Effectiveness of fentanyl buccal soluble film in cancer patients with inadequate breakthrough pain control.

BACKGROUND: Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the-clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration. METHODS: The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale. RESULTS: A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF. CONCLUSION: FBSF can be administrated "on demand" by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min. TRIAL REGISTRATION: This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .

The clinical application of traditional Chinese medicine NRICM101 in hospitalized patients with COVID-19.

BACKGROUND: The aim of this study was to assess the efficacy and safety of NRICM101 in hospitalized patients with COVID-19. RESEARCH DESIGN AND METHODS: We conducted a retrospective study from 20 April 2021 to 8 July 2021, and evaluated the safety and outcomes (mortality, hospital stay, mechanical ventilation, oxygen support, diarrhea, serum potassium) in COVID-19 patients. Propensity score matching at a 1:2 ratio was performed to reduce confounding factors. RESULTS: A total of 201 patients were analyzed. The experimental group (n = 67) received NRICM101 and standard care, while the control group (n = 134) received standard care alone. No significant differences were observed in mortality (10.4% vs. 14.2%), intubation (13.8% vs. 11%), time to intubation (10 vs. 11 days), mechanical ventilation days (0 vs. 9 days), or oxygen support duration (6 vs. 5 days). However, the experimental group had a shorter length of hospitalization (odds ratio = 0.12, p = 0.043) and fewer mechanical ventilation days (odds ratio = 0.068, p = 0.008) in initially severe cases, along with an increased diarrhea risk (p = 0.035). CONCLUSION: NRICM101 did not reduce in-hospital mortality. However, it shortened the length of hospitalization and reduced mechanical ventilation days in initially severe cases. Further investigation is needed.

Predicting the successful application of high-flow nasal oxygen cannula in patients with COVID-19 respiratory failure: a retrospective analysis.

BACKGROUND: The right time of high-flow nasal cannulas (HFNCs) application in COVID-19 patients with acute respiratory failure remains uncertain. RESEARCH DESIGN AND METHODS: In this retrospective study, COVID-19-infected adult patients with hypoxemic respiratory failure were enrolled. Their baseline epidemiological data and respiratory failure related parameters, including the Ventilation in COVID-19 Estimation (VICE), and the ratio of oxygen saturation (ROX index), were recorded. The primary outcome measured was the 28-day mortality. RESULTS: A total of 69 patients were enrolled. Fifty-four (78%) patients who intubated and received invasive mechanical ventilatory (MV) support on day 1 were enrolled in the MV group. The remaining fifteen (22%) patients received HFNC initially (HFNC group), in which, ten (66%) patients were not intubated during hospitalization were belong to HFNC-success group and five (33%) of these patients were intubated later due to disease progression were attributed to HFNC-failure group. Compared with those in the MV group, those in the HFNC group had a lower mortality rate (6.7% vs. 40.7%, p = 0.0138). There were no differences in baseline characteristics among the two groups; however, the HFNC group had a lower VICE score (0.105 [0.049-0.269] vs. 0.260 [0.126-0.693], p = 0.0092) and higher ROX index (5.3 [5.1-10.7] vs. 4.3 [3.9-4.9], p = 0.0007) than the MV group. The ROX index was higher in the HFNC success group immediately before (p = 0.0136) and up to 12 hours of HFNC therapy than in the HFNC failure group. CONCLUSIONS: Early intubation may be considered in patients with a higher VICE score or a lower ROX index. The ROX score during HFNCs use can provide an early warning sign of treatment failure. Further investigations are warranted to confirm these results.

High flow nasal cannulas (HFNCs) were widely used in patients with COVID-19 infection related hypoxemic respiratory failure. However, there were concerns about its failure and related delayed intubation may be associated with a higher mortality rate. This retrospective study revealed patients with higher baseline disease severity and higher VICE scores may be treated with primary invasive mechanical ventilation. On the contrary, if their baseline VICE score is low and ROX index is high, HFNCs treatment might be safely applied initially. The trends of serial ROX index values during HFNC use could be a reliable periscope to predict the HFNC therapy outcome, therefore avoided delayed intubation.

Outcome prediction in hospitalized COVID-19 patients: Comparison of the performance of five severity scores.

