First-line Treatment Research Articles

Predicted Expenditure for Prescription Drugs for Multiple Sclerosis in the Italian Market Between 2023 and 2028: Results of the Oracle Project.

Multiple sclerosis (MS) is a chronic neurodegenerative disease that leads to impaired cognitive function and accumulation of disability, with significant socioeconomic burden. Serious unmet need in the context of managing MS has given rise to ongoing research efforts, leading to the launch of new drugs planned for the near future, and subsequent concerns about the sustainability of healthcare systems. This study assessed the changes in the Italian MS market and their impact on the expenditures of the Italian National Healthcare Service between 2023 and 2028. A horizon-scanning model was developed to estimate annual expenditure from 2023 to 2028. Annual expenditure for MS was calculated by combining the number of patients treated with each product (clinical inputs) and the yearly costs of therapy (economic inputs). Baseline inputs (2020-2022) were collected from IQVIA® real-world data, while input estimation for the 5-year forecast was integrated with analog analyses and the insights of clinicians and former payers. The number of equivalent patients treated in 2028 in Italy was estimated at around 67,000, with an increase of 10% versus 2022. In terms of treatment pattern evolution, first-line treatments are expected to reduce their shares from 47% in 2022 to 27% in 2028, and Bruton tyrosine kinase inhibitors are expected to reach 23% of patient shares. Overall, expenditure for MS is estimated to decrease from €721 million in 2022 to €551 million in 2028, mainly due to losses of exclusivity and renegotiation of drug prices. Despite the increase in the number of patients treated for MS and the launch of new molecules that will reach high market penetration, the model confirmed sustainability for the Italian National Healthcare Service.

Combined oral contraceptive use and obesity in women with polycystic ovary syndrome. A meta-analysis of randomized clinical trials.

Polycystic ovary syndrome (PCOS) is a heterogenous endocrine condition and combined oral contraceptives (COCs) have been demonstrated to be the first-line treatment to women who do not intend to become pregnant. The combination of COCs and PCOS may or may not amplify the risks of cardiovascular events. To investigate whether surrogates for obesity may be influenced by the use of COCs containing different formulations in women with PCOS. From January 2024 a literature search was conducted in Google Scholar and Pubmed databases using PCOS, COC, and obesity terms. Hand search of randomized clinical trials in the references of obtained manuscripts was also performed. After the exclusion of reviews and articles that did not fulfill eligibility criteria, compared the results obtained before and after the use of COCs in 13 randomized clinical trials (RCTs). Random-effects model was used to estimate the standardized mean differences (SMD) and standard errors (SE). Risk of bias was examined using the Rob2 tool. Thirteen heterogeneous RCTs reported no difference in waist circumference with the use of different COC formulations (p = 0.714). On the contrary, body fat mass increased with the use of pill (p = 0.013). Waist triglyceride index and lipid accumulation product tended to be higher after the use of COCs (p = 0.073 and p = 0.064, respectively). Combined oral contraceptives with different formulations might increase fat mass accumulation in women with PCOS. Lipids may also be increased in PCOS users. Because some concerns about the quality and heterogeneity identified in various RCTs, caution should be taken before a definitive conclusion regarding the use of COCs and obesity.

Cryptorchidism: An update of advances in its diagnosis and treatment

The absence of one or both testicles in the scrotal position is defined as cryptorchidism. It occurs in 1 - 8 % of full-term newborns and up to 45 % of preterm newborns. Its detection is of great importance due to its association with fertility disorders and the risk of malignancy. The National Endocrinology Committee of the Sociedad Argentina de Pediatría decided to prepare an update document on advances in the diagnosis and treatment of cryptorchidism that contributes to the performance of pediatric practice and allows recognition of conditions that may be accompanied by cryptorchidism, but need more evaluation and referral to a specialist, such as alterations/differences in sexual development, anorchia, genetic syndromes, among others. The first-line treatment is early orchiopexy before 12 to 18 months, always in the hands of pediatric surgeons.

