Drug Regimens Research Articles

A comparative in vivo study of hyperthermic intraperitoneal chemotherapy with cisplatin versus doxorubicin versus cisplatin plus doxorubicin for the treatment of intra-abdominally disseminated alveolar rhabdomyosarcoma in mice.

Treatment options for advanced intra-abdominal pediatric rhabdomyosarcoma (RMS) with peritoneal sarcomatosis (PS) include cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). However, optimal dosages and combination regimens of drugs used for HIPEC are underexplored. We aimed to evaluate the efficacy of HIPEC with cisplatin, doxorubicin, and their combination in vivo. We established PS/RMS mouse model by intraperitoneally injecting RH30 cells into NOD/LtSz-scid IL2Rγ-null mice. Two weeks post xenotransplantation, mice underwent a single HIPEC procedure at 42°C for 60minutes. Treatment groups received cisplatin (50, 100, and 150mg/m2) and doxorubicin (30, 45, and 60mg/m2), administered alone or combined. The control group underwent an intraperitoneal lavage with isotonic saline. Peritoneal cancer index (PCI) was used to quantify the extent of peritoneal tumor spread. Tissue samples were evaluated regarding proliferation (Ki-67) and apoptosis (caspase 3). Mice treated with cisplatin at 100mg/m2 (PCI of 3.875, p=.007) and 150mg/m2 (PCI of 4.556, p=.026), and doxorubicin at 30mg/m2 (PCI of 2.875, p<.001) and 45mg/m2 (PCI of 4.143, p=.021) showed reduced PCI, with the combination of cisplatin 50mg/m2 and doxorubicin 30mg/m2 showing the most prominent effect (PCI of 3.333, p<.001) compared to the control group (PCI of 8.615). Histologically, there was no difference in Ki-67 or caspase 3 expression among the groups. The cisplatin- and doxorubicin-based HIPEC significantly reduces peritoneal tumor dissemination in vivo. Further investigations are needed to explore the underlying molecular responses to optimize therapeutic strategies.

6731 Initial therapeutic effects of weekly growth hormone replacement therapy: somapacitan

Abstract Disclosure: S. Fujio: None. R. Makino: None. J. Sugata: None. T. Hanada: None. R. Hanaya: None. Introduction: In Japan, the restriction on the administration of somapacitan, a long-acting growth hormone (GH) analogue, was lifted in December 2022, allowing the drug to be administered to many patients with severe growth hormone deficiency (sGHD). [Patients and methods] We have 10 patients for whom somapacitan was started as a new drug regime and 26 patients who switched from their daily GH replacement therapy. Among these 36 patients, 21 patients (5 new cases and 16 switched cases) who were followed for more than 6 months after the start of treatment were included in the present study. We compared lipid metabolism, glucose tolerance, liver function, and quality-of-life before and after treatment with somapacitan. [Result] The study population included 12 men and 9 women with a median age of 65 years. Cases included 15 NF-PitNET, 2 Lactotroph PitNET, 2 germ cell tumor, 1 craniopharyngioma, and 1 granuloma. Starting doses of somapacitan were 1.5 mg/week for adults to 60 years of age and 1.0 mg/week for patients aged &amp;gt;60 years. In the switched cases, the median levels of T-chol dropped from 214.5 to 198.5 mg (p&amp;lt;0.05). The median levels of HbA1c dropped from 5.9 to 5.8% (p&amp;lt;0.05). In the newly prescribed cases, the median levels of γ-GTP dramatically improved from 53 to 34I U/L, but this was not statistically significant. In the newly prescribed cases, quality-of-life assessment by Adult Hypopituitarism Questionnaire; AHQ showed improvement in both psychological/social aspects and physical function, but the number of cases was small and no significant difference was obtained. Body fat percentage measured by the impedance method showed no significant change in either the switched or newly prescribed groups. There were no adverse events, but some participants commented that it was easier to forget weekly injections of somapacitan than the daily GH. [Discussion] We were able to introduce somapacitan without any major problems. In newly prescribed cases, somapacitan resulted in a significant improvement in liver function. Improvements in lipid metabolism and glucose tolerance were observed in the switched patients. Compared to the daily GH replacement therapy, somapacitan may have a higher GH replacement effect. Presentation: 6/3/2024

