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BMC Infectious Diseases Jun 2024Healthcare-Associated Infections (HAIs) are a global public health issue, representing a significant burden of disease that leads to prolonged hospital stays,...
BACKGROUND
Healthcare-Associated Infections (HAIs) are a global public health issue, representing a significant burden of disease that leads to prolonged hospital stays, inappropriate use of antimicrobial drugs, intricately linked to the development of resistant microorganisms, and higher costs for healthcare systems. The study aimed to measure the prevalence of HAIs, the use of antimicrobials, and assess healthcare- and patient-related risk factors, to help identify key intervention points for effectively reducing the burden of HAIs.
METHODS
A total of 28 acute care hospitals in the Lombardy region, Northern Italy, participated in the third European Point Prevalence Survey (PPS-3) coordinated by ECDC for the surveillance of HAIs in acute care hospitals (Protocol 6.0).
RESULTS
HAIs were detected in 1,259 (10.1%, 95% CI 9.6-10.7%) out of 12,412 enrolled patients. 1,385 HAIs were reported (1.1 HAIs per patient on average). The most common types of HAIs were bloodstream infections (262 cases, 18.9%), urinary tract infections (237, 17.1%), SARS-CoV-2 infections (236, 17.0%), pneumonia and lower respiratory tract infections (231, 16.7%), and surgical site infections (152, 11.0%). Excluding SARS-CoV-2 infections, the overall prevalence of HAIs was 8.4% (95% CI 7.9-8.9%). HAIs were significantly more frequent in patients hospitalized in smaller hospitals and in intensive care units (ICUs), among males, advanced age, severe clinical condition and in patients using invasive medical devices. Overall, 5,225 patients (42.1%, 95% CI 41.3-43.0%) received systemic antimicrobial therapy. According to the WHO's AWaRe classification, the Access group accounted for 32.7% of total antibiotic consumption, while Watch and Reserve classes accounted for 57.0% and 5.9% respectively. From a microbiological perspective, investigations were conducted on only 64% of the HAIs, showing, however, a significant pattern of antibiotic resistance.
CONCLUSIONS
The PPS-3 in Lombardy, involving data collection on HAIs and antimicrobial use in acute care hospitals, highlights the crucial need for a structured framework serving both as a valuable benchmark for individual hospitals and as a foundation to effectively channel interventions to the most critical areas, prioritizing future regional health policies to reduce the burden of HAIs.
Topics: Humans; Italy; Male; Cross Infection; Female; Aged; Middle Aged; Prevalence; Adult; Aged, 80 and over; Adolescent; Young Adult; Hospitals; Child, Preschool; Child; Risk Factors; Infant; Infant, Newborn; COVID-19; Anti-Infective Agents; Anti-Bacterial Agents; Surveys and Questionnaires; Urinary Tract Infections
PubMed: 38918691
DOI: 10.1186/s12879-024-09487-7 -
Asian Pacific Journal of Cancer... Jun 2024Tongue cancer is the most prevalent type of oral cancer. Recently, natural compounds have been considered important resources for several anticancer drugs. Thymoquinone...
BACKGROUND
Tongue cancer is the most prevalent type of oral cancer. Recently, natural compounds have been considered important resources for several anticancer drugs. Thymoquinone (TQ) exhibits a potent anti-cancer effect. 5-Fluorouracil (5-FU) is a chemotherapeutic drug that has been utilized in the treatment of cancer. Recently, combination therapy has gained popularity as a treatment option for patients with cancer.
OBJECTIVES
The present study was carried out to assess the cytotoxic effect of 5-Fluorouracil (5-FU), Thymoquinone (TQ), and their combination on tongue squamous cell carcinoma cell line (HNO-97).
