Naproxen adjunct to fluoxetine for moderate-to-severe obsessive-compulsive disorder: A randomized, double-blind, placebo-controlled trial.

AIM: Current treatments for obsessive-compulsive disorder (OCD) encounter resistance and limiting adverse events, necessitating novel therapeutic strategies. This study aimed to investigate the benefits of naproxen, a medication with effects on inflammation and neuronal function, on OCD. METHODS: One hundred and four OCD outpatients with a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score of >21 were equally assigned to receive fluoxetine plus either naproxen 250 mg or matched placebo q12hr. Patients were assessed using the Y-BOCS by recording the subscale scores at baseline and weeks 5 and 10 to evaluate efficacy. They were also assessed in terms of tolerability. RESULTS: Data from 96 patients were analyzed. The baseline characteristics were comparable between the groups. There were significant time-treatment interaction effects on the obsession subscale ( η P 2 $$ {\eta}_P^2 $$ = 0.055) and total ( η P 2 $$ {\eta}_P^2 $$ = 0.043) scores of Y-BOCS. Reductions in the obsession subscale and total scores of Y-BOCS were significantly greater in the fluoxetine plus naproxen group until the endpoint (Cohen's d = 0.560 and Cohen's d = 0.477, respectively). However, the difference in compulsion subscale score changes between the groups was not significant. Respondents with a reduction of ≥35% in Y-BOCS total scores were significantly more in the fluoxetine plus naproxen group (80.0% versus 47.8%). The side effect frequencies were comparable between the groups. CONCLUSION: Naproxen, adjunct to fluoxetine, outperformed adjunctive placebo in treating obsession and total symptoms of OCD patients in a safe and tolerable manner. CLINICAL TRIAL REGISTRATION: The study protocol was registered and published in the Iranian Registry of Clinical Trials (http://www.irct.ir; registration number IRCT20090117001556N139).

Dysregulation of RAS proteostasis by autosomal-dominant LZTR1 mutation induces Noonan syndrome-like phenotypes in mice.

Leucine-zipper-like post translational regulator 1 (LZTR1) is a member of the BTB-Kelch superfamily, which regulates the RAS proteostasis. Autosomal dominant (AD) mutations in LZTR1 have been identified in patients with Noonan syndrome (NS), a congenital anomaly syndrome. However, it remains unclear whether LZTR1 AD mutations regulate the proteostasis of the RAS subfamily molecules or cause NS-like phenotypes in vivo. To elucidate the pathogenesis of LZTR1 mutations, we generated two novel LZTR1 mutation knock-in mice (Lztr1G245R/+ and Lztr1R409C/+), which correspond to the human p.G248R and p.R412C mutations, respectively. LZTR1-mutant male mice exhibit low birth weight, distinctive facial features, and cardiac hypertrophy. Cardiomyocyte size and the expression of RAS subfamily members, including MRAS and RIT1, were significantly increased in the left ventricles (LVs) of mutant male mice. LZTR1 AD mutants did not interact with RIT1 and functioned as dominant-negative forms of wild-type LZTR1. Multi-omics analysis revealed that the MAPK signaling pathway was activated in the LVs of mutant mice. Treatment with the MEK inhibitor trametinib ameliorated cardiac hypertrophy in mutant male mice. These results suggest that MEK/ERK pathway is a therapeutic target for NS-like phenotype resulting from dysfunction of RAS proteostasis by LZTR1 AD mutations.

Non­obstructive mesenteric ischaemia during drug therapy for maxillary cancer: A case report.

Non-occlusive mesenteric ischaemia (NOMI) refers to irreversible intestinal ischaemia and necrosis in the absence of organic obstruction to the mesenteric blood vessels. In cases of delayed diagnosis, the prognosis is poor and the mortality rate is 58-70%, being the highest among patients with acute mesenteric ischaemia. The risk factors for this disease include heart disease, sepsis, and administration of catecholamines and digitalis; however, there are few reports of its onset during drug therapy for malignant tumours. The present study reported the case of an 85-year-old man who developed NOMI during drug therapy for maxillary cancer. The patient was diagnosed with right maxillary carcinoma, for which paclitaxel, carboplatin and cetuximab (PCE) therapy was administered. Four days after starting the second course of PCE therapy, the patient visited the emergency department of our hospital with chief complaints of melena and abdominal pain. Contrast-enhanced computed tomography revealed ischaemia from the transverse to the descending colon, leading to a diagnosis of NOMI. Colectomy and colostomy were performed during the emergency surgery on the same day. Although the patient's general condition improved, he was transferred to a recuperation facility for palliative care.