7745 Hirsutism in young girls, Beyond PCOS

Abstract Disclosure: I. Mishra: None. A. Baliarsinha: None. Hirsutism is excessive terminal hair that appears in a male pattern in women.Though obesity,insulin resistance and PCOS are common cause of hirsutism in young girls,suspicion of other etiologies must be made on a background of overlapping features.We describe 3 cases of young females presenting with hirsutism with varied etiologies. Case 1.16 year 11months old female presented with oligomenorrhea -3years,excessive hair growth over face -2 years.On examination,BMI was 25.2 kg/m2,Grade 2 acanthosis,A3P5B5,modified FG- 16/36,clitoral length-1.3cm and clitoral index - 70 mm2.Biochemical evaluation revealed normal thyroid function tests,s.prolactin- 23.65 ng/ml,ONDST- 1.2 mcg/dl,LH - 1.49 IU/ml,FSH- 7.44IU/ml,serum testosterone- 70ng/dl,17OHP- 7.03 ng/ml,DHEAS- 553mcg/dl and post synacthen 17OHP- 36.89 ng/ml respectively. USG abdomen &amp; pelvis was normal.HOMA-IR was 4.1. Diagnosis was LOCAH Case 2.19 year old female presented with hair growth in androgen dependent areas-5years, regular predictable menstrual cycles and was treated as a case of PCOS for 5 years with no changes in hair growth pattern.She was off therapy since 1 year prior presenting to us.On examination,BMI was 24 kg/m2,acanthosis absent,A3P5B5,modified FG- 18/36, clitoral length- 6 mm,clitoral index - 25mm2.Biochemical evaluation revealed normal thyroid function tests,s.prolactin- 22.9 ng/ml,ONDST- 0.508 mcg/dl,LH - 5.98 IU/ml,FSH- 5.29 IU/ml, serum testosterone- 23.4 ng/dl,17OHP- 1.01 ng/ml and DHEAS- 298 mcg/dl respectivelyUSG Abdomen &amp; pelvis;RO - 5.7cc,LO - 5.6 cc with B/L PCOM.Review TVS was normal.In view of discordant results DHT and luteal phase serum progesterone were done which were 80.5 pg/ml and 2.1ng/ml respectively.HOMA IR was 1.9.Diagnosis was IDIOPATHIC HIRSUTISM. Case 3.12 year old female child presented with excessive hair growth over face,chest,back and abdomen- 1yr,hoarseness of voice - 1 yr,onset of breast enlargement apprx 8 to 9yrs with non-attainment of menarche.On examination BMI was 30 kg/m2,Grade 3 acanthosis, A3P5B3,modified FG- 15/36,clitoral length- 2.8 cm &amp; clitoral index - 120 mm2. Biochemical evaluation revealed normal thyroid function tests,LH - 15.3 IU/ml,FSH- 6 IU/ml,s.prolactin- 11.2 ng/ml,ONDST- 0.38 mcg/dl,DHEAS- 161 mcg/dl,serum testosterone- 140 ng/dl,17OHP- 3.9 ng/ml and post synacthen 17OHP- 4.10 ng/ml respectively.USG abdomen-s/o PCOS with normal adrenals. In view of discordant results short DAST was done which was Testosterone(ng/dl)baseline-125;4hr-91.1, DHEAS (mcg/dl) baseline-180;4hr-188 cortisol (mcg/dl) baseline-7.04;4hr-0.95.HOMA-IR was 5.4. Diagnosis was PCOS(OVARIAN THECOSIS).Varied presentations of hyperandrogenic disorders occurs in young females.A need to revise the diagnosis must be made if no response is obtained with initial drug regimes. Presentation: 6/3/2024

Three spectrophotometric quantitative analysis of bisoprolol fumarate and telmisartan in fixed-dose combination utilizing ratio spectra manipulation methods