METHODS
Tongue carcinoma cell line (HNO-97) was maintained in cultured flasks and the cells were divided into four groups; group Ι: control untreated group, group ΙΙ: HNO-97-treated cells with different concentrations of 5-FU from 0.5 µM/ml to 3µM/ml, group ΙIΙ: HNO-97-treated cells with different concentrations of TQ from 7.25µM/ml to 23.05µM/ml, and group ΙV: HNO-97-treated cells with both 5-FU and TQ in serial concentrations till (IC50) in a dose of 27.44 µM/ml. Determination of the cytotoxic effect of the tested agents on the HNO-97 cell line was done using methyl thiazole tetrazolium assay, nuclear morphometric analysis, microscopic examination, and annexin-v/ propidium iodide staining assay.
RESULT
The findings revealed that the cytotoxic effect of 5-FU, TQ, and their combination on tongue squamous cell carcinoma cell line (HNO-97) was dose-dependent. The microscopic examination revealed that 5-FU, TQ alone, or their combination induced apoptotic cell death. P-value < 0.05 was statistically significant.
CONCLUSION
The combination of 5-FU and TQ produced a marked cytotoxic effect on HNO-97 cells.
Topics: Humans; Fluorouracil; Benzoquinones; Tongue Neoplasms; Carcinoma, Squamous Cell; Apoptosis; Cell Proliferation; Tumor Cells, Cultured; Antineoplastic Combined Chemotherapy Protocols; In Vitro Techniques; Cell Line, Tumor; Drug Synergism
PubMed: 38918680
DOI: 10.31557/APJCP.2024.25.6.2169 -
Asian Pacific Journal of Cancer... Jun 2024Cytochrome P450 (CYP) are phase I metabolizing enzymes involved in detoxification of chemotherapeutic agents. Among the CYP gene family, including CYP1A1, CYP1B1, CYP2C,...
BACKGROUND
Cytochrome P450 (CYP) are phase I metabolizing enzymes involved in detoxification of chemotherapeutic agents. Among the CYP gene family, including CYP1A1, CYP1B1, CYP2C, CYP2D, CYP2E and CYP17, their significance in cancer susceptibility is well established. However, there remains limited understanding regarding the polymorphisms of CYP2C19*2 and CYP17 and their potential correlation with chemotherapy-induced toxicity reactions in breast cancer (BC) patients. In this study we intended to identify the association of CYP2C19*2 and CYP17 gene polymorphisms on drug response as well as toxicity reactions in BC patients undergoing adriamycin/paclitaxel based chemotherapy within Indian population.
METHODS
Two hundred BC patients receiving adriamycin and paclitaxel chemotherapy were enrolled in this study and chemotherapy induced hematological and non-hematological toxicity reactions were noted. The polymorphisms of CYP2C19*2 (681G>A) and CYP17 (34T>C) isoforms of cytochrome p 450 gene was studied by PCR and RFLP analysis.
RESULTS
The univariate logistic regression analysis revealed significant associations between CYP2C19*2 (681 G>A) polymorphisms with hematological toxicities i.e., anemia (OR=9.77, 95% CI: 2.84-33.52; p=0.0003), neutropenia (OR=5.72, 95% CI: 1.75-18.68; p=0.003), febrile neutropenia (OR=4.29, 95% CI: 1.32-13.87; p=0.014) and thrombocytopenia (OR=5.86, 95% CI: 1.15-29.72); p=0.032) in BC patients. Additionally BC patients treated with adriamycin exhibited significant association between CYP2C19*2 polymorphism with chemotherapy induced nausea and vomiting (CINV) (OR=99.73, 95% CI: 5.70-174.64); p=0.001), fatigue (OR=83.29, 95% CI: 4.77-145.69); p=0.002), bodyache (OR=4.44, 95% CI: 1.24-15.91); p=0.021) and peripheral neuropathy (OR=12.00, 95% CI: 1.80-79.89); p=0.010. Furthermore, the regression analysis indicated an association between CYP17 with body ache (OR=2.77, 95% CI: 1.21-6.34; p=0.015) and peripheral neuropathy (OR=3.90, 95% CI: 1.59-9.53; p=0.002) in BC patients treated with paclitaxel chemotherapy.
