Occurrence Of Side Effects Research Articles

Up-titration of Guideline Directed Medical Therapy (GDMT) and the occurrence of side effects in Heart Failure with reduced Ejection Fraction (HFrEF)

Abstract Background The ESC Guidelines recommend early, full-dose use of heart failure (HF) medications to enhance survival, but real-world application often faces delays and inconsistencies. Clinicians often fear side effects during up-titration to the recommended target dose (TD), i.e. hypotension, bradycardia, renal impairment, and hyperkalemia (HK). The dependency of side effects during dose escalation from the severity of HF remains unclear. Purpose This study aimed to evaluate the relationship between the occurrence of side effects during up-titration of HF medication and HF severity reflected by N-terminal pro B-type natriuretic peptide (NT-proBNP). Methods 425 patients with HFrEF and a complete data set of patient characteristics, medications and laboratory values at baseline (BL), 2 months (2M), and 6 months (6M) were included from our outpatient HF unit's prospective registry. Significant side effects were defined as: systolic blood pressure (SBP) <90mmHg, heart rate (HR) <50 beats per minute (bpm), potassium (K) >5.0mmol/l or K >5,5mmol/l and estimated glomerular filtration rate (eGFR) <30ml/min/1.73m2. Patients were categorized into three risk groups based on their NT-proBNP levels, i.e. low-risk with NT-proBNP <1000pg/ml, medium-risk with NT-proBNP 1000-2000pg/ml or high-risk with NT-proBNP >2000pg/ml. The occurrence of side effects was recorded and the development compared among the HF risk groups. Results Figure 1 shows up-titration of HF medication. Mean daily dosages of betablockers (BB), mineralocorticoid receptor antagonists (MRA) and renin-angiotensin-system inhibitors (RASi) increased significantly during follow-up (BL vs 2M and BL vs 6M, p<0.001 for all). The majority of patients received ≥50% of the recommended TDs at 6M (89% for BB, 83% for MRA, 88% for RASi and 91% for total mean TDs ≥50%), and the achieved daily dosages at 6M were largely comparable across the HF risk groups at 6M, except for RASi (p=0.030). Figure 2 depicts the side effects. Side effects developed almost exclusively at short-term within 2M except for lower SBP (Figure 2A). Newly developed side effects occurring after up-titration (2B) were even more rare and predominantly occurred within the highest NT-proBNP group. The occurrence of hypotension and bradycardia was infrequent and comparable within the HF risk groups. Renal dysfunction (at 6M p=0,041) and HK occurred predominantly in higher risk patients (HK at 2M p=0,001 and at 6M p<0,001). Conclusions Up-titration of HF medications is highly feasible, particularly in low- and medium-risk patients. Despite rare side effects such as hyperkalemia and renal impairment, up-titration remains unimpeded, especially in patients with NT-proBNP levels below 2000pg/ml. These findings emphasize the safety of up-titration in HF.

Do more with less? Impact of personalized very low doses of amlodipine in the PERSONAL-CovidBP trial

Abstract Introduction The Personal-CovidBP study1 tested remote patient use of a drug-device combination of a smartphone application (App) to record blood pressure (BP), novel personalized milligram-by-milligram drug (amlodipine) dose, and relevant side effects daily during the COVID-19 pandemic. Purpose In supplementary data analyses, we examined the effect of using small doses (1 mg) and small increments (1-2 mg) of amlodipine on the BP response and side effects. Methods In this community-based trial with remote monitoring and remote medical management from the investigational site, hypertensive participants aged 18 years + with poor BP control (prior 7 day mean of 135 mmHg systolic BP or above and/or 85 mmHg diastolic BP and above) were enrolled to intervention with open label dose titration over 14 weeks, allowing personalized dosing of liquid amlodipine (1–2 mg steps from 1–10 mg daily). Results 205 patients were enrolled into the intervention group between October 2020 and July 2021. Average BP in intervention fell from 141/87 to 131/81 (difference −10/6 p < 0.001). Even low doses or small increments: 1 or 2 mg amlodipine or 5 mg to 6 mg, produced meaningful BP responses. Here we report that the addition of amlodipine during the study reduced blood pressure regardless of being amlodipine naive at baseline (n=141), or receiving amlodipine 2.5mg or 5mg at baseline (n=62). The response slopes were comparable, and mean reductions in SBP were consistent across groups: -11.7 (95% CI: -12.9 to -10.6); -9.4 (-11.1 to -7.7); respectively (Figure 1). For the amlodipine naive, the majority (76%) achieved BP control at low doses (<1 to 3mg) with occurrence of side effects increasing with dose (Figure 2). Conclusions Our real-world remote care study demonstrated that very low doses of amlodipine as little as 1 mg were effective and for 1mg-3mg gained BP control in the majority and were associated with fewer side effects which is consistent with previous meta-analyses.2 Personalized treatment titration was effective even at very low doses and also regardless of whether amlodipine naive or not at baseline.Changes in SBP- baseline amlodipine useAmlodipine dose at control vs oedema