Hypertension is a chronic condition with multiple drug regimens. Limiting these medicines is critical to patient compliance. Therefore, bisoprolol and telmisartan were recently developed in a fixed-dose combination to control blood pressure. The UV absorption spectra of bisoprolol and telmisartan overlapped significantly. Thus, three spectrophotometric methods have been developed for simultaneous determination of bisoprolol and telmisartan without prior separation. Method A is ratio difference of ratio spectra (RD), which measures the amplitude difference between (210–224) nm for bisoprolol and between (255–365) nm for telmisartan. Method B, the first derivative of ratio spectra (1DD), measures amplitude signals at 232 and 243 nm for bisoprolol and telmisartan, respectively. Method C is the mean centering of ratio spectra (MC), which measures the mean-centered ratio spectra's values at 223 nm for bisoprolol and 245 nm for telmisartan. The applied methods showed good linearity 2–20 µg/mL for bisoprolol, 4–32 µg/mL for telmisartan, with sufficient accuracy and precision. The methods were sensitive, with LOD values of 0.243 µg/mL and 0.596 µg/mL in RD method, 0.313 µg/mL and 0.914 µg/mL in 1DD method, and 0.406 and 0.707 µg/mL in MC method for bisoprolol and telmisartan, respectively, the methods were validated per ICH criteria. The novel methods are precise and accurate and can be used for routine analysis and quality control of bisoprolol and telmisartan in pure and dosage form. Furthermore, the greenness of the approaches was evaluated using Analytical Greenness assessment (AGREE), and the suggested method received a high greenness score.

HCC spatial transcriptomic profiling reveals significant and potentially targetable cancer-endothelial interactions.

HCC is a highly vascular tumor, and many effective drug regimens target the tumor blood vessels. Prior bulk HCC subtyping data used bulk transcriptomes, which contained a mixture of parenchymal and stromal contributions. We utilized computational deconvolution and cell-cell interaction analyses to cell type-specific (tumor-enriched and vessel-enriched) spatial transcriptomic data collected from 41 resected HCC tissue specimens. We report that the prior Hoshida bulk transcriptional subtyping schema is driven largely by an endothelial fraction, show an alternative tumor-specific schema has potential prognostic value, and use spatially paired ligand-receptor analyses to identify known and novel (LGALS9 tumor-HAVCR2 vessel) signaling relationships that drive HCC biology in a subtype-specific and potentially targetable manner. Our study leverages spatial gene expression profiling technologies to dissect HCC heterogeneity and identify heterogeneous signaling relationships between cancer cells and their endothelial cells. Future validation and expansion of these findings may validate novel cancer-endothelial cell interactions and related drug targets.

P108-3 Oncology drug regimen prediction using machine learning for knowledge graph

P108-3 Oncology drug regimen prediction using machine learning for knowledge graph

Prevalence, rate, and predictors of virologic failure among adult HIV-Infected clients on second-line antiretroviral therapy (ART) in Tanzania (2018–2020): a retrospective cohort study

BackgroundAntiretroviral therapy (ART) has been proven to be highly effective in reducing the impact of human immunodeficiency virus (HIV) infection. However, as more people receive initial ART treatment, the risk of developing resistance and eventual treatment failure increases, leading to the need for second-line treatment regimens. Understanding the factors that contribute to virologic failure to second-line ART is crucial in preventing switching to the more expensive and toxic third-line regimens. This study provides information on the prevalence, rate, and predictors of virologic failure (VF) among clients on second-line ART in Tanzania.ResultsWe followed 4718 clients for 15100 person-years (PY) of observations. Of them, 1402 (29.72%) experienced virologic failure at a rate of 92.85 per 1000 PY of observations (95% CI 88.11, 97.84). Factors that were associated with VF included: having a viral load count of ≥ 1000 copies/mL during first-line ART, with a hazard ratio (HR) 4.65 (95% CI 3.57, 6.07), using lopinavir (LPV/r) as a protease inhibitor during second-line ART (HR 4.20 (95% CI 3.12, 7.10), having a CD4 count < 200 cells/mm3 during second-line ART (HR 1.89 (95% CI 1.46, 2.44), and being on ART for 13–35 months (HR 8.22 (95% CI 2.21, 30.61). Paradoxically, having a CD4 count < 200 cells/mm3 during first-line ART treatment was associated with a reduced risk of virologic failure (HR 0.77 (95% CI 0.60, 0.99).ConclusionsIn Tanzania, approximately 30% of adult clients on second-line ART experience VF at a rate of 92.71 per 1000 person-years. This high virologic failure rate underscores the urgent need for targeted interventions, such as enhancing adherence support, optimizing drug regimens, and regular viral load monitoring. These interventions will reduce the need for switching to the more costly and toxic third-line ART therapy and are also crucial for achieving the UNAIDS goal of 95% viral suppression among treated individuals by 2030.