Chinese expert consensus on the systemic treatment of advanced clear cell renal cell carcinoma (2024 edition)

Renal cell carcinoma (RCC) accounts for approximately 2% to 3% of malignant tumors in adults, with a male-to-female ratio of approximately 1.5∶1 worldwide. It can occur in all age groups, with a peak incidence in the 60-70 age range, and the median age is approximately 64 years. The current causes of kidney cancer are still unclear, but smoking, obesity, hypertension, and some genetic factors are considered risk factors for kidney cancer development. Conducive to the gradual popularization of physical examination and screening, more and more patients with kidney cancer are being detected and treated in the early stages. However, nearly 30% of patients still have locally advanced or metastatic kidney cancer at the time of initial diagnosis. Traditional chemotherapy drugs are generally ineffective for advanced RCC, and currently, advanced RCC is mainly treated with anti-vascular and immunotherapy. At present, first-line treatment is mostly stratified based on clinical characteristics such as International mRCC Database Consortium (IMDC) prognosis risk, and there are multiple options available, including anti vascular therapy, anti-vascular combined immunotherapy, and dual immunotherapy. Subsequently, first-line treatment often selects drugs based on the composition, effectiveness, and safety of first-line treatment plans. In recent years, research has found that the molecular typing and metastasis characteristics of RCC also affect the prognosis of patients, leading to many controversies in the treatment of advanced RCC. This consensus is guided by the controversial clinical issues in the management of advanced RCC. After discussion and voting by multidisciplinary clinical experts, a consensus of 10 clinical issues has been reached. At the same time, experts recommend domestic clinical and research institutions to lead or participate in more large-scale clinical trials, providing more basis for clinical decision-making and the selection of the best beneficiaries.

Cost–effectiveness of aumolertinib as first-line treatment for EGFR-mutated advanced nonsmall-cell lung cancer

cost–effectiveness of aumolertinib as first-line treatment for EGFR-mutated advanced nonsmall-cell lung cancer

Novel immunotherapeutic approaches in gastric cancer

Abstract Gastric cancer is a malignant tumor that ranks third in cancer-related deaths worldwide. Early-stage gastric cancer can often be effectively managed through surgical resection. However, the majority of cases are diagnosed in advanced stages, where outcomes with conventional radiotherapy and chemotherapy remain unsatisfactory. Immunotherapy offers a novel approach to treating molecularly heterogeneous gastric cancer by modifying the immunosuppressive tumor microenvironment. Immune checkpoint inhibitors and adoptive cell therapy are regarded as the promising modalities in cancer immunotherapy. FDA-approved PD1 inhibitors, such as Pembrolizumab, in combination with chemotherapy, have significantly extended overall survival in gastric cancer patients and is recommended as a first-line treatment. Despite challenges in solid tumor applications, adoptive cell therapy has demonstrated efficacy against various targets in gastric cancer treatment. Among these approaches, CAR-T cell therapy research is the most widely explored and CAR-T therapy targeting claudin18.2 has shown acceptable safety and robust anti-tumor capabilities. However, these advancements primarily remain in preclinical stages, and further investigation should be made to promote their clinical application. This review summarizes the latest research on immune checkpoint inhibitors and adoptive cell therapy and their limitations, as well as the role of nanoparticles in enhancing immunotherapy.

Long-Term Survival of Patients with Adult T-Cell Leukemia/Lymphoma Treated with Amplified Natural Killer Cell Therapy

Background: Adult T-cell leukemia/lymphoma (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1) after a long latent infection. HTLV-1 induces the indolent or aggressive type of leukemia in 5% of HTLV-1 carriers. ATL, especially the aggressive type, is resistant to multi-agent chemotherapy. The indolent type often progresses to the aggressive type. Even in the most indolent-type cases, that is, smoldering ATL, the average survival time is 55.0 months. Case Presentation: Five patients with ATL were followed up for their clinical course after amplified natural killer cell (ANK) therapy. Four patients who received ANK therapy as first-line therapy achieved complete remission and showed long-term survival without aggressive conversion or relapse for more than 5 years. One patient was treated with multiagent chemotherapy due to acute exacerbation but relapsed 2 months later. She was subsequently treated with radiation and ANK therapy and survived for more than 6 years. Furthermore, ANK therapy enhanced the immune function of ATL patients to a level higher than that of normal individuals. Conclusions: ANK therapy has great potential as first-line treatment for ATL.