Acupuncture combined with opioid for treatment of lung cancer-related pain: A systematic review and meta-analysis.

Many individuals diagnosed with lung cancer suffer from tremendous pain, and it is crucial to implement more effective measures to assist these patients in alleviating their pain. The present study utilizes a meta-analysis to evaluate the safety and efficacy of acupuncture combined with opioids for treating lung cancer-related pain in patients. We have searched 8 electronic databases: The Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and SinoMed. We included all randomized controlled trials of acupuncture combined with opioids for lung cancer-related pain in adults. We observed the main outcome indicators, including pain relief rates, numeric rating scale scores, and adverse events. Two researchers independently conducted literature screening, literature data extraction, and assessment of bias risk in the literature quality. Any disagreements were resolved through discussions between the 2 researchers or consultations with a third researcher. The risk of bias in the included studies was assessed using the revised risk of bias assessment tool. The overall quality of evidence for each outcome was evaluated using Grading of Recommendations, Assessment, Development and Evaluations. We retrieved 812 lung cancer patients from 11 trials. The study showed that compared to opioids alone, the combination of acupuncture and opioids significantly reduced numeric rating scale scores, increased pain relief rates, and decreased the occurrence of side effects. The current evidence indicates that combining acupuncture with opioid analgesics is superior to using opioid analgesics alone for managing lung cancer-related pain. Additionally, this combination therapy has fewer adverse reactions.

The efficacy of Salvia-ligustrazine and Ligustrazine in treating gestational hypertension: A systematic review and meta-analysis.

Pregnancy-induced hypertension syndrome (PIH), a prevalent and critical condition, has garnered increasing attention due to its significant impact on maternal and fetal health outcomes. The conventional treatment approaches rely on magnesium sulfate and various antihypertensive drugs; however, the clinical efficacy of these treatments is limited, highlighting the need to explore alternative avenues for improvement. Recently, a growing number of clinical studies have investigated the use of Salvia-ligustrazine or Ligustrazine in combination with conventional therapy. A comprehensive synthesis and critical analysis of these studies is necessary to evaluate the efficacy and safety of Salvia-ligustrazine or Ligustrazine in treating PIH. We sought all articles published prior to December 2, 2023, from seven databases to identify randomized controlled trials (RCTs) that involved traditional Chinese medicine Salvia-ligustrazine or Ligustrazine in combination with Western medicines for the conventional treatment of PIH, according to predefined inclusion criteria. The studies were assessed using the Cochrane Risk of Bias tool (ROB2.0), and meta-analyses were conducted using Stata 15.0 statistical software. We analyzed 47 RCTs encompassing 4,517 patients. The results demonstrated that combining Salvia-ligustrazine or Ligustrazine with Western medications was more efficacious than using Western medications alone. This combination improved the overall response rate, reduced the incidence of adverse pregnancy outcomes for mothers and infants, and decreased the occurrence of side effects associated with PIH treatment. While we evaluated the efficacy of traditional Chinese medicine injections of Salvia-ligustrazine or Ligustrazine alongside conventional Western treatments, our conclusions must be considered provisional due to potential bias and the limited availability of RCTs.

Crossfeat: a transformer-based cross-feature learning model for predicting drug side effect frequency.

