Amoxicillin: When the essential is missing.

The antibiotic amoxicillin is usually recommended as a first-line treatment for many common infections affecting children. Repeated lockdowns related to the coronavirus disease 2019 pandemic have contributed to supply difficulties for many drugs, including antibiotics. However, the risks associated with amoxicillin supply shortages appear not to have been sufficiently assessed, and the crisis we are facing today is serious and particularly dangerous for children's health. Without rigorous measures to prevent shortages related to drug production and distribution, populations could face a post-antibiotic era in which common infections and minor injuries can result in serious life-threatening situations. The availability of medicines declared by WHO as essential should be guaranteed not only in production but also in fair distribution. And this principle must be ensured by national and international regulatory agencies.Copyright © 2023 Medico e Bambino. All rights reserved.

Association of state-level COVID-19 mortality rates with real-world progression and real-world overall survival among patients with advanced non-small cell lung cancer, 2020-2022

Background: The COVID-19 pandemic impacted the delivery of cancer care and outcomes in the United States (US). We examined the association between time-varying state-level weekly COVID19 mortality and progression-free survival (rwPFS), time to progression (rwTTP), and survival (rwOS) among pts with advanced non-small cell lung cancer (advNSCLC). Method(s): This retrospective study used the nationwide Flatiron Health electronic health recordderived de-identified database. The cohort included community oncology pts diagnosed with advNSCLC between March 1, 2020 and December 31, 2021 (follow-up through March 30, 2022). We extracted US data on COVID-19 deaths from the COVID-19 Data Repository by the Center for Systems Science and Engineering at Johns Hopkins University. We calculated state-level weekly COVID-19 death rates as weekly COVID-19 deaths per state population size from the 2019 American Community Survey. We categorized rates into quintiles based on all weekly rates during the observation period. Analyses were restricted to treated pts and indexed to start of first-line therapy. For rwPFS analyses, first occurrence of progression or death was considered an event, and pts were censored at last clinic note date. For rwTTP, only progression (not death) was considered an event, and pts with no event were censored at last clinic note date. For rwOS analyses, pts who did not die were censored at last structured activity. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between weekly time-varying state-level COVID-19 mortality rates and outcomes of rwPFS, rwTTP, and rwOS, adjusted for age at diagnosis, race/ethnicity, and state. Result(s): Among 7,813 advNSCLC pts, the median age at diagnosis was 70 years, the majority of the cohort was non-Hispanic White (59%), had non-squamous cell histology (68%) and a history of smoking (87%). Compared to pts living in states with the lowest quintile of COVID-19 mortality rates (Q1), pts living in states with the highest COVID-19 mortality (Q5) had worse rwOS (Q5 vs. Q1: HR 1.46, 95% CI 1.26-1.69) and rwPFS (Q5 vs. Q1: HR 1.18, 95% CI 1.05-1.33). No association was observed with rwTTP (Q5 vs. Q1: HR 1.05, 95% CI 0.90-1.22). Conclusion(s): In this study of real-world oncology data, we demonstrated the use of publicly-available COVID-19 mortality data to measure the time-varying impact of COVID-19 severity on outcomes in pts with advNSCLC. Higher state-level COVID-19 mortality rates were associated with worse rwOS and rwPFS among advNSCLC pts. The association with increased mortality among pts with advNSCLC may be related to COVID-19-related mortality or other factors such as pre-existing comorbidities which were not explored in this study.

A retrospective analysis of first-line PD-1 monoclonal antibodies treatment in patients with leptomeningeal metastasis from solid tumors.

