Safety Of Treatment In Patients Research Articles

Efficacy and Safety of Dual-Targeting Chimeric Antigen Receptor-T Therapy for Relapsed or Refractory B Cell Lymphoid Malignancies: A Systematic Review and Meta-Analysis.

Dual-targeting chimeric antigen receptor (CAR)-T cell therapy has been proposed as a potential solution for overcoming antigen escape during anti-CD19 CAR-T treatment. We performed this systematic review and meta-analysis to investigate the efficacy and safety of this novel treatment in patients with B cell non-Hodgkin lymphoma (B-NHL) and B cell acute lymphoblastic leukemia (B-ALL). We systematically searched relevant literature based on databases (PubMed, Web of Science, Embase and Cochrane) and conference abstracts. The primary outcomes measured were the best objective response rate (ORR) or complete response (CR), 12-month overall survival (OS) and progression-free survival (PFS), cytokine release syndrome (CRS), and neurotoxicity. Fifteen registered prospective open-label clinical trials were included. Among the 260 patients with B-NHL, the pooled best ORR and CR were 77% (95% confidence interval [CI]: 0.71-0.82) and 52% (95% CI: 0.40-0.63), respectively, and the pooled 12-month PFS and OS were 54.0% (95% CI: 0.47-0.61) and 66.0% (95% CI: 0.56-0.77), respectively. In the 159 patients with B-ALL, the combined best CR was observed to be 92% (95% CI: 0.82-0.99) and the pooled 12-month PFS and OS were 65.0% (95% CI: 0.51-0.77) and 73.0% (95% CI: 0.56-0.92), respectively. Moreover, in B-NHL patients, grade ≥3 CRS was observed in 14.0% (95% CI: 0.04-0.29) of these patients, and 5.0% (95% CI: 0.02-0.08) showed grade ≥3 neurotoxicity; in the case of B-ALL patients, grade ≥3 CRS and neurotoxicity occurred in 11.0% (95% CI: 0.04-0.19) and 2.0% (95% CI: 0.00-0.06), respectively. This study demonstrates the safety and clinical efficacy of dual-targeting CAR-T cell therapies in B cell malignancies. Further, well-designed randomized controlled trials are required to establish the role of dual-targeting CAR-T cell therapy in patients with B cell malignancies.

Real-life effectiveness and safety of tofacitinib treatment in patients with ulcerative colitis: a KASID multicenter cohort study.

Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with ulcerative colitis (UC). However, the real-life data on tofacitinib in Asian UC patients are limited. To investigate the real-life effectiveness and safety of tofacitinib induction and maintenance treatment in Korean patients with UC. This was a retrospective study on patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Clinical remission at week 52, defined as a partial Mayo score of ⩽2 with a combined rectal bleeding subscore and stool frequency subscore of ⩽1, was used as the primary outcome. Adverse events (AEs), including herpes zoster and deep vein thrombosis, were also evaluated. A total of 148 patients with UC were started on tofacitinib. Clinical remission rates of 60.6%, 54.9%, and 52.8% were reported at weeks 16, 24, and 52, respectively. Clinical response rates of 71.8%, 67.6%, and 59.9% were reported at weeks 16, 24, and 52, respectively. Endoscopic remission rates at weeks 16 and 52 were 52.4% and 30.8% based on the Mayo endoscopic subscore and 20.7% and 15.2% based on the UC endoscopic index of severity (UCEIS), respectively. A higher UCEIS at baseline was negatively associated with clinical response [adjusted odds ratio (aOR): 0.774, p = 0.029] and corticosteroid-free clinical response (aOR: 0.782, p = 0.035) at week 52. AEs occurred in 19 patients (12.8%) and serious AEs in 12 patients (8.1%). Herpes zoster occurred in four patients (2.7%). One patient (0.7%) suffered from deep vein thrombosis. Tofacitinib was an effective induction and maintenance treatment with an acceptable safety profile in Korean patients with UC. Real-life effectiveness and safety of tofacitinib treatment in Korean patients with ulcerative colitis Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa that usually presents with bloody diarrhea and abdominal pain. Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with UC. However, real-life data on the effectiveness of tofacitinib in Asian patients with UC are limited. To investigate the real-life effectiveness and safety of tofacitinib treatment in Korean patients with UC, we retrospectively analyzed the data of 148 patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Clinical remission (i.e. complete improvement of symptoms) was achieved in 60.6% and 52.8% of patients at weeks 16 and 52, respectively. Endoscopic remission was achieved in 52.4% and 30.8% of patients at weeks 16 and 52, respectively. A higher baseline score of the UC endoscopic index of severity, which is one of the endoscopic indices that evaluate the severity of inflammation of the colon, was negatively associated with clinical response (i.e. partial improvement of symptoms). Adverse events (AEs) including herpes zoster and deep vein thrombosis occurred in 19 patients (12.8%) and serious AEs occurred in 12 patients (8.1%). Our real-life study shows that tofacitinib is a clinically effective treatment for Korean patients with UC, and the incidence of AEs was also similar to those observed in other real-world studies.

