Maintenance Treatment Research Articles

Validation of the alcohol, smoking and substance involvement screening test (ASSIST) for identifying methamphetamine use among people on methadone maintenance treatment in Vietnam.

Identifying those who use methamphetamine or are at high risk of using methamphetamine is essential so that early, appropriate intervention can be made. This study evaluated the use of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) for identifying methamphetamine use among people on methadone maintenance treatment (MMT) in Vietnam. From June 2021 to May 2023, all people on MMT at 15 methadone clinics in Hanoi and Ho Chi Minh City, Vietnam, were invited to participate in this study. Participants underwent a face-to-face interview to complete the 8-item ASSIST. Participants also had a urine drug test (UDT) for methamphetamine use. Discriminant properties of the ASSIST were evaluated using UDT as the reference. Among 6709 participants, 10.7% (n = 717) tested positive for methamphetamine use via UDT. The ASSIST demonstrated robust discriminant abilities to identify those who used methamphetamine [area under the curve (AUC) = 0.872; 95% confidence interval(CI) = 0.856-0.887]. At the commonly used cutoff of 4, the ASSIST had a sensitivity of 83.8% and a specificity of 82.0%. At this cutoff, 82.2% of the ASSIST results aligned with UDT outcomes (kappa coefficient = 0.41, P < 0.001) and the ASSIST identified a prevalence of 25.0%. At higher cutoffs, the sensitivity of the ASSIST decreased but both the specificity and the agreement with the UDT results increased. The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) appears to be reliable and valid in identifying methamphetamine use among people on methadone treatment in Vietnam. Cutoff adjustments may help to reduce false positive rates.

Baseline Liquid Biopsy in Relation to Tissue-Based Parameters in Metastatic Colorectal Cancer: Results From the Randomized FIRE-4 (AIO-KRK-0114) Study.

The FIRE-4 study randomly assigned patients with first-line RAS wild-type (RASwt) metastatic colorectal cancer to either flourouracil (FU), folinic acid, and irinotecan (FOLFIRI) plus cetuximab until progression or intolerable toxicity (standard arm) or to FOLFIRI plus cetuximab followed by a switch maintenance treatment using FU plus bevacizumab (experimental arm). Here, we investigate the relevance of liquid biopsy (LB) RAS and BRAF testing compared with tissue-based analyses. LBs were taken at baseline and during treatment and were analyzed for RAS and BRAFV600E mutations using the in vitro diagnostics-certified ONCOBEAM RAS procedure (Sysmex Inostics) and digital-droplet polymerase chain reaction technology. Six hundred seventy-two RASwt patients were randomly assigned. LBs of 540 patients were evaluable at baseline. Of those, 70 (13%) were RAS mutant (RASmut) and 38 (7%) BRAFV600E mutant. RASmut patients had significantly shorter survival compared with RASwt patients (progression-free survival [PFS], 9.0 months v 11.5 months; P < .001; hazard ratio [HR], 1.66; overall survival [OS], 22.1 months v 33.6 months; P < .001; HR, 1.85). RASmut patients had a numerically greater benefit from early switch maintenance compared with continuation of FOLFIRI/cetuximab (PFS, 10.1 months v 6.4 months; HR, 0.82; OS, 24.9 months v 16.3 months; HR, 0.57). Patients with a BRAFV600E mutation in LB showed poor outcome (PFS, 5.4 months; OS, 12.0 months). On the basis of serial LB analyses, the conversion rate from RASwt to RASmut at disease progression was significantly higher in the arm with continuous cetuximab administration than in the switch maintenance arm. LB allows the detection of RAS and BRAF mutations in patients deemed RASwt on the basis of tissue analyses. These patients show outcome characteristics expected for RAS- and BRAF-mutant patients in tissue. The study thus confirms the high clinical relevance of LB performed at baseline before the start of therapy.