INTRODUCTION: Patients whose solid tumors (ST) show leptomeningeal metastasis (LM) have very poor prognosis and short overall survival. The aim of this study was to evaluate the efficacy of first-line programed death-1(PD-1) monoclonal antibody (mAb) treatment in these patients. METHODS: We retrospectively evaluated patients diagnosed with LM from ST who were treated with first-line PD-1 mAb at our hospital between April 1 and November 30, 2019. We analyzed their clinicopathological characteristics and response to the treatment. RESULTS: We collected and analyzed data from 6 patients with different primary ST. 5 patients received PD-1 mAb combined with chemotherapy and/or anti-angiogenic drugs, while one received only PD-1 mAb. The median (range) number of treatment cycles was 5.5 (1-21). PD-1 mAb treatment did not cause neurotoxicity. The time period of first assessment varied from 21 to 65 days after treatment. Among 5 patients who got obvious symptoms relief, 4 patients persisted for > 3 months and even showed a reduction in the number of tumor cells in cerebrosprinal fluid. Ventriculoperitoneal (VP) shunt was used to treat hydrocephalus observed beneficial in 3 patients: 2 before and 1 after PD-1 mAb treatment. The median (range) follow-up time was 214 (57-460) days. 4 patients died. The overall survival ranged from 57 days to at least 460 days. 1 of the two alive patients continued to show no worsening of symptoms after 457 days. CONCLUSIONS: Patients with LM from ST can benefit from first-line PD-1 mAb combined treatment without additional neurotoxicity. Further research is required to validate the safety and efficacy.

Multisystemic inflammatory syndrome of the adult post-COVID-19.

BACKGROUND: Multisystemic inflammatory syndrome of the adult, a new condition associated with an irregular immune response similar to that of children, is characterized by shock, heart failure or persistent hypotension, dyspnea on exertion, mild-moderate hypoxemia, gastric symptoms and elevated markers of systemic inflammation after severe COVID-19 pneumonia. CLINICAL CASE: A 56-year-old patient, uncontrolled diabetic, who presented symptoms associated with dyspnea, desaturation, chest pain and persistent fever, previously with severe pneumonia after one month of treatment. He was treated with oxygen, steroids and antibiotics for 3 weeks, but his symptoms worsened and he developed severe orthopnea, hypotension, chest pain, dyspnea at rest and severe desaturation, as well as elevation of inflammation markers (C-reactive protein, ESR, D-dimer, ferritin). Tomography of the chest showed residual pneumonia based on consolidation and ground glass. Echocardiogram evidenced diastolic dysfunction, myopericarditis and secondary endocarditis. Multisystemic inflammatory syndrome of the adult was diagnosed and patient was treated with IV immunoglobulin and steroid with a favorable response to treatment. CONCLUSION(S): This case shows that the adult systemic inflammatory syndrome is a differential diagnosis in a patient with shock of unknown etiology, heart failure and severe dyspnea previously infected by SARS-CoV-2. Immunoglobulin and steroid are the effective first-line treatment with excellent clinical response.Copyright © 2022 Comunicaciones Cientificas Mexicanas S.A. de C.V.. All rights reserved.

Clinical outcome of patients with severe malignant pericardial effusion due to neoplastic disease undergoing percutaneous balloon pericardiotomy during COVID-19 pandemic

Background: Neoplastic pericardial effusion (NPE) is a serious complication that occurs in the setting of advanced oncological disease and is associated with a high recurrence rate. Currently, pericardiocentesis (PCT) remains the first therapeutic option and the use of percutaneous balloon pericardiotomy (PBP) is limited to the treatment of recurrences. However, it is not known whether some aspects of the procedure during PBP lead to different outcomes in terms of survival and recurrence, and no such patients have been included in studies during COVID-19 pandemic. Purpose(s): The aim is to analyses the success, complications and recurrence rate (defined as recurrence of NPE requiring PCT, PBP or surgical pericardial window (SPW) of both procedures (BP) in order to establish the optimal entry treatment for these patients. Method(s): This research analyzed the clinical characteristics and prognostic factors of patients with severe pericardial effusion of neoplastic etiology who underwent PBP during the COVID-19 pandemic. A prospective study was conducted involving 23 patients admitted between January 2020 and January 2022 for severe NPE who underwent PCT or PBP as initial treatment of NPE. Result(s): We included 23 patients, 62.9% were male with a mean age of 51.2+/-14.9 years NPE was the first manifestation of the oncological process in 12 patients (52.1%) with lung cancer being the most frequently associated primary cancer (58.7%) followed by breast cancer in 12.7% of cases. A total of 26 procedures were performed, 10 PCT, 15 PBP, 1 SPW, with tumors cells identified in the pericardial fluid in 13.0% of cases. PCT was used as an entry point in 10 patients (43.5%), 6 patients were COVID-19 positive and PCT was performed as the first treatment. While PBP was chosen as the first therapeutic option in 13 patients (56.5%) (2 Re-PBP). The initial efficacy of the procedure was 93.1% and 92.2% respectively (p=0.88), with 1 complication occurring in the PBP group but not requiring scheduled SPW. In the former group, the percentage of recurrences was higher (34.7%;8 recurrences in 10 patients) compared to patients treated with upfront PBP (8.6%;2 recurrences in 13 patients), p=0.09. In addition, only one patient had to resort to surgery. When analyses according to the BP. used, the recurrence rate was 4.0 times higher for PCT (34.7 vs. 8.6% recurrences), although without reaching statistical significance (p=0.16). Conclusion(s): The PBP is a simple, safe and effective technique for the treatment of NPE during the COVID-19 pandemic, in our series it was associated with a lower recurrence rate. Therefore, it could replace PCT in these patients during the COVID-19 pandemic as optimal first line treatment, providing better quality of life and reducing the need for re-interventions. (Figure Presented).