Interplay of Statins, Clopidogrel, and Repaglinide: Unraveling the Nexus of Hypoglycemia and Myopathy in a Geriatric Type 2 Diabetes Patient: A Case Report

Abstract Background: The management of cardiovascular diseases often includes the use of statins, which, while reducing cardiovascular risk, can interact with other medications leading to significant adverse effects. This case report explores the complex interactions between atorvastatin, clopidogrel, and repaglinide, which precipitated severe hypoglycemia and myopathy in a patient with multiple comorbidities. Case Presentation: We describe a 68-year-old female with a history of type 2 diabetes mellitus, hypertension, and ischemic heart disease, who developed severe hypoglycemia and myopathy following the adjustment of her statin therapy post-cardiac diagnosis. Her treatment regimen was modified to include an increased dose of atorvastatin and the introduction of clopidogrel, shortly after which she presented with hypoglycemia and symptoms of myopathy. Investigations revealed significantly elevated muscle injury markers and magnetic resonance imaging findings consistent with myositis. Discussion: The pharmacokinetic interactions between clopidogrel with repaglinide and repaglinide with atorvastatin exacerbated by the increased dose of atorvastatin, likely led to the observed clinical manifestations. This case highlights the critical need for careful monitoring of drug interactions, especially in patients with polypharmacy. Adjustments in drug dosages and consideration of alternative medications with fewer interaction risks are essential components of managing similar cases. Conclusion: This case underscores the importance of vigilant therapeutic management and individualized patient care in the context of complex drug regimens. Understanding and anticipating drug interactions can prevent significant adverse effects and improve patient outcomes in a population at high risk of polypharmacy complications.

Time to benefit of intensive lipid lowering therapy in individuals with cardiovascular disease

The timing of the clinical benefit of intensive lipid-lowering therapy in reducing major adverse cardiovascular events (MACE) in individuals with established cardiovascular disease (CVD), both before and after the advent of novel medications (proprotein convertase subtilisin/kexin type 9 inhibitor [PCSK9i] and ezetimibe) in 2010, is unclear. To evaluate the time to benefit (TTB) from intensive lipid-lowering therapy. The investigators systematically searched for randomized controlled trials evaluating intensive lipid-lowering therapy. The primary outcome was MACEs. Utilizing reconstructed individual participant data, Weibull survival curves were fitted to estimate the TTB for specific absolute risk reduction thresholds (0.002, 0.005, and 0.01). Seven trials randomizing 92,180 adults aged between 58.2 and 63.6 years were identified. A TTB of 19.6 months (95 % confidence interval [CI]: 12.3 to 31.4) of intensive lipid-lowering was needed to prevent 1 MACE per 100 patients. Before 2010, when statin as the only option, a TTB for high-intensity statin therapy of 15.2 months (95 % CI: 6.52 to 35.5) was needed. After 2010, the TTB for PCSK9i-based, ezetimibe-based intensive lipid-lowering on a background of statin therapy was 17.7 (95 % CI: 12.2 to 25.6) and 47.3 (95 % CI: 20.4 to 110) months, respectively. In contemporary practice, to prevent 1 MACE in 100 individuals with established CVD, a TTB of 17.7 and 47.3 months was needed for PCSK9i-based and ezetimibe-based intensive lipid-lowering therapy on a background of statin therapy, respectively. The observed variations across different drug regimens highlight the need for a personalized approach to treatment decisions.

