-
Frontiers in Public Health 2024In Europe, the combination of cabotegravir (CAB) with rilpivirine (RPV) has been approved as a dual injection long-acting (LA) therapy for the treatment of human...
BACKGROUND
In Europe, the combination of cabotegravir (CAB) with rilpivirine (RPV) has been approved as a dual injection long-acting (LA) therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections in adults since December 2020. Studies have shown that between 36 and 61% of people living with HIV (PLWHIV) prefer LA therapy. However, there are no real-world data on the number of people receiving LA therapy, in Germany or internationally. The aim of this study was to assess the current situation and trends in usage of LA therapy for the treatment of HIV-1 in Germany.
METHODS
Based on pharmacy prescription data derived from Insight Health, the monthly number of prescriptions for oral CAB, CAB-LA, and RPV-LA over the entire period of availability in Germany was analyzed and evaluated (May 2021 to December 2023). The number of 1st and 2nd initiation injections and subsequent maintenance injections was calculated on the basis of the prescriptions for oral CAB initiation.
RESULTS
The bimonthly schedule resulted in two growing cohorts from September 2021 with an estimated 14,523 CAB-LA prescriptions over the entire period. Accordingly, in December 2023, there were approximately 1,364 PLWHIV receiving LA therapy, of whom 1,318 were receiving maintenance therapy. Only treatments with bimonthly regimens were carried out. Accounting for people not covered by statutory health insurance (~13%), a total of ~1,600 PLWHIV were receiving LA therapy in Germany in December 2023. The average rounded annual cost of therapy in 2023 was €11,940 (maintenance therapy with initiation) and €10,950 (maintenance therapy without initiation).
CONCLUSION
To our knowledge, this is the first study of real-world use and number of people receiving LA therapy. A strength of our study is the nearly complete coverage of people with statutory health insurance in Germany. The predicted demand for LA therapy does not match the actual number of people receiving LA therapy. Although the number of PLWHIV receiving LA therapy increased steadily, they accounted for just under 2% of the estimated total number of people receiving HIV therapy in Germany in 2023, almost 2 years after the market launch. No significant increase in prescriptions is expected; on the contrary, the trend is leveling off and is unlikely to change drastically in the near future. Hence, the need for this mode of therapy in Germany appears to be limited. Follow-up studies at regular intervals on the further course would be useful and are recommended, as well as investigations into the possible reasons for the slow uptake to inform public health experts and possibly broaden treatment options.
Topics: Humans; Germany; HIV Infections; Anti-HIV Agents; HIV-1; Rilpivirine; Drug Prescriptions; Male; Adult; Female; Pyridones; Diketopiperazines
PubMed: 38873299
DOI: 10.3389/fpubh.2024.1404255 -
Hepatic Medicine : Evidence and Research 2024The hepatitis C virus (HCV) poses a significant risk to global public health and is linked to life-threatening clinical outcomes. According to the WHO, there are an... (Review)
Review
The hepatitis C virus (HCV) poses a significant risk to global public health and is linked to life-threatening clinical outcomes. According to the WHO, there are an estimated 58 million people worldwide who have a chronic hepatitis C virus (HCV) infection; there are 1.5 million new cases and more than 350,000 fatalities from HCV-related illnesses each year. Even though there are numerous diagnostic techniques, the lack of funding, inadequate healthcare infrastructure, and low public awareness of the Hepatitis C virus can make diagnosis and treatment difficult to obtain throughout the continent. The frequency of hepatitis C virus infection is highest in African nations (1-26%), raising serious concerns about the virus's impact on public health. The world's highest rate of Hepatitis C virus infection was found in Egypt, an African nation. Its nationwide hepatitis C elimination program stands out as a prime example of achievement, having screened, and treated over 60 million people, significantly reducing the disease's incidence and prevalence. Other African nations facing similar difficulties might benefit greatly from Egypt's methods, which provide valuable insights and flexible frameworks. This review aims to shed light on Egypt's successes and challenges while offering strategic recommendations to African nations to quicken their progress in eliminating hepatitis C.