Hairy Cell Leukemia in a Filipino Male during the COVID-19 Pandemic - Report of a Rare Case

Hairy cell leukemia (HCL) is a rare, chronic, mature B-cell lymphoproliferative disorder accounting for 2% of all leukemias. In this paper, we would like to present our experience in the management of HCL in a financially limited setting where other diagnostic tests and chemotherapy are unavailable. The case report aims to emphasize the recognition of the distinctive morphology of hairy cells in the peripheral blood in the consideration of the initial diagnosis. A 60-year-old Filipino male was incidentally found to have anemia, thrombocytopenia and an absolute neutrophilic count below 1,000 in a pre-operative clearance for elective herniorrhaphy. Blood smear revealed atypical lymphocytes with hair like cytoplasmic projections. CT-scan of the abdomen showed splenomegaly and prominent paraaortic nodes. Flow cytometry of the bone marrow aspirate was consistent with an involvement of a Mature B cell neoplasm markers CD19, CD20, CD22 and surface immunoglobulin lambda and hairy cell leukemia markers CD11c, CD103 and CD25. He responded to six-weekly sessions of Cladribine with remission of the bone marrow and hematologic parameters. HCL is a rare type of a mature B cell neoplasm characterized by pancytopenia, splenomegaly, bone marrow fibrosis and the presence of atypical lymphoid cells with hairy projections in blood, bone marrow and spleen. Immunophenotyping express CD11c, CD103, CD123, and CD25. BRAF V600E mutation is the disease defining genetic event. Cladribine and Pentostatin are the first line of treatment. Cases of leukemia can be easily overlooked because of the mild derangement in the complete blood count. A meticulous differential review of the atypical lymphocyte, is the first step in the diagnosis of this rare disease.Copyright © 2022, Philippine College of Physicians. All rights reserved.

Bronchiolitis obliterans and SARS-CoV-2: the beginning of an association.

SARS-CoV-2 infection in the pediatric population usually mani-fests with mild symptoms;however, in patients with comorbidities, there may be a severe pulmonary compromise. We present the case of a 3-month-old patient with acute SARS-CoV-2 infection, with persistent respiratory symptoms up to 8 weeks after the initial infection, with a persistently positive PCR test, requiring several hospitalizations, supplemental oxygen, and even invasive mechanical ventilation. Clinical and radiological manifestations were found consistent with bronchiolitis obliterans associated with SARS-CoV-2 infection. An adequate clinical response was documented after starting first-line treatment for bronchiolitis obliterans with satisfactory evolution during follow-up to date, evidencing the importance of considering this association in clinical practice.Copyright © 2022, Sociedad Chilena de Infectologia. All rights reserved.

Cyclin-dependent kinase 4/6 inhibitor in advanced breast cancer during the COVID pandemic period: efficacy in relation to vaccination for SARS-COV 19