Safe drug treatment requires an understanding of the potential side effects. Identifying the frequency of drug side effects can reduce the risks associated with drug use. However, existing computational methods for predicting drug side effect frequencies heavily depend on known drug side effect frequency information. Consequently, these methods face challenges when predicting the side effect frequencies of new drugs. Although a few methods can predict the side effect frequencies of new drugs, they exhibit unreliable performance owing to the exclusion of drug-side effect relationships. This study proposed CrossFeat, a model based on convolutional neural network-transformer architecture with cross-feature learning that can predict the occurrence and frequency of drug side effects for new drugs, even in the absence of information regarding drug-side effect relationships. CrossFeat facilitates the concurrent learning of drugs and side effect information within its transformer architecture. This simultaneous exchange of information enables drugs to learn about their associated side effects, while side effects concurrently acquire information about the respective drugs. Such bidirectional learning allows for the comprehensive integration of drug and side effect knowledge. Our five-fold cross-validation experiments demonstrated that CrossFeat outperforms existing studies in predicting side effect frequencies for new drugs without prior knowledge. Our model offers a promising approach for predicting the drug side effect frequencies, particularly for new drugs where prior information is limited. CrossFeat's superior performance in cross-validation experiments, along with evidence from case studies and ablation experiments, highlights its effectiveness.

Pseudo polyarthrite rhizomélique: mise au point

Polymyalgia rheumatica (PMR) is a rheumatologic condition characterized by inflammatory pain of the pelvic and scapular girdles associated with a biological inflammatory syndrome in patients > 50 years old. It is associated with giant cell arteritis (GCA) in 16-21% of cases. There is no specific biological test for PMR. The diagnosis is based on the exclusion of diseases that could mimic PMR. In recent years, imaging has undergone significant development helping clinicians for the diagnostic. Treatment of PMR is based on glucocorticoid therapy, which is gradually tapered over 12 months. Over the last few years, assessment of glucocorticoid-sparing agents has been developed, to reduce the occurrence of glucocorticoid associated side effect in an elderly population, who often has cardiovascular, metabolic and/or fracture-related comorbidities. The aim of this review is to provide clinicians an overview of the epidemiological, clinical, imaging and therapeutic features of PMR.

Comparison of the ED50 of Ciprofol Combined With or Without Fentanyl for Laryngeal Mask Airway Insertion in Children: A Prospective, Randomized, Open-Label, Dose-Response Trial.

This study aimed to estimate the effect of different doses of fentanyl on the median effective dose (ED50) of ciprofol for attenuating the airway and motor response to laryngeal mask airway (LMA) insertion response in healthy children. 90healthy preschool patients undergoing inguinal hernia repair surgery were randomly assigned to one of three groups: C0 (ciprofol+saline), C1 (ciprofol + fentanyl 1µg/kg), C2 (ciprofol + fentanyl 2µg/kg). Anesthesia was induced with either prepared fentanyl or saline, followed by ciprofol. The dose of ciprofol for each patient was determined using the up-and-down sequential study design. The primary outcome was the ED50 of ciprofol required for smooth LMA insertion in the three groups. Additionally, the time to loss of consciousness and any perioperative adverse events were recorded. Compared with the C0 group, the ED50 (95% confidence interval) of ciprofol in the C1 and C2 groups were significantly lower (1.81 [1.73-1.90]mg/kg versus 0.67 [0.64-0.71]mg/kg and 0.48 [0.42-0.54] mg/kg, respectively; P<0.05). Additionally, the ED50 of ciprofol in the C2 group was lower than that in the C1 group (0.42 [0.42-0.54] mg/kg vs 0.67 [0.64-0.71]mg/kg; P<0.05). Furthermore, the time to loss of consciousness in the C1 and C2 groups decreased by 60% and 53%, respectively, compared to the C0 group. There were no significant differences in the incidence of drug-related hypotension after anesthesia induction among the three groups. No adverse events of hypoxia, bradycardia, or injection pain were observed in any groups. In healthy, non-obese Chinese children undergoing elective inguinal hernia repair surgery, fentanyl 1µg/kg and 2µg/kg before ciprofol injection significantly reduced the ED50 of ciprofol for attenuating LMA response, with minimal occurrence of severe side effects.