Contribution of direct InhA inhibitors to novel drug regimens in a mouse model of tuberculosis.

Isoniazid is an important first-line medicine to treat tuberculosis (TB). Isoniazid resistance increases the risk of poor treatment outcomes and development of multidrug resistance, and is driven primarily by mutations involving katG, encoding the prodrug-activating enzyme, rather than its validated target, InhA. The chemical tractability of InhA has fostered efforts to discover direct inhibitors of InhA (DIIs). In this study, we bridge the gap in understanding the potential contribution of DIIs to novel combination regimens and demonstrate a clear distinction of DIIs, like GSK693 and the newly described GSK138, from isoniazid, based on activity against clinical isolates and contribution to novel drug regimens. The results suggest that DIIs, specifically GSK138 and GSK693, could be promising partners in novel drug regimens, including those used against isoniazid-resistant TB, potentially enhancing their efficacy and/or preventing the selection of resistant mutants and supporting the continued exploration of InhA as a promising target for TB drug development.

IMPACT OF ANTIHYPERTENSIVE DRUGS ON C REACTIVE PROTEIN (HS-CRP) AND NEUTROPHIL LYMPHOCYTE RATIO (NLR)

Many studies showed the association between inflammation and Hypertension. Inflammatory markers may highlight the state of inflammation in hypertensive patients. This study aimed to investigate impact of antihypertensive drugs on high sensitive C-reactive protein (hsCRP) and neutrophil lymphocyte ratio (NLR). A comparative cross sectional study was conducted on 86 hypertensive patients attending cardiology outpatient clinic in Al-Gamhuoria Modern General Hospital, Aden, in the period from October to December 2023. Participants were divided into three groups: patients treated with mono-therapy from inhibitors of renin angiotensin aldosterone system (RAASI), patients treated with mono-therapy antihypertensive not acting on RAAS (NRAASI) and patients treed with combination of them (drug combination). Data on Age, Sex, BP level, BMI, duration of hypertension (HTN), family history of HTN, and medications used were collected. Blood samples for measuring HsCRP, neutrophils, lymphocytes were drawn. Descriptive statics and chi-square tests were used for data analysis. Almost equivalent distribution for males and females between groups, with a large proportion of the patients within each group laid in the age group 35-55 years. The median values of hypertension duration were 36, 48, and 54 months for RAASIs, NRAASIs and drug combination group, respectively. The target BP was obtained by 46.9% 45.5% and 50% of patients treated with RAASIs, NRAASIs and drug combination respectively. There was a statistically significant difference between SBP and DBP in patients with controlled BP and those with uncontrolled SBP levels and treated by different drug regimens (P=0.000 for each Bp level). There were significant differences between values of hs-CRP of patients with controlled (P=0.000) or uncontrolled (P=0.046) BP and treated with different modalities. The median differences in NLR between the groups were statistically significant; including groups of all patients P=.032, of patients having controlled BP P=0.014 as well as uncontrolled BP P=0.038. Comparing the uncontrolled of BP of the three groups we found the highest prevalence (9.3%)of patients with uncontrolled BP and had the lower level hsCRP (≤3mg /l) was in RAASIs group, while those with higher prevalence (11.6%) of uncontrolled BP and higher level of hs-CRP ( &gt;3mg/l) was in drug combination group. In conclusion, hypertensive patients treated with RAASI, NRAASI and drug combination and reached BP target showed significant reduction in hsCRP and NLR. Patients with uncontrolled BP treated with RAASIs revealed slightly lower hs-CRP than other groups. Careful selection of antihypertensive drugs may affect risks of CVD. This study recommends further prospective studies exploring the anti-inflammatory effect of antihypertensive drugs to ameliorate possible risks of cardiovascular disease.

Opportunities for Helicobacter pylori Eradication beyond Conventional Antibiotics.