Introduction: More than 2 years after the WHO declaration of a pandemic, SARS-Cov-2 still represents a public health problem The pandemic has increased the complexity of cancer treatments including breast cancer. These difficulties were highlighted in adjuvant treatments but above all in metastatic disease. Vaccination has been one of the most important public health factors that has reduced deaths, hospitalizations and the severity of symptoms related to infection. In metastatic breast cancer hormone receptor positive and HER2/neu negative currently the first line of treatment is given by the association between cyclin 4/6 inhibitors and hormone therapy (aromatase inhibitors or fulvestrant) A well-known and frequent side effect of this therapy is the reduction of white blood cell values and neutrophils. The hypothesis that this study is to evaluate whether treatment with cyclin inhibitors initiated before the period of vaccinations may have influenced, due to the reduction in white blood cell values, an increased risk of infection in these patients. Material(s) and Method(s): In our study, we selected patients who had started treatment with cyclin inhibitors before starting the vaccination cycle (in Italy up to the fourth dose in cancer patients) and continue it without evidence of disease progression. All patients were offered a vaccination cycle with mRNA COVID vaccines and were followed during their cancer treatments. All patients, at least 90 days after the last dose of vaccine, have been tested for antibodies against SARS CoV-2 (trimeric spike protein) with a value expressed in binding antibodies unit (BAU) according to international standard WHO During the observation period (starting from the first dose of vaccine administered) the patients were clinically checked and in case of suspicion of infectious pathology with symptoms suggestive of SARS-COV-19 infection, they were tested with molecular swab Results: We evaluated 52 patients who started cyclin treatment before the vaccination course and who are currently without signs of disease recurrence During the study period we found 14 SARSCOV19 infections (28% of patients) and one patient with two infectious episodes. No patients needed treatment in a hospital or resuscitation setting. All patients have fully recovered from the infection and at most after 21 days have resumed the treatment still in place Statistically, a linear regression calculation was applied to evaluate a functional relationship between variables measured on the basis of sample data. We did not find a relationship between spikes or infections compared to the start date of the vaccination cycle;instead we observed a relationship between the value of the spike and the date of last immunization (considered as an active infection or fourth dose of vaccine) with a reduction in the values the further you go away Conclusion(s): The data of the study show that there is a correlation between the time elapsed between the last vaccination and the risk of getting sick. For this reason, the fourth recall represents a strong help to reduce this risk. We did not find any ranges we could refer to regarding the dosage of trimeric spike protein. Considering the positivity rate of infections that does not exceed the general vaccinated population and the absence of serious infectious symptoms with hospitalization, treatment with cyclin inhibitors appears to be a safe treatment even in a pandemic period. (Table Presented).

Fifteen-year experience with natalizumab in the treatment of multiple sclerosis - a description of 15 clinical cases.

Natalizumab, a humanized anti-alpha4-integrin antibody, is a valuable therapeutic option for relapsing-remitting multiple sclerosis and has been widely used in this indication since 2006. The growing body of data on its high efficacy and safety profile, both from randomised trials and clinical practice, has allowed to identify risk factors for progressive multifocal leukoencephalopathy and to develop a preventive algorithm, which increased the therapeutic safety. Natalizumab also seems relatively safe in pregnant women as there is no indication in the available literature suggesting that exposure to this drug has a significant impact on pregnancy outcomes. However, adequate and well-controlled studies are still lacking and natalizumab should only be used in pregnancy if clearly needed. The mechanism of action of natalizumab also proved successful during the COVID-19 pandemic. Most patients receiving this therapy experienced only mild infection and developed normal vaccine-induced immunity after immunisation. We present a description of 15 patients with relapsing-remitting multiple sclerosis treated with natalizumab in 15 different centres throughout Poland. The drug was included both due to first-line treatment failure and in cases of rapidly progressing, severe form of multiple sclerosis. The patients differed in terms of disease duration, the length of natalizumab therapy, and JCV serological status. The described cases include patients from the natalizumab registration trial, women who became pregnant while on the therapy, and patients who developed COVID-19. The presented case reports summarise the experience to date with the use of natalizumab in the treatment of relapsing-remitting multiple sclerosis in PolandCopyright © 2022 Buchajewicz et al.