Preliminary Clinical Study of the Effects and Safety of 308-nm Excimer Light Treatment in Patients with Atopic Dermatitis.

Atopic dermatitis (AD) is a common skin disease which, depending on its severity, can have a significant impact on the quality of life of affected individuals. In cases of severe AD, systemic immunomodulatory agents can be considered for treatment. However, the available treatment options for moderate AD are limited. According to previous reports, however, 308-nm excimer light is a potential treatment for localized, moderate AD. This study aimed to assess the clinical efficacy and safety of 308-nm excimer light in Korean adults with AD. This study included Korean patients aged over 19 years, who were diagnosed with AD by a dermatologist, with bilateral, symmetric, and eczematous lesions. The symmetrical lesions in each patient were treated as control-test pairs. Treatment with 308-nm excimer light was applied to the test lesion twice a week for 4 weeks. The severity of the eczema, trans-epidermal water loss, and epidermal capacitance were measured. A total of 25 participants were enrolled in the study. After the first visit, two participants withdrew, whereas the remaining 23 completed the study. There was a statistically significant improvement in AD severity in the test group than in the control group (p<0.001). Skin barrier function also improved in the test than in the control group (p<0.01). This study provides preliminary evidence for the use of 308-nm excimer light as a treatment option to improve symptoms and skin barrier function in moderately localized AD.

P197: Long term efficacy and safety of carglumic acid treatment in patients with organic acidemia in East Asia population

P197: Long term efficacy and safety of carglumic acid treatment in patients with organic acidemia in East Asia population

Efficiency and Reliability of Bronchoscopic Lung Volume Reduction Coil Application in Patients with Severe Emphysema.

In the past years, surgery has been used for the non-medical treatment of severe emphysema. However, in recent years, bronchoscopic lung volume reduction (LVR) treatment has become more preferred because it is less invasive. Bronchoscopic coil treatment is the most frequently applied technique among these methods. The aim of the investigation was to determine the efficacy and safety of bronchoscopic volume reduction coil treatment for patients with severe emphysema. The patients who were performed bronchial volume reduction coil treatment between 2015 and 2017 and were followed in our outpatient clinic were retrospectively examined. They were followed for 1 year at quarterly intervals after the procedure. All the safety and efficacy of the patient's records, including the modified Medical Research Council (MRC) dyspnea score, the St. George's Respiratory Questionnaire (SGRQ) quality of life scale, the 6 min walk distance (6-MWT), pulmonary function tests, and adverse events, were evaluated. Sixteen patients were included in the study. The mean of the preoperative mMRC clinic dyspnea score was 3.38, the mean of the 3rd month's mMRC score was 2.62 (p=0.007), and the mean of the 12th month's mMRC was 2.37 (p=0.003). The preoperative SGRQ quality of life parameter was 71.95±15.7, the 3rd month was 66.7±16.2 (p=0.007), and the 12th month was 62.9±16.4 (p=0.003). Preoperative mean of 6-MWT was 247.25±112.36 m, 3rd month 264.25±95 m (p=0.148), and 12th month 317±122.9 m (p=0.034). Patients' preoperative residual volume was 5.28±1.96 L, 3rd month 4.52±1.35 L (p=0.023), and 12th month 4.545±1.83 L (p=0.163). Patients' preoperative forced expiratory volume in one second, respectively, was 0.79±0.29 L, 3rd month 0.79±0.3 L (p=0.917), and 12th month 0.86±0.3 L (p=0.756). It seems that bronchoscopic LVR coil treatment, which is an effective and reliable procedure that reduces shortness of breath rather than respiratory function test parameters and improves the quality of daily life, will become even more widespread.