Helicobacter pylori (H. pylori) is a bacterium known to be associated with a significant risk of gastric cancer in addition to chronic gastritis, peptic ulcer, and MALT lymphoma. Although only a small percentage of patients infected with H. pylori develop gastric cancer, Gastric cancer causes more than 750,000 deaths worldwide, with 90% of cases being caused by H. pylori. The eradication of this bacterium rests on multiple drug regimens as guided by various consensus. However, the efficacy of empirical therapy is decreasing due to antimicrobial resistance. In addition, biofilm formation complicates eradication. As the search for new antibiotics lags behind the bacterium's ability to mutate, studies have been directed toward finding new anti-H. pylori agents while also optimizing current drug functions. Targeting biofilm, repurposing outer membrane vesicles that were initially a virulence factor of the bacteria, phage therapy, probiotics, and the construction of nanoparticles might be able to complement or even be alternatives for H. pylori treatment. This review aims to present reports on various compounds, either new or combined with current antibiotics, and their pathways to counteract H. pylori resistance.

Administration sequences in single-day chemotherapy regimens for breast cancer: a comprehensive review from a practical perspective.

Breast cancer is one of the most prevalent malignant tumors globally, posing a severe threat to human life and health. Chemotherapy, a cornerstone in the treatment of breast cancer, often overlooks the sequence of drug administration within single-day regimens. This study aims to explore the impact of drug administration order on the efficacy and toxicity of combination chemotherapy protocols for breast cancer. Through a comprehensive review and analysis based on current evidence from evidence-based medicine, we delved into how the order of drug administration affects both efficacy and toxicity. We systematically classified and analyzed commonly used combination drug regimens, providing graded recommendations and a reasoned analysis to offer valuable references for clinical decision-making. Our findings indicate that the sequence of drug administration in complex combination chemotherapy protocols is not arbitrary but necessitates multifaceted considerations. Rational drug sequencing can maximize synergistic effects between drugs, thereby augmenting therapeutic efficacy while effectively mitigating drug-related adverse effects. Additionally, some drug labels and clinical trials have explicitly highlighted the therapeutic benefits of specific drug sequences. This study underscores the importance of considering the sequence of drug administration in clinical practice. It is recommended to prioritize the sequential drug administration according to official drug product labeling, while also considering factors such as the administration sequence from large randomized controlled trials, cell proliferation kinetics specific to cancer types, drug interactions, chronopharmacology, drug irritability, clinical experiences, and patient preferences. By taking these factors into account, the goal is to maximize treatment efficacy and minimize the occurrence of adverse reactions.

‘Saving the youth’: Children and young people as moral subjects in the Philippines’ punitive drug regime

Background The Philippines has one of the must punitive drug regimes in the world, as evidenced not just by Rodrigo Duterte’s drug war but previous anti-drug campaigns. This article examines the place of ‘the youth’ in the longstanding moral panic around drugs and drug policy in the Philippines. Methods This article uses critical discourse analysis to analyze figurations of young people across three distinct periods in the Philippines’ contemporary history: Ferdinand Marcos Sr.’s early dictatorship (1972–1975), Gloria Macapagal-Arroyo’s presidency (2001–2010), and Rodrigo Duterte’s administration (2016–2022). Results In all three periods, young people were simultaneously invoked as a group that needs saving) and as a group that needs surveillance and discipline. Further, across the three periods, both the youth and drug use were enfolded into larger socio-political discourses (e.g. Martial Law; corruption and poverty; anti-elite politics). Conclusion The ambivalence in the ways in which young people are treated in drug policy reflects and reinforces their societal construction as passive victims. Interrogating and challenging the ways in which young people figure in ‘morality politics’ can pave the way for meaningful youth engagement in drug policies and programs.

Insights of Pergularia daemia in Neurodegenerative Conditions: An Overview.