Epidemiology And Treatment Of Pain Associated With Osteoarthritis Of The Knee In Germany: A Retrospective Health Claims Data Analysis

Purpose: Osteoarthritis of the knee (knee OA) is the most prevalent form of OA, frequently leading to significant pain and an overall reduction in quality of life. The available options for managing pain, associated with knee OA, are well documented. They include various oral analgesic medications (for example, NASIDs and opioids), intraarticular agents, notably, hyaluronic acid and corticosteroids, and where pharmacological and lifestyle options have been exhausted, orthopedic surgery, including total knee replacement (TKR). The treatment option(s) a patient may receive, in which order and at what time point, post-diagnosis may vary significantly between healthcare centers. The current study focuses specifically on knee OA in Germany, aiming to determine the epidemiology, patient characteristics and treatment schemes for the management of pain associated with knee OA. Method(s): A non-interventional, retrospective health claims data analysis was performed with an anonymized, age- and sex-representative sample of the Institute for Applied Health Research Berlin GmbH (InGef) database. The database that was used for this study includes approximately 4.8 million persons from approx. 60 statutory health insurances (SHI). Patients >=18 years of age were analyzed cross-sectionally for each year 2015-2020. Using ICD-10 and ATC codes, newly diagnosed patients in 2015 were also analyzed longitudinally until end of 2020. Result(s): The average period prevalence of knee OA was 7.34%, with a slight increase during the years 2015-2020. Incidence ranged from 1.71% of patients in 2015 to 1.46% of patients in 2020. Females and patients aged >=66 years had both a higher prevalence and incidence proportion compared to males and younger persons. Approximately 62% of newly diagnosed patients in 2015 received medical treatment during follow-up, most of whom were prescribed non-opioid analgesics;WHO I category (96.84%), followed by WHO II (2.45%) and WHO III (0.71%), as first line treatment. This analysis could not account for the use of any over the counter medications, or medicines prescribed in hospital, prior to, or after diagnosis. As many as 16.58% of newly diagnosed patients had surgery within 5 years. Knee replacement was the most common type of surgery with rising prevalence. The number of patients in whom surgery was performed decreased slightly from 5,38% to 4,03% during the study years considered (Figure 1);the decrease in 2020 may, in-part, be a reflection of the COVID-19 pandemic and the knock-on impact on healthcare systems. Of the 8,318 surgical patients, 2,101 patients (25.26%) had no record of having received any prescription pharmacological treatment prior to first surgery. The median time from first diagnosis until surgery in newly diagnosed patients was 346 days for any surgery, and 564 days for knee replacement. [Formula presented] Conclusion(s): With a stable incidence and a growing population, the number of patients with knee OA in Germany is slowly rising. In parallel, there is an slight decrease in total knee surgeries occurring each year with an increasing proportion of TKRs. Time until first surgery, in general, and TKR in newly diagnosed patients is relatively short, compared to other countries, with some patients having no record of having received any prescription medication prior to first surgery. Other treatment options such as opioids and intraarticular agents, appear to play a relatively minor role, in newly diagnosed patients, in current practice in Germany.Copyright © 2023

The Swedish Osteoarthritis Registry. Trends in swedish osteoarthritis health care between 2008- 2021

Purpose: To describe the trends over time from 2008 to 2021 for people who have received first-line interventions for hip and knee osteoarthritis in Sweden and adherence of the healthcare staff to the national guidelines. Method(s): Descriptive registry-based study including people with hip or knee OA who participated in first-line interventions including education and exercise. Data were extracted from the Swedish Osteoarthritis registry between January 1st, 2008, and December 31, 2021. The registry contains patient-reported outcomes and physiotherapist-reported outcomes. In this study the following physiotherapist-reported outcomes were described over time: radiological examination before first-line treatment, if the first-line treatment was given the first time the patient seek health care caused of OA, which explanation patients had been given about their disease, intake of painkillers before the start of first-line treatment and the percent who got supervised exercise >10 times according to the guidelines of OA in Sweden. The following patient-reported outcomes were described over time: mean BMI at the first visit, and mean age at the first visit. To be included in the study, participants had to meet the following criteria: i) clinical diagnosis of OA, with hip or knee OA as the most symptomatic joint, ii) provided 3-month follow-up Results: A total of 175 764 participants with hip or knee OA were included in the study. The trends from 2008-2021 showed that the proportion of people who had a radiological examination before entering the first-line treatment decreased from 97 % to 65 % in men and from 95% to 62 % in women. The proportion of people who get assess to first-line treatment the first time they seek for their symptoms increased from 4 % to 10 % both in men and women. People that get the correct information about OA increased from 15% to 40 %, and people that get the explanation that OA was a tear and wear disease decreased from 30 % to 5%. The mean BMI (28) is unchanged over time. The mean age increased from 64 years to 67 years between 2008-2020 but decreased during the covid-19 pandemic to 64 years. The percentage that was given supervised exercise more than 10 times was constant between 2012-2020 at 30 % but decreased during the covid-19 pandemic to 20%. Conclusion(s): The results implicit that the implementation of a supported osteoarthritis self-management program in Sweden has been successful and changed the care given to people with OA in Sweden. However, the national guidelines for OA, published in 2012, have still not been fully implemented. We need to keep implementing the guidelines so all patients with osteoarthritis get the first-line treatment at the right time.Copyright © 2023