The effectiveness of Transcranial Photobiomodulation therapy (tPBM) on reducing anxiety, depression, and opioid craving in patients undergoing methadone maintenance treatment: a double-blind, randomized, controlled trial

BackgroundThe effects of tPBMT are from influencing compounds by triggering specific reactions, which stimulate Adenosine triphosphate biosynthesis and neurogenesis. According to these effects, tPBMT has been applied as a potential treatment for various neural-related diseases. The purpose of this study was to evaluate the impact of tPBMT on reducing anxiety, depression, and opioid craving in patients undergoing MMT.MethodsThis randomized controlled clinical trial included two groups of substance-dependent patients undergoing MMT. They were randomly assigned to receive tPBMT or a sham tPBMT. The intervention group received PBM in the form of Light- Emitting Diodes (LEDs) for four minutes of light exposure at 810 nm wavelength producing 250 mW/cm2 when applied to 4 mm skin depth (totaling 60 J/cm2) in both forehead locations. The levels of anxiety, depression, and opioid craving were compared between the two groups before and after the intervention, as well as at one-month and three-month follow-up assessments.ResultsBoth groups consisted of 32 (91.4%) males and 3 (8.6%) females, with the mean age of patients in the intervention group being 37.97 ± 10.58 years, and 39.66 ± 9.94 years in the control group (P = 0.495). There were no significant differences between the two groups in terms of depression, anxiety, and opioid craving scale scores before the intervention (p>0.05). However, the tPBMT group had statistically significant reductions in their scores compared to the sham tPBMT group. (p<0.05).ConclusiontPBMT led to significant improvements in anxiety, depression, and opioid craving among individuals in MMT, and these improvements were sustained at one month and three months after treatment, indicating a long-lasting positive effect.Trial registrationTrial registration: IRCT code: IRCT20210502051162N1, Approval ID: IR.SBMU.MSP.REC.1400.111, registered on 01.06.2021

A data-and-knowledge-driven framework for automated generation of asphalt pavement maintenance strategies

ABSTRACT Due to the inefficiency of manual decision-making, automation of pavement maintenance strategy-making (PMSM) has become a focal point of attention in pavement engineering. The current automated PMSM processes lack a framework capable of integrating engineering prior knowledge into decision. In this paper, a data-and-knowledge-driven (DKD) framework was proposed to achieve the automated generation of asphalt pavement maintenance strategies. A pavement performance prediction model Convolutional Neural Network (CNN) was trained considering multiple influencing factors to analyse pavement deterioration, and maintenance thresholds were set according to predicted performance data distribution. The model incorporating Bidirectional Encoder Representations from Transformers (BERT), Bidirectional Long-Short-Term Memory (Bi-LSTM) and Conditional Random Field (CRF) was employed to extract the name entities from pavement maintenance domain knowledge, constructing the knowledge graph to achieve maintenance treatment determination. A freeway in Eastern China was selected for case study. The result demonstrated that 87 one-hundred-meter pavement sections on the freeway need preventive maintenance totally, utilising micro-surfacing in 2023. Furthermore, a level of automation assessment method and a reasonableness of decision process assessment method were proposed to assess this framework. The results indicate that this framework significantly enhances the level of automation compared to traditional PMSM methods while maintaining decision reasonableness.

Bentham and Beccaria in Methadonia: Justifications of Addiction Professionals for Imposing Sanctions Against Patients Who Violate Rules in Opioid Maintenance Treatment

ABSTRACT The daily work of addiction professionals in opioid maintenance treatment (OMT) involves various dual loyalty conflicts; among the most challenging is the conflict between treatment provision and imposition of sanctions. Although not trained to deal with penological issues, addiction professionals participate in judicial processes, which have huge impact on patients’ recovery process. This article presents an excerpt of a staff meeting in an OMT program which deals with the case of a patient who violated a rule. This is accompanied by analysis of various justifications for punishment according to different penological schools of thought. Practical implications are suggested to enrich addiction professionals’ knowledge and understanding of the impact of the sanctions on patients’ recovery process.

An Adapted Friendship Bench Counseling Intervention (FB) to Improve Mental Health and HIV Care Engagement Outcomes Among People Living with HIV (PWH) Who Inject Drugs in Hanoi, Vietnam: Results from the VITAL Pilot Randomized Controlled Trial.