Bronchoscopic Lung Volume Reduction in Patients with Emphysema due to Alpha-1 Antitrypsin Deficiency

Background: Bronchoscopic lung volume reduction using one-way endobronchial valves (EBVs) is a valid therapy for severe emphysema patients. However, alpha-1 antitrypsin (AAT)-deficient patients were excluded from the majority of clinical trials investigating this intervention. Objectives: The aim of this study was to investigate the feasibility, efficacy, and safety of EBV treatment in patients with AAT deficiency (AATD) or a reduced AAT level. Method: A retrospective analysis was performed of all patients treated with EBV with confirmed AATD or with a reduced AAT serum level at the University Medical Center Groningen between 2013 and 2021. Baseline and 6-month follow-up assessment included chest CT, pulmonary function measurement, 6-min walking distance (6MWD), and St. George’s Respiratory Questionnaire (SGRQ). Results: In total, 53 patients were included, 30 patients in the AATD group (AAT <0.6 g/L or confirmed ZZ phenotype) and 23 patients in the reduced AAT group (AAT 0.6–1 g/L). In both groups, all response variables improved significantly after treatment. There was a median increase in forced expiratory volume in 1 s of 105 mL (12% relative) and 280 mL (31% relative) in the AATD and reduced AAT groups, respectively. 6MWD increased by 62 min and 52 min, and SGRQ decreased by 12.5 patients and 18.7 patients, respectively. A pneumothorax occurred in 10% and 13% of patients, and no patients died. Conclusions: EBV treatment in patients with emphysema and AATD or a reduced AAT level is feasible and results in significant improvements in pulmonary function, exercise capacity, and quality of life and has an acceptable safety profile.

Impact of systemic therapies in metastatic melanoma of unknown primary: A study from MELBASE, a French multicentric prospective cohort

Clinical outcomes of advanced melanoma of unknown primary (MUP) in the era of novel therapies have been scarcely studied. To investigate the efficacy and safety of systemic treatments in patients with advanced MUP compared to patients with stage-matched melanoma of known cutaneous primary (cMKP). Based on the nationwide MelBase prospective database, this study included advanced melanoma patients treated from March 2013 to June 2021 with first-line immunotherapies, targeted therapies, or chemotherapy. Co-primary outcomes were progression-free survival and overall survival. Secondary outcome was treatment-related toxicities. Multivariate and propensity score analyses were performed. Of 1882 patients, 265 (14.1%) had advanced MUP. Patients with advanced MUP displayed more often unfavorable initial prognostic factors than those with cMKP. Progression-free and overall survival did not differ significantly between the groups (P = .73 and P = .93, respectively), as well as treatment-related toxicity rate and severity, regardless of treatment type. No record of standard diagnostic criteria of MUP used in the participating centers. Although patients with MUP had less favorable baseline prognostic factors, they benefited from the novel therapies as much as those with cMKP. They should be managed according to similar strategies.

The efficacy and safety of alteplase treatment in patients with acute ischemic stroke with unknown time of onset: -Real world data-

IntroductionTreatment with alteplase for acute ischemic stroke patients with an unknown time of onset is safe and effective. However, clinical trials have some selection bias. The purpose of this study was to clarify the efficacy and safety of alteplase treatment in patients with unknown time of onset in a real-world clinical setting. MethodsWe included consecutive patients with acute ischemic stroke visited within 4.5 h of onset or symptom recognition. We divided patients into two groups: onset clear group (C-group) and unknown time of onset group (U-group). We treated patients with an unknown time of onset if the DWI-FLAIR mismatch was positive. We calculated the prevalence of alteplase treatment in each group and compared prognosis between the two groups. ResultsSix hundred thirty-two patients arrived within 4.5 h of onset or symptom recognition. Of these, 446 patients (71 %) were in the C-group and 186 (29 %) in the U group. Alteplase treatment was performed in 35 % of patients in the C group and in 18 % in the U group (p < 0.001). Favorable outcomes at 90 days in patients treated with alteplase were comparable between the C group (52 %) and the U group (53 %) (p = 0.887). All hemorrhagic complications, including non-symptomatic hemorrhagic transformation, occurred in 11 of 157 patients (7 %) in the C-group and one of 34 patients (3 %) in the U-group (p = 0.696). ConclusionIn a real-world clinical setting, alteplase treatment was performed safe in 18% of patients with an unknown time of stroke onset based on patient selection using the DWI-FLAIR mismatch.