Unleashing the antitumor power of cyclophosphamide by arabinogalactan and aptamer conjugation

Cyclophosphamide (CPA) (2-oxo-2-di(β-chloroethyl)amino tetrahydro-2,1,3-phosphoxazine) is an alkylating cytostatic compound with a broad spectrum of antitumor activity. Despite its efficacy, the clinical application of CPA is hindered by the significant occurrence of adverse side effects. To address these limitations, a promising approach involves the mechanochemical treatment of CPA with arabinogalactan (AG) to facilitate the dispersion of the drug within the AG matrix. AG stands out from other polymers due to its uniformity, low molecular weight, water solubility, and ability to form drug conjugates, thereby enhancing their therapeutic potency. Moreover, AG possesses immune-modulating properties that have the potential to counteract the immunosuppressive effects induced by CPA. By means of mechanical treatment, we successfully obtained CPA-AG complexes with a CPA:AG ratio of 1:10. These complexes were further modified with As42 aptamers that specifically target Erlich ascites cells. Aptamers, a novel class of oligonucleotide ligands obtained through SELEX technology, possess high affinity and specificity for binding to various receptors. An ascitic form of Ehrlich carcinoma was chosen as an in vitro and in vivo tumor model due to its notable drug resistance. In vitro and in vivo evaluations were conducted to compare the antitumor activity of both the CPA-AG and CPA-AG-As42 complexes with pure CPA. In vitro experiments revealed that the CPA-AG complex displayed superior antitumor activity compared to pure CPA, leading to complete tumor cell death primarily through necrosis. Notably, no toxic effects were observed with the CPA-AG and CPA-AG-As42 complexes, and they significantly prolonged the lifespan of tumor-bearing mice by more than 3.5 times. Histological studies further supported the antitumor efficacy of these complexes. These results underscore the potential of utilizing CPA-AG mechanocomposites, functionalized with aptamers, for the targeted delivery of CPA to tumors.

Core-Shell Microspheres with Encapsulated Gold Nanoparticle Carriers for Controlled Release of Anti-Cancer Drugs.

Cancer is one of the major threats to human health and lives. However, effective cancer treatments remain a great challenge in clinical medicine. As a common approach for cancer treatment, chemotherapy has saved the life of millions of people; however, patients who have gone through chemotherapy often suffer from severe side effects owing to the inherent cytotoxicity of anti-cancer drugs. Stabilizing the blood concentration of an anti-cancer drug will reduce the occurrence or severity of side effects, and relies on using an appropriate drug delivery system (DDS) for achieving sustained or even on-demand drug delivery. However, this is still an unmet clinical challenge since the mainstay of anti-cancer drugs is small molecules, which tend to be diffused rapidly in the body, and conventional DDSs exhibit the burst release phenomenon. Here, we establish a class of DDSs based on biodegradable core-shell microspheres with encapsulated doxorubicin hydrochloride-loaded gold nanoparticles (DOX@Au@MSs), with the core-shell microspheres being made of poly(lactic-co-glycolic acid) in the current study. By harnessing the physical barrier of the biodegradable shell of core-shell microspheres, DOX@Au@MSs can provide a sustained release of the anti-cancer drug in the test duration (which is 21 days in the current study). Thanks to the photothermal properties of the encapsulated gold nanoparticle carriers, the core-shell biodegradable microspheres can be ruptured through remotely controlled near-infrared (NIR) light, thereby achieving an NIR-controlled triggered release of the anti-cancer drug. Furthermore, the route of the DOX-Au@MS-enabled controlled release of the anti-cancer drug can provide durable cancer cell ablation for the long period of 72 h.

