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Expert Review of Vaccines 2024The global measles incidence has decreased from 145 to 49 cases per 1 million population from 2000 to 2018, but evaluating the economic benefits of a second...
INTRODUCTION
The global measles incidence has decreased from 145 to 49 cases per 1 million population from 2000 to 2018, but evaluating the economic benefits of a second measles-containing vaccine (MCV2) is crucial. This study reviewed the evidence and quality of economic evaluation studies to guide MCV2 introduction.
METHODS
The systematic review of model-based economic evaluation studies was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search yielded 2231 articles, with 876 duplicates removed and 1355 articles screened, with nine studies included for final analysis.
RESULTS
Six studies reported a positive benefit-cost ratio with one resulting in net savings of $11.6 billion, and two studies estimated a 2-dose MMR vaccination program would save $119.24 to prevent one measles case, and a second dose could prevent 9,200 cases at 18 months, saving $548.19 per case. The most sensitive variables were the discount rate and vaccination administration cost.
CONCLUSIONS
Two MCV doses or a second opportunity with an additional dose of MCV were highly cost-beneficial and resulted in substantial cost savings compared to a single routine vaccine. But further research using high-quality model-based health economic evaluation studies of MCV2 should be made available to decision-makers.
PROSPERO REGISTRATION
CRD42020200669.
Topics: Humans; Cost-Benefit Analysis; Immunization Programs; Immunization, Secondary; Measles; Measles Vaccine; Measles-Mumps-Rubella Vaccine; Vaccination
PubMed: 38924461
DOI: 10.1080/14760584.2024.2367451 -
Cancer Medicine Jun 2024Pancreatic cancer (PC) first-line therapy often consists of polychemotherapy regimens, but choosing a second-line therapy after disease progression, especially following...
BACKGROUND
Pancreatic cancer (PC) first-line therapy often consists of polychemotherapy regimens, but choosing a second-line therapy after disease progression, especially following first-line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab-paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions.
METHODS
The study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice.
RESULTS
AG was well-tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second-line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first-line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first-line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second-line OS and PFS.
CONCLUSIONS
This study represents the largest real-world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first-line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first-line therapy.
Topics: Humans; Pancreatic Neoplasms; Gemcitabine; Male; Female; Deoxycytidine; Albumins; Paclitaxel; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Aged; Retrospective Studies; Prognosis; Adult; Aged, 80 and over; Treatment Outcome; Italy; Neoplasm Metastasis
PubMed: 38924262
DOI: 10.1002/cam4.7345 -
Epilepsia Open Jun 2024Perampanel belongs to a novel class of antiseizure medications (ASMs). Studies examining the effect of hemodialysis on perampanel serum levels in clinical settings are...
Perampanel belongs to a novel class of antiseizure medications (ASMs). Studies examining the effect of hemodialysis on perampanel serum levels in clinical settings are lacking. We aimed to evaluate the changes in serum perampanel levels during hemodialysis. We studied patients with seizures who received oral perampanel between April 2020 and March 2023 and whose serum concentration of perampanel was measured before and after hemodialysis. We analyzed the serum concentrations of levetiracetam and lacosamide for comparison. Fourteen patients, with a mean age of 76.1 ± 7.88 years, were included. The dose of perampanel was 2.14 ± 1.27 mg. The hemodialysis clearance rate of perampanel, levetiracetam, and lacosamide was 0 ± 13%, 69 ± 11%, and 59.6 ± 8.2%, respectively. The post-dialysis CD ratio decreased significantly with levetiracetam but not with perampanel. Adverse but acceptable effects of perampanel were observed in two patients. The serum concentrations of several ASMs have been shown to be reduced during hemodialysis. Our study revealed that the serum perampanel concentration does not decrease during hemodialysis. Owing to the low rate of adverse effects and the stability of perampanel serum concentration during hemodialysis, perampanel could be a favorable choice as an ASM for patients with seizures undergoing hemodialysis. PLAIN LANGUAGE SUMMARY: Our study looked at how hemodialysis affects the serum levels of perampanel, a new type of medication for seizures. In 14 patients who started treatment between April 2020 and March 2023, perampanel serum levels did not decrease during hemodialysis, unlike other seizure medications. This shows that perampanel can be a good option for patients with seizures who need hemodialysis, with fewer side effects compared to other medications.
