Successful Switch Research Articles

Situs inversus with dextrocardia and transposition of great arteries.

Transposition of the great arteries with left ventricle outflow tract obstruction in combination with situs inversus totalis and dextrocardia is a very rare anomaly and carries high morbidity and mortality. Only few cases have been reported with this anomaly. We describe a 21-day of infant girl with transposition of the great arteries and mirror image dextrocardia and pulmonary stenosis who underwent successful neonatal arterial switch operation and left ventricle outflow tract obstruction resection following PDA stent implantation.

Final analysis of 2-THE-TOP: A phase 2 study of TTFields (Optune) plus pembrolizumab plus maintenance temozolomide (TMZ) in patients with newly diagnosed glioblastoma.

2024 Background: TTFields induce anti-tumor immunity via simultaneous activation of type-1 interferon (T1IFN) pathways of the STING and AIM2 inflammasomes and immunogenic cell death. Thus, TTFields-treated GBM cells may provide a complete in situ vaccination platform and synergize with immune checkpoint inhibitors to prolong survival in GBM patients. Methods: We enrolled 26 newly diagnosed GBM patients in a pilot phase 2 study combining TTFields, pembrolizumab and maintenance temozolomide (TMZ). To distinguish immune effects of TTFields from those of pembrolizumab, TTFields was started at cycle 1 of TMZ while pembrolizumab (200 mg IV every 3 weeks) at cycle 2 of TMZ. Primary endpoints were progression-free survival (PFS) versus case-matched controls treated with TTFields plus TMZ only in the EF-14 study. Secondary endpoints included overall survival (OS), toxicity, and signature and mechanism of response by multiomics analyses of PBMCs and tumors. Results: The median age was 60.5 years. Fourteen (54%) had biopsy only or partial resection. Nineteen (73%) had unmethylated MGMT and 3 (11.5%) had an IDH mutation. Median PFS was 12.0 months versus 5.8 months in a case-matched control cohort of 26 patients (HR = 0.466; 95% CI: 0.234-0.936; Log Rank P = 0.007). Twelve-month PFS was 50.0% versus 28.2% in controls; P = 0.058. Median OS was 24.8 months versus 14.7 months in controls (HR = 0.388; 95% CI: 0.194-0.775; P = 0.039). Two-year OS was 52.4% versus 12.0% in controls; P = 0.004. Six of 15 (40%) patients with measurable disease achieved partial to complete response. In a Cox regression analysis adjusting for key prognostic factors, P-value reached 0.0317 for PFS and 0.0074 for OS. The most common serious adverse events were thromboses, seizures, and metabolic disturbances in 4 (15%), 3 (11.5%), and 2 (7.7%) patients, respectively. Molecular analyses prior to the addition of pembrolizumab confirmed robust T cell activation by TTFields via the T1IFN trajectory, as evidenced by a high correlation between TCRab clonal expansion and T1IFN responsive plasmacytoid dendritic cells (Spearman coefficient = -0.8; P = 0.014) and defined a T cell-based gene signature of TTFields effects. Subsequently, the ability of the top expanded TCRab clones to adapt to the everchanging tumor microenvironment through successful clonal switching by 2 months after the addition of pembrolizumab strongly predicted response to the triple combination in a Cox HR fit model for OS with a concordance rate of 0.876, Log Rank P = 0.031. Conclusions: The triple combination was well tolerated and demonstrated promising efficacy in newly diagnosed GBM. Multiomics analyses confirmed the robust in situ immunizing property of TTFields with synergy with pembrolizumab and identified potential signatures of response to TTFields and the triple combination. Correlative analysis will be updated. Clinical trial information: NCT03405792 .

Simulation study on physical parameters ruling unipolar resistance switching of sputter-deposited silicon oxide film on Si substrate

This paper performs Monte Carlo simulations to elucidate the physical parameters that rule the unipolar switching process in sputter-deposited Si oxide films, where the metal/sputter-deposited Si oxide film/Si substrate stack structure is assumed. Simulation parameters are based on the results of experiments performed in parallel. Generations of simple bond breaking, oxygen vacancies, metallic Si sites, and E″ centers are implemented in the simulation algorithm, where various chemical parameters are used to control bonding conditions. In this study, the impact of hole injection from the Si substrate on the switching operation is also discussed. All-positive voltage stress mode for both the electroforming process (or set process) and the reset process and all-negative voltage stress mode for both the electroforming process (or set process) and the reset process are compared in detail as to their effect on the film’s degradation process.The comparison of the two different stress modes reveals that the positive stress mode does not yield devices with stable, repeatable switching. On the other hand, the negative stress mode results in stable, repeatable switching. It is strongly suggested that the difference stems from the physical asymmetry of the electrode materials; that is, the energy spectra of electrons injected from the Si substrate has a wide range in the all-positive stress mode and the energy transfer efficiency from electrons injected from Si substrate to the atomic bonding sites is small due to the large tunnel probability, which does not result in the successful switching of the Si oxide film. The role of hole injection from the n-Si substrate on the negative-stress-mode switching process is also discussed. These new findings should contribute to the design methodology of such resistance switching devices.