Prospective acceptability of mass drug administration for malaria in Kedougou region in Senegal: a mixed method study

BackgroundIn Senegalese high-burden regions, the existing package of interventions is insufficient to reach the malaria elimination goal. Asymptomatic carriers of Plasmodium contribute significantly to malaria persistence and are not targeted by current interventions. The systematic treatment of all individuals in a community (mass drug administration, MDA) is a relevant intervention to tackle asymptomatic infections. The intervention can only be effective with a high participation of the population and, therefore, depends largely on its acceptability. This study aims to investigate the prospective acceptability of MDA in the Kedougou region to inform its potential use in a future strategy.MethodsFollowing a 7-construct theoretical framework, prospective acceptability of MDA implemented in the rainy season was studied. In four villages, a sequential mixed design, from qualitative to quantitative, was used. In November 2021, interviews with healthcare professionals and focus groups with villagers were conducted. Findings from thematic analysis informed the development of a questionnaire administered to individuals aged ≥ 15 years in March 2022. Based on the questionnaire, an acceptability score was constructed and associations with socio-demographic factors were investigated using a linear mixed model.ResultsThe 7 interviews, the 12 focus groups, and the questionnaire administered to 289 individuals demonstrated a good acceptability of MDA. Two potential barriers were identified: the contradiction of taking a medication without feeling sick and the occurrence of side effects; and four facilitators: the perception of malaria as a burden, a good understanding of MDA, a good perceived effectiveness, and the resulting economic benefits. The average acceptability score was 3.5 (range from -7 to + 7). Young adults aged 15 to 21 had a lower acceptability score compared to the other age groups, indicating an additional barrier to acceptability (β = -0.78 [-1.67;0.1]).ConclusionMDA is a priori acceptable to communities of Kedougou region in Senegal. Sensitization campaigns co-constructed with the communities, especially targeting young adults, are essential to ensure good acceptability.

A potent therapeutic scaffold fusing quinazolinone/melatonin for future colorectal cancer interventions: design, one-pot synthesis, biological and ADME-tox modeling studies

AbstractColorectal cancer is one of the most incident and lethal cancers in the world. The search for new compounds to treat this disease is being motivated by the occurrence of side effects and the rising in the resistance to chemotherapy. We synthesized a new class of conjugates bearing quinazolinone and melatonin which were prepared in good yields (63–93%) through one-pot three-component approach. quinazolinone/melatonin conjugates were proved against SW480 human colorectal adenocarcinoma cells and non-malignant colonic cells (NCM460). The cytotoxic and antiproliferative activities were determined through the sulforhodamine B assay. Compounds 1f, 1g and 1i–l displayed the best activity, being hybrids 1i–l the most selective against malignant cells, causing either a cytostatic and/or cytotoxic effect with evident morphological changes. Moreover, a theoretical drug-like/pharmacokinetics/toxicological study suggested that the hit-promising compounds 1i and 1j would have a great chance to advance to further preclinical studies as anti-cancer therapeutic candidate for oral oncological management. Our study evidently identified the potency of these quinazolinone/melatonin hybrids to be a prototype drug for further investigations toward novel therapeutics treatments of colorectal cancer.

Comparison of oral caffeine and oral theophylline for apnea of prematurity: A randomized clinical trial

Background Caffeine and theophylline are methylxanthine compounds that have been widely used in the treatment of apnea of prematurity (AOP). Previous studies comparing the two agents have shown inconsistent results and have mostly used intravenous preparations. Objective To assess the effectiveness of oral administration of caffeine compared to oral theophylline as therapy for apnea of prematurity. Methods Fifty consecutively recruited premature neonates (gestational age 28-34 weeks, birth weight &lt;2,500 g) with AOP who were able to tolerate at least 10 mL/kg of enteral feeding were randomized to receive either oral caffeine or oral theophylline for seven days. The main outcome was the daily frequency of apnea after treatment. Secondary outcomes were duration of oxygen or CPAP administration, duration of oxygen fraction (FiO2) taper to reach 21%, time to achievement of full feeding tolerance, length of hospital stay, and side effects. Results We randomized 25 subjects into each group. The distribution of baseline characteristics (gender, gestational age, mode of delivery, birth weight and length, age at onset of AOP, and initial frequency of AOP) was similar between both groups. The mean daily number of apnea episodes after treatment was significantly higher in the caffeine group compared to the theophylline group [3.16 (SD 1.31) vs. 2.28 (SD 1.40); P=0.031]. The caffeine group, compared to the theophylline group, also had a longer mean duration of oxygen or CPAP use [12.56 (SD 7.67) days vs. 8.40 (SD 6.41) days; P=0.030] and duration of FiO2 taper [5.76 (SD 2.68) vs. 4.08 (SD 2.54); P=0.035]. There were no significant differences in mean time to full feeding and mean length of hospital stay. There was no significant difference in the occurrence of side effects between the two groups. Conclusion In premature neonates with AOP, oral theophylline is slightly more effective than oral caffeine in reducing the frequency of apnea and is associated with a shorter duration of oxygen or CPAP use and duration to reach 21% FiO2.