Rationale and protocol design of a phase II study of first-line osimertinib treatment for patients with poor performance status and EGFR mutation-positive non-small cell lung cancer (OPEN/TORG2040)

BackgroundCancer chemotherapy indications for patients with poor performance status and advanced lung cancer are limited. Molecular targeted drugs, including epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, can be used in patients with poor performance status owing to their high efficacy and safety. The third-generation EGFR-tyrosine kinase inhibitor osimertinib has demonstrated effectiveness in the initial treatment of advanced EGFR mutation-positive non-small cell lung cancer in patients with good performance status; however, no evidence exists of the drug’s effectiveness in patients with poor performance status in a prospective study. We designed a study that aims to investigate the efficacy and safety of first-line osimertinib treatment in patients with advanced non-small cell lung cancer harboring sensitive EGFR mutations and with poor performance status.MethodsThe OPEN/TORG2040 study is a multicenter, single-arm, phase II trial for patients with unresectable, advanced EGFR mutation-positive non-small cell lung cancer with a poor performance status (≥ 2). Eligible patients will receive osimertinib until disease progression or unacceptable toxicity. The primary endpoint is the objective response rate of the first-line osimertinib treatment. Considering a threshold value of 45%, expected value of 70% for objective response rate, one-sided significance level of 5%, statistical power of 80%, and ineligible patients, the sample size was set to 30. The secondary endpoints are disease control rate, performance status improvement rate, and safety and patient-reported outcomes using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Quality of Life Questionnaire and Lung Cancer 13. Time to treatment failure, progression-free survival, and overall survival will also be assessed.DiscussionOur study can determine the clinical benefits of osimertinib treatment in patients with poor performance status, since the clinical outcomes of patients with EGFR mutation-positive non-small cell lung cancer with poor performance status treated with this drug as a first-line treatment have not been sufficiently evaluated.Trial registrationJapan Registry of Clinical Trials: jRCTs041200100 (registration date: February 12, 2021).

Efficacy and safety of rituximab treatment in patients with idiopathic inflammatory myopathies: A systematic review and meta-analysis.

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune diseases with various subtypes, myositis-specific antibodies, and affect multiple systems. The treatment of IIMs remains challenging, especially for refractory myositis. In addition to steroids and traditional immunosuppressants, rituximab (RTX), a B cell-depleting monoclonal antibody, is emerging as an alternative treatment for refractory myositis. However, the therapeutic response to RTX remains controversial. This meta-analysis aimed to systematically evaluate the efficacy and safety of RTX in patients with IIMs, excluding sporadic inclusion body myositis. PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and WanFang Data were searched for relevant studies. The overall effective rate, complete response rate, and partial response rate were calculated to assess the efficacy of RTX. The incidences of adverse events, infection, severe adverse events, severe infection, and infusion reactions were collected to evaluate the safety of RTX. Subgroup analyses were performed using IIM subtypes, affected organs, continents, and countries. We also performed a sensitivity analysis to identify the sources of heterogeneity. A total of 26 studies were included in the quantitative analysis, which showed that 65% (95% confidence interval [CI]: 54%, 75%) of patients with IIMs responded to RTX, 45% (95% CI: 22%, 70%) of patients achieved a complete response, and 39% (95% CI: 26%, 53%) achieved a partial response. Subgroup analyses indicated that the overall efficacy rates in patients with refractory IIMs, dermatomyositis and polymyositis, as well as anti-synthetase syndrome were 62%, 68%, and 62%, respectively. The overall efficacy rates for muscle, lungs, and skin involvement were 59%, 65%, and 81%, respectively. In addition, studies conducted in Germany and the United States showed that patients with IIMs had an excellent response to RTX, with an effective rate of 90% and 77%, respectively. The incidence of severe adverse events and infections was 8% and 2%, respectively. RTX may be an effective and relatively safe treatment choice in patients with IIMs, especially for refractory cases. However, further verification via randomized controlled trials is warranted.

Anlotinib in patients with relapsed or refractory thymic epithelial tumors: a study of 50 cases.

The optimal pharmaceutical regimen for advanced thymic epithelial tumors (TETs) remains controversial when first-line chemotherapy fails. This retrospective study aims to evaluate the efficacy and safety of anlotinib treatment for patients with relapsed and refractory TETs. Patients with progressive disease after failure of platinum-based chemotherapy were enrolled in this study. Anlotinib was orally taken once a day at an initial dose of 12 mg (10 mg when body weight <60 kg). The cycle was repeated every 3 weeks (2 weeks of treatment followed by 1-week rest). Objective response rate (ORR) and progression-free survival (PFS) were recorded as primary endpoints. There were 50 patients enrolled in this study from October 2018 to June 2021 at a median age of 50 (range 23-79) years old. Patients with thymoma and thymic carcinoma were 33 (66%) and 17 (34%), respectively. The ORR in thymoma and thymic carcinoma patients were 33% (11/33) and 41% (7/17), respectively. The median PFS (mPFS) was 7 (95% CI, 5.9-10.2) months in thymoma patients and 6 (95% CI, 4.6-9.3) months in the thymic carcinoma group. Eleven patients experienced dose reduction due to toxicities, among whom, eight patients discontinued treatment even after dose reduction. Six patients with thymoma showed myasthenia gravis deterioration during treatment, and two of them died of myasthenia gravis crisis. Anlotinib is active in patients with advanced TETs refractory to routine chemotherapy. Prescription of anlotinib to patients with myasthenia gravis should be made cautiously.