CONCLUSION
The findings obtained from this study illustrated significant association of CYP2C9*2 (681G>A) polymorphism with adreamicin based chemotherapy induced toxicities and CYP17 (34T>C) polymorphism with paclitaxel induced bodyache and peripheral neuropathy in BC patients.
Topics: Humans; Female; Breast Neoplasms; Paclitaxel; Doxorubicin; Cytochrome P-450 CYP2C19; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Polymorphism, Single Nucleotide; Adult; Steroid 17-alpha-Hydroxylase; Prognosis; Follow-Up Studies; Aged
PubMed: 38918659
DOI: 10.31557/APJCP.2024.25.6.1977 -
Asian Pacific Journal of Cancer... Jun 2024The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without substantially increasing the required sample size. In view of the considerable preclinical evidence for Curcumin and Metformin in preventing the development and progression of head and neck squamous cell carcinoma (HNSCC), this study describes the protocol of the clinical trial towards applying the drug combination in prevention of second primary tumors.
METHODS
We have applied the trial design to a large phase IIB/III double-blind, multi-centric, placebo-controlled, randomized clinical trial to determine the safety and efficacy of Metformin and Curcumin in the prevention of second primary tumours (SPT) of the aerodigestive tract following treatment of HNSCC (n=1,500) [Clinical Registry of India, CTRI/2018/03/012274]. Patients recruited in this trial will receive Metformin (with placebo), Curcumin (with placebo), Metformin, and Curcumin or placebo alone for a period of 36 months. The primary endpoint of this trial is the development of SPT, while the secondary endpoints are toxicities associated with the agents, incidence of recurrence, and identifying potential biomarkers. In this article, we discuss the 2x2 factorial design and how it applies to the head and neck cancer chemoprevention trial.
CONCLUSION
2x2 factorial design is an effective trial design for chemoprevention clinical trials where the effectiveness of multiple interventions needs to be tested parallelly.
Topics: Humans; Metformin; Curcumin; Head and Neck Neoplasms; Double-Blind Method; Neoplasms, Second Primary; Male; Female; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Combined Chemotherapy Protocols; Middle Aged; Adult; Follow-Up Studies; Prognosis; Research Design; Aged; Randomized Controlled Trials as Topic
PubMed: 38918654
DOI: 10.31557/APJCP.2024.25.6.1935 -
The Journal of Clinical Psychiatry Jun 2024To test esmethadone (REL-1017) as adjunctive treatment in patients with major depressive disorder (MDD) and inadequate response to standard antidepressants. In this... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and Safety of Esmethadone (REL-1017) in Patients With Major Depressive Disorder and Inadequate Response to Standard Antidepressants: A Phase 3 Randomized Controlled Trial.
To test esmethadone (REL-1017) as adjunctive treatment in patients with major depressive disorder (MDD) and inadequate response to standard antidepressants. In this phase 3, double-blind, placebo-controlled trial, outpatients with MDD () were randomized to daily oral esmethadone (75 mg on day 1, followed by 25 mg daily on days 2 through 28) or placebo between December 2020 and December 2022. The primary efficacy measure was change from baseline (CFB) to day 28 in the Montgomery-Asberg Depression Rating Scale (MADRS) score. The intent-to-treat (ITT) population included all randomized participants. The per-protocol (PP) population included completers without major protocol deviations impacting assessment. Post hoc analyses included participants with severe depression (baseline MADRS score ≥35). For the ITT analysis (n = 227), mean CFB was 15.1 (SD 11.3) for esmethadone (n = 113) and 12.9 (SD 10.4) for placebo (n = 114), with a mean difference (MD) of 2.3, which was not statistically significant ( = .154; Cohen effect size [ES] = 0.21). Remission rates were 22.1% and 13.2% ( = .076), and response rates were 39.8% and 27.2% ( = .044) with esmethadone and placebo, respectively. For the PP analysis (n = 198), mean CFB was 15.6 (SD 11.2) for esmethadone (n = 101) and 12.5 (SD 9.9) for placebo (n = 97), with an MD of 3.1 ( = .051; ES =0.29). In post hoc analyses of patients with baseline MADRS ≥35 in the ITT population (n = 112), MD was 6.9; = .0059; ES = 0.57, and for the PP population (n = 98), MD was 7.9; = .0015; ES = 0.69. Adverse events (AEs) were predominantly mild or moderate and transient, with no significant differences between groups. The primary end point was not met. Esmethadone showed stronger efficacy in PP than in ITT analyses, with the discrepancy not attributable to AEs impacting treatment adherence. Significant efficacy occurred in post hoc analyses of patients with severe depression. Esmethadone was well tolerated, consistent with prior studies. ClinicalTrials.gov identifier: NCT04688164.