Profile of Dermatologic Side Effects of Tyrosine Kinase Inhibitor (EGFR-TKIs) in Lung Cancer Patients

Background: Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKIs) drugs are commonly used target therapies in patients with advanced-stage non-small cell carcinoma lung cancer (NSCLC).Objectives: This study aims to provide an overview of dermatologic side effects and quality of life index of NSCLC patients who received EGFR-TKIs targeted therapy at Dharmais Cancer Hospital.Methods: This study used a cross-sectional design. Inclusion criteria were patients who received EGFR-TKIs targeted therapy, namely gefitinib, erlotinib, and afatinib, in September - October 2023, who were willing to be research subjects, and patients who were not in a medical emergency. In total, 52 patients filled out the dermatology life quality index (DLQI) questionnaire through interviews and medical records. Data evaluation was performed descriptively in the form of percentages.Results: The most common occurrence of dermatologic side effects was skin hypersensitivity reactions with mild severity (grade 1) by 59.6%, moderate severity (grade 2) by 19.2%, and severe severity (grade 3) by 1.9%, and no drug dermatologic side effects by 19.2%. In comparison, the most DLQI was in the category of not affecting patient life. In general, side effects with moderate (grade 2) and severe (grade 3). The severity will decrease to mild severity (grade 1) when already getting topical corticosteroid drugs or combinations with oral antibiotics and antihistamine drugs.Conclusion: The most severe side effect was grade 1, which slightly affected the patient's quality of life. Education and monitoring of side effects and management of symptoms are necessary to reduce the severity and improve patients' quality of life.

Efficacy and safety of anlotinib as maintenance therapy in patients with advanced non-small cell lung cancer achieving SD post first-line chemotherapy combined with immunotherapy.

Advanced non-small cell lung cancer (NSCLC) remains a significant clinical challenge, particularly in patients who exhibit stable disease (SD) following first-line chemotherapy combined with immunotherapy. This study aims to evaluate the efficacy and safety of Anlotinib, a novel multitarget tyrosine kinase inhibitor, as maintenance therapy in this patient cohort. This retrospective, single-center study enrolled patients with advanced NSCLC who showed SD after receiving a combination of first-line chemo-immunotherapy for 4 cycles, then add anlotinib to subsequent standard maintenance therapy, continuing treatment until disease progression or the occurrence of intolerable toxic side effects. The primary endpoint was progression-free survival (P FS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety profile. A total of 52 patients were enrolled, the median P FS and OS was 5.0m and 10.0m, respectively. The ORR and DCR was 28.85% and 67.31%. subgroup analysis indicated that its efficacy correlate with certain Adverse Effects (AEs, such as hypertension, proteinuria, and hand-foot syndrome). Further mechanistic analysis suggests that this regimen may likely reduce immune suppression by depleting Tregs, thereby further activating the immune system to exert synergistic anti-tumor effects. Besides promising efficacy, the toxicity can be tolerated. Anlotinib demonstrates promising efficacy as a maintenance therapy in patients with advanced NSCLC who have achieved SD following first-line chemotherapy combined with immunotherapy. The manageable safety profile and the observed extension in P FS and OS suggest that Anlotinib could be a valuable therapeutic option for this challenging patient population. Further large-scale randomized controlled trials are warranted to confirm these findings and to optimize patient selection and management strategies.