AB002. Anlotinib as salvage treatment for patients with relapsed and refractory thymic epithelial tumors

Background: Optimal pharmaceutical regimen for advanced thymic epithelial tumors (TETs) remains controversial when first-line chemotherapy fails. This retrospective study aims to evaluate the efficacy and safety of anlotinib treatment for patients with relapsed and refractory TETs.

Efficacy and Safety of Long-Term Ropeginterferon Alfa-2b Treatment in Patients with Low-Risk and High-Risk Polycythemia Vera (PV)

Introduction: Patients with "low-risk” (LR) PV are managed conservatively despite higher risk of vascular events and impaired quality of life compared to a population without PV. Acknowledging new evidence (LOW-PV study, Barbui et al 2021), recent treatment guidelines (European LeukemiaNet [ELN] 2021) recommend ropeginterferon alfa-2b (BESREMi®) as a cytoreductive treatment in LR PV patients meeting specific criteria as well as in high-risk (HR) PV patients. Final data from the phase 3 PROUD-PV and CONTINUATION-PV trials (NCT01949805; NCT02218047) demonstrated the long-term efficacy and safety of ropeginterferon alfa-2b compared with hydroxyurea/best available treatment (HU/BAT); here we report results in the ropeginterferon alfa-2b arm by risk stratum. Methods: PV patients were randomized 1:1 and received ropeginterferon alfa-2b or HU/BAT for ≥6 years. In the ropeginterferon alfa-2b arm, subgroup analyses were performed post-hoc by risk stratum (LR: age ≤60 years and no history of thrombosis; all others HR). Complete hematologic response (CHemR) and molecular response defined by modified ELN criteria were assessed in the full analysis set for CONTINUATION-PV (N=95); safety analyses included all data regardless of roll-over (N=127). Results: CONTINUATION-PV enrolled 46 LR and 49 HR patients in the ropeginterferon alfa-2b arm. At baseline, mean age was 50.7 vs 63.7 years respectively, and median duration since PV diagnosis was 1.9 months vs 1.5 months. HR patients had higher platelet and leukocyte counts at baseline and more frequently presented with clinically significant splenomegaly or PV-related symptoms. Median JAK2V617F allele burden was similar for LR and HR patients (37.0% vs 39.4%), however LR patients were less likely to harbor additional non-driver mutations (11.4% vs 24.4%). The median 4-weekly ropeginterferon alfa-2b dose was comparable in LR and HR patients throughout the study (in the 6th year, 499 µg and 489µg respectively) as was the use of an extended 3-4 weekly dose regimen (6th year: 59.5% vs 65.4%). LR patients achieved a significantly higher CHemR rate than HR patients during long-term treatment (Month 72: 73.2% vs 38.3% in LR and HR respectively [RR: 2.41; 95% CI: 1.50 to 3.90; p=0.0003]). Higher CHemR among LR patients was confirmed in a sensitivity analysis including discontinued patients (last observation carried forward [LOCF]; 80.4% in LR vs 65.3% in HR patients at Month 72) indicating that in the HR group, more patients discontinued despite CHemR. In general, discontinued patients were older than those who completed the study (mean age 62.8 years vs 55.2 years) but did not have a longer duration of PV or markedly greater symptom burden at baseline. Importantly, regardless of risk stratum, most patients receiving ropeginterferon alfa-2b did not require any phlebotomy for the entire 6th year (85.7% of LR patients and 75.0% of HR patients entering the 6th year [p=0.3]). LR patients had a higher molecular response rate than HR patients (LOCF at Month 72: 84.4% vs 49.0% respectively, RR: 2.15 [95% CI: 1.37 to 3.37]; p=0.0009) and achieved molecular response more rapidly (median time to first response: 12 months [95% CI: 12 to 18] vs 18 months [95% CI: 12 to 24]; Log-rank test p=0.03). The median JAK2V617F allele burden was 5.6% for LR and 17.9% for HR patients at Month 72 (p<0.0001). During the entire PROUD-PV/CONTINUATION-PV studies (≥6 years exposure), adverse drug reactions (ADRs) to ropeginterferon alfa-2b led to withdrawal of treatment in 1 (1.8%) LR patient (due to sarcoidosis), and in 13 (18.3%) HR patients (due to thrombocytopenia [n=1], elevated transaminases [n=1], psychiatric disorders [n=2], autoimmune disorders [n=6], hypothyroidism [n=2] and dyspnea/pneumonitis [n=1]). LR patients were also less likely than HR patients to experience ADRS of grade ≥3 severity (5.4% vs 23.9%). Conclusion: These results demonstrate the benefit of ropeginterferon alfa-2b therapy in both HR and LR patient populations. LR patients may have a greater potential benefit: higher hematologic and molecular response rates can be safely achieved, and the patients are more likely to remain on long-term treatment. These data provide further evidence for an early treatment start as recently outlined by the updated ELN guidelines.