Common mental disorders (CMDs) are prevalent among people living with HIV (PWH) and cause morbidity, jeopardize HIV care engagement, and worsen HIV outcomes. In Vietnam, PWH who inject drugs are at high risk for poor HIV and CMD outcomes. However, few evidence-based interventions are available to address this population. We conducted a three-arm individually randomized pilot trial assigning 75 PWH with opiate use disorder and a CMD from methadone maintenance treatment clinics to either FB by a professional counselor, FB by a peer counselor, or enhanced usual care. Primary outcomes were feasibility, acceptability, and fidelity of FB; we also assessed preliminary indicators of CMD improvement and HIV care engagement. Feasibility was high, with 99% retention at 6weeks and 96% retention at 6months. 100% of patients receiving FB attended all 6 weekly sessions. Acceptability of FB was high for participants in both the professional and peer counselor groups. Providers were highly satisfied with the FB experience. Fidelity was adequate: 72% of professional counselors met or exceeded fidelity expectations, while 44% of peer counselors did. Preliminary indicators of effectiveness for CMDs were promising. Participants in the professional counselor arm had the greatest improvement as measured by CMD symptom improvement and CMD response rates at most follow-up visits. The adapted FB intervention should be scaled up and evaluated in a larger, fully powered randomized controlled trial to evaluate its efficacy in improving CMDs and HIV engagement for PWH and CMDs at greatest risk of poor HIV and CMD outcomes.Clinical Trial Number: NCT04790201 registered 3/10/2021.

Fruquintinib combined with PD-1 inhibitors and chemotherapy in the first-line treatment of HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma (FDZL-FIX): A single-arm, open-label phase 2 study.

461 Background: For unresectable locally advanced or metastatic HER2-negative gastric cancer (GC), the combination of chemotherapy with immunotherapy, specifically PD-1 inhibitors, has emerged as a new standard of care in first-line treatment of advanced GC, but the patients’ outcomes remain poor. Early clinical studies investigating the combination of immunotherapy with anti-angiogenic drugs have demonstrated favorable efficacy. Therefore, it is worth exploring whether the addition of fruquintinib, a potent VEGFR-1,2,3 inhibitor, to the combination of PD-1 inhibitor and chemotherapy can further enhance the survival benefits for patients with unresectable locally advanced or metastatic HER2-negative GC. Methods: This is an open-label, single-center clinical study. The enrolled patients were all no less than 18 years old with HER2 negative locally advanced unresectable or metastatic gastric or gastrooesophageal junction adenocarcinoma, without any systemic anticancer treatment for advanced disease. Eligible patients received 6 cycles of combined first line treatment with fuquinitinib (4mg daily, d1-14, q3w, oral) combined with PD-1 inhibitor (sintilimab 200mg or nivolumab 360mg intravenously q3w) and chemotherapy (XELOX or SOX) regimen. The following maintenance treatment was fuquinitinib combined with PD-1 inhibitor and S-1/capecitabine until disease progression or intolerable toxicity. The primary endpoint was progress free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), duration of response (DoR), disease control rate (DCR) and safety. Results: At the cutoff date on Sep 18, 2024, a total of 27 patients were enrolled and received at least one dose of treatment. 23 patients had received the response evaluation, with an ORR of 60.9% (14/23; 95%CI 38.5-80.3) and DCR of 100% (23/23 95%CI 85.2-100.0). In the intention to treatment (ITT) population, the median PFS was 9.79 months (95% CI 5.29-NA). Safety profile indicated that 22.2% (6/27) experienced grade≥3 adverse events. The most common grade ≥ 3 adverse reactions mainly include neutropenia (7.4%, 2/27) and thrombocytopenia (7.4%%, 2/27). Conclusions: The combination of fruquintinib and chemotherapy with PD-1 blockade in the first-line treatment for unresectable locally advanced or metastatic HER2-negative GC had shown promising efficacy and acceptable safety profile. Enrollment in the trials is still ongoing. Clinical trial information: NCT06158919 .