Curcumin and exercise prevent depression via alleviating hippocampus injury and improve depressive-like behaviors in chronically stressed depression rats

Background and purpose: Depression is a growing public health concern worldwide, characterized by cognitive impairment and structural abnormalities of the hippocampus. Current antidepressant treatment sometimes causes the late onset of results and the much faster occurrence of side effects. For this reason, the interest in new treatment strategies including exercise and natural products such as curcumin has increased to treat depression. The present study investigated the role of curcumin and exercise in improving depressive-like behavior and hippocampal damage induced by mild unpredictable chronic stress in male rats. Experimental approach: This study analyzed the effects of curcumin (100 mg/kg/day, P.O for 14 days) and exercise (treadmill running, 45 min/day for 14 days) on immobility behavior (forced swimming test), locomotor activity (open field test), anhedonia (sucrose preference test) and cell survival (Nissl staining) of the hippocampal CA3 region in chronically stressed depression rats. Findings/Results: In the current study, curcumin treatment combined with exercise effectively improved immobility behavior, locomotor activity, and increased hippocampal cell survival resulted in preventing the development of hippocampus dysfunction and depressive-like behaviors. Conclusion and implications: This study demonstrated a new prospect for treating depression. The current findings give researchers the confidence to continue the investigations on the effects of curcumin accompanied with exercise as a novel therapy for the treatment of depression.

The risk of second malignancies following prostate cancer radiotherapy in the era of conformal radiotherapy: astatement of the Prostate Cancer Working Group of the German Society of Radiation Oncology (DEGRO).

Asignificant number of prostate cancer patients are long-term survivors after primary definitive therapy, and the occurrence of late side effects, such as second primary cancers, has gained interest. The aim of this editorial is to discuss the most current evidence on second primary cancers based on six retrospective studies published in 2021-2024 using large data repositories not accounting for all possible confounding factors, such as smoking or pre-existing comorbidities. Overall, prostate cancer patients treated with curative radiotherapy have an increased risk (0.7-1%) of the development of second primary cancers compared to patients treated with surgery up to 25years after treatment. However, current evidence suggests that the implementation of intensity modulated radiation therapy is not increasing the risk of second primary cancers compared to conformal 3D-planned radiotherapy. Furthermore, increasing evidence indicates that highly conformal radiotherapy techniques may not increase the probability of second primary cancers compared to radical prostatectomy. Consequently, future studies should consider the radiotherapy technique and other confounding factors to provide amore accurate estimation of the occurrence of second primary cancers.

Gastroretentive Delivery Approach to Address pH-Dependent Degradation of (+)- and (-)-Phenserine.

(-)-Phenserine ("phenserine") and (+)-phenserine (posiphen; buntanetap) are longer-acting enantiomeric analogs of physostigmine with demonstrated promise in the treatment of Alzheimer's and Parkinson's diseases. Both enantiomers have short plasma half-lives, and their pharmacokinetics might be improved through the use of either once or twice-daily administration of an extended-release dosage form. Phenserine was observed to form a colored degradation product in near-neutral and alkaline pH environments, and at pH 7, the half-life of posiphen was determined to be ~ 9 h (40 °C). To limit luminal degradation which would reduce bioavailability, a gastroretentive tablet composed of a polyethylene oxide-xanthan gum matrix was developed. When placed in simulated gastric fluid (pH 1.2), approximately 70% of the phenserine was released over a 12 h period, and no degradants were detected in the release medium. In comparison, a traditional hydrophilic-matrix, extended-release tablet showed measurable amounts of phenserine degradation in a pH 7.2 medium over an 8 h release interval. These results confirm that a gastroretentive tablet can reduce the luminal degradation of phenserine or posiphen by limiting exposure to neutral pH conditions while providing sustained release of the drug over at least 12 h. Additional advantages of the gastroretentive tablet include reduced gastric and intestinal concentrations of the drug resulting from the slower release from the gastroretentive tablet whichmay also limit the occurrence of the dose-limiting GI side effects previously observed with immediate-release phenserine capsules.

A Cross-Sectional Investigation on Drug-Drug Interactions in Prescriptions of Pediatric Outpatient Clinics at a Referral Center in Southern Iran