Testing a Consumer Wearables Program to Promote the Use of Positive Airway Pressure Therapy in Patients With Obstructive Sleep Apnea: Protocol for a Pilot Randomized Controlled Trial.

Although positive airway pressure (PAP) therapy is considered first-line treatment for obstructive sleep apnea (OSA), nonadherence is common. Numerous factors influence PAP use, including a belief that the therapy is important and effective. In theory, providing information to patients about their blood oxygen levels during sleep (which may be low when PAP is not used), juxtaposed to information about their PAP use, may influence a patient's beliefs about therapy and increase PAP use. With the advent of consumer wearable smartwatches' blood oxygen saturation monitoring capability (and the existing routine availability of PAP use data transmitted via modem to clinical dashboards), there is an opportunity to provide this combination of information to patients. This study aims to test the feasibility, acceptability, and preliminary efficacy of the Chronic Care Management With Wearable Devices in Patients Prescribed Positive Airway Pressure Therapy (mPAP), a program that augments current PAP therapy data with consumer-grade wearable device to promote self-management of PAP therapy for OSA in a pilot randomized waitlist-controlled clinical trial. This is a single-blinded randomized controlled trial. We will randomize 50 individuals with a history of OSA, who receive care from a Department of Veterans Affairs medical center in the Los Angeles area and are nonadherent to prescribed PAP therapy, into either an immediate intervention group or a waitlist control group. During a 28-day intervention, the participants will wear a study-provided consumer wearable device and complete a weekly survey about their OSA symptoms. A report that summarizes consumer wearable-provided oxygen saturation values, PAP use derived from modem data, and patient-reported OSA symptoms will be prepared weekly and shared with the patient. The immediate intervention group will begin intervention immediately after randomization (T1). Assessments will occur at week 5 (T3; 1 week after treatment for the immediate intervention group and repeat baseline for the waitlist control group) and week 11 (T5; follow-up for the immediate intervention group and 1 week after treatment for the waitlist control group). The primary outcome will be the change in 7-day PAP adherence (average minutes per night) from T1 to T3. The primary analysis will be a comparison of the primary outcome between the immediate intervention and the waitlist control groups (intention-to-treat design), using a 2-sample, 2-sided t test on change scores (unadjusted). Recruitment began in October 2023. Data analysis is expected to begin in October 2024 when all follow-ups are complete, and a manuscript summarizing trial results will be submitted following completion of data analysis. Findings from the study may provide additional insights on how patients with OSA might use patient-generated health data collected by consumer wearables to inform self-management of OSA and possibly increase their use of PAP therapy. ClinicalTrials.gov NCT06039865; https://clinicaltrials.gov/study/NCT06039865. DERR1-10.2196/60769.

The p-MYH9/USP22/HIF-1α axis promotes lenvatinib resistance and cancer stemness in hepatocellular carcinoma

Lenvatinib is a targeted drug used for first-line treatment of hepatocellular carcinoma (HCC). A deeper insight into the resistance mechanism of HCC against lenvatinib is urgently needed. In this study, we aimed to dissect the underlying mechanism of lenvatinib resistance (LR) and provide effective treatment strategies. We established an HCC model of acquired LR. Cell counting, migration, self-renewal ability, chemoresistance and expression of stemness genes were used to detect the stemness of HCC cells. Molecular and biochemical strategies such as RNA-sequencing, immunoprecipitation, mass spectrometry and ubiquitination assays were used to explore the underlying mechanisms. Patient-derived HCC models and HCC samples from patients were used to demonstrate clinical significance. We identified that increased cancer stemness driven by the hypoxia-inducible factor-1α (HIF-1α) pathway activation is responsible for acquired LR in HCC. Phosphorylated non-muscle myosin heavy chain 9 (MYH9) at Ser1943, p-MYH9 (Ser1943), could recruit ubiquitin-specific protease 22 (USP22) to deubiquitinate and stabilize HIF-1α in lenvatinib-resistant HCC. Clinically, p-MYH9 (Ser1943) expression was upregulated in HCC samples, which predicted poor prognosis and LR. A casein kinase-2 (CK2) inhibitor and a USP22 inhibitor effectively reversed LR in vivo and in vitro. Therefore, the p-MYH9 (Ser1943)/USP22/HIF-1α axis is critical for LR and cancer stemness. For the diagnosis and treatment of LR in HCC, p-MYH9 (Ser1943), USP22, and HIF-1α might be valuable as novel biomarkers and targets.