Vitamin C, doxycycline, and azithromycin (VDA) targeted changes in cellular senescence-related genes in human adipose-derived mesenchymal stem cells.

Objectives: Adipose-derived Mesenchymal stem cells (ASCs) have garnered attention for their regenerative potential; therefore, their cellular senescence-related gene expression remains crucial in therapeutic contexts. Nowadays, combination therapies have shown promising results in reducing senescent cells. This study investigated the effects of vitamin C, doxycycline, and azithromycin co-treatment on the key cellular senescence-associated genes in ASCs. Materials and Methods: Human ASCs were cultured and treated for 24 hr with vitamin C, doxycycline, azithromycin, and a combination of three drugs. Total RNAs were extracted, and the expression of p21, p16, Nanog, Oct4, and Sox2 genes was assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, cell cycle alterations were analyzed via flow cytometry after treatment with these compounds. Results: Notably, vitamin C treatment resulted in a significant down-regulation of p21 gene expression (P<0.01), implicating the potential role of vitamin C in promoting cell cycle progression. Doxycycline treatment led to a significant up-regulation of p21 and p16 gene expression (P<0.05), as it has previously been shown to induce cell cycle arrest. Similarly, azithromycin treatment predominantly increased p21 expression (P<0.05). Besides, cell cycle analysis revealed that each compound had changed the distribution of cells across different phases of the cell cycle. Conclusion: The combined use of all three drugs yielded intricate interactions, suggesting a complex yet promising approach to future research. According to our findings, the major difference in the combination drug-treated group (VDA) can be explained by the neutralizing effect of these three components in the environment.

Corrigendum: Study on the effects of intestinal flora on gouty arthritis.

[This corrects the article DOI: 10.3389/fcimb.2024.1341953.].

Should Hypertonic Saline Be Considered for the Treatment of Intracranial Hypertension? A Review of Current Evidence and Clinical Practices.

Intracranial hypertension (IH) is a critical neurological emergency that requires prompt intervention because failure to treat it properly can lead to severe outcomes, including secondary brain injury. Traditionally, mannitol (MNT) has been the cornerstone of hyperosmolar therapy. However, the use of hypertonic saline (HTS) has become increasingly important because of its unique advantages. Both HTS and MNT effectively reduce intracranial pressure by creating an osmotic gradient that draws fluid from brain tissue. However, unlike MNT, HTS does not induce diuresis or significantly lower blood pressure, making it more favorable for maintaining cerebral perfusion. Additionally, HTS does not cause rebound edema and carries a lower risk of renal injury than MNT. However, it is important to note that the use of HTS comes with potential risks, such as hypernatremia, hyperchloremia, and fluid overload. Due to its unique properties, HTS is a crucial agent in the management of IH, and understanding its appropriate use is essential to optimize patient outcomes.

Safety profile of drugs used in non-cystic fibrosis bronchiectasis: a narrative review.

Non-cystic fibrosis bronchiectasis is a long-term lung disease characterised by abnormal dilatation of the bronchi, with patients experiencing chronic productive cough and recurrent exacerbations. Currently, there are no licensed drugs for use in bronchiectasis while clinical trials have been conducted to either test new drugs or repurpose existing ones. These drugs target the underlying pathophysiology of bronchiectasis which is known to include infection, inflammation, mucus hypersecretion and retention. Most of the drugs used in daily clinical practice for bronchiectasis are off-label with no randomised trials exploring their safety. This review aims at exploring the safety profile of drugs frequently used in clinical practice to manage bronchiectasis, including antibiotics (e.g. macrolides, aminoglycosides, polymyxins, fluoroquinolones, aztreonam), mucoactive therapy (e.g. hypertonic saline, mannitol, DNase and carbocisteine), anti-inflammatory therapy (inhaled corticosteroids) and drugs currently in development for use in bronchiectasis (e.g. brensocatib, benralizumab and itepekimab).