PubMed: 38923803
DOI: 10.1002/epi4.12996 -
CPT: Pharmacometrics & Systems... Jun 2024Significant pharmacokinetic (PK) differences exist between different forms of valproic acid (VPA), such as syrup and sustained-release (SR) tablets. This study aimed to...
Significant pharmacokinetic (PK) differences exist between different forms of valproic acid (VPA), such as syrup and sustained-release (SR) tablets. This study aimed to develop a population pharmacokinetic (PopPK) model for VPA in children with epilepsy and offer dose adjustment recommendation for switching dosage forms as needed. The study collected 1411 VPA steady-state trough concentrations (C) from 617 children with epilepsy. Using NONMEM software, a PopPK model was developed, employing a stepwise approach to identify possible variables such as demographic information and concomitant medications. The final model underwent internal and external evaluation via graphical and statistical methods. Moreover, Monte Carlo simulations were used to generate a dose tailoring strategy for typical patients weighting 20-50 kg. As a result, the PK characteristics of VPA were described using a one-compartment model with first-order absorption. The absorption rate constant (k) was set at 2.64 and 0.46 h for syrup and SR tablets. Body weight and sex were identified as significant factors affecting VPA's pharmacokinetics. The final PopPK model demonstrated acceptable prediction performance and stability during internal and external evaluation. For children taking syrup, a daily dose of 25 mg/kg resulted in the highest probability of achieving the desired target C, while a dose of 20 mg/kg/day was appropriate for those taking SR tablets. In conclusion, we established a PopPK model for VPA in children with epilepsy to tailor VPA dosage when switching between syrup and SR tablets, aiming to improve plasma VPA concentrations fluctuations.
PubMed: 38923247
DOI: 10.1002/psp4.13191 -
Toxics Jun 2024Chiang Mai province of Thailand is known for having the highest natural background radiation in the country, as well as being recognized as one of the world's most...
Chiang Mai province of Thailand is known for having the highest natural background radiation in the country, as well as being recognized as one of the world's most polluted cities for air quality. This represents the major contributor to the development of lung cancer. This research aims to estimate the comprehensive dose of both internal and external exposure due to natural background radiation and related health perspectives in the highly polluted area of Chiang Mai. The average values of indoor radon and thoron concentrations in 99 houses over 6 months were 40.8 ± 22.6 and 17.8 ± 16.3 Bq/m, respectively. These results exceed the worldwide value for indoor radon and thoron (40 and 10 Bq/m), respectively. During burning season, the average values of indoor radon (56.7 ± 20 Bq/m) and thoron (20.8 ± 20.4 Bq/m) concentrations were higher than the world-wide averages. The radon concentration in drinking water (56 samples) varied from 0.1 to 91.9 Bq/L, with an average value of 9.1 ± 22.8 Bq/L. Most of the drinking water samples (87%) fell below the recommended maximum contamination limit of 11.1 Bq/L. The average values of natural radionuclide (Ra, Th and K) in 48 soil samples were 47 ± 20.9, 77.9 ± 29.7 and 700.1 ± 233 Bq/kg, respectively. All values were higher than the worldwide average of 35, 30 and 400 Bq/kg, respectively. The average value of outdoor absorbed gamma dose rate (98 ± 32.5 nGy/h) exceeded the worldwide average of 59 nGy/h. Meanwhile, the average activity concentrations of Ra, Th and K in 25 plant food samples were 2.7 ± 0.1, 3.2 ± 1.6 and 1000.7 ± 1.9 Bq/kg, respectively. The K concentration was the most predominant in plant foods. The highest concentrations of Ra, Th and K were found in Chinese cabbage, celery and cilantro, respectively. The total annual effective dose for residents in the study area varied from 0.6 to 4.3 mSv, with an average value of 1.4 mSv. This indicates a significant long-term public health hazard due to natural background radiation and suggests a heightened radiation risk for the residents. The excess lifetime cancer risk value (5.4) associated with natural background radiation was found to be higher than the recommended value. Moreover, the number of lung cancer cases per year per million average of 25.2 per million persons per year was in the limit range 170-230 per million people. Overall, our results will be used for future decision making in the prevention of lung cancer risk associated with natural background radiation.
PubMed: 38922108
DOI: 10.3390/toxics12060428 -
Insects Jun 2024Arthropod vectors are responsible for a multitude of human and animal diseases affecting poor communities in sub-Saharan Africa. Their control still relies on chemical...