Evaluation of the efficacy and safety of first- and second-line immunotherapy in patients with metastatic colorectal cancer: a systematic review and network meta-analysis based on randomized controlled trials

BackgroundA multitude of randomized controlled trials (RCTs) conducted in both the initial and subsequent treatment settings for patients diagnosed with metastatic colorectal cancer (mCRC) have provided clinical evidence supporting the efficacy of immunotherapy with the use of immune checkpoint inhibitors (ICIs). In light of these findings, the U.S. Food and Drug Administration (FDA) has authorized the use of several ICIs in specific subpopulations of mCRC patients. Nevertheless, there remains a dearth of direct comparative RCTs evaluating various treatment options. Consequently, the most effective ICI therapeutic strategy for microsatellite-stable (MSS) subgroup and microsatellite instability (MSI) subgroup in the first- and second-line therapies remains undefined. To address this gap, the present study employs a Bayesian network meta-analysis to ascertain the most effective first- and second-line ICI therapeutic strategies.MethodsA comprehensive literature search was conducted across multiple databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, with the retrieval date ranging from the databases’ inception to August 20, 2024. A total of 875 studies were identified, and seven were ultimately included in the analysis after a screening process. A systematic review and network meta-analysis were conducted on the basis of the search results.ResultsThis comprehensive analysis, comprising seven RCTs, evaluated first-line and second-line immunotherapy regimens in 1,358 patients diagnosed with mCRC. The treatments under investigation consisted of five initial treatments, including three focusing on MSS patients and two on MSI patients, as well as two secondary immunotherapy regimens, both focusing on MSS patients. A total of 1051 individuals underwent first-line treatment, while 307 received second-line treatment. The application of ICIs proved to offer varying degrees clinical benefits when compared to standard-of-care therapy alone, both in two subgroups of the first and the second treatment phases. Of particular note is the performance of Nivolumab combination with ipilimumab, which demonstrated superior efficacy in improving progression-free survival (PFS) (HR=0.21; 95% CI, 0.13-0.34),. Moreover, the treatment demonstrated an optimal safety profile, with a relatively low risk of adverse events (OR = 0.33; 95% CI, 0.19–0.56), compared to other first-line treatment modalities for MSI subgroup. Regarding MSS subgroup, the improvement of PFS by Nivolumab plus standard-of-care (SOC) was relatively significant (HR = 0.74; 95% CI, 0.53-1.02). In the realm of second-line therapies for MSS subgroup, the administration of Atezolizumab plus SOC has proven to be an effective approach for prolonging PFS, exhibiting an HR of 0.66 (95% CI, 0.44–0.99). These findings underscore the clinical benefits and safety profiles of ICIs in the treatment of mCRC across various treatment lines.ConclusionsThe clinical application of ICIs in both first- and second-line treatment strategies for patients with mCRC yields substantial therapeutic benefits. A detailed assessment in this study indicates that first-line treatment with Nivolumab combination with ipilimumab may represent an efficacious and well-tolerated therapeutic approach for MSI subgroup. In terms of MSS subgroup in first-line therapy, Nivolumab plus SOC may be a relative superior choice. In the context of second-line therapy for MSS subgroup, it is evident that a combination of Atezolizumab and SOC represents a preferable option for enhancing PFS. Furthermore, it is noteworthy that other ICIs treatment regimens also exhibit great value in various aspects, with the potential to inform the development of future clinical treatment guidelines and provide a stronger rationale for the selection of ICIs in both first- and second-line therapeutic strategies for mCRC.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42024543400.