PubMed: 38854483
DOI: 10.2147/HMER.S470344 -
Open Forum Infectious Diseases Jun 2024Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) offers a novel drug delivery option for persons with human immunodeficiency virus (PWH) but requires...
Patient Attitudes Toward Self- or Partner-, Friend-, or Family-Administered Long-acting Injectable Antiretroviral Therapy: A Mixed-Methods Study Across 3 Urban Human Immunodeficiency Virus Clinics.
BACKGROUND
Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) offers a novel drug delivery option for persons with human immunodeficiency virus (PWH) but requires administration every 4 or 8 weeks by a medical professional.
METHODS
To facilitate LAI antiretroviral therapy (ART) scale-up, we evaluated patient interest in alternative administration approaches via a mixed-methods, serial cross-sectional study across 3 US HIV clinics. We surveyed PWH (December 2021 to May 2022) on appeal of self- or partner/friend/family-administered LAI-CAB/RPV; multivariable ordinal logistic regression explored associated characteristics. To contextualize survey results, we thematically analyzed semi-structured interview data collected from PWH (August 2020 to July 2021) on attitudes toward out-of-clinic LAI-ART administration.
RESULTS
Among 370 surveyed PWH (median age, 46 years; 26% cisgender female, 59% Black, 56% sexual minority, 34% housing instability), self-administering LAI-CAB/RPV appealed to 67%. PWH who were White (adjusted odds ratio [aOR], 3.30 [95% confidence interval {CI}, 1.42-7.64]), stably housed (aOR, 2.16 [95% CI, 1.30-3.59]), or gay/bisexual (aOR, 1.81 [1.14-2.89]) were more likely to endorse self-administration. Fewer PWH (60%) reported partner/friend/family administration as appealing; adjusted models revealed similar sociodemographic preferences for this outcome. In 72 interviews, PWH noted that acceptability of out-of-clinic LAI-ART administration was qualified by convenience, prior injection experience, and potential fear of self-inflicted pain, dependence on others, and/or HIV disclosure.
CONCLUSIONS
In a multisite sample of PWH, self- and, to a lesser extent, partner/friend/family-administration of LAI-CAB/RPV appealed to most; however, was less appealing among populations more impacted by health disparities. Innovative LAI-ART delivery options could free up in-clinic resources to focus scale-up among marginalized populations.
PubMed: 38854389
DOI: 10.1093/ofid/ofae265 -
BMC Sports Science, Medicine &... Jun 2024Multi-ingredient pre-workout dietary supplements (MIPS), which are combinations of different ingredients acting on different physiological mechanisms, can have a...
BACKGROUND
Multi-ingredient pre-workout dietary supplements (MIPS), which are combinations of different ingredients acting on different physiological mechanisms, can have a synergistic effect and improve performance. The aim of the study was to determine the acute effects of a multi-ingredient pre-workout supplement containing: beta-alanine, taurine, caffeine, L-tyrosine, and cayenne pepper (capsaicin) on anaerobic performance.
METHODS
A randomized, crossover, single-blind study was designed. Twelve young, healthy, untrained men aged 22.4 ± 1.44 years participated in the study. The participants performed a supramaximal all-out test (20 s Wingate test) twice, day by day, in random order: test after placebo or MIPS consumption. In both trials, the following variables were measured in the exercise test: total work performed, peak power, mean power, time to reach peak power, and power decrease.
RESULTS
MIPS was found to be effective in improving peak power (p = 0.009, ES = 0.77) and mean power (p = 0.04, ES = 0.62) in the Wingate test. However, the supplement consumption did not affect the amount of total work done (p = 0.10, ES = 0.48) in the test or power decrease (p = 0.07, ES = 0.53). The data indicate, that the improvement in anaerobic power was due to a significant improvement in pedaling speed, which was manifested in a significant improvement (i.e. shortening) in time to peak power (p = 0.003, ES = 0.88).
CONCLUSION
A multi-ingredient pre-workout dietary supplement was found to be effective in improving Wingate (anaerobic) performance.