A review on the safety aspects of drugs currently being used in bronchiectasis This review aims to detail the safety aspects of drugs that are currently prescribed to patients with bronchiectasis. These drugs are used in bronchiectasis without some of the high quality trials seen for other lung conditions. The drugs used have shown clinical benefits in patients who are suffering from infective exacerbations or worsening of the disease. The idea behind the use of these drugs is that they target the pathological processes in bronchiectasis such as inflammation, infection and excess mucus production. In this review, we have included the results from clinical trials that assessed the use of antibiotics (both oral and inhaled) during pulmonary infections and long-term antibiotics to prevent infections. Mucus production is a major symptom of bronchiectasis, and hence the drugs that target mucus secretion and consistency are used in an attempt to improve the quality of life and prevent infections. Inflammation is a key component of bronchiectasis, and we report on the safety of inhaled steroids in bronchiectasis. Some new drugs are currently being tried in clinical trials worldwide and are discussed. The occurrence of multiple other medical problems are recognized in people living with bronchiectasis has been seen to increase symptoms and linked with higher infection rates and hospitalizations. This means patients are often on lots of different medications for multiple conditions; we highlight the importance of considering the fact these drugs in combination can lead to potential issues and side effects linked to polypharmacy.

Engine of Innovation in Hospital Pharmacy: Applications and Reflections of ChatGPT.

Hospital pharmacy plays an important role in ensuring medical care quality and safety, especially in the area of drug information retrieval, therapy guidance, and drug-drug interaction management. ChatGPT is a powerful artificial intelligence language model that can generate natural-language texts. Here, we explored the applications and reflections of ChatGPT in hospital pharmacy, where it may enhance the quality and efficiency of pharmaceutical care. We also explored ChatGPT's prospects in hospital pharmacy and discussed its working principle, diverse applications, and practical cases in daily operations and scientific research. Meanwhile, the challenges and limitations of ChatGPT, such as data privacy, ethical issues, bias and discrimination, and human oversight, are discussed. ChatGPT is a promising tool for hospital pharmacy, but it requires careful evaluation and validation before it can be integrated into clinical practice. Some suggestions for future research and development of ChatGPT in hospital pharmacy are provided.

Sublingual administration of atropine eye drops for treating sialorrhea after stroke: A randomized controlled trial.

BACKGROUND: Sialorrhea is a common concern in patients with swallowing disorders after stroke. Atropine sulfate blocks the muscarinic receptors in the salivary glands and leads to reduced saliva production. OBJECTIVE: The present study aimed to assess the safety, efficacy, and tolerability of sublingual administration of atropine eye drops for treating sialorrhea after stroke. DESIGN: This was a prospective cohort study. SETTING: This study was conducted at Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Hubei Province, China. POPULATION: Stroke patients with sialorrhea were analyzed. METHODS: One hundred stroke patients with sialorrhea were randomly assigned to the control group and the test group (n = 50 per group). The control group received routine swallowing rehabilitation training and neuromuscular electrical stimulation. The test group received therapy with 1% atropine eye drops, wherein one drop was administered sublingually 3 times per day. The Sialorrhea Scoring Scale and the incidence of adverse events were used to compare the severity of sialorrhea in the two groups. RESULTS: The mean (standard deviation) sialorrhea score improved from 5.12 for the control group with routine rehabilitation training to 3.94 for the test group with atropine eye drop administration (P < 0.01). No significant differences in the incidence of adverse events were observed between the two groups. CONCLUSIONS: The sublingual administration of 1% atropine eye drops three times per day can reduce the degree of sialorrhea to an extent more than that achieved with routine rehabilitation training; thus, this approach is effective, safe, and minimally invasive for treating sialorrhea after stroke.

Efficacy and safety in early-phase clinical trials for refractory colorectal cancer: A meta-analysis.

BACKGROUND: Despite recent metastatic colorectal cancer (mCRC) therapeutic innovations a comprehensive synthesis of patient outcome and risk-benefit assessment of phase 1/2 trials is missing. The aim of this meta-analysis is to assess efficacy, safety, and trends over time for phase 1 and 2 mCRC trials by examining clinical benefit rate (CBR), overall response rate (ORR), grade 3 or higher adverse events (AE), and discontinuation due to AE. METHODS: The PRISMA guidelines were followed. We searched PubMed and Embase for publications of phase 1/2 trials between 2010-2021. Trials reporting on new therapies for treatment-refractory mCRC were included. RESULTS: The search strategy yielded 4175 unique reports, of which 258 publications were eligible. These publications report data of 277 unique treatment arms. Overall ORR was 6 %, CBR was 27 % in phase 1 % and 36 % in phase 2 trials. CBR increased from 23 % in 2010-2012 to 42 % in 2019-2021. Compared to 2010-2012, trials in 2019-2021 more often tested immunomodulators (4 % vs 23 %), included molecularly preselected populations (4 % vs 38 %) and younger patients (median age<60 44 % vs 66 %). Grade 3 + AE occurred in 35 % of patients, most frequently in trials investigating targeted treatments. CONCLUSIONS: Treatment efficacy in phase 1/2 trials is modest but improved from 2010 to 2021. This improvement is accompanied by a shift towards testing in a younger, fitter, and more strictly molecularly preselected population, as well as an increased focus on targeted and immunotherapies.