Observation of Enantiomeric Switching of Individual Plasmonic Metamolecules.

Active plasmonic metamolecules under microscopic observation are promising for optical reporters in single molecule sensing applications. While self-assembled reconfigurable chiral plasmonic metamolecules can be conveniently engineered with sensing functionalities, their observation is usually based on ensemble measurements, where the chiroptical response of enantiomers tend to cancel each other in ensemble circular dichroism. Herein, we demonstrate microscopic observation of enantiomeric switching of individual active DNA origami-assembled plasmonic metamolecules. The metamolecules are immobilized on a glass substrate in a microfluidic chamber, in which the plasmonic metamolecule can maintain their activities upon certain local stimuli as in solution. In circular differential scattering, two enantiomeric states controlled by the strand-displacement reaction display opposite spectral signals to each other, representing successful enantiomeric switching of the chirality. Moreover, in a close-to-racemic mixture of chiral metamolecules controlled by pH-sensitive strands, the coexistence of enantiomeric individuals, which is concealed in ensemble measurements, is clearly identified.

Rate of Colectomy Increases Within 12 Months of Sequential Therapy for Ulcerative Colitis.

Patients with medically refractory ulcerative colitis who previously would have undergone surgery can now elect for subsequent medical therapy. In a commercially insured population, we evaluated the proportion of patients initiating second-line, third-line, or fourth-line treatment who underwent colectomy in the following 12 months. Among 3,325 patients with ulcerative colitis, the colectomy rate within 12 months of a switch in therapy increased from 12% with the first switch to 17% and 19% with the second and third switches, respectively ( P < 0.001). Treatment effectiveness declines with successive switching; however, even after initiating fourth-line therapy, most patients remain surgery-free.

Chlorocholine perchlorate is an organic ferroelectric with two-step ladder-like dielectric, second harmonic generation effects, and ferroelectricity.

The simple organic salt chlorocholine perchlorate [ClCH2CH2N(CH3)3 ·ClO4] (CCP) is found to be a molecular ferroelectric with a high theoretical spontaneous polarization (Ps) value up to 17.09 μC cm-2. CCP could undergo two successive order-disorder phase transition at 332 and 365 K with space group changing from Cc to Cmc21 and then P63/mmc, accompanying with unusual two-step ladder-like dielectric, SHG signal with obvious "on/off" contrasts. This finding provides a new instance of further exploring successive thermal-stimuli multi-responsive switching materials applied as switches and sensors.

The feasibility of the use of monoclonal antibodies to interleukin 23 in the therapy of severe psoriasis with the eluding effect of genetically engineered biological drugs

Psoriatic disease is a condition characterised by the development of a progressive chronic inflammatory process caused by various immunological pathways, among which the IL-23/Th17 axis plays a key role. Therefore, the efficacy of IL-23 p19 inhibitors is currently being actively studied. To date, quite a large number of therapeutic options among genetically engineered biological drugs (GEBDs) exist for the treatment of psoriasis, but in real clinical practice patients may lose efficacy or suffer from adverse events, resulting in the need to switch to other classes of GEBDs. Guselkumab is a fully human IgG1λ monoclonal antibody that binds selectively to the p19 subunit of interleukin 23 (IL-23) with high specificity and affinity. The implementation of the drug into clinical practice has improved the efficacy, safety and survival rate of genetically engineered biological therapy for psoriasis. Finding optimal approaches to the treatment of psoriatic disease by analysing data from clinical trials and actual practice is the real challenge for practicing clinicians. However, a current problem is the lack of sufficient information on the use of guselkumab in real clinical practice when it is initiated subsequent to administration of other classes of GEBDs – anti-TNF-α, anti-IL-17 and/or anti-IL-12/23. This article provides a review of the existing literature, as well as our own clinical observations of non-bionaive patients with successful therapy switching to the IL-23 inhibitor guselkumab. Understanding the basic aspects of GEBD therapy for psoriasis will help to achieve successful control of the disease and improve the quality of life of patients in general.