TRIAL REGISTRATION
NCT06363669, retrospectively registered on 11.04.2024 (ClinicalTrials.gov).
PubMed: 38853269
DOI: 10.1186/s13102-024-00918-1 -
Journal of Advanced Research Jun 2024Salmonella Enteritidis has brought great harm to public health, animal production and food safety worldwide. The biofilm formed by Salmonella Enteritidis plays a...
INTRODUCTION
Salmonella Enteritidis has brought great harm to public health, animal production and food safety worldwide. The biofilm formed by Salmonella Enteritidis plays a critical role in microbial cross-contamination. Small non-coding RNAs (sRNAs) have been demonstrated to be responsible for regulating the formation of biofilm. The sRNA SaaS has been identified previously, that promotes pathogenicity by regulating invasion and virulence factors. However, whether the SaaS is implicated in regulating biofilm formation in abiotic surfaces remains unclear.
OBJECTIVES
This study aimed to clarify the effect of SaaS in Salmonella Enteritidis and explore the modulatory mechanism on the biofilm formation.
METHODS
Motility characteristics and total biomass of biofilm of test strains were investigated by the phenotypes in three soft agar plates and crystal violet staining in polystyrene microplates. Studies of microscopic structure and extracellular polymeric substances (EPS) of biofilm on solid surfaces were carried out using confocal laser scanning microscope (CLSM) and Raman spectra. Transcriptomics and proteomics were applied to analyze the changes of gene expression and EPS component. The RNA-protein pull-down and promoter-reporter β-galactosidase activity assays were employed to analyze RNA binding proteins and identify target mRNAs, respectively.
RESULTS
SaaS inhibits biofilm formation by repressing the adhesion potential and the secretion of EPS components. Integration of transcriptomics and proteomics analysis revealed that SaaS strengthened the expression of the flagellar synthesis system and downregulated the expression of curli amyloid fibers. Furthermore, RNA-protein pull-down interactome datasets indicated that SaaS binds to Hfq (an RNA molecular chaperone protein, known as a host factor for phage Qbeta RNA replication) uniquely among 193 candidate proteins, and promoter-reporter β-galactosidase activity assay confirmed target mRNAs including hilD, cheA, and csgA.
CONCLUSION
SaaS inhibits the properties of bacterial mobility, perturbs the secretion of EPS, and contributes to the inhibition of biofilm formation by interacting with target mRNA (hilD, cheA, and csgA) through the Hfq-mediated pathway.
PubMed: 38852803
DOI: 10.1016/j.jare.2024.06.008 -
Medicina Clinica Jun 2024The present systematic review analyses the role of soluble fms-like tyrosine kinase-1 (sFLT-1) as an indirect biomarker of endothelial dysfunction in sepsis or septic...
INTRODUCTION
The present systematic review analyses the role of soluble fms-like tyrosine kinase-1 (sFLT-1) as an indirect biomarker of endothelial dysfunction in sepsis or septic shock from articles published in PubMed between 2010 and March 2022.
MATERIALS AND METHODS
A systematic review of studies studying sFLT-1 monitoring in intensive care units in adults with sepsis or septic shock vs. controls for sepsis diagnosis and prognosis has been carried out (PROSPERO CRD42023412929 Registry).
RESULTS
The endothelial dysfunction of sepsis is one of the keys to the development of the disease. VEGF binds to sFLT-1 acting as a competitive inhibitor of VEGF signalling in endothelial cells and thus neutralizes its pro-inflammatory effects. Endothelial dysfunction is reflected in increased sFLT-1 levels. High values of sFLT-1 were used for the differential diagnosis of sepsis versus other inflammatory pathologies, septic shock versus other types of shock, were elevated over time, estimation of disease prognosis, correlation with sepsis severity, organ dysfunction, and mortality prediction.
CONCLUSIONS
It is evident that sepsis is based on endothelial dysfunction. sFLT-1 is one of the main biomarkers of microvascular alteration and is a predictive diagnostic and prognostic biomarker.