Arthropod vectors are responsible for a multitude of human and animal diseases affecting poor communities in sub-Saharan Africa. Their control still relies on chemical agents, despite growing evidence of insecticide resistance and environmental health concerns. Biorational agents, such as the entomopathogenic fungus , might be an alternative for vector control. Recently, the isolate ICIPE 7 has been developed into a commercial product in Kenya for control of ticks on cattle. We were interested in assessing the potential of controlling not only ticks but also disease-transmitting mosquitoes and tsetse flies using cattle as blood hosts, with the aim of developing a product for integrated vector management. Laboratory bioassays were carried out with , isolate ICIPE 7 and isolate ICIPE 30, to compare efficacy against laboratory-reared . ICIPE 7 was further tested against wild and spp. Dose-response tests were implemented, period of mosquito exposure was evaluated for effects on time to death, and the number of spores attached to exposed vectors was assessed. Exposure to 10 spores/mL of ICIPE 7 for 10 min resulted in a similar mortality of as exposure to ICIPE 30, albeit at a slower rate (12 vs. 8 days). The same ICIPE 7 concentration also resulted in mortalities of tsetse flies (LT: 16 days), tick nymphs (LT: 11 days), and adult ticks (LT: 20 days). Mosquito mortality was dose-dependent, with decreasing LT of 8 days at a concentration of 10 spores/mL to 6 days at 10 spores/mL. Exposure period did not modulate the outcome, 1 min of exposure still resulted in mortality, and spore attachment to vectors was dose-dependent. The laboratory bioassays confirmed that ICIPE 7 has the potential to infect and cause mortality to the three exposed arthropods, though at slower rate, thus requiring further validation under field conditions.
PubMed: 38921163
DOI: 10.3390/insects15060449 -
Insects Jun 2024The bean flower thrip (Bagnall) is a severe pest on cowpeas and causes a 20-30% reduction in cowpeas in Hainan, China, with even complete crop failure in severe cases....
The bean flower thrip (Bagnall) is a severe pest on cowpeas and causes a 20-30% reduction in cowpeas in Hainan, China, with even complete crop failure in severe cases. Spinetoram is currently the most important pesticide against in cowpea production. In the main producing areas of cowpeas in Hainan, however, the efficacy of spinetoram against is not well known. In the present study, we employed the maximum dose bioassay to evaluate the efficacy of the mortality rates of adult thrips at F in spinetoram, freshly collected from 212 field populations of collected from 20 villages in the Yazhou District of Hainan. Our results showed that the mortality rates of these thrip populations exposed to spinetoram were from 3.31% to 100%. Among them, the mortality rates of 66.98% (142/212) of the populations exceeded 80%, while that of 33.96% (72/212) of the populations surpassed 90%. Only a small proportion of 0.47% (1/212) the populations exhibited a mortality rate below 10%, and 4.72% (10/212) displayed rates below 50%. Furthermore, significant differences were also observed in the mortality rates of thrips among different villages. Taken together, the maximum dosage bioassay method is a rapid and easily implemented approach providing valuable insights into the field efficacy of insecticides and offers guidance in determining the optimal dosage required in the field. Spinetoram is still effective against in the main producing areas of cowpeas in Hainan, but caution should be exercised in its combined use with other methods to reduce potential resistance.
PubMed: 38921127
DOI: 10.3390/insects15060412 -
Current Oncology (Toronto, Ont.) Jun 2024Immune-mediated diarrhea represents a serious complication of checkpoint inhibitor therapy, especially following ipilimumab-based treatment. Efficient diagnosis and...
Immune-mediated diarrhea represents a serious complication of checkpoint inhibitor therapy, especially following ipilimumab-based treatment. Efficient diagnosis and control of diarrhea remains an ongoing challenge. We developed an accelerated management paradigm for patients with ipilimumab-induced diarrhea. Patients who developed significant diarrhea (>five loose stools/day) were presumed to be developing immune colitis. Therapy was interrupted and patients were treated with a methylprednisolone dose pack. If diarrhea was not completely resolved, high-dose steroids and infliximab were promptly added. Only non-responding patients underwent further evaluation for infection or other causes of diarrhea. A total of 242 patients were treated with ipilimumab-based regimens. Forty-six developed significant diarrhea (19%) and thirty-four (74.4%) had a rapid resolution of diarrhea following glucocorticosteroid and infliximab treatment. The median time to resolution of diarrhea was only 8.5 ± 16.4 days. Accelerated treatment for presumed immune-mediated diarrhea resulted in the rapid control of symptoms in the majority of patients. There were no intestinal complications or deaths. Immunosuppressive therapy for diarrhea did not appear to decrease the remission rate or survival. After the control of diarrhea, most patients were able to continue their planned immunotherapy. Further testing in 11/46 patients with unresponsive diarrhea revealed additional diagnoses, allowing their treatment to be adjusted.