Topics: Humans; Depressive Disorder, Major; Male; Adult; Female; Double-Blind Method; Middle Aged; Antidepressive Agents; Depressive Disorder, Treatment-Resistant; Treatment Outcome; Drug Therapy, Combination
PubMed: 38917366
DOI: 10.4088/JCP.24m15265 -
Rhode Island Medical Journal (2013) Jul 2024The molecular pathogenesis of exocrine pancreatic cancer involves mutations K-RAS, TP53, CDKN2A, and SMAD4. The KRAS oncogene leads to constitutively active tumor cell... (Review)
Review
The molecular pathogenesis of exocrine pancreatic cancer involves mutations K-RAS, TP53, CDKN2A, and SMAD4. The KRAS oncogene leads to constitutively active tumor cell proliferation and is present in 90% of unresectable or metastatic pancreatic adenocarcinomas. Of these, the G12C variant of K-RAS genes accounts for 1-2% of mutations. A 65-year-old woman initially diagnosed with T3N0M0 pancreatic adenocarcinoma, underwent six cycles of neoadjuvant chemotherapy with mFOLFIRINOX followed by Whipple procedure. Her pathological stage was T4N2. She then received adjuvant mFOLFIRINOX but unfortunately her disease progressed through multiple lines of chemotherapy. Molecular analysis by Next Generation Sequence(NGS) panel revealed KRAS G12C mutation. Based on this mutational status, she was started on Sotorasib to which she had clinical response lasting for about 11 months prior to disease progression. Off-label use of Sotorasib as fourth-line treatment in our patient with KRAS G12C mutated pancreatic cancer was efficacious and relatively well tolerated.
Topics: Humans; Pancreatic Neoplasms; Female; Aged; Adenocarcinoma; Triazoles; Antineoplastic Combined Chemotherapy Protocols; Proto-Oncogene Proteins p21(ras); Pyrimidines; Mutation; Antineoplastic Agents; Irinotecan; Oxaliplatin; Fluorouracil; Leucovorin; Off-Label Use; Piperazines; Pyridines
PubMed: 38917307
DOI: No ID Found -
PloS One 2024Sickle cell disease (SCD) is an inherited blood disorder that affects approximately 100,000 Americans, primarily from underrepresented racial minority populations, and...
Study protocol for ADHERE (Applying Directly observed therapy to HydroxyurEa to Realize Effectiveness): Using small business partnerships to deliver a scalable and novel hydroxyurea adherence solution to youth with sickle cell disease.