As a growing cause of mortality and morbidity, neurodegenerative diseases (NDs) are becoming increasingly prevalent throughout the world, particularly among elderly people. The symptoms of Huntington’s disease and Parkinson’s disease (PD) are characterized by the loss of neurons and the degeneration of neurons. Neurodegenerative diseases are understood to have several causes, but their causes remain a mystery. It is important to note that there are many approved drug regimens for NDs, which can be used to treat symptoms but cannot heal the condition. It may be possible to utilize natural products to prevent and treat NDs in a very positive way. Several perennial herbs grow along Indian roadsides, including Pergularia daemia (Asclepiadaceae). Thespecies can be found widely in tropical and subtropical regions. Natural medicine has developed a significant interest in this plant species, which is rich in flavonoids, glycosides, tannins, and terpenoids. Several chronic diseases, including cancer, arthritis, diabetes, and neurodegenerative disorders, have been successfully treated with these secondary metabolites. Aside from this, they have notable pharmacological properties, including analgesic, anorectic, and antioxidant properties. This review provides a synthesis of existing knowledge regarding the anti-inflammatory and neuroprotective effects of P. daemia, emphasizing its potential as a natural medicine source.

DOTTs-Database of Therapeutic Plants against Tuberculosis: Rationalizing traditional medicine for therapeutic applications

DOTTs-Database of Therapeutic Plants against Tuberculosis: Rationalizing traditional medicine for therapeutic applications

Regional diversity in drug-induced lung diseases among the USA, European Union, and Japan.

Drug-induced lung disease (DILD) is a considerable and potentially fatal adverse event with poorly understood risk factors. Large-scale, data-driven analyses investigating regional discrepancies in DILD incidence are lacking. The aim of this study was to investigate the potential association among DILD prevalence, regional differences and other factors based on large-scale data base. This retrospective observational study analyzed spontaneous adverse event reports from the FDA Adverse Event Reporting System (FAERS) database between January 2010 and December 2020. Regional disparities in DILD incidence were assessed among reports from the United States of America (USA), the European Union (EU), and Japan (JP). Using multivariate logistic regression accounting for age, sex, and reporting years, we calculated the reporting odds ratios (RORs) with 95% confidence intervals. Subgroup analyses were performed for different types of anticancer agents, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and cytotoxic agents. Regional differences in RORs were observed for anticancer drugs in reports from JP and the EU compared with those from the USA (JP, ROR 4.432; EU, ROR 1.291) and for non-anticancer drugs (JP, ROR 3.481; EU, ROR 1.086). Significantly higher RORs were observed for all anticancer drug regimens reported in JP than in the USA (TKIs, ROR 3.274; ICIs, ROR 2.170; ADCs, ROR 2.335; cytotoxic agents, ROR 3.989). The EU reports exhibited higher RORs for TKIs and cytotoxic agents than the USA reports, with no significant differences in ICIs or ADCs (TKIs, ROR 1.679; ICIs, ROR 1.041; ADCs, ROR 1.046; cytotoxic agents, ROR 1.418). The prevalence of DILD in JP, the EU, and the USA differed. These findings have important implications in evaluating the safety profiles of drugs and patient safety in drug development and clinical practice. This study is the first to identify regional differences in DILDs using a large global database.

Role of Natural Phytoconstituents as a Potential Bioenhancer of Anti-Cancer and Anti-Microbial Agents: Spotlight on the Mechanism of Action, Clinical Studies and Patents

A drug design strategy with reduced side effects and economic feasibility is desirable for fatal diseases. Increasing the bioavailability of a drug using a bioenhancer is a smart strategy. Herbal/natural bioenhancers with no probable side effects are an ideal choice to enhance the pharmacokinetics of a therapeutic drug synergistically. The mechanism of bioenhancers relies on the retention of the drug molecule in the cell without causing any changes in the metabolic activity. Most of the herbal bioenhancers achieve this feat by inhibiting metabolic enzymes such as cytochrome P450 and Uridine 5′-diphospho-glucuronosyltransferase. The efflux pump p-glycoprotein, responsible for removal of xenobiotics, is also inhibited by herbal/natural bioenhancers. The increased bioavailability because of the higher Cmax and tmax of chemotherapeutics or anti-infectious agents such as rifampicin can result in a lower drug dosage regimen. The reduction in drug dosage is directly linked to fewer side effects and economic viability. Further, there is a significant effort in clinical trials to incorporate bioenhancers in drug regimens for cancer. The role of herbal/natural bioenhancers and their potential to augment the bioavailability of therapeutics used in cancer and infectious diseases, with a focus on the mechanisms of action, clinical studies and patents, have been summarized in this review article.