Effectiveness of Switching to Long-acting Injectable Aripiprazole in Patients with Recent-onset and Chronic Schizophrenia.

This study investigated the effectiveness of switching to once-monthly long-acting injectable (LAI) aripiprazole from other second-generation antipsychotics including LAI paliperidone palmitate in both recent-onset and chronic schizophrenia patients. This was a 24-week prospective, open-label, flexible dose-switching study in patients with schizophrenia. Scores on the Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP) scale, Clinical Global Impression (CGI), Subjective Well-being Under Neuroleptics-Short Form (SWN-K), and a computerized emotional recognition test (ERT) were evaluated. Subjects were divided into two groups (recent onset and chronic) based on 5 years' duration of the illness. Among the 82 patients participating, 67 (81.7%) completed the 24-week study. The discontinuation rate after switching to LAI aripiprazole did not differ according to clinical characteristics including type of previous antipsychotics. Scores on the PANSS, PSP, SWN-K, CGI, and ERT were significantly improved after a switch to LAI aripiprazole without exacerbation of metabolic parameters and bodyweight. The improvements in the PANSS, PSP, and CGI scores were significantly greater in patients with recent-onset than in those with chronic schizophrenia; the improvement in metabolic parameters was significantly greater in the latter group. High rates of successful switching to LAI aripiprazole from other antipsychotics suggest its good tolerability and effectiveness. Improvements in psychopathology and social functioning were more evident in patients with recent- onset schizophrenia, and improvements in metabolic abnormalities were more prominent in patients with chronic schizophrenia.

Successful Management of a Very Unusual Coronary Pattern in Transposition of the Great Arteries.

Coronary artery anatomy is the key to a successful arterial switch operation in transposition of the great arteries. We came across an unusual coronary pattern in a child with transposition in which the three major coronary arteries were seen arising from all three aortic sinuses. This coronary pattern is the first of its kind in transposition, and this case report emphasizes the difficulty in translocating such a rare coronary pattern while performing an arterial switch operation.

Multiple infliximab biosimilar switches appear to be safe and effective in a real-world inflammatory bowel disease cohort.

Switching from originator infliximab (IFX) to biosimilar IFX is effective and safe. However, data on multiple switching are scarce. The Edinburgh inflammatory bowel disease (IBD) unit has undertaken three switch programmes: (1) Remicade to CT-P13 (2016), (2) CT-P13 to SB2 (2020), and (3) SB2 to CT-P13 (2021). The primary endpoint of this study was to assess CT-P13 persistence following switch from SB2. Secondary endpoints included persistence stratified by the number of biosimilar switches (single, double and triple), effectiveness and safety. We performed a prospective, observational, cohort study. All adult IBD patients on IFX biosimilar SB2 underwent an elective switch to CT-P13. Patients were reviewed in a virtual biologic clinic with protocol driven collection of clinical disease activity, C-reactive protein (CRP), faecal calprotectin (FC), IFX trough/antibody levels, and drug survival. 297 patients (CD n=196 [66%], ulcerative colitis/inflammatory bowel disease unclassified n=101, [34%]) were switched (followed-up: 7.5months [6.8-8.1]). This was the third, second and first IFX switch for 67/297 (22.5%), 138/297 (46.5%) and 92/297 (31%) of the cohort respectively. 90.6% of patients remained on IFX during follow-up. The number of switches was not independently associated with IFX persistence after adjusting for confounders. Clinical (p=0.77), biochemical (CRP ≤5mg/ml; p=0.75) and faecal biomarker (FC<250µg/g; p=0.63) remission were comparable at baseline, week 12 and week 24. Multiple successive switches from IFX originator to biosimilars are effective and safe in patients with IBD, irrespective of the number of IFX switches.

A Shift in Asthma Treatment According to New Guidelines: An Evaluation of Asthma Patients' Attitudes towards Treatment Change.