Bifunctional anti-PD-L1/TGF-βRII agent SHR-1701 plus chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): Survival results of a phase II trial.

411 Background: Recently, several clinical trials have demonstrated synergistic efficacy by combining immune checkpoint inhibitors (ICIs) with chemotherapy. However, only a subset of patients (pts) derived benefits. Combining ICIs with agents blocking immunosuppressive pathway may expand the clinical benefit of ICIs to more pts. Transforming growth factor β (TGF-β) participates in tumor immune escape. SHR-1701, a novel bifunctional fusion protein consisting of a monoclonal antibody targeting PD-L1 fused with the extracellular domain of TGF-β receptor II, was evaluated in a phase II trial (ChiCTR2000039909) to assess its efficacy and safety when combined with chemotherapy for pts with unresectable locally advanced, recurrent or metastatic ESCC in China. Methods: This trial enrolled treatment-naive pts with histologically or cytologically confirmed unresectable locally advanced, recurrent, or metastatic ESCC. Eligible pts received SHR-1701 (30mg/kg, iv, d1, q3w) in combination with up to six cycles of albumin-bound paclitaxel (125mg/m 2 , iv, d1, d8, q3w) and cisplatin (75mg/m 2 , iv, d1, q3w). For those without progressive disease, maintenance treatment was administered with SHR-1701 monotherapy until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Results: At the data cut-off, March 1, 2024, 24 pts had received at least one dose of the study treatment and were included in both the intention-to-treat (ITT) analysis and safety analysis sets. 3 and 12 pts achieved confirmed complete and partial responses, respectively. The confirmed ORR was 62.5% and DCR was 87.5%. With a median follow-up of 20.8 months (95% CI, 15.5-NR), the median duration of response was 9.1 months (95% CI, 6.9-NR). The median PFS was 10.8 months (95% CI, 7.8-NR) and the median OS was 26.1 months (95% CI, 8.6-NR). 12-month PFS and OS rates were 41.4% (95% CI, 22.5-76) and 64.8% (95% CI, 47.8-87.9), respectively. Grade 3-4 treatment-related adverse events occurred in 11 (45.8%) pts and no treatment-related death was observed. Conclusions: The results highlighted that SHR-1701 plus chemotherapy as first-line therapy maintained long-term, durable survival benefit in pts with advanced ESCC. Clinical trial information: ChiCTR2000039909.

Efficacy and safety of fruquintinib alternating with bevacizumab plus capecitabine as maintenance therapy after first-line treatment in metastatic colorectal cancer (mCRC): A multicenter, open-label, phase II study.

166 Background: Maintenance therapy with bevacizumab (Bev) plus capecitabine (Cap) is widely recommended to unresectable mCRC patients (pts). Fruquintinib (Fru) is a highly selective TKI that inhibits vascular endothelial growth factor receptor (VEGFR)-1,2,3. This study is to compare the therapeutic potential of alternating treatment with fruquintinib and bevacizumab plus capecitabine as maintenance therapy for mCRC (NCT05659290). Methods: Eligible mCRC pts aged 18-75 years with stable disease or better after induction treatment with chemotherapy in combination with Bev, ECOG PS 0-2, adequate bone marrow, liver, and renal function were enrolled. Forty patients were included (20 in phase IIa, 40 in phase IIb). In phase IIa, pts were orally administered with Fru (5 mg, qd, d1-14, q3w) alternating with Bev (7.5 mg/kg, iv.gtt, d1, q3w) plus Cap (850 mg/m 2 , orally, twice daily, d1-14, q3w). In phase IIb, pts were randomly assigned (1:1) to either maintenance treatment with Fru alternating with Bev plus Cap or Bev plus Cap. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR) and safety. Results: At cutoff date of Sep 5, 2024, In phase IIa, 20 pts (14 males and 6 females) were enrolled with the median age was 59.0 years (range 27-75), ECOG PS 1 (95.0%), liver metastasis (55.0%), left-sided colon and rectal primary (70.0%). 11 pts had received at least one tumor assessment. the DCR was 100.0% (11/11) and the mPFS was immature, but 4 pts showed the PFS of ≥ 8 months (8.3, 8.6, 9.2, 13.4 m, respectively). The most common treatment-emergent adverse events (TEAEs) were proteinuria (60.0%), hypoalbuminemia (40.0%), hypertension (35.0%); The most common grade ≥ 3 adverse events were hypertension (10.0%), proteinuria (5.0%), and platelet count decreased (5.0%). After fully considering about patient′s tolerance and safety, the phase IIb of Fru was adjusted from 5mg to 3mg, these results provided further evidence that 3mg can ensure the safety and tolerance. Conclusions: Fruquintinib alternating with bevacizumab plus capecitabine as maintenance therapy after first-line treatment in mCRC showed preliminary anti-tumor activity and manageable toxicity. The phase IIb is ongoing and warrants further exploration in mCRC. Clinical trial information: NCT05659290 .