Clinical Profile and Histopathological Pattern of Major Salivary Gland Tumors in a Nigerian Tertiary Hospital

Abstract Background: Varieties of tumors can arise from major salivary glands primarily or secondarily. Over 30 histological subtypes have been documented by the World Health Organization, serving as a guide in diagnosis and management. Objectives: To evaluate the clinical and histological pattern of presentation of major salivary gland tumors. Materials and Methods: This is a clinical retrospective study, done at the University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria, assessing records of patients with major salivary gland tumors seen between January 2018 and December 2022. Data obtained were analyzed using Statistical Package for Social Sciences version 26. The results were presented in tables and charts and comparisons were made using the Chi-squared test. Results: Out of the 57 patients with major salivary gland tumors studied, 30 (52.6%) were benign tumors, and 27 (47.4%) were malignant tumors. About 63.2% of patients were predominantly females, whereas 36.8% were males with a male-to-female ratio of 1:1.7. The most common presenting symptom was swelling. The average duration of symptoms before presentation was 24 and 12 months for benign and malignant tumors, respectively. The parotid gland (61.4% total) was the most common site of tumor presentation for both benign and malignant tumors followed by the submandibular and sublingual the least. The most common histological variant was pleomorphic adenoma (40.4%) for benign and mucoepidermoid carcinoma (28.1%) for malignant. Surgery was the first line of treatment given. Conclusion: The observed pattern of clinical and histological presentation of major salivary gland tumors will guide clinicians on the approach for the management.

Amlodipine-Induced gingival hyperplasia in a nepalese patient experiencing high dosages: a case report

Introduction and Importance: Amlodipine is a third-generation calcium channel blocker used in the treatment of Hypertension. One of the side effects associated with amlodipine is gingival hyperplasia mostly occurring at a higher dose (10 mg). There are very few cases of gingival hyperplasia associated with amlodipine at a lower dose (5 mg) or short-term administration. Case presentation: A 51-year-old male patient with diagnosed hypertension sought medical attention for gingival swelling and bleeding from the gums while brushing. He had been under amlodipine 5 mg for 12 months, which was increased to 10 mg for the last 2 months. The history and physical examination were consistent with amlodipine-induced gingival hyperplasia. The first line of treatment consisted of discontinuation of amlodipine and substitution with another class of anti-hypertensive. Clinical discussion and conclusion: The presented case highlights the challenge of balancing economic considerations with potential side effects in the use of amlodipine for hypertension in low-income countries like Nepal. Given its availability at no cost or minimal expense, amlodipine is often initiated as a first-line therapy. However, the decision to increase the dosage to 10 mg/day, influenced by economic constraints and the drug’s affordability, raises the risk of gingival hyperplasia. This case emphasizes the importance of physicians being mindful of potential adverse effects when prescribing higher doses of amlodipine and underscores the need for continued vigilance in managing hypertension in resource-limited settings.

Excellent RAI therapeutic response on a patient presenting skull metastasis of follicular thyroid cancer after 15 years.

Bone is the second most common site of metastasis for differentiated thyroid carcinoma (DTC). Bone metastasis (BMs) occur in about 10% of patients with DTC and is observed more often in follicular thyroid carcinoma (FTC) (7-28%) than papillary thyroid carcinoma (PTC) (1-7%). Bone metastasis is associated with unfavorable clinical outcomes mainly including skeletal-related events (SREs), such as pathologic fractures, bone pain, spinal cord compressions, and hypercalcemia, which negatively impact the quality of life of patients and reduce their life expectancy. Patients with BMs from DTC require comprehensive and multimodal treatment approaches, including radioiodine (RAI) therapy, palliative care, surgery, external beam radiotherapy, and targeted drug therapy. RAI therapy is the first-line treatment, despite being rather ineffective, especially in large BMs. The response to RAI therapy, either alone or in combination with BM focal treatment depends on iodine avidity. This study reports a rare case of metachronous skull bone metastasis from FTC in a 72-year-old female patient 15 years after initial treatment. The patient had an excellent response to RAI therapy, which resulted in the abnormal uptake disappearing. Following treatment, the patient has been disease-free for six years. This case confirms that a complete response to RAI treatment for BM depends on the degree of dedifferentiation of cancer cells, which highlights the need for long-term follow-up, especially for FTC patients.