The Global Initiative for Asthma (GINA) has presented a shift in pharmacological asthma treatment. The objective of this study was to explore factors influencing a successful switch to a new asthma treatment approach with a focus on asthma patients' attitudes toward treatment change and supportive initiatives. This study was performed as a case study involving a quantitative questionnaire and a qualitative semi-structured interview. A total of 284 responses were collected from the questionnaire, and 141 responses were included. The results showed that asthma patients thought that effectiveness of the new treatment approach, doctor recommendation, and knowledge of the new treatment approach were the most important factors influencing treatment change considerations. Nine interviews were conducted where the main themes were barriers to a shift in asthma treatment, such as effects and side effects of the new treatment, the role of the general practitioner (GP) and conflicts in agreeing on a treatment plan; as well as facilitators to a shift in asthma treatment, such as trust in the GP and easier inhaler use. We found several supportive initiatives, such as consultation with the GP, handing out information leaflets and a consultation at the pharmacy. In conclusion, this study uniquely identified factors that may influence successful treatment shifts in asthma patients that may be instrumental in understanding similar situations in other pharmacological settings.

P745 Multiple infliximab biosimilar switches appear to be safe and effective in a real-world inflammatory bowel disease cohort

Abstract Background Switching from originator to biosimilar infliximab (IFX) is effective and safe. However, data on multiple switching are scarce. The Edinburgh IBD unit has undertaken three switch programmes: (1) Remicade to CT-P13 (2016), (2) CT-P13 to SB2 (2020), and (3) SB2 to CT-P13 (2021). The primary endpoint of this study was to assess CT-P13 persistence following switch from SB2. Secondary endpoints included persistence stratified by the number of biosimilar switches (single, double and triple), effectiveness and safety. Methods We performed a prospective, observational, cohort study. All adult IBD patients on IFX biosimilar SB2 underwent an elective switch to CT-P13. Patients were reviewed in a virtual biologic clinic with protocol driven collection of clinical disease activity, CRP, faecal calprotectin (FC), IFX trough / antibody levels, and drug survival. Results 297 patients (CD n=196 [66%], UC/IBDU n=101, [34%]) were switched. This was the third, second and first IFX switch for 67 /297 (22.5%), 138 /297 (46.5%) and 92 /297 (31%) of the cohort respectively. Patients who underwent multiple IFX biosimilar switches had longer disease duration (p=0.0001) and IFX duration (p=0.0001) and were less often on combination therapy with an immunomodulator (p=0.0001). 90.6% of patients remained on IFX during a median follow-up of 7.5 months [6.8-8.1] (figure 1). The number of switches was not independently associated with IFX persistence after adjusting for confounders (table 1). Clinical (p=0.77), biochemical (CRP ≤5mg/mL; p=0.75) and faecal biomarker (FC&amp;lt;250µg/g; p=0.63) remission were comparable at baseline, week 12 and week 24 (figure 2). Conclusion Multiple successive switches from IFX originator to biosimilars are effective and safe in patients with IBD, irrespective of the number of IFX switches.

Transcatheter closure with a "single lobe" Amplatzer Vascular Plug of a tubular patent ductus arteriosus in a neonate with transposition of the great arteries and heart failure.

A patent ductus arteriosus in patients with transposition of the great arteries is usually beneficial to allow shunting between pulmonary and systemic circulations. However, if the duct is too large, it can cause haemodynamic instability, pulmonary oedema and compromised organ perfusion. We present a neonate in whom a 5 mm short and tubular ductus arteriosus was causing significant cardiac failure with necrotising enterocolitis and liver impairment, leaving him too unstable for the arterial switch operation. At day 14 of life (3.1 kg), the baby underwent successful transcatheter closure using an Amplatzer vascular plug (Abbott, Chicago, Il, USA) delivered through a 5Fr catheter from the aortic side. The procedure was uncomplicated and successful as the neonate was extubated 2 days later. He subsequently underwent successful arterial switch surgery.

Photoresponse of CVD grown crystalline quantum dot-embedded covalent organic framework thin film.

Covalent organic frameworks (COFs) are a new family of novel 2D materials which are highly sought after for integration into future sensors and other devices for their highly porous structures and large surface areas. However, low-temperature large-area growth of these semiconductive materials with a clean surface for direct device applications is still a challenging task. To provide an on-chip photonic device, a COF366-Quantum dot (COF366-QDs) thin-film-based device fabricated by in situ chemical vapor deposition (CVD) is presented. The high-resolution transmission electron microscopy (HRTEM) displays the formation of the periodic, crystalline and porous framework of the COF layer with mono-dispersed QDs of average particle size of ∼2.5-3 nm. The fabricated COF366-QD layer acts as a photoactive layer in the photonic device with an Au-COFQD-Au structure where a conduction path is formed between the metal electrodes through a network of COF layer with embedded QDs. The device shows photoactive response under 514 nm visible light with a very low dark current of 4.36 × 10-11 A with a minimum light detection capability of 160 nW and a responsivity of ∼3.42 A W-1. The photonic device was highly stable for successive switching cycles with very low attenuation. To our knowledge, this is the first report of a Quantum dot embedded COF366 thin-film by chemical vapor deposition. The proposed interfacing of COF366-QD thin-films on silicon substrate using in situ low-temperature CVD technique can be highly valuable for the development of transfer-free, clean, and low-cost preparation of industrial-scale organic electronics, optoelectronic device applications, and lab-on-chip based technologies for a wide range of future applications.