Health-related quality of life and symptoms in patients with previously untreated, locally advanced or metastatic non-squamous non-small cell lung cancer treated with sintilimab or placebo plus pemetrexed and platinum (ORIENT-11): A randomized, double-blind, phase 3 trial.

In the phase 3 ORIENT-11 study, sintilimab plus pemetrexed-platinum provided statistically significant longer overall survival and progression-free survival versus placebo plus pemetrexed-platinum as first-line treatment in patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). Here, we report the patient-reported outcomes (PRO) analysis findings in ORIENT-11. PROs were measured using the European Organization for Research and Treatment of Cancer Quality of Life of Cancer Patients Questionnaire Core 30 items (EORTC QLQ-C30) and the Lung Cancer Symptom Scale (LCSS) questionnaire. PRO endpoints included evaluation of least square (LS) mean changes from baseline to week 12 (platinum-containing treatment) and week 21 (maintenance treatment), time to true deterioration (TTD), and overall improvement or stability rate for QLQ-C30 and LCSS scales. PRO scores in two groups were compared using the Mann-Whitney test. Least squares (LS) mean changes from baseline to week 12, week 21, and other time points were assessed with mixed-effect model repeated measures analysis. TTD was calculated using the Kaplan-Meier method and compared with the Cox proportional hazards model between groups. 252 (94.7%) patients in the sintilimab-combination group and 123 (93.9%) patients in the placebo-combination group had a baseline and at least one postbaseline PRO assessment. Change from baseline to week 12 or 21 favored the sintilimab-combination group on QLQ-C30 global health status/quality of life (GHS/QoL), most function and symptoms scales, and most LCSS scales. Notably, the QLQ-C30 pain score change gradually deteriorated in the placebo-combination group with increased treatment. At the same time, it improved in the sintilimab-combination group significantly from 6weeks later, with the improvement sustained in subsequent courses of treatment. Sintilimab plus chemotherapy significantly delayed the TTD in most QLQ-C30 and LCSS scales compared with placebo plus chemotherapy, and the overall improvement or stability rates were higher in the former. The addition of sintilimab to chemotherapy maintained or improved health-related quality of life and symptoms compared with chemotherapy. Along with the previous efficacy and safety results, these data support the addition of sintilimab to standard chemotherapy as first-line therapy in locally advanced or metastatic non-squamous NSCLC. NCT03607539.

Methadone Maintenance Treatment Adherence and Opioids Use Among Patients Engaging Methamphetamine Use in Vietnam

Methadone Maintenance Treatment Adherence and Opioids Use Among Patients Engaging Methamphetamine Use in Vietnam

A Pilot Study Examining the Feasibility of a Virtual Reality Pain Management Intervention Groups in Methadone Maintenance Treatment

A Pilot Study Examining the Feasibility of a Virtual Reality Pain Management Intervention Groups in Methadone Maintenance Treatment

Real-world effectiveness of pharmacological maintenance treatment of bipolar depression: a within-subject analysis in a Swedish nationwide cohort.