PubMed: 38851948
DOI: 10.1016/j.medcli.2024.03.027 -
International Immunopharmacology Jul 2024This report drives insights for the investigation of the underlying mechanisms of antitumor effects of Teucrium ramosissimum (TrS) essential oil (EO) that elicits colon...
This report drives insights for the investigation of the underlying mechanisms of antitumor effects of Teucrium ramosissimum (TrS) essential oil (EO) that elicits colon tumor protection via activation of cell death machinery. A study of the aerial part phytocomplex was performed by FTIR spectra and GC/MS. In vivo colon carcinogenesis induced by LPS was carried out using mouse model. HCT-116 cells were coincubated with TrS EO and TRAIL-resistant cancer cells, and then cell lysates were assessed using Western blotting technique for death and decoy receptor expression. TrS essential oil potentiates TRAIL-mediated apoptosis cell death of HCT-116 as detected by PARP cleavage and caspase activation. Further data suggest that TrS up-regulates DR 5/4 expression, and down-regulates DcRs expression. Additionally, TrS potentiates apoptosis in TRAIL-resistant tumor cells through induction of MAPK signalling components, including ERK, p38 kinase, JNK, and activation of CHOP, and SP1, involved in DR5 expression. Moreover, Teucrium EO phytoconstituents mediate HCT-116 cells apoptosis by evoking cell cycle arrest at the G1 and G2/M phase through diminishing the expression of cyclin D1 acting as a potent multitargeted factors of inhibition of JAK/STAT oncogenic signaling pathway. These results demonstrate that TRAIL-induced apoptosis enhancing effect of TrS mediated through proto-oncogene expression in HCT-116. TrS administered intragastrically is able to prevent tumor of colon by stopping carcinogenesis process and impede tumor cell growth in in vivo analysis promoted by LPS. On the whole, our results revealed that TrS is an effective antitcancer agent through the induction of transcription factor and kinases, either are needed to trigger Apo2L receptors.
Topics: Humans; Animals; Oils, Volatile; HCT116 Cells; TNF-Related Apoptosis-Inducing Ligand; Colorectal Neoplasms; Mice; Apoptosis; Teucrium; Proto-Oncogene Mas; Mice, Inbred BALB C; Receptors, TNF-Related Apoptosis-Inducing Ligand; Male; Antineoplastic Agents, Phytogenic; Lipopolysaccharides
PubMed: 38850792
DOI: 10.1016/j.intimp.2024.112405 -
Scientific Reports Jun 2024Knowledge, Attitude, and Practice (KAP) survey, as an effective measure tool, is of practical significance for identifying the susceptible population in high-incidence...
Knowledge, Attitude, and Practice (KAP) survey, as an effective measure tool, is of practical significance for identifying the susceptible population in high-incidence regions of tuberculosis (TB). We aim to identify the health education targeted susceptible population of TB and discuss the acting pathway of KAP in Ningxia. A multistage random sampling method was used to conduct a face-to-face questionnaire survey for residents. The latent class analysis (LCA) model was used to classify susceptible populations of TB, and the structural equation modeling (SEM) model was also employed to investigate the interaction mechanisms of KAP (mediation analysis). We further applied the ordered logistic regression model to explore the associated factors. A total of 973 residents were enrolled, 70.6% were male, aged from 16 to 89. The LCA analysis demonstrated that 3 categories of susceptible populations of TB ("overall good", "positive attitude" and "overall poor") have optimal goodness of fit (BIC = 7889.5, Entropy = 0.923). SEM model indicated that the attitude plays a significant mediation effect from knowledge to practice toward TB (an indirect effect of 0.038, and a direct effect of 0.138). The ordered logistic regression results found that age, sex, marital status, education level, occupation, family income, self-perceived health status, having a family member or friend with TB, and knowing the DOTS strategy were significantly associated with classifications of KAP level towards TB. Based on the LCA model, we accurately classified the susceptible population of TB into 3 groups with different degrees of KAP. We found that TB attitude plays a mediating role between knowledge and practice. Therefore, we should pay more attention and carry out targeted health education in the community to these populations with overall poor KAP towards TB, and develop effective strategies and measures to realize the End TB Plan.