Therapeutic Management of Advanced Hodgkin Lymphoma in Patients with Pulmonary Comorbidities

Introduction: Hodgkin lymphoma (HL) accounts for 30% of all lymphomas. The standard of care in the first-line treatment of advanced HL remains chemotherapy regimens containing bleomycin, a drug associated with lung toxicity. Brentuximab vedotin (BV), an anti-CD30 antibodydrug conjugate, combined with AVD (Adriamycin, Vinblastin and Dacarbazin) has been approved as a treatment for patients with untreated CD301 stage IV HL. No data (outside of clinical trials) were found on this use of BV-AVD in routine clinical practice. In this report, we describe 4 cases of HL treated with BV-AVD as first-line therapy. Material(s) and Method(s): Cases reported by the hematology department. Data were collected from CHIMIO software and medical records from 6/29/2021 to 3/21/2022. Results and discussion: Four patients (3 men, 1 woman, mean age 59 years [52-67], performance status 1-2) with advancedHL (2 stage III, 2 stage IV, all CD30+) were treated with BV-AVD as first-line treatment. Two patients had lung disease (1 HIV with a history of pneumocystis, tuberculosis and 1 emphysema) and 2 patients had active smoking, a major risk factor for lung disease. Three complete responses and one partial response were achieved, with no relapse to date. Treatment was well tolerated, with no pulmonary complications, no BV-induced neurotoxicity greater than grade 1, and no neutropenia (G-CSF prophylaxis). Although the drug is not reimbursed in this therapeutic indication in our country, our data suggest that BV-AVD is an attractive first-line treatment option in clinical practice for patients with advanced HL and risk factors for pulmonary complications, even in patients older than 60 years. Conclusion(s): Based on these results and in the context of the COVID pandemic, we redefined our therapeutic strategy for the front-line treatment of advanced HL with the BV-AVD indication in patients with pulmonary frailty.

Diamond-blackfan anemia in an adult

Case Report: A 25-year-old woman with history of Diamond-Blackfan anemia (DBA) presented with a 3- week history of weakness and fatigue. The patient was in her usual state of health until 3 weeks prior when she was diagnosed with COVID-19, at which time she experienced cough, congestion, weakness, and fatigue. She reported that the cough and congestion improved after a few days, but the fatigue and weakness progressively worsened. Admission labs were notable for a hemoglobin of 5.5 g/dL with a MCV of 119.3 fL. She received 2 units of packed RBCs with improvement in hemoglobin to 8.9 g/dL. The patient was diagnosed with DBA at birth via bone marrow biopsy and had been stable on chronic prednisone with a baseline hemoglobin around 8 g/dL. Prior to this admission, she has only required one transfusion at 3 months old. Her outpatient management involved close monitoring of her hemoglobin and increasing/decreasing prednisone based on her trending hemoglobin. She had been stable on 15 mg/day of prednisone for the past few years. Her hematologist was consulted, and the decision was made to increase her dose of prednisone to 20 mg/day resulting in resolution of symptoms and stabilization of her hemoglobin level. Discussion(s): We present a rare case of DBA with worsening anemia in the setting of a recent COVID-19 infection. The literature regarding the risk and complications of COVID-19 in these patients is severely limited, with no current data on disease management, outcomes, or predictors of morbidity. DBA is a rare, congenital erythroid red cell aplasia that typically presents in infancy with an estimated incidence of 5 cases per 1 million births. DBA is characterized by progressive macrocytic anemia, congenital malformations, and increased risk of endocrine dysfunction and malignancies. Glucocorticoids are the first-line therapy for DBA, although the exact mechanism of how they stimulate erythropoiesis in DBA remains unknown. In terms of patient prognosis, approximately 40% are steroid-dependent, 40% are transfusiondependent, and 20% go into remission by age 25 years. Copyright © 2023 Southern Society for Clinical Investigation.