Explaining the Experiences of the Reasons for Non-Adherence to Treatment of Leukemia Cancer Patients in the Least Privileged Province of the Country: A Qualitative Study

Introduction: One of the most important challenges in cancer patients is the long treatment period, and as a result, non-compliance with the treatment, considering the cultural and indigenous context of Sistan and Baluchistan province, the importance of this position is felt more. Therefore, the present study was conducted with the aim of explaining the experiences of non-adherence to treatment in Leukemia cancer patients. Methods: This cross-sectional study was conducted qualitatively with a content analysis approach via a purpose-based sampling method on 34 leukemia cancer patients with a mean age of 46±7 in 2022. The data collection tool was a semi-structured interview guide. All interviews were recorded and implemented daily on paper. Finally, the data was coded using conventional content analysis method. Results: In this study, 17 women and 17 men were included in the study. 9 (26/5%) of them were more than 50 years old. After summarizing and coding the issues raised by the participants, 114 initial codes were obtained, five main themes (financial problems, lack of access to medical services, distrust of the health system and treatment, drug interactions and lack of motivation to continue treatment) and 10 sub-themes were extracted. Conclusion: It can be concluded that adherence to drug regimen in cancer patients is a complex issue that depends on many factors. The financial and spiritual support of the government, increasing insurance coverage, and developing infrastructure for better access of patients to medicines and medical centers are among the implementation suggestions of this study.

Socioeconomic status, reserve capacity, and depressive symptoms predict pain in Rheumatoid Arthritis: an examination of the reserve capacity model

BackgroundGuided by the reserve capacity model, we evaluated the unique relationships between socioeconomic status (SES), reserve capacity (helplessness, self-efficacy, social support), and negative emotions on pain in patients with Rheumatoid Arthritis (RA).MethodsThe secondary analysis used baseline, cross-sectional data from 106 adults in a clinical trial comparing behavioral treatments for RA. Patients were eligible if they were ≥ 18 years old, met the ACR criteria for RA (determined by study rheumatologist), had stable disease and drug regimens for 3 months, and did not have a significant comorbid condition. Structural equation modeling evaluated the direct effects of SES, reserve capacity (helplessness- Arthritis Helplessness Index, self-efficacy -Personal Mastery Scale, social support- Social Provisions Scale) and negative emotions (stress and depressive symptoms- Perceived Stress Scale and Hamilton Depression Rating Scale) on pain (Rapid Assessment of Disease Activity in Rheumatology-RADAR & visual analog scale-VAS), and the indirect effects of SES as mediated by reserve capacity and negative emotions. The SEM model was evaluated using multiple fit criteria: χ2 goodness-of-fit statistic, the comparative fit index (CFI), the standardized root mean square residual (SRMR), and the root mean square error of approximation (RMSEA).ResultsParticipants were mostly female (85%), 55.45 years old on average, self-identified as white (61%), Hispanic (16%), black (13%), and other (10%), and had RA for an average of 10.63 years. Results showed that low SES contributed to worse pain, through lower reserve capacity and higher negative emotions. Mediational analyses showed that reserve capacity and negative emotions partially mediated the effect of SES on pain. The final model explained 39% of the variance in pain.ConclusionsThe findings indicate that lower SES was related to worse clinical pain outcomes and negative emotions and reserve capacity (helplessness, social support, and self-efficacy) mediated the effect of SES on pain. A primary limitation is the small sample size; future studies should evaluate this model further in larger, longitudinal approaches. Interventions that target negative emotions in patients with low SES may facilitate better pain control with RA.Trial registrationclinicaltrials.gov NCT00072657 01/02/2004 20/03/2009.