Experiences and management strategies of Norwegian GPs during the COVID-19 pandemic: a longitudinal interview study

Objective When the COVID-19 pandemic reached Norway, primary health care had to reorganize to ensure safe patient treatment and maintain infection control. General practitioners (GPs) are key health care providers in the municipalities. Our aim was to explore the experiences and management strategies of Norwegian GPs during the COVID-19 pandemic - over time, and in the context of a sudden organizational change. Design Longitudinal qualitative interview study with two interview rounds. The first round of interviews was conducted from September–December 2020, the second round from January–April 2021. In the first interview round, we performed eight semi-structured interviews with GPs from eight municipalities in Norway. In the second round, five of the GPs were re-interviewed. Consecutive interviews were performed 2–4 months apart. To analyze the data, we used thematic analysis. Results The COVID-19 pandemic required GPs to balance several concerns, such as continuity of care and their own professional efforts. Several GPs experienced challenges in the collaboration with the municipality and in relation to defining their own professional position. Guided by The Norwegian Association of General practitioners, The Norwegian College of General Practice and collegial support, they found viable solutions and ended up with a feeling of having adapted to a new normal. Conclusions Although our study demonstrates that the GPs adapted to the changing conditions, the current municipal health care models are not ideal. There is a need for clarification of responsibilities between GPs and the municipality to facilitate a more coordinated future pandemic response. Key Points Facing the COVID-19 pandemic, the primary health care service in Norway had to reorganize to ensure safe patient treatment and maintain infection control. Several GPs experienced challenges in collaboration with the municipalities. There is a need for clarification of responsibilities between GPs and the municipality.

363P A multicentre, real-world observational study of efficacy and safety of first-line osimertinib treatment in patients with epidermal growth factor receptor (EGFR) activating mutation-positive advanced non-small cell lung cancer (Reiwa study)

Osimertinib is a third-generation, irreversible EGFR-tyrosine kinase inhibitor (TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR-T790M-resistant mutations. In a phase III trial (FLAURA), osimertinib showed efficacy superior to that of first-generation gefitinib and erlotinib, with a similar safety profile and lower rates of serious adverse events. Osimertinib is currently being used as the first-line treatment for patients with advanced EGFR mutation-positive NSCLC. However, the efficacy and safety of osimertinib treatment in clinical practice have not been fully verified.

Safety of Electrotherapy Treatment in Patients with Knee Osteoarthritis and Cardiac Diseases.

To assess the safety of electrotherapy applied in the knee area in patients with known atrial arrhythmias or ischemic heart disease, as it is not known whether this treatment induces or aggravates arrhythmias during or immediately after therapy. The analytical and transversal study involved 46 patients with degenerative knee osteoarthritis (OA), with or without cardiac diseases, from the Clinical Rehabilitation Hospital inpatient center, Cluj-Napoca, Romania. All patients underwent a 10-day physical therapy program for knee OA (electrotherapy, massage and kinesiotherapy). Heart rate and the total number of ventricular and supraventricular extrasystoles were evaluated before and after treatment, by 24 h Holter ECG monitoring. There was no significant increase in heart rate or in the number of ventricular or supraventricular extrasystoles before or after electrotherapy treatment, regardless of the positive or negative history of arrhythmia or ischemic heart disease (all p &gt; 0.05). Mean values during day 1 were: 35.15 (95% CI [9.60-60.75]) for ventricular ones extrasystoles and 91.7 (95% CI [51.69-131.7]) for supraventricular ones, which during day 2 were 38.09 (95% CI [3.68-72.50]), 110.48 (95% CI [48.59-172.36]), respectively. One of the most important things to consider when dealing with an OA patient is that they are most likely older than 65 years, which increases the chance of having a cardiac disease. This raises the need for viable interventions regarding the management of this disease in patients that probably have multiple comorbidities, and where pharmacological and surgical management are not possible, limited or have multiple side effects. Electrotherapy used for treating knee OA did not cause a significant increase in heart rate or number of ventricular and supraventricular extrasystoles in this category of patients.