A clinician perspective on the treatment of chronic myeloid leukemia in the chronic phase.

Tyrosine kinase inhibitors (TKIs) have vastly improved long-term outcomes for patients with chronic myeloid leukemia (CML). After imatinib (a first-generation TKI), second- and third-generation TKIs were developed. With five TKIs (imatinib, dasatinib, bosutinib, nilotinib, and ponatinib) targeting BCR::ABL approved in most countries, and with the recent approval of asciminib in the USA, treatment decisions are complex and require assessment of patient-specific factors. Optimal treatment strategies for CML continue to evolve, with an increased focus on achieving deep molecular responses. Using clinically relevant case studies developed by the authors of this review, we discuss three major scenarios from the perspective of international experts. Firstly, this review explores patient-specific characteristics that affect decision-making between first- and second-generation TKIs upon initial diagnosis of CML, including patient comorbidities. Secondly, a thorough assessment of therapeutic options in the event of first-line treatment failure (as defined by National Comprehensive Cancer Network and European LeukemiaNet guidelines) is discussed along with real-world considerations for monitoring optimal responses to TKI therapy. Thirdly, this review illustrates the considerations and importance of achieving treatment-free remission as a treatment goal. Due to the timing of the writing, this review addresses global challenges commonly faced by hematologists treating patients with CML during the COVID-19 pandemic. Lastly, as new treatment approaches continue to be explored in CML, this review also discusses the advent of newer therapies such as asciminib. This article may be a useful reference for physicians treating patients with CML with second-generation TKIs and, as it is focused on the physicians' international and personal experiences, may give insight into alternative approaches not previously considered.

Economic Evaluation of First-Line Camrelizumab for Advanced Non-small-cell Lung Cancer in China.

Background: As the first domestic PD-1 antibody approved for lung cancer in China, camrelizumab has exhibited proven effectiveness for non-small-cell lung cancer (NSCLC) patients. However, the cost-effectiveness of this new regimen remains to be investigated. Objective: To evaluate the cost-effectiveness of camrelizumab combination therapy vs. chemotherapy for previously untreated patients with advanced, non-squamous NSCLC without Alk or Egfr genomic aberrations from the perspective of China's healthcare system. Methods: Based on the CameL trial, the study developed a three-health state Markov model to evaluate the cost-effectiveness of adding camrelizumab to chemotherapy compared to chemotherapy alone in NSCLC patients. The analysis models were conducted for patients unselected by PD-L1 tumor expression (the base case) and the patient subgroup with PD-L1-expressing tumors (≥1%). Primary model outcomes included the costs in US dollars and health outcomes in quality-adjusted life-years (QALYs) as well as the incremental cost-effectiveness ratio (ICER) under a willingness-to-pay threshold of $31,500 per QALY. Additionally, a scenario analysis that adjusted within-trial crossover was employed to evaluate camrelizumab combination therapy compared to chemotherapy without subsequent use of PD1/PD-L1 antibodies. Results: Camrelizumab combination therapy was more costly and provided additional 0.11 QALYs over chemotherapy in the base case analysis (0.86 vs. 0.75 QALYs), 0.12 QALYs over chemotherapy in the subgroup analysis (0.99 vs. 0.88 QALYs), and 0.34 QALYs over chemotherapy in the scenario analysis (0.86 vs. 0.52 QALYs). Correspondingly, the ICER was $63,080 per QALY, $46,311 per QALY, and $30,591 per QALY, in the base case, the subgroup, and the scenario analysis, respectively. One-way sensitivity analyses revealed that ICERs of the base case and the subgroup analysis were most sensitive to the cost of camrelizumab, the cost of pemetrexed. Besides, the base case and subgroup analysis were more sensitive to the risk of neutrophil count decreased in the camrelizumab and the utility of stable disease, respectively. Conclusion: Although camrelizumab combination therapy is not cost-effective as first-line therapy for NSCLC patients in China in the base case, adjusting within-trial crossover would move the treatment regimen toward cost-effectiveness in the scenario analysis.