Sickle cell disease (SCD) is an inherited blood disorder that affects approximately 100,000 Americans, primarily from underrepresented racial minority populations, and results in costly, multi-organ complications. Hydroxyurea, the primary disease-modifying therapy for SCD, is effective at reducing most complications; however, adherence to hydroxyurea remains suboptimal and is the primary barrier to clinical effectiveness. Video directly observed therapy (VDOT) has shown promise as an adherence-promoting intervention for hydroxyurea, yet previous VDOT trials were limited by high attrition from gaps in technology access, use of unvalidated adherence measures, and healthcare system limitations of delivering VDOT to patients. As such, we fostered a small business partnership to compare VDOT for hydroxyurea to attention control to address previous shortcomings, promote equitable trial participation, and maximize scalability. VDOT will be administered by Scene Health (formerly emocha Health) and adherence monitoring will be performed using a novel electronic adherence monitor developed to meet the unique needs of the target population. Adolescent and young adult patients as well as caregivers of younger patients (<11 years of age) will be recruited. In addition to visit incentives, all participants will be offered a smartphone with a data plan to ensure all participants have equal opportunity to complete study activities. The primary objectives of this pilot, multi-center, randomized controlled trial (RCT) are to assess retention and sustained engagement and to explore needs and preferences for longer-term adherence monitoring and interventions. This RCT is registered with the National Institutes of Health (NCT06264700). Findings will inform a future efficacy RCT applying VDOT to hydroxyurea to address adherence gaps and improve outcomes within this vulnerable population.
Topics: Humans; Anemia, Sickle Cell; Hydroxyurea; Adolescent; Child; Medication Adherence; Young Adult; Antisickling Agents; Male; Female; Adult
PubMed: 38917111
DOI: 10.1371/journal.pone.0304644 -
PloS One 2024Non-adherence to immunosuppressive medication after kidney transplant is an important cause of graft rejection and loss. Approaches to minimization of non-adherence have...
Study protocol for the development and validation of a questionnaire evaluating predisposition to immunosuppressant medication non-adherence of kidney pre-transplant patients. The KATITA project.
Non-adherence to immunosuppressive medication after kidney transplant is an important cause of graft rejection and loss. Approaches to minimization of non-adherence have focused on the identification of episodes of medication non-adherence, but by then irreparable harm to the graft may already have occurred, and a more effective approach would be to adopt preventive measures in patients who may have difficulty in adhering to medication. The aim of this study protocol is to develop and validate a clinical questionnaire for assessing, in kidney transplant candidate patients in the pre-transplant setting, the predisposition to non-adherence to immunosuppressive medication. In this multicenter, prospective study, a pilot questionnaire in Brazilian Portuguese language, composed of Likert-scaled statements expressing patients' beliefs, behaviors and barriers regarding medication taking will be assembled from a literature review, from focus groups, and an expert panel. The pilot questionnaire will be administered to a minimum of 300 patients in kidney transplant waiting lists and exploratory factor analysis will be used for development of the definitive questionnaire. A random subsample of a minimum of 60 patients will have the scale re-administered after one month for evaluation of test-retest reliability. A multicenter, external validation study will include 364 kidney transplant candidates who will be evaluated immediately before surgery and at months 3, 6 and 12 post-transplant for assessment of concurrent validity, by comparison with two scales that assess medication non-adherence, and for determination of predictive validity using a triangulation method for assessment of medication non-adherence. Structural validity will be assessed with confirmatory factor analysis using structural equation modeling. Cross-cultural generalizability and validity will be assessed by a multicenter study, in which a translation of the scale to another language will be administered to kidney transplant candidate patients from a different culture, with a subsample being selected for test-retest. This study will be conducted in Spain with a Spanish translation of the scale.
Topics: Humans; Kidney Transplantation; Immunosuppressive Agents; Surveys and Questionnaires; Medication Adherence; Prospective Studies; Reproducibility of Results; Graft Rejection; Pilot Projects; Female; Male
PubMed: 38917103
DOI: 10.1371/journal.pone.0305953 -
Supportive Care in Cancer : Official... Jun 2024Adherence to oral anticancer treatments (OATs) is a critical issue in metastatic breast cancer (MBC) to enhance survivorship and quality of life. The study is aimed to... (Observational Study)
Observational Study
PURPOSE
Adherence to oral anticancer treatments (OATs) is a critical issue in metastatic breast cancer (MBC) to enhance survivorship and quality of life. The study is aimed to analyze the main themes and attributes related to OATs in MBC patients. This research is part of a project titled "Enhancing Therapy Adherence Among Metastatic Breast Cancer Patients" designed to produce a predictive model of non-adherence, a decision support system, and guidelines to improve adherence to OATs.