Gly-ß-MCA is a potent anti-cholestasis agent against "human-like" hydrophobic bile acid-induced biliary injury in mice.

Cholestasis is a chronic liver disease with limited therapeutic options. Hydrophobic bile acid-induced hepatobiliary injury is a major pathological driver of cholestasis progression. This study investigates the anti-cholestasis efficacy and mechanisms of action of glycine-conjugated ß-muricholic acid (Gly-ß-MCA). We use female Cyp2c70 KO mice, a rodent cholestasis model that do not produce endogenous muricholic acid (MCA) and exhibit a "human-like" hydrophobic bile acid pool and female-dominant progressive hepatobiliary injury and portal fibrosis. The efficacy of Gly-ß-MCA and ursodeoxycholic acid (UDCA), the 1st line drug for cholestasis, on cholangiopathy and portal fibrosis are compared. At a clinically relevant dose, Gly-ß-MCA shows comparable efficacy as UDCA in reducing serum transaminase, portal inflammation and ductular reaction, and better efficacy than UDCA against portal fibrosis. Unlike endogenous bile acids, orally administered Gly-ß-MCA is absorbed at low efficiency in the gut and enters the enterohepatic circulation mainly after microbiome-mediated deconjugation, which leads to taurine-conjugated MCA enrichment in bile that alters enterohepatic bile acid pool composition and reduces bile acid pool hydrophobicity. Gly-ß-MCA also promotes fecal excretion of endogenous hydrophobic bile acids and decreases total bile acid pool size, while UDCA treatment does not alter total bile acid pool. Furthermore, Gly-ß-MCA treatment leads to gut unconjugated MCA enrichment and reduces gut hydrophobic lithocholic acid (LCA) exposure. In contrast, UDCA treatment drives a marked increase of LCA flux through the large intestine. In conclusion, Gly-ß-MCA is a potent anti-cholestasis agent with potential clinical application in treating human cholestasis.

Risk of alterations in neurodevelopment in infants and preschool children with cancer.

BACKGROUND: Some cancer survivors experience difficulties with concentration, attention, and memory; however, there are no studies on neurodevelopment in patients under 5 years of age who are undergoing cancer treatment. Our aim was to evaluate neurodevelopment in cancer patients under 5 years of age using the Early Development Instrument (EDI) test, considering factors such as nutritional status, type of cancer, and treatment effect. METHODS: A cross-sectional study was conducted from February 2018 to March 2019. Patients with cancer diagnoses outside the central nervous system in any phase of cancer treatment were included. RESULTS: A total of 45 patients were included. Regarding fine motor skills, 28% of patients with retinoblastoma and 23% of patients with leukemia or lymphoma had a risk of developmental delay compared to 0% of patients with solid tumors (p = 0.025). The final results showed that 19 (42.2%) patients had normal neurodevelopment (gray), 7 (15.5%) had a delay in neurodevelopment (light gray), and 19 (42.2%) had a risk of developmental delay (black). Regarding developmental delay, 52% of patients in the leukemia and lymphoma group, 71% in the retinoblastoma group, and 23% in the solid tumor group presented developmental delay (p = 0.06). CONCLUSIONS: The risk of delay and lag in neurodevelopment is common in cancer patients under 5 years of age undergoing treatment. However, more studies are required to evaluate the effect of treatment on this group of patients as it may be affected by various factors.