Long-term add-on antidepressant use for bipolar depression remains controversial. This study aimed to investigate primarily the association between psychopharmacological treatments and hospitalisation (ie, hospital admission) for bipolar depression, and secondarily the association between psychopharmacological treatments and hospitalisation for bipolar mania and somatic reasons in a registry-based national Swedish cohort. In this within-subject analysis, people diagnosed with bipolar disorder were identified from Swedish nationwide registers of inpatient and specialised outpatient care, sickness absence, and disability pension between Jan 1, 2006, and Dec 31, 2021. Data for hospitalisations, and antidepressant, antipsychotic, and mood stabiliser medication use were also retrieved from national databases. Treatment periods were modelled using the PRE2DUP method. Data were analysed with a within-individual design with stratified Cox Regression models, to eliminate selection bias when calculating adjusted hazard ratios (aHRs) and 95% CIs. The main outcome was hospitalisation due to depression and secondary outcomes were mania-related and somatic hospitalisations to address the risk-benefit ratio of antidepressant treatment. The reference was non-use of antidepressant, antipsychotic, and mood stabiliser medications. We also did head-to-head comparisons (ie, comparing different drug use periods within the same individual against each other) between medications to obtain results on comparative effectiveness while minimising confounding by indication. Ethnicity data were not available. People with related lived experience were involved in the research and writing process. The study cohort included 105 495 individuals (mean age 44·2 years, SD 18·8; 65 607 [62·2%] women and 39 888 [37·8%] men). In medication class-based analyses, a higher risk of depression-related hospitalisation was associated with the use of antidepressant only (aHR 1·25, 95% CI 1·16-1·34), antipsychotic only (1·39, 1·24-1·55), antidepressant-antipsychotic combination (1·28, 1·18-1·39), and antipsychotic-mood stabiliser combination treatment (1·13, 1·03-1·24). By contrast, use of mood stabilisers only (0·89, 0·81-0·98) was associated with lower risk. For specific monotherapies, only lithium was associated with lower depression-related hospitalisation risk (0·75, 0·67-0·85). No specific antidepressant monotherapy was associated with reduced depression-related hospitalisation, while several antidepressants and antipsychotics were related to an increased risk. In head-to-head comparisons, lithium monotherapy was associated with a superior outcome compared with antidepressant monotherapy (0·59, 0·51-0·68), antipsychotic monotherapy (0·54, 0·44-0·66), lamotrigine monotherapy (0·69, 0·53-0·91), and quetiapine monotherapy (0·54, 0·41-0·71). Lithium was associated with the lowest risk of somatic hospitalisation (0·86, 0·80-0·93) when compared with non-use of antidepressants, antipsychotics, and mood stabilisers. Finally, antidepressant-only treatment (1·22, 1·03-1·44) was associated with increased risk of mania-related hospitalisation and other monotherapies and combinations were associated with a lower risk. Since medications are typically started when depressive symptoms re-emerge, all treatments might appear less effective than they actually are when the reference is non-use of medication. Lithium was the only specific monotherapy with significantly reduced risk of depression-related hospitalisations when compared with non-use of antidepressants, antipsychotics, and mood stabilisers, and with more than 30% lower risk than any antidepressant, any antipsychotic, quetiapine, or lamotrigine monotherapy in the head-to-head analysis. Lithium was also associated with the lowest risk of somatic hospitalisation. Our findings supported the use of lithium as the mainstay of treatment in bipolar disorder. The Swedish Research Council for Health, Working Life and Welfare, FORTE (grant number 2021-01079).

Co-Occurring Methamphetamine Use and Depressive Symptoms Among Patients in Methadone Maintenance Treatment in Vietnam

Co-Occurring Methamphetamine Use and Depressive Symptoms Among Patients in Methadone Maintenance Treatment in Vietnam

Avelumab maintenance treatment for advanced urothelial cancer: plain language summary of long-term results from the JAVELIN Bladder 100 study.

Avelumab maintenance treatment for advanced urothelial cancer: plain language summary of long-term results from the JAVELIN Bladder 100 study.