METHODS
The study consists of an exploratory observational and qualitative analysis using a focus group method. A semi-structured interview guide was developed to handle relevant OAT themes. Wordcloud plots, network analysis, and sentiment analysis were performed.
RESULTS
Nineteen female MBC patients participated in the protocol (age mean 55.95, SD = 6.87). Four main themes emerged: (theme 1) individual clinical pathway; (theme 2) barriers to adherence; (theme 3) resources to adherence; (theme 4) patients' perception of new technologies. The Wordcloud and network analysis highlighted the important role of treatment side effects and the relationship with the clinician in the modulation of adherence behavior. This result is consistent with the sentiment analysis underscoring patients experience fear of issues related to clinical values and ineffective communication and discontinuity of the doctor in charge of the patient care.
CONCLUSION
The study highlighted the key role of the individual, relational variables, and side effects as internal and external determinants influencing adherence to MBC. Finally, the opportunity offered by eHealth technology to connect with other patients with similar conditions and share experiences could be a relief for MBC patients.
Topics: Humans; Female; Breast Neoplasms; Middle Aged; Medication Adherence; Administration, Oral; Antineoplastic Agents; Focus Groups; Neoplasm Metastasis; Aged; Qualitative Research; Quality of Life
PubMed: 38916761
DOI: 10.1007/s00520-024-08639-4 -
European Journal of Anaesthesiology Jun 2024Drug challenge is the gold standard for identifying causative agents of drug allergies. Although clinical guidelines have recently been published, they do not recommend...
BACKGROUND
Drug challenge is the gold standard for identifying causative agents of drug allergies. Although clinical guidelines have recently been published, they do not recommend neuromuscular blocking agent (NMBA) drug challenges. NMBA challenges are rendered difficult by the lack of homogeneity of routine allergy work-ups and the necessity of a specialised setting. Several scenarios support NMBA challenges, such as an ambiguous allergy work-up, a high suspicion of a false-positive skin test or identification of a well tolerated alternative NMBA strategy. Furthermore, routine allergy work-ups may not recognise non-IgE mechanisms, such as IgG or MRGPRX2, whereas drug challenges may reveal them. Finally, if the culprit NMBA is not identified, subsequent anaesthesia regimens will be challenging to implement, resulting in increased risk.
OBJECTIVES
This literature review discusses the indications, strategies, doses, monitoring methods, limitations, and unresolved issues related to drug challenges for NMBAs.
DESIGN
The literature review included randomised controlled trials, observational studies, reviews, case reports, series, and comments on humans.
DATA SOURCES
Studies were retrieved from databases (PubMed) and electronic libraries (OVID, EMBASE, Scopus, etc.).
ELIGIBILITY CRITERIA
All studies that referred to the NMBA challenge were included without publication date limitations.
RESULTS
NMBA challenge may be considered in NMBA anaphylaxis patients with inconclusive or ambivalent IgE diagnostic work-up under controlled conditions (presence of anaesthetists and allergists with continuous monitoring in a secured environment). To illustrate its utility, a case report of a double NMBA challenge in a patient with NMBA cross-reactivity is presented, along with biological explorations to detect subclinical cellular activation, a novel aspect of this procedure.
CONCLUSION
Drug challenges could be implemented during the NMBA allergy work-up under strict safety conditions at specialised centres with close collaboration between anaesthetists and allergists. This could decrease uncertainty and contribute to defining a safer strategy for subsequent anaesthetic drug regimens.
PubMed: 38916219
DOI: 10.1097/EJA.0000000000002033