S790 The Safety of Ustekinumab Treatment in Patients With Moderate-to-Severe Crohn’s Disease and Latent Tuberculosis/HBV Infection: A Nationwide Retrospective Study

Introduction: Ustekinumab is a human monoclonal antibody specially blocking interleukin-12/23 has been approved in China for moderate-to-severe Crohn's disease in 2020. There is concern about the risk of infectious among biological agents treated patients, because of the high prevalence of tuberculosis and hepatitis B viral (HBV) infection in China and the expected risk of reactivation is higher in these patients. We aimed to assess the risk of tuberculosis and hepatitis B virus reactivation in Crohn’s disease patients with latent tuberculosis infection (LTBI) and previous HBV infection who are receiving Ustekinumab. Methods: A multi-center retrospective cohort study was performed at 68 hospitals in China of 721 adult patients with CD receiving ustekinumab from May 1, 2020 to October 31, 2021, Crohn's disease with concomitant LTBI or HBV carrier were included. All patients were tested for hepatitis B serology, T-SPOT TB and tuberculin skin tests at baseline. LTBI was defined as positive of T-SPOT TB or tuberculin skin tests, HBV carrier was defined as hepatitis B surface antigen and isolated anti-HBc positivity. The primary outcome of this study was tuberculosis or hepatitis B reactivation. Results: Patients with Crohn's disease concomitant LTBI or HBV carrier receiving ustekinumab therapy were retrospectively enrolled from 17 hospitals in China. Fifty-three Crohn’s disease with LTBI patients and seventeen Crohn’s disease patients with HBV carrier patients receiving ustekinumab were included. Figure summarized the inclusion of the latent TB patients treated with ustekinumab. The average follow-up was 32 ± 20 weeks and 28 ± 16 weeks, respectively. Twenty-five Crohn’s disease patients with LTBI received chemoprophylaxis regimen and eleven HBV carrier patients received antiviral prophylaxis. No cases of LTBI reactivation, virologic reactivation, and liver dysfunction were observed during the follow-up period. (Figure) Conclusion: The risk of reactivation of HBV/TB infection during immunosuppressant treatment is dependent on many factors and it influences the choice of practice significantly. This study has a medium time follow-up period and it is the largest studies involving patients with CD coexistent with TB or HBV receiving ustekinumab therapy in a high TB/HBV burden region. The outcomes indicate that ustekinumab could be safe for Crohn’s disease since whether received prophylaxis regimen or not, none developed tuberculosis, liver enzymes increasing, persistent hepatitis or acute liver failure during therapy.Figure 1.: Analysis of the incidence of active TB in the latent TB infection with UST therapy

Guidance Value of Procalcitonin Detection in Selecting Switching Points for Sequential Therapy in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease Complicated by Respiratory Failure.

ObjectiveTo analyse the guiding value of procalcitonin (PCT) for the selection of ventilation switching points in sequential mechanical ventilation for patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and respiratory failure, and to provide a reference for the optimisation of mechanical ventilation for patients with COPD and respiratory failure.MethodsThe study included 160 patients with an acute exacerbation of COPD complicated by respiratory failure who received sequential mechanical ventilation treatment. They were divided into two groups of 80 participants. The critical point of the pulmonary infection observation window (PIC) was used as the switching point for sequential mechanical ventilation treatment in the control group, and PCT clinical node was used as the switching point for sequential mechanical ventilation treatment in the observation group. The invasive ventilation time, non-invasive mechanical ventilation time, total mechanical ventilation time, intensive care unit (ICU) treatment time, complication rate and prognosis were compared for the two groups.Results(1) There was no significant difference in the respiratory rate, heart rate, arterial systolic pressure, arterial oxygen partial pressure, arterial carbon dioxide partial pressure or pH value between the two groups after 1 day of treatment, and (2) invasive mechanical ventilation time, non-invasive mechanical ventilation time, total mechanical ventilation time, ICU treatment time and the incidence of complications were significantly different in the two groups (P = 0.0001).ConclusionDetecting PCT can guide the selection of ventilation switching points in sequential mechanical ventilation therapy for patients with COPD with respiratory failure in the acute exacerbation stage, effectively reduce the misevaluation of PIC switching points so that patients can obtain stable criteria for judgement and effectively improve the efficiency and safety of mechanical ventilation treatment for patients in the acute exacerbation stage.