Guided bone regeneration therapy based on plaque control of peri-implantitis with follow-up at 7 years.

Peri-implantitis is a pathologic condition associated with dental plaque that occurs in the implant tissue and is characterized by inflammation of the mucous membrane surrounding the implant, followed by the progressive loss of supporting bone. In this study, a case of guided bone regeneration therapy based on plaque control of peri-implant inflammation was reported. Four years after surgery for the left second premolar implant, the patient presented with "left lower posterior tooth swelling and discomfort for more than 2 years". The X-ray periapical film showed a decrease in distal bone mineral density of implant, and the clinical diagnosis was peri-implantitis of the left second premolar. Implants underwent guided bone regeneration and regular periodontal maintenance treatment. Re-examination at 3.5 months, 11 months, 18 months, and 7 years showed that the alveolar bone height and bone mineral density were stable, and the periodontal depth became shallow. However, the gingival recession was mild. In the present case, follow-up at 7 years demonstrated that the clinical periodontal indexes could be remarkably improved after complete periodontal treatment for peri-implantitis, and the alveolar bone could be well restored and regenerated.

Homologous recombination deficiency testing in patients with high grade ovarian cancer: factors influencing test success.

Testing for tumor BRCA mutations and homologous recombination deficiency (HRD) is recommended for all patients with advanced high-grade epithelial ovarian cancer. Delays in the HRD testing process can significantly affect the treatment offered to patients. HRD testing pathways and sampling processes were analyzed for tests sent from a tertiary gynae-oncology referral center between December 2020 and January 2023. A total of 148hRD tests were performed in 125 patients. The overall success rate of HRD testing was 69.6%. The success rates of obtaining results were: from diagnostic image-guided biopsy 66.7% (n = 40/60), at primary surgery 91.5% (n = 42/47), and at interval debulking surgery 51.2% (n = 21/41). The use of a larger 16-gauge needle used at image-guided biopsy produced a 100% success rate. Of 148 tests carried out, the median time for result was 28 days (range 14-158 days), with only 27% returned results in 21 or fewer days. In successful tests, 44.7% were classified as HRD-positive. 97% of patients with HRD-positive tumors treated at the center received a PARP inhibitor as part of their first-line maintenance treatment. By optimizing the factors affecting HRD test success, we can obtain faster results and offer patients appropriate treatment at earlier time points to improve patient outcomes.

Niraparib restricts intraperitoneal metastases of ovarian cancer by eliciting CD36-dependent ferroptosis.

Ovarian cancer (OC) is prone to peritoneum or omentum dissemination, thus giving rise to the formidable challenge of unresectable surgery and a dismal survival rate. Although niraparib holds a pivotal role in the maintenance treatment of OC, its effect on suppressing metastases during primary intervention remains enigmatic. Recently, we initiated a prospective clinical study (NCT04507841) in order to evaluate the therapeutic efficacy of neoadjuvant niraparib monotherapy for advanced OC with homologous recombination deficiency. An analysis of patient tumor burden before and after the niraparib challenge showed a remarkable vulnerability of OC intraperitoneal metastases to niraparib exposure. This killing capacity of niraparib was closely associated with the accumulation of fatty acids within the abdomen, which was confirmed by the increased susceptibility of tumor cells to niraparib treatment in the presence of fatty acids. In the context of abundant fatty acids, niraparib elevated intracellular levels of fatty acids and lipid peroxidation, leading to subsequent tumor cell ferroptosis in a p53 and BRCA-independent manner. Notably, under niraparib exposure, a critical fatty acid transporter CD36 was dramatically upregulated in tumors, facilitating excessive uptake of fatty acids. Pharmacological inhibition of either ferroptosis or CD36 impaired the anti-tumor activity of niraparib both in vitro and in murine intraperitoneal ID8 tumor models. Our findings demonstrate ferroptosis as a novel mechanism underlying the regression of OC metastases induced by niraparib, thereby offering tantalizing prospects for the frontline application of this agent in the management of OC.