Conversion ratios for opioid switching: a pragmatic study.

The final conversion ratios among opioids used for successful switching are unknown. The aim of this study was to determine the initial and final conversion ratios used for a successful opioid switching in cancer patients, and eventual associated factors. Ninety-five patients who were successfully switched were evaluated. The following data were collected: age, gender, Karnofsky performance score, primary cancer, cognitive function, the presence of neuropathic, and incident pain. Opioids, route of administration, and their doses expressed in oral morphine equivalents used before OS were recorded as well as opioids use for starting opioid switching, and at time of stabilization. Physical and psychological symptoms were routinely evaluated by Edmonton Symptom Assessment Scale. No statistical changes were observed between the initial conversion ratios and those achieved at time of stabilization for all the sequences of opioid switching. When considering patients switched to methadone, there was no association between factors taken into considerations. Opioid switching is a highly effective and safe technique, improving analgesia and reducing the opioid-related symptom burden. The final conversion ratios were not different from those used for starting opioid switching. Patients receiving higher doses of opioids should be carefully monitored for individual and unexpected responses in an experienced palliative care unit, particularly those switched to methadone. Future studies should provide data regarding the profile of patients with difficult pain to be hospitalized.

Molecular Basis of the Toxigenic Vibrio cholerae O1 Serotype Switch from Ogawa to Inaba in Haiti.

Toxigenic Vibrio cholerae O1 serotype Ogawa was introduced involuntarily into Haiti in October 2010, and virtually all of the clinical strains isolated during the first 5 years of the epidemic were Ogawa. Inaba strains were identified intermittently prior to 2015, with diverse mutations resulting in a common phenotype. In 2015, the percentage of clinical infections due to the Inaba serotype began to rapidly increase, with Inaba supplanting Ogawa as the dominant serotype during the subsequent 4 years. We investigated the molecular basis of the serotype switch and confirmed that all Inaba strains had the same level of mRNA expression of the wbeT genes, as well as the same translation levels for the truncated WbeT proteins in the V. cholerae Inaba isolates. Neither wbeT gene expression levels, differential mutations, or truncation size of the WbeT proteins appeared to be responsible for the successful Inaba switch in 2015. Our phylodynamic analysis demonstrated that the V. cholerae Inaba strains in Haiti evolved directly from Ogawa strains and that a significant increase of diversifying selection at the population level occurred at the time of the Ogawa-Inaba switch. We conclude that the emergence of the Inaba serotype was driven by diversifying selection, independent of the mutational pattern in the wbeT gene. IMPORTANCE Our phylodynamic analysis demonstrated that Vibrio cholerae Inaba strains in Haiti evolved directly from Ogawa strains. Our results support the hypothesis that after an initial Ogawa-dominated epidemic wave, V. cholerae Inaba was able to become the dominant strain thanks to a selective advantage driven by ongoing diversifying selection, independently from the mutational pattern in the wbeT gene.

Interleukin 6 receptor inhibitors in the treatment of rheumatoid arthritis during the COVID-19 pandemic, Moscow experience

Objective: to confirm the efficacy and safety of levilimab in patients with rheumatoid arthritis (RA) switched from other interleukin 6 receptor inhibitors (iIL6R) for non-medical reasons.Patients and methods. A retrospective analysis of data from the register of patients with RA who during the COVID-19 pandemic were switched from foreign iIL6Rs to the Russian drug levilimab. Treatment regimens with levilimab in combination with synthetic diseasemodifying antirheumatic drugs (sDMARDs) and/or glucocorticoids (GCs) were used, as well as a monotherapy regimen in case of DMARDs intolerance.Results and discussion. In 150 patients with RA, a successful non-medical switch to levilimab was demonstrated with the preservation and intensification of the clinical effect achieved on previous therapy with iIL6R. After switching to levilimab, the DAS28-CRP index decreased by an average of 0.098 at 3 months and by 0.25 at 6 months (p=0.214 for both time points). There was a decrease in the proportion of patients with elevated levels of CRP, as well as with high RA activity. In a number of patients who showed high efficacy of levilimab, it became possible to reduce the dose or number of DMARDs, as well as cease GCs intake. Good tolerability and a favorable safety profile of levilimab were noted, including in relation to the new coronavirus infection that developed during therapy.Conclusion. Therapy with Russian iIL6R levilimab is effective and safe, including in patients switched from other drugs for non-medical reasons, as well as in relation to the novel coronavirus infection that developed during therapy.