INTRODUCCIÓN: En algunos pacientes supervivientes de cáncer se presentan dificultades de concentración, atención y memoria, sin embargo no hay estudios en relación al neurodesarrollo en pacientes menores de 5 años que se encuentran en tratamiento oncológico. Por lo que el objetivo fue valorar el neurodesarrollo en pacientes con cáncer durante el tratamiento oncológico mediante la prueba EDI tomando en cuenta diversos factores como su estado nutricional, tipo de cancer, y el efecto del tratamiento. MÉTODOS: Se realizó un estudio transversal, de febrero de 2018 a marzo de 2019. Se incluyeron pacientes mayores de 1 año y menores de 5 años con diagnóstico de cáncer fuera del sistema nervioso central, en tratamiento oncológico. RESULTADOS: Se incluyeron 45 pacientes. En el área motor fina el 28% de los pacientes con retinoblastoma y 23% con leucemias y linfomas se encontraron en rojo (retraso) en comparación con 0% de los pacientes con tumores sólidos (p = 0.025). En el resultado global se encontró que 19 (42.2%) pacientes tuvieron neurodesarrollo normal (gris), 7 (15.5%) rezago en el neurodesarrollo (gris claro) y 19 (42.2%) con riesgo de retraso en el desarrollo (negro). De los pacientes que presentaron riesgo de retraso el 52% fueron del grupo de leucemias y linfomas, el 71% en el grupo de retinoblastoma y el 23% del grupo de tumores sólidos (p = 0.06). CONCLUSIONES: La presencia de riesgo de retraso y rezago en el neurodesarrollo es frecuente en menores de 5 años con diagnóstico de cáncer. Se requieren más estudios, para evaluar el efecto del tratamiento en este grupo de pacientes, ya que pueden influir diversos factores.

The additional benefit of computed tomography in cancer patients: impacts of sarcopenia and cachexia on quality of life during chemotherapy.

Objective: This study evaluates the effects of sarcopenia and cachexia on the quality of life (QoL) of patients with gastrointestinal cancer during their initial cycle of chemotherapy, emphasizing the significance of computed tomography (CT) in assessing muscle mass. Materials and Methods: In this prospective study, we evaluated 60 adult patients with gastrointestinal cancer who started chemotherapy between January and December of 2017. Sarcopenia was diagnosed on the basis of CT findings, and QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Results: The mean age was 60.9 years, and 33 (55.0%) of the patients were men. Of the 60 patients, 33 (55.0%) had cachexia and 14 (23.3%) had sarcopenia. Chemotherapy significantly reduced QoL, particularly in the physical, role functioning, and social domains, with no differences between the cachexia and sarcopenia groups. Conclusion: Among patients with gastrointestinal cancer submitted to chemotherapy, the chemotherapy-induced decline in QoL does not seem to differ significantly between those with cachexia or sarcopenia, as classified by CT-measured muscle mass, and those without. However, CT-based muscle mass evaluation remains crucial for guiding customized intervention strategies. Integrating this evaluation in radiological reports can provide valuable insights for planning specific care, thus improving patient QoL during treatment.

Objetivo: Este estudo avalia os efeitos da sarcopenia e da caquexia na qualidade de vida de pacientes com câncer gastrointestinal durante o ciclo inicial de quimioterapia, enfatizando a importância da tomografia computadorizada (TC) na avaliação da massa muscular. Materiais e Métodos: Estudo prospectivo com 60 pacientes adultos com câncer gastrointestinal que iniciaram quimioterapia de janeiro a dezembro de 2017. A TC foi utilizada para o diagnóstico de sarcopenia e o Quality of Life Questionnaire Core 30 da European Organization for Research and Treatment of Cancer foi utilizado para avaliar a qualidade de vida. Resultados: A média de idade dos pacientes foi 60,9 anos e 33 (55%) eram homens. Entre os pacientes, 33 (55%) eram caquéticos e 14 (24%) eram sarcopênicos. A quimioterapia reduziu significativamente a qualidade de vida, especialmente nos domínios físico, de desempenho de papéis e social, sem diferenças entre os grupos caquéticos e sarcopênicos. Conclusão: A diminuição da qualidade de vida não difere significativamente entre pacientes caquéticos/sarcopênicos e não caquéticos/não sarcopênicos com câncer gastrointestinal submetidos a quimioterapia, conforme classificado pela massa muscular medida por TC. No entanto, a avaliação da massa muscular por TC continua crucial para orientar estratégias de intervenção personalizadas. A integração dessa avaliação nos laudos radiológicos pode fornecer informações valiosas para o planejamento de cuidados específicos, melhorando a qualidade de vida dos pacientes durante o tratamento.

Olanzapine vs. magnesium valproate vs. lamotrigine in anti-N-methyl-D-aspartic acid receptor encephalitis: a retrospective study.