Economic evaluation of NALIRIFOX vs. nab-paclitaxel and gemcitabine regimens for first-line treatment of metastatic pancreatic ductal adenocarcinoma from U.S. perspective

BackgroundThe cost-effectiveness of NALIRIFOX as a potential new standard of care for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) has yet to be established. Our objective was to evaluate the cost-effectiveness of NALIRIFOX vs. nab-paclitaxel and gemcitabine in this indication from the perspective of U.S. public payers.MethodsA partitioned survival model was constructed from the perspective of U.S. public payers, drawing on baseline patient characteristics and vital clinical data from the NAPOLI-3 trial. Costs and utilities were sourced from publicly accessible databases and literature. A lifetime horizon was applied, with an annual discount rate of 3%. We calculated and compared cumulative costs, life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER). To evaluate the model’s robustness, sensitivity analyses, scenario analyses, and subgroup analyses were carried out. Additionally, a price simulation for the costly liposomal irinotecan was conducted to inform the pricing strategy at the given willingness to pay (WTP) threshold.ResultsIn the base-case analysis, NALIRIFOX provided an additional 0.29 QALYs with an ICER of $206,340.69 /QALY compared to nab-paclitaxel and gemcitabine, indicating it is not cost-effective at a $150,000/QALY threshold. Sensitivity analysis showed the model was most sensitive to the costs of liposomal irinotecan, capecitabine, and post-progression care. Probabilistic sensitivity analysis indicated a 17.66% probability of NALIRIFOX being cost-effective at $150,000/QALY, rising to 47.48% at $200,000/QALY. Pricing simulations suggested NALIRIFOX could become cost-effective at $150,000/QALY if the price of irinotecan liposome drops to $53.24/mg (a 14.8% reduction).ConclusionsNALIRIFOX may not be cost-effective at its current price as a first-line treatment for patients with mPDAC in the long term. The cost of liposomal irinotecan has the greatest impact. It may become cost-effective only if its cost is reduced by 14.8%, with a WTP threshold of $150,000 /QALY.

Chemotherapy combined with regorafenib and immune checkpoint inhibitors as a first-line treatment for patients with advanced biliary tract cancer: a single arm phase II trial

ObjectiveThis study aimed to investigate the efficacy, long-term prognosis and safety of combining chemotherapy with regorafenib and immune checkpoint inhibitors as first-line treatment for patients with advanced biliary tract carcinoma (BTC).MethodsIn this single arm phase II trial, twenty-nine patients with advanced BTC were included, all of whom received gemcitabine-based chemotherapy combined with regorafenib and immune checkpoint inhibitors as the first-line treatment. And the study analyzed anti-tumor efficacy, long-term prognosis, and adverse reactions.ResultsAmong the patients, 0 patient achieved complete response, 18 patients (62.1%) achieved partial response, 8 patients (27.6%) had stable disease, and 3 patients (10.3%) experienced progressive disease. The corresponding objective response rate (ORR) was 18/29 (62.1%), and the disease control rate (DCR) was 26/29 (89.7%). The median overall survival (OS) was 16.9 months (95% confidence interval [CI]: 12.0 -21.8) and the median progress free survival (PFS) was 10.2 months (95% CI: 7.8- 12.6). The 1-year OS and PFS were 65% (95% CI: 0.479-0.864) and 41% (95% CI: 0.234-0.656), respectively. The incidence of adverse reactions was 27/29 (93.1%), and the incidence of grade III/IV adverse reactions was 5/29 (17.2%).ConclusionThe combination of chemotherapy, regorafenib, and immune checkpoint inhibitors as a first-line treatment for patients with advanced BTC may has good anti-tumor efficacy without causing serious adverse reactions, and can significantly improve the long-term prognosis.

An economic model to understand the cost-effectiveness of olanzapine orally dispersible tablets (ODT) and olanzapine film coated tablets as a group compared with other oral atypical antipsychotics for treating schizophrenia in Morocco