Photo-induced cascaded harmonic and comb generation in silicon nitride microresonators.

Silicon nitride (Si3N4) is an ever-maturing integrated platform for nonlinear optics but mostly considered for third-order [χ(3)] nonlinear interactions. Recently, second-order [χ(2)] nonlinearity was introduced into Si3N4 via the photogalvanic effect, resulting in the inscription of quasi-phase-matched χ(2) gratings. However, the full potential of the photogalvanic effect in microresonators remains largely unexplored for cascaded effects. Here, we report combined χ(2) and χ(3) nonlinear effects in a normal dispersion Si3N4 microresonator. We demonstrate that the photo-induced χ(2) grating also provides phase-matching for the sum-frequency generation process, enabling the initiation and successive switching of primary combs. In addition, the doubly resonant pump and second-harmonic fields allow for effective third-harmonic generation, where a secondary optically written χ(2) grating is identified. Last, we reach a broadband microcomb state evolved from the sum-frequency-coupled primary comb. These results expand the scope of cascaded effects in microresonators.

Salt-Toggled Capture Selection of Uric Acid Binding Aptamers.

Uric acid is the end-product of purine metabolism in humans and an important biomarker for many diseases. To achieve the detection of uric acid without using enzymes, we previously selected a DNA aptamer for uric acid with a Kd of 1 μM but the aptamer required multiple Na+ ions for binding. Saturated binding was achieved with around 700 mM Na+ and the binding at the physiological condition was much weaker. In this work, a new selection was performed by alternating Mg2+ -containing buffers with Na+ and Li+ . After 13 rounds of selection, a new aptamer sequence named UA-Mg-1 was obtained. Isothermal titration calorimetry confirmed aptamer binding in both selection buffers, and the Kd was around 8 μM. The binding of UA-Mg-1 to UA required only Mg2+ . This is an indicator of successful switching of metal dependency via the salt-toggled selection method. The UA-Mg-1 aptamer was engineered into a fluorescent biosensor based on the strand-displacement assay with a limit of detection of 0.5 μM uric acid in the selection buffer. Finally, comparison with the previously reported Na+ -dependent aptamer and a xanthine/uric acid riboswitch was also made.

Methadone switching for refractory cancer pain

BackgroundMethadone is commonly considered an alternative opioid treatment for refractory cancer pain. This study aims to investigate the efficacy, safety, and cost of methadone in the treatment of refractory cancer pain.MethodsA retrospective study was conducted in patients who used methadone for refractory cancer pain from April 2016 to December 2020 at a cancer specialized hospital. Pain control, evaluated via pain score and breakthrough pain frequency, and adverse events of methadone were compared with analgesic regimens prior to methadone administration. The factors potentially affecting the switching outcome were analyzed via multivariate analysis. Moreover, the cost of pain control was estimated.ResultsNinety patients received methadone for poor pain control (74.4%), intolerable adverse events (10.0%), or both (15.6%) after prior opioid treatments. Sixty-four patients (71.1%) were successfully switched to methadone with median pain score significantly decreased from 4.0 to 2.0 (p < 0.001) and median daily frequency of breakthrough pain from 3.0 to 0.0 (p < 0.001) at a maintained median conversion ratio of 6.3 [interquartile range (IQR): 4.0–10.0] to prior opioid treatment. Similar adverse event profiles of constipation, nausea, vomiting, and dizziness were observed between methadone and prior opioid regimens. The median daily cost of analgesic regimens was significantly reduced from $19.5 (IQR: 12.3–46.2) to $10.8 (IQR: 7.1–18.7) (p < 0.01) after switching to methadone. The 3-day switch method significantly improved the rate of successful switching compared with the stop and go method (odds ratio = 3.37, 95% CI: 1.30–8.76, p = 0.013).ConclusionMethadone is an effective, safe, and cost-saving treatment for patients with refractory cancer pain.