Efficacy and safety of glibenclamide therapy after intracerebral haemorrhage (GATE-ICH): A multicentre, prospective, randomised, controlled, open-label, blinded-endpoint, phase 2 clinical trial.

SummaryBackgroundGlibenclamide is a promising agent for treating brain oedema, but whether it improves clinical outcomes in patients with intracerebral haemorrhage (ICH) remains unclear. In this study, we aimed to explore the efficacy and safety of glibenclamide treatment in patients with acute ICH.MethodsThe Glibenclamide Advantage in Treating Oedema after Intracerebral Haemorrhage (GATE-ICH) study was a randomised controlled phase 2 clinical trial conducted in 26 hospitals in the northwest of China, recruiting patients with acute ganglia ICH no more than 72 h after onset from Dec 12, 2018 to Sept 23, 2020. During the first 7 days after enrolment, patients randomly assigned to the glibenclamide group were given glibenclamide orally (1.25 mg, 3/day) and standard care, while patients randomly assigned to the control group were given standard care alone. The computer-generated randomisation sequence was prepared by a statistician not involved in the rest of the study. Randomisation was computer-generated with a block size of four. The allocation results were unblinded to participants and investigators. The primary outcome was the percentage of patients with poor outcome (defined as modified Rankin Scale [mRS] score of ≥3) at day 90. The trial was registered at ClinicalTrials.gov (NCT03741530).Findings220 participants were randomised and 200 participants (mean [standard deviation] age, 56 [11] years; sex, 128 [64.0%] male and 72 [36.0%] female) were included in the final analysis, with 101 participants randomly assigned to the control group and 99 to the glibenclamide group. The incidence of poor outcome at day 90 was 20/99 (20.2%) in glibenclamide group and 30/101 (29.7%) in control group (absolute difference, 9.5%; 95% confidence interval [CI], -3.2%−21.8%; P = 0.121) with adjusted odds ratios of 0.54 (95% CI, 0.24−1.20; P = 0.129). No significant difference was found in the overall rates of adverse events or serious adverse events between groups. However, the incidence of asymptomatic hypoglycaemia was significantly higher in glibenclamide group than control group (15/99 [15.2%] vs 0/101 [0.0%]; absolute difference, 15.2%; 95% CI, 7.5%−24.1%; P < 0.001).InterpretationOur study provides no evidence that glibenclamide (1.25 mg, 3/day) significantly reduces the proportion of poor outcome at day 90 after ICH. In addition, glibenclamide could result in higher incidence of hypoglycaemia. Larger trials of glibenclamide with optimised medication regimen are warranted.FundingShaanxi Province Key Research and Development Project (2017DCXL-SF-02-02) and Shaanxi Province Special Support Program for Leading Talents in Scientific and Technological Innovation (tzjhjw).

Safety of Vitamin K in mechanical heart valve patients with supratherapeutic INR: A systematic review and meta-analysis.

Patients who had mechanical heart valves and an international normalized ratio (INR) of >5.0 should be managed by temporary cessation of vitamin K antagonist. This study aimed to investigate the safety of low-dose vitamin K1 in patients with mechanical heart valves who have supratherapeutic INR. CINAHL, Cochran Library, Clinical trial.gov, OpenGrey, PubMed, ScienceDirect, and Scopus were systematically searched from the inception up to October 2021 without language restriction. Studies comparing the safety of low-dose vitamin K1 treatment in patients with placebo or other anticoagulant reversal agents were included. We used a random-effect model for the meta-analysis. Publication bias was determined by a funnel plot with subsequent Begg's test and Egger's test. From 7529 retrieved studies, 3 randomized control trials were included in the meta-analysis. Pooled data demonstrated that low-dose vitamin K was not associated with thromboembolism rate (risk ratio [RR] = 0.94; 95% CI: 0.19-4.55) major bleeding rate (RR = 0.58; 95% CI: 0.07-4.82), and minor bleeding rate (RR = 0.60; 95% CI: 0.07-5.09). Subgroup and sensitivity analysis demonstrated the nonsignificant effect of low-dose vitamin K on the risk of thromboembolism. Publication bias was not apparent, according to Begg's test and Egger's test (P = .090 and 0.134, respectively). The current evidence does not support the role of low-dose vitamin K as a trigger of thromboembolism in supratherapeutic INR patients with mechanical heart valves. Nevertheless, more well-designed studies with larger sample sizes are required to justify this research question.