BackgroundAntipsychotic medications are the primary treatment for schizophrenia, with olanzapine being an effective medication for schizophrenia. The economic cost for each individual with schizophrenia is high, with antipsychotic medication being a major expense. This study aims to develop an economic decision model that compares different treatment options for schizophrenia patients, including olanzapine Orally Dispersible Tablets (ODT), olanzapine [ODT + Standard Oral Tablet (SOT)], risperidone (ODT + SOT), and aripiprazole (ODT + SOT), to determine their cost-effectiveness with an objective to optimize healthcare resource allocation in Morocco.MethodsThe study used published medical literature and a clinical expert panel to develop a decision analytic model. This model was designed to capture parameters such as adherence levels, treatment discontinuation, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment-related adverse events, healthcare resource utilization, and associated costs. The main outcomes of interest included the total annual direct cost per treatment, QALYs, and incremental cost-effectiveness ratio (ICER) per 1 QALY gained. One-way and probabilistic sensitivity analyses were employed to account for parameter uncertainty.ResultsAccording to the simulation model, the ODT and ODT + SOT as a group form of olanzapine was the most effective treatment option in terms of the lowest percentages of inpatient relapse, and patients who remained stable (11% and 79% respectively) than risperidone (19% and 62% respectively) and aripiprazole ODT (26% and 50% respectively) and ODT + SOT formulation groups. Olanzapine (ODT + SOT) therapy group was cost-effective when compared to the combined group of ODT + SOT forms of risperidone [ICER: Moroccan Dirham (MAD) 103,907], and aripiprazole (ICER: MAD 65,047). Additionally, olanzapine ODT was found to be cost-effective compared to olanzapine SOT with an ICER of MAD 3921, risperidone ODT with an ICER of MAD 1,02,298, risperidone SOT with an ICER of MAD 31,088, and aripiprazole ODT or SOT formulations. All the above ICERs fall under the willingness-to-pay threshold in Morocco of MAD 250,832.40. Sensitivity analyses confirmed the reliability of the findings.ConclusionsThe model concluded that olanzapine ODT is the most cost-effective first-line treatment option for schizophrenia in Morocco when compared to other atypical antipsychotic medications in ODT and SOT formulations.

2024 UK and Ireland modified Delphi consensus on myopia management in children and young people.

This work aimed to establish the largest UK and Ireland consensus on myopia management in children and young people (CYP). A modified Delphi consensus was conducted with a panel of 34 optometrists and ophthalmologists with expertise in myopia management. Two rounds of voting took place and 131 statements were agreed, including that interventions should be discussed with parents/carers of all CYP who develop myopia before the age of 13 years, a recommendation for interventions to be publicly funded for those at risk of fast progression and high myopia, that intervention selection should take into account the CYP's hobbies and lifestyle and that additional training for eye care professionals should be available from non-commercial sources. Topics for which published evidence is limited or lacking were areas of weaker or no consensus. Modern myopia management contact and spectacles are suitable first-line treatments. The role and provision of low-concentration atropine needs to be reviewed once marketing authorisations and funding decisions are in place. There is some evidence that a combination of low-concentration atropine with an optical intervention can have an additive effect; further research is needed. Once an intervention is started, best practice is to monitor non-cycloplegic axial length 6 monthly. Research is needed to identify those at risk of progression, the long-term effectiveness of individual and combined interventions, and when to discontinue treatment when myopia has stabilised. As further evidence continues to emerge, this consensus work will be repeated to ensure it remains relevant.

CRAFITY score as a predictive marker for refractoriness to atezolizumab plus bevacizumab therapy in hepatocellular carcinoma: a multicenter retrospective study.

Although atezolizumab plus bevacizumab (Atezo/Bev) therapy has been used as the preferred first-line treatment for advanced hepatocellular carcinoma (HCC), up to 26% of patients do not achieve disease control, suggesting alternative treatments might be more beneficial for such patients. We investigated key predictors for refractoriness to Atezo/Bev therapy, particularly in the first-line setting. We retrospectively analyzed 302 patients with HCC who received Atezo/Bev therapy between October 2020 and September 2022 across nine hospitals in Japan. Refractoriness was defined as best overall response (BOR) of progressive disease or stable disease and a progression-free survival (PFS) of < 180days (RECIST v1.1). Clinical benefit was defined as BOR of partial/complete response or stable disease with PFS of ≥ 180days. Baseline characteristics and potential predictors, identified through literature review, were compared between these groups. Stratifications of overall survival (OS), and PFS were also assessed. Refractoriness was observed in 126 (41.7%) patients, while 154 (51.0%) achieved clinical benefit. Due to a significant association between the treatment line and refractory rate, the subsequent analysis focused on the first-line cohort (n = 214; 72 [33.6%] patients showed refractoriness). Among 13 potential predictors, the CRP and AFP in immunotherapy (CRAFITY) score had the best predictive performance, with refractory rates of 24.6%, 44.6%, and 57.9% in CRAFITY-0, 1, and 2 patients, respectively (p < 0.001). OS and PFS were also well-stratified by this scoring system. Approximately one-third of patients were refractory to first-line Atezo/Bev therapy. The CRAFITY score demonstrated superior performance in predicting refractoriness.