Background: The aim of our study was to externally validate the predictive capability of five developed coronavirus disease 2019 (COVID-19)-specific prognostic tools, including the COVID-19 Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), Shang COVID severity score, COVID-intubation risk score-neutrophil/lymphocyte ratio (IRS-NLR), inflammation-based score, and ventilation in COVID estimator (VICE) score. Methods: The medical records of all patients hospitalized for a laboratory-confirmed COVID-19 diagnosis between May 2021 and June 2021 were retrospectively analyzed. Data were extracted within the first 24 h of admission, and five different scores were calculated. The primary and secondary outcomes were 30-day mortality and mechanical ventilation, respectively. Results: A total of 285 patients were enrolled in our cohort. Sixty-five patients (22.8%) were intubated with ventilator support, and the 30-day mortality rate was 8.8%. The Shang COVID severity score had the highest numerical area under the receiver operator characteristic (AUC-ROC) (AUC 0.836) curve to predict 30-day mortality, followed by the SEIMC score (AUC 0.807) and VICE score (AUC 0.804). For intubation, both the VICE and COVID-IRS-NLR scores had the highest AUC (AUC 0.82) compared to the inflammation-based score (AUC 0.69). The 30-day mortality increased steadily according to higher Shang COVID severity scores and SEIMC scores. The intubation rate exceeded 50% in the patients stratified by higher VICE scores and COVID-IRS-NLR score quintiles. Conclusion: The discriminative performances of the SEIMC score and Shang COVID severity score are good for predicting the 30-day mortality of hospitalized COVID-19 patients. The COVID-IRS-NLR and VICE showed good performance for predicting invasive mechanical ventilation (IMV).

Clinical benefits of inhaled ciclesonide for hospitalized patients with COVID-19 infection: a retrospective study.

BACKGROUND: The successful management of patients infected with coronavirus disease 2019 (COVID-19) with inhaled ciclesonide has been reported, however few studies have investigated its application among hospitalized patients. METHODS: This retrospective cohort study enrolled all adult patients admitted to our hospital with confirmed COVID-19 infection from May to June 2021. Critical patients who received mechanical ventilation within 24 h after admission and those who started ciclesonide more than 14 days after symptom onset were excluded. The in-hospital mortality rate was compared between those who did and did not receive inhaled ciclesonide. RESULTS: A total of 269 patients were enrolled, of whom 184 received inhaled ciclesonide and 85 did not. The use of ciclesonide was associated with lower in-hospital mortality (7.6% vs. 23.5%, p = 0.0003) and a trend of shorter hospital stay (12.0 (10.0-18.0) days vs. 13.0 (10.0-25.3) days, p = 0.0577). In subgroup analysis, the use of inhaled ciclesonide significantly reduced mortality in the patients with severe COVID-19 infection (6.8% vs. 50.0%, p < 0.0001) and in those with a high risk of mortality (16.4% vs. 43.2%, p = 0.0037). The use of inhaled ciclesonide also reduced the likelihood of receiving mechanical ventilation in the patients with severe COVID-19 infection. After multivariate analysis, inhaled ciclesonide remained positively correlated with a lower risk of in-hospital mortality (odds ratio: 0.2724, 95% confidence interval: 0.087-0.8763, p = 0.0291). CONCLUSIONS: The use of inhaled ciclesonide in hospitalized patients with COVID-19 infection can reduce in-hospital mortality. Further randomized studies in patients with moderate to severe COVID-19 infection are urgently needed.

EGFR Q787Q Polymorphism Is a Germline Variant and a Prognostic Factor for Lung Cancer Treated With TKIs.

The prevalence and impact of epidermal growth factor receptor (EGFR) Q787Q polymorphism on the treatment of lung adenocarcinoma remains unclear. We retrospectively analyzed patients with stage IV lung adenocarcinoma to evaluate the prevalence of the EGFR Q787Q polymorphism and its influence on effects of tyrosine kinase inhibitor (TKI) treatment. A total of 333 patients were included in this study. The prevalence of the EGFR Q787Q polymorphism was 38%, 42%, and 35% in the total patients, EGFR mutation negative, and EGFR mutation positive groups, respectively. The prevalence of EGFR Q787Q polymorphism was significantly higher in EGFR wild-type patients than in the general non-cancerous population from Taiwan Biobank and 1000 Genome Project databases, respectively. EGFR Q787Q polymorphism had significant protective effects on the overall survival of EGFR-mutant lung adenocarcinoma treated with EGFR TKIs (aHR =0.61, p=0.03). Our study demonstrated that EGFR Q787Q polymorphism is a germline variant in the general population. It is a protective predictor of overall survival in patients with stage IV EGFR-mutated lung adenocarcinoma treated with TKIs.