Long-term efficacy and safety of perampanel monotherapy in patients with newly diagnosed or currently untreated recurrent focal-onset seizures: Results from the open-label extension phase of FREEDOM (Study 342).

FREEDOM (Study 342; NCT03201900) assessed the long-term treatment effect of perampanel monotherapy in adolescent and adult patients (12-74 years of age) with untreated focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS). In the Core Study, after a 4-week Pretreatment Phase, perampanel was up-titrated to 4 mg/day during a 6-week Titration Period followed by a 26-week Maintenance Period. Patients experiencing seizure(s) during the 4-mg/day Maintenance Period could have perampanel up-titrated to 8 mg/day over 4 weeks then could enter the 26-week 8-mg/day Maintenance Period. Patients could enter Extension to continue treatment upon the completion of the Core Study. Seizure-freedom rates, time to seizure recurrence or withdrawal since the initiation of maintenance treatment, and safety outcomes were assessed. In FREEDOM, 89 patients who received ≥ 1 perampanel dose were included for safety assessments (Safety Analysis Set), and 73 of them entered the 4-‍‍‍mg/day Maintenance Period (the modified Intent-to-Treat Analysis set) with 21 patients having perampanel up-titrated to 8 mg/day; 46 patients entered Extension with 38 patients completing. Overall, 42/89 (47.2 %) patients had cumulative exposure to perampanel for > 52 weeks. Among patients who entered Extension, 52.2 % (n = 24/46; 95 % confidence interval [CI] 36.9, 67.1) remained seizure free for 52 weeks at perampanel 4 mg/day and 67.4 % (n = 31/46; 95 % CI 52.0, 80.5) at 4-8 mg/day. The cumulative probabilities of seizure recurrence and withdrawal at 4-8 mg/day over 52 weeks were 28.9 % (95 % CI 19.0, 42.4) and 43.8 % (95 % CI 33.4, 55.9), respectively. Treatment-emergent adverse events (TEAEs) occurred in 74/89 (83.1 %) patients, with 9/89 (10.1 %) discontinuing because of TEAEs. Dizziness occurred in 34/89 (38.2 %) patients and was the most common event. Patients with untreated FOS (with or without FBTCS) are able to maintain seizure freedom for up to 52 weeks with perampanel monotherapy at a dose of 4-8 mg/day. The tolerability profile was manageable, and the safety profile was consistent with previous findings.

Predictors for the Development of Hypergastrinemia in Maintenance Treatment for Mild Gastroesophageal Reflux Disease Using a Half-dose Proton Pump Inhibitor.

Serum gastrin levels may be elevated following proton pump inhibitor (PPI) therapy. We aim to elucidate the predictors for the development of hypergastrinemia in maintenance treatment for mild gastroesophageal reflux disease (GERD) using a half-dose PPI. This study analyzed data from a prospective randomized trial to compare continuous versus on-demand maintenance treatment modalities in patients with mild GERD. Age, sex, body mass index, Helicobacter pylori infection, serum gastrin levels, pepsinogen (PG) I/II ratios, total days of PPI intake, and weight-based PPI dosage (mg/kg) were evaluated. Data from 293 patients who completed a randomized trial were analyzed (continuous group, n = 147 vs on-demand group, n = 146). In univariate analysis, age (P < 0.001), H. pylori infection (P = 0.012), baseline gastrin levels (P < 0.001), and baseline PG ratios (P = 0.016) significantly correlated with post-treatment gastrin levels. In multivariate analysis, age, baseline gastrin levels, and baseline PG ratios were independently associated with final serum gastrin levels. In univariate analysis, age (P = 0.018), H. pylori infection (P = 0.028), baseline gastrin levels (P = 0.011), and baseline PG ratios (P = 0.031) significantly correlated with the development of hypergastrinemia. In multivariate analysis, age, baseline gastrin levels, and baseline PG ratios were independently associated with the development of hypergastrinemia. Old age, high baseline serum gastrin levels, and low baseline PG ratios are significant predictors of the development of hypergastrinemia in maintenance treatment for mild GERD using a half-dose PPI.