEV group (45.45%) than that in the PB group (22.54%; p = 0.045). This study underscores LEV's superior safety profile over PB in neonatal seizure management, evidenced by a significantly lower rate of adverse events. PB seems to be more effective in the second-line treatment of neonatal seizures. Despite the lack of significant differences in the discharge rates, the higher mortality rate associated with LEV warrants further investigation. These findings advocate the cautious selection of antiepileptic drugs in neonatal care, with a preference for LEV based on its safety profile.

Tucatinib Combination Treatment After Trastuzumab-Deruxtecan in Patients With ERBB2-Positive Metastatic Breast Cancer

Little is known regarding the outcomes associated with tucatinib combined with trastuzumab and capecitabine (TTC) after trastuzumab-deruxtecan exposure among patients with ERBB2 (previously HER2)-positive metastatic breast cancer (MBC). To investigate outcomes following TTC treatment in patients with ERBB2-positive MBC who had previously received trastuzumab-deruxtecan. This cohort study included all patients with MBC who were treated in 12 French comprehensive cancer centers between August 1, 2020, and December 31, 2022. Tucatinib combined with trastuzumab and capecitabine administered at the recommended dose. Clinical end points included progression-free survival (PFS), time to next treatment (TTNT), overall survival (OS), and overall response rate (ORR). A total of 101 patients with MBC were included (median age, 56 [range, 31-85] years). The median number of prior treatment lines for metastatic disease at TTC treatment initiation was 4 (range, 2-15), including 82 patients (81.2%) with previous trastuzumab and/or pertuzumab and 94 (93.1%) with previous ado-trastuzumab-emtansine) exposure. The median duration of trastuzumab-deruxtecan treatment was 8.9 (range, 1.4-25.8) months, and 82 patients (81.2%) had disease progression during trastuzumab-deruxtecan treatment, whereas 18 (17.8%) had stopped trastuzumab-deruxtecan for toxic effects and 1 (1.0%) for other reasons. Tucatinib combined with trastuzumab and capecitabine was provided as a third- or fourth-line treatment in 37 patients (36.6%) and was the immediate treatment after trastuzumab-deruxtecan in 86 (85.1%). With a median follow-up of 11.6 (95% CI, 10.5-13.4) months, 76 of 101 patients (75.2%) stopped TTC treatment due to disease progression. The median PFS was 4.7 (95% CI, 3.9-5.6) months; median TTNT, 5.2 (95% CI, 4.5-7.0) months; and median OS, 13.4 (95% CI, 11.1 to not reached [NR]) months. Patients who received TTC immediately after trastuzumab-deruxtecan had a median PFS of 5.0 (95% CI, 4.2-6.0) months; median TTNT of 5.5 (95% CI, 4.8-7.2) months, and median OS of 13.4 (95% CI, 11.9-NR) months. Those who received TTC due to trastuzumab-deruxtecan toxicity-related discontinuation had a median PFS of 7.3 (95% CI, 3.0-NR) months. Best ORR was 29 of 89 patients (32.6%). Sixteen patients with active brain metastasis had a median PFS of 4.7 (95% CI, 3.0-7.3) months, median TTNT of 5.6 (95% CI, 4.4 to NR), and median OS of 12.4 (95% CI, 8.3-NR) months. In this study, TTC therapy was associated with clinically meaningful outcomes in patients with ERBB2-positive MBC after previous trastuzumab-deruxtecan treatment, including those with brain metastases. Prospective data on optimal drug sequencing in this rapidly changing therapeutic landscape are needed.

Repurposing of dextromethorphan as an adjunct therapy in patients with major depressive disorder: a randomised, group sequential adaptive design, controlled clinical trial protocol

BackgroundTherapeutic latency, lack of efficacy and adverse drug reactions are the major concerns in current antidepressant therapies. To overcome these treatment hurdles, add-on therapy to conventional antidepressant medications may lead...

Clinical status and perspective on the application of immunotherapy combined with chemotherapy in advanced non-small cell lung cancer: a review.

The therapeutic landscape of advanced non-small cell lung cancer (NSCLC) has been significantly improved by developing immunotherapy represented by programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitors (ICI). Furthermore, immunotherapy combined with chemotherapy is an essential treatment strategy for driver-negative advanced NSCLC, especially in a population with PD-L1 <50%, and leads to long-term survival in the entire population regardless of the PD-L1 expression status. However, specific challenges must be overcome, including how to use immunotherapy with chemotherapy in clinics. Furthermore, the application of immunotherapy with chemotherapy in populations such as elderly patients and patients with brain metastases, oligometastases, epidermal growth factor receptor (EGFR) gene mutation, anaplastic lymphoma kinase (ALK) gene rearrangements, and other driver gene-positive populations must be further explored. The biomarkers associated with immunotherapy and chemotherapy are still unclear, and the search for predictive biomarkers can contribute toward more precise and personalized immunotherapy. Furthermore, treatment strategies after immunotherapy and chemotherapy resistance are of significant focus clinically, and clinical studies with multiple combination therapy strategies are ongoing. Therefore, based on the reported status of immunotherapy combined with chemotherapy for advanced NSCLC, this study conducted a comprehensive literature review by searching keywords "PD-1 and PD-L1, immune checkpoint inhibitor (ICI), and NSCLC" in MEDLINE, major conferences, and major clinical research projects to elucidate the therapeutic efficacy of immunotherapy combined with chemotherapy as the current first-line treatment approach for various types of NSCLC patients. Additionally, it addresses several pressing challenges associated with immunotherapy combined with chemotherapy, including enhancing treatment response and survival rate in specific patient populations and identifying potential biomarkers.