Background: Drug interactions can lead to treatment failure, the occurrence of side effects, complicate the clinical course and severity of the disease, and prolong hospitalization duration. Pediatrics are particularly vulnerable to drug interactions. Objectives: This study aims to evaluate prescribed medications and the incidence of drug interactions in pediatric patients. Methods: This study was conducted as a cross-sectional investigation. Over nine months, we evaluated pediatric patients referred to Bandar Abbas Children’s Hospital, affiliated with Hormozgan University of Medical Sciences, who received outpatient treatment services. The medications these patients received were assessed for drug interactions. Only interactions with clinical importance (i.e., category C-D-X) were considered. Using the Lexi-Interact online database, the prescribed drugs were evaluated in terms of the number and type of potential drug-drug interactions. Results: A total of 1011 patients were included in the study based on the determined criteria. The mean age was 4.52 ± 0.11 years, and the male-to-female ratio was 1.2:1. More than two-thirds of the patients were seen by general physicians. Among all participants, 26.7% had at least one clinically significant interaction in their prescriptions. Furthermore, 309 interactions were identified, of which 6.39% were of significant severity, and 93.61% were of moderate severity. The risk rating of C was the most common interaction, followed by X and D (87.7%, 7.4%, and 4.8%, respectively). Regarding reliability, 0.30% had fair reliability, 64.20% had good reliability, and 35.50% had excellent reliability ratings. Patients with underlying conditions were at increased risk of interaction occurrence (OR = 1.8, P = 0.008). Conclusions: Drug interactions with high clinical significance were identified at a high prevalence rate. These interactions can have significant consequences. Pharmacists and physicians play an important role in identifying and managing drug-drug interactions.

Biosurfactant Nanomicelles and Peptide Integration: Novel Approaches to Targeted Gene Delivery in Colon Cancer Treatment.

A notable breakthrough in the treatment of colon cancer involves the utilisation of a cutting-edge drug delivery technology known as biosurfactant-derived nanomicelles. These nanomicelles, composed of natural biosurfactant molecules, possess the distinct capability to enclose pharmaceuticals or genetic material, such as DNA, siRNA, or mRNA, within spherical formations. With a size ranging from 10 to 100 nanometers, these nanomicelles exhibit precision targeting capabilities towards colon cancer cells, hence minimising the occurrence of side effects typically associated with treatment. Upon being specifically targeted, the nanomicelles liberate their cargo into cancer cells, resulting in enhanced therapy efficacy. This novel strategy utilises the specific attributes of the tumour microenvironment to administer precise and focused treatment. These nanomicelles improve the absorption by cells and reduce harm to healthy tissues by imitating important nutrients or utilising compounds that specifically target tumours. Furthermore, the incorporation of stimuli-responsive components allows for regulated medication release in reaction to the acidic environment seen in tumours. The review focuses on examining the use of biosurfactants and natural peptides in nanomicellar carriers as ways to fight against colon cancer. Folate-coated nanomicelles incorporating curcumin facilitate precise gene delivery, while the partnership of biosurfactants, such as surfactin from Bacillus subtilis and natural peptides, enables the transportation of particular cyclopeptides into the tumour network. Peptides, similar to bombesin, direct nanomicelles to specific places, while peptides based on curcumin control the release of medicinal substances. While preclinical investigations demonstrate promise, obstacles remain in formulation and regulatory issues. However, biosurfactant-based nanomicelles, particularly folate-coated carriers loaded with curcumin, show tremendous potential in overcoming biological barriers and delivering medicines efficiently to colon cancer cells.

Treatment of Acquired Deforming Hypertonia with Botulinum Toxin in Older Population: A Retrospective Study.

Acquired deforming hypertonia (ADH) affects the daily care of numerous nursing home residents. The aim of this study was to analyze the practice, aims, and effectiveness of botulinum toxin injections (BTxis) in the treatment of older patients with contractures, an indication for which BTxis are still underused. Data were extracted retrospectively from medical records regarding population, contractures, and injections. A prospective analysis was conducted to evaluate treatment goals set by goal attainment scaling (GAS) at T0 and at T1, to evaluate the therapeutic effects. We also recorded the occurrence of side effects, using a telephone questionnaire. This study included 41 patients older than 70 years who had received one or more BTxis for the first time between January 2018 and December 2021. Most of the older people we included lived in an institution (66%), manifested severe dependence, and presented significant morbi-mortality (37% of the patients died in the year after the last injection). The main objectives of these injections were purely comfort, without any functional goals. The GAS scores suggested effectiveness for comfort GAS scores. No complications were recorded. This study highlights the BTxis potential to address the needs of a larger number of older patients with ADH.