Topics: Humans; Male; Female; Middle Aged; Adult; China; Adolescent; Aged; Tuberculosis; Health Knowledge, Attitudes, Practice; Young Adult; Health Education; Aged, 80 and over; Surveys and Questionnaires
PubMed: 38844544
DOI: 10.1038/s41598-024-63961-5 -
Discover Oncology Jun 2024Gastric precancerous lesions are a critical stage in the development of gastric cancer or gastric adenocarcinoma, and their outcome plays an important role in the...
BACKGROUND
Gastric precancerous lesions are a critical stage in the development of gastric cancer or gastric adenocarcinoma, and their outcome plays an important role in the malignant progression of gastric cancer. Coptidis Rhizoma has a good effect on Gastric precancerous lesions. However, the specific mechanisms of its action remain incompletely elucidated.
METHODS
Network pharmacology and molecular docking techniques were used to explore the active ingredients and molecular mechanism of Coptidis Rhizoma in treating gastric precancerous lesions. The active compounds of Coptidis Rhizoma and their potential gastric precancerous lesions related targets were obtained from TCMSP, GeneCards, and OMIM databases. An interaction network based on protein-protein interactions (PPIs) was constructed to visualize the interactions between hub genes. Analysis of GO enrichment and KEGG pathway were conducted using the DAVID database. An investigation of interactions between active compounds and potential targets was carried out by molecular docking. Finally, animal experiments were conducted to verify the effect and mechanism of Coptidis Rhizoma in treating precancerous lesions of gastric cancer.
RESULTS
A total of 11 active compounds and 95 anti-gastric precancerous lesions targets of Coptidis Rhizoma were screened for analysis. GO enrichment analysis showed that the mechanism of Coptidis Rhizoma acting on gastric precancerous lesions involves gene expression regulation and apoptosis regulation. KEGG pathway enrichment analysis showed that Coptidis Rhizoma against gastric precancerous lesions involving the AKT /HIF-1α/VEGF signalling pathway. Molecular docking simulations indicated potential interactions between these compounds and core targets involved in anti-gastric precancerous lesions activity. In addition, it was confirmed in vivo that Berberine and Coptidis Rhizoma may reverse atrophy and potential intestinal metaplasia by inhibiting the expression of p-AKT, HIFA, and VEGF.
CONCLUSION
Bioactive compounds in Coptidis Rhizoma have the potential to prevent atrophy and intestinal metaplasia. These compounds function by regulating the proteins implicated in AKT /HIF-1α/VEGF signalling pathways that are crucial in gastric epithelial cell differentiation, proliferation and maturation.
PubMed: 38837097
DOI: 10.1007/s12672-024-01070-5 -
Federal Practitioner : For the Health... Feb 2024Regardless of age, first-line therapy for uncomplicated hypertension includes thiazide diuretics, long-acting calcium channel blockers, and renin-angiotensin system...
BACKGROUND
Regardless of age, first-line therapy for uncomplicated hypertension includes thiazide diuretics, long-acting calcium channel blockers, and renin-angiotensin system inhibitors. Even though older adults are often at increased risk of adverse drug events, specific guidelines for choosing between different classes of antihypertensives are lacking. Given the prevalence of hypertension in older adults, clinicians should be aware of the increased risk of electrolyte disorders after the initiation of thiazide diuretics in this population.
CASE PRESENTATION
A patient aged > 90 years fell getting out of his bed 2 weeks following initiation of hydrochlorothiazide 25 mg daily medication therapy. Laboratory tests revealed a urine sodium of 35 mmol/L most consistent with hypovolemic hypoosmotic hyponatremia secondary to thiazide initiation. Hydrochlorothiazide was discontinued and sodium gradually normalized over the next 2 weeks without any other intervention.
CONCLUSIONS
Despite being recommended as first-line therapy for uncomplicated hypertension, thiazide diuretics may cause more harm than good in older adults with risk factors for thiazide-induced hyponatremia, which should be considered before initiation.
PubMed: 38835924
DOI: 10.12788/fp.0443