Emergency Department and Critical Care Use of Clevidipine for Treatment of Hypertension in Patients with Acute Stroke.

Clevidipine is a parenteral dihydropyridine calcium channel blocker that received Food and Drug Administration (FDA) approval in 2008 for the reduction of blood pressure (BP) when oral therapy is not feasible or not desirable. Soon after approval, our institution incorporated clevidipine into protocols for management of hypertension among acute stroke patients, based on the drug's rapid onset of action and straightforward titration to goal. A subsequent retrospective review of its use in otherwise alteplase-eligible ischemic stroke patients with BP greater than 185/110 mmHg (n=32, in 2014) revealed that clevidipine in that setting demonstrated the shortest median time to BP control, the shortest median door to alteplase administration time, and the lowest administered volume of any parenteral antihypertensive used. As a result, clinical protocols in our institution were modified to make clevidipine first-line antihypertensive in both ischemic and hemorrhagic acute stroke. In this study we report our institution's experience with clevidipine in acute stroke, comprising the largest such report to date. . We conducted a retrospective chart review of all acute stroke patients who received clevidipine in the Emergency Department (ED) or intensive care unit (ICU) (n=295) for the management of clinically significant hypertension between January 1, 2015 and December 31, 2017. Metrics analyzed included target (goal) BP for thrombolysis eligibility among patients intended for lytic therapy according to stroke management guidelines in effect at the time of care. The median time for initial parenteral antihypertensive Dose-to-Goal (DTG) BP for all ischemic stroke patients (both those intended for and those not intended for lytic therapy) with complete data (n= 71 of 204) was 15 minutes; median time for Door-to-IV-alteplase administration for ischemic stroke patients with complete data (n=14 of 34 treated patients) was 59 minutes. The median time for initial parenteral antihypertensive DTG BP for all hemorrhagic stroke patients with complete data (n=33 of 91 treated patients) was 39 minutes. We conclude that the salutary findings of the initial small study are valid across a larger patient sample of all acute stroke types. Based on these data, clevidipine is shown to be safe, consistent, and effective in the treatment of acute hypertension in ischemic and hemorrhagic stroke events, and is a reasonable first-line treatment option for acute hypertension in this setting.

Pharmacomechanical thrombectomy in management of pulmonary embolism

BackgroundAcute pulmonary embolism is recorded as one of the most common and critical medical conditions, resulting in a notable mortality rate requiring a multidisciplinary management. In this series, we address the management of massive and sub-massive pulmonary embolism utilizing catheter-based intervention, in particular the conjunction of mechanical thrombus disruption and aspiration with pharmacological thrombolysis (pharmacomechanical thrombectomy).Results37 patients were diagnosed with massive and sub-massive pulmonary embolism based on the clinical and radiological findings. Pre-procedural vital parameters were obtained, including oxygen saturation, pulse rate, and blood pressure. Under continuous monitoring and conscious sedation, a pulmonary angiography via right common femoral vein access was performed for pre-procedural assessment. Pharmacomechanical thrombectomy was performed using the AngioJet Ultra System (Boston Scientific). Using the power pulse option, a fibrinolytic agent was infused into the thrombus. After 5–10 min, mechanical thrombectomy is performed with a maximum 3 passes through the thrombus. This technique is performed in the main pulmonary artery and lower branch. The procedure is repeated on the other side. The maximum duration of thrombectomy is 2–3 min on each side. Procedure success was based on improvement of vital signs and not related to post-procedure angiographic findings. All patients showed immediate improvement of vital signs (blood pressure, 02 saturation, and pulse rate) with progressive improvement over the following days. There were no procedure-related complications.ConclusionPharmacomechanical thrombectomy is a safe and effective technique in the treatment of massive and submassive pulmonary embolism. It can be a first-line treatment even in patients without absolute contraindication to systemic thrombolysis.