Resistance profiles of anaplastic lymphoma kinase tyrosine kinase inhibitors in advanced non-small-cell lung cancer: a multicenter study using targeted next-generation sequencing.

INTRODUCTION: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib are approved for advanced non-small-cell lung cancer (NSCLC) with ALK rearrangement. However, the mechanisms of resistance remain largely unclear. METHODS: This prospective multicenter study analyzed cell-free DNA (cfDNA) and/or cancer tissues of patients with NSCLC after progression on ALK TKI(s), using targeted next-generation sequencing. Patients' clinicopathologic characteristics and treatment outcomes were analyzed. RESULTS: Overall, 88 patients were enrolled; 31 cancer tissues and 90 cfDNA samples were analyzed. Five (16%) ALK mutations (L1196M ×2, I1171T, D1203N, G1269A/F1174L) and 3 possible bypass mutations (NRAS G12V, EGFR R108K, PIK3CA E545K) were found in 32 crizotinib-resistant cancers. Four (22%) ALK mutations (G1128A, G1202R, G1269A, I1171T/E1210K) and 3 possible bypass mutations (KIT D820E, MET E1012∗, EGFR P265_C291del) were found in 18 ceritinib-resistant cancers. Four (17%) ALK mutations (G1202R ×2, W1295C, G1202R/L1196M) and 1 possible bypass mutation (EGFR P753S) were found in 24 alectinib-resistant cancers. Two (11%) ALK mutations (G1202R/G1269A ×2) and 2 possible bypass mutations (BRAF V600E, MET D1246N) were found in 18 lorlatinib-resistant cancers. In patients with simultaneous paired tissue and cfDNA samples (n = 20), mutations were identified in 9 (45%) and 6 (30%) cases, respectively; the concordance rate was 45%. CONCLUSIONS: The mechanisms of ALK TKI resistance were heterogeneous; ALK mutations were found in less than one-third of patients. Compound ALK mutations, which may confer lorlatinib resistance, may occur in crizotinib, ceritinib, and alectinib-resistant lung cancers.

Targeted Temperature Management for In-Hospital Cardiac Arrest: 6 Years of Experience.

Targeted temperature management (TTM) is widely used for postcardiac arrest management of patients with out-of-hospital cardiac arrest. However, the use of TTM for patients with in-hospital cardiac arrest (IHCA) is controversial. The aim of this study was to investigate the role of TTM in the management of patients with IHCA. The medical records of all IHCA patients who were resuscitated and returned to spontaneous circulation from January 2011 to December 2016 were reviewed. After excluding patients with new do not resuscitate orders and those who died within 24 hours, 262 patients were eligible for analysis. Thirty-five of the 262 patients (13.3%) received TTM after IHCA. Patients who received TTM and standard supportive care (SSC) had similar baseline epidemiological status. The TTM patients were older and had a longer cardiac pulmonary resuscitation duration; however, the differences were not statistically significant. The 28-day survival rate was not significantly different between groups (12/35 in the TTM group [34%] vs. 114/225 in the SSC group [50%], p = 0.079). In the patients with good neurological status before arrest (Glasgow-Pittsburgh cerebral performance category [GP-CPC] scores: 1-2), there was no significant difference in the 28-day survival between groups (11/26 in the TTM group [42.3%] vs. 81/154 [52.6%] in the SSC group; p = 0.332). In this subgroup, the TTM patients had poorer neurological outcomes at discharge (GP-CPC score 1-2) than the SSC patients (1/26 in the TTM group [3.8%] vs. 57/154 in the SSC group [37%]; p = 0.001). TTM was not associated with better 28-day survival than usual care among the patients with IHCA in this study, and the TTM patients had less favorable neurological outcomes at discharge. Randomized clinical trials are needed to assess the efficacy of TTM for IHCA patients.