Topics: Humans; Ipilimumab; Diarrhea; Male; Female; Middle Aged; Immunotherapy; Aged; Algorithms; Neoplasms; Adult; Treatment Outcome
PubMed: 38920743
DOI: 10.3390/curroncol31060260 -
The Oncologist Jun 2024Daratumumab-hyaluronidase-fihj (Dara-SQ) is frequently used in the treatment of plasma cell disorders and is associated with improved outcomes. Dara-SQ was shown to be...
BACKGROUND
Daratumumab-hyaluronidase-fihj (Dara-SQ) is frequently used in the treatment of plasma cell disorders and is associated with improved outcomes. Dara-SQ was shown to be non-inferior to intravenous daratumumab (Dara-IV) in efficacy, safety, and associated with fewer administration-related reactions (ARRs). Despite the lower ARR risk with Dara-SQ, package labeling still recommends indefinite premedication. In this study, we investigated the safety of premedication discontinuation after one cycle of Dara-SQ.
MATERIALS AND METHODS
This pre-post interventional quality improvement study included all patients aged 18 years and older diagnosed with multiple myeloma or light chain (AL) amyloidosis who received at least one dose of Dara-SQ. Patients in Arm 1 received Dara-SQ per package labeling, while patients in Arm 2 had premedication omitted (excluding dexamethasone) after cycle 1. The primary endpoint was the incidence of ARR after cycle 1. Overall ARR rate and therapy time saved were also evaluated.
RESULTS
A total of 102 patients (63 in Arm 1 and 39 in Arm 2) were included. There were zero reactions in either arm after cycle 1 across 1479 Dara-SQ doses administered over a 30-month period with or without premedication omission. The overall ARR rate was 2.9% (3/102), which all occurred prior to premedication omission. Therapy timed saved from premedication omission was 194 hours in a 6-month period, equating to approximately $140 000 USD.
CONCLUSION
ARRs to Dara-SQ were rare, mild, and occurred during cycle 1 prior to premedication omission. Omission of noncorticosteroid premedication is safe, feasible, and carries substantial time and cost savings for patients and infusion centers.
PubMed: 38920281
DOI: 10.1093/oncolo/oyae158 -
HemaSphere Jun 2024Mitapivat is an investigational, oral, small-molecule allosteric activator of pyruvate kinase (PK). PK is a regulatory glycolytic enzyme that is key in providing the red...
Mitapivat is an investigational, oral, small-molecule allosteric activator of pyruvate kinase (PK). PK is a regulatory glycolytic enzyme that is key in providing the red blood cell (RBC) with sufficient amounts of adenosine triphosphate (ATP). In sickle cell disease (SCD), decreased 2,3-DPG levels increase the oxygen affinity of hemoglobin, thereby preventing deoxygenation and polymerization of sickle hemoglobin. The PK activator mitapivat has been shown to decrease levels of 2,3-DPG and increase levels of ATP in RBCs in patients with SCD. In this phase 2, investigator-initiated, open-label study (https://www.clinicaltrialsregister.eu/ NL8517; EudraCT 2019-003438-18), untargeted metabolomics was used to explore the overall metabolic effects of 8-week treatment with mitapivat in the dose-finding period. In total, 1773 unique metabolites were identified in dried blood spots of whole blood from ten patients with SCD and 42 healthy controls (HCs). The metabolic phenotype of patients with SCD revealed alterations in 139/1773 (7.8%) metabolites at baseline when compared to HCs (false discovery rate-adjusted < 0.05), including increases of (derivatives of) polyamines, purines, and acyl carnitines. Eight-week treatment with mitapivat in nine patients with SCD altered 85/1773 (4.8%) of the total metabolites and 18/139 (12.9%) of the previously identified altered metabolites in SCD (unadjusted < 0.05). Effects were observed on a broad spectrum of metabolites and were not limited to glycolytic intermediates. Our results show the relevance of metabolic profiling in SCD, not only to unravel potential pathophysiological pathways and biomarkers in multisystem diseases but also to determine the effect of treatment.
PubMed: 38919958
DOI: 10.1002/hem3.109