BACKGROUND: This study aimed to compare the impact of olanzapine, magnesium valproate, and lamotrigine as adjunctive treatments for anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. And it is expected to add supporting points related to the rebalance of neurotransmitters in the brain through adjuvant therapy in the clinical management of anti-NMDAR encephalitis. METHODS: This retrospective study included patients diagnosed with anti-NMDAR encephalitis who received standardized immunotherapy at Hunan Brain Hospital between January 2018 and December 2020. RESULTS: Compared to the olanzapine group, both the magnesium valproate and lamotrigine groups showed lower scores on the positive and negative symptom scale (PANSS) total score after 3 weeks of treatment (all P < 0.05). The Montreal Cognitive Assessment Scale (MoCA) scores in the magnesium valproate and lamotrigine groups were significantly higher than in the olanzapine group after 3 weeks and 3 months of treatment (all P < 0.05). After 3 months of treatment, the proportions of patients with a modified Rankin scale score (mRS) of 0-1 in the magnesium valproate and lamotrigine groups were significantly higher than in the olanzapine group (all P < 0.05). The electroencephalogram (EEG) abnormality ranks at 3 months were significantly lower in the magnesium valproate and lamotrigine groups compared with the olanzapine group (all P < 0.05). Furthermore, the Glx/Cr ratio significantly decreased after 3 months of treatment (all P < 0.05) in the magnesium valproate and lamotrigine groups, while the Glx/Cr ratio in the olanzapine group showed no significant change (P > 0.05). CONCLUSION: Compared with olanzapine, the addition of magnesium valproate or lamotrigine to immunotherapy might be associated with a lower PANSS score, higher MoCA score, and lower mRS score. The improvement of neurological functions and cognitive function may be related to the decreased Glx/Cr ratio.

Rapid achievement of low-density lipoprotein cholesterol goals within 1 month after acute coronary syndrome during combination therapy with rosuvastatin, ezetimibe and bempedoic acid: Initial experience from the LAI-REACT study.

Rapid reduction of low-density lipoprotein cholesterol (LDL-C) to target levels immediately following acute coronary syndrome (ACS) event is critical to prevent future events. High-dose statins alone often fail to achieve LDL-C goals. Proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) combined with high-dose statins improves LDL-C goal attainment, but is unaffordable for many patients in India and worldwide. In a real-world open-label study, we demonstrated in a cohort of 122 patients with ACS, concurrent triple therapy with rosuvastatin 40 mg/d, ezetimibe 10 mg/d, and bempedoic acid 180 mg/d (REB) started at the time of hospital admission was associated with 57.7%, 61.7%, 61.9% and 60.6% reductions in LDL-C from 115.6 mg/dL at baseline to 48.9 mg/dL at week 1, 44.3 mg/dL at week 2, 44.1 mg/dL at week 4, and 45.6 mg/dL at week 6, respectively (each p < 0.001 compared to baseline; p < 0.001 across repeated measures). REB provided significant reductions in LDL-C within as early as one week and enabled 76.3% and 92.2% of patients to achieve the Lipid Association of India and American College of Cardiology recommended LDL-C targets of <50 mg/dl and <70 mg/dl within 2-weeks, respectively, which were sustained at 4-6 weeks. REB was generally well tolerated. Our study demonstrates the capacity to rapidly achieve LDL-C goals after ACS with triple REB therapy, an affordable regimen in India.

Reversible chemoresistance of pancreatic cancer grown as spheroids.

Better in vitro models are needed to identify active drugs to treat pancreatic adenocarcinoma (PAC) patients. We used 3D hanging drop cultures to produce spheroids from five PAC cell lines and tested nine FDA-approved drugs in clinical use. All PAC cell lines in 2D culture were sensitive to three drugs (gemcitabine, docetaxel and nab-paclitaxel), however most PAC (4/5) 3D spheroids acquired profound chemoresistance even at 10 µM. In contrast, spheroids retained sensitivity to the investigational drug triptolide, which induced apoptosis. The acquired chemoresistance was also transiently retained when cells were placed back into 2D culture and six genes potentially associated with chemoresistance were identified by microarray and confirmed using quantitative RT-PCR. We demonstrate the additive effect of gemcitabine and erlotinib, from the 12 different combinations of nine drugs tested. This comprehensive study shows spheroids as a useful multicellular model of PAC for drug screening and elucidating the mechanism of chemoresistance.

Steroid-Dependent Recurrent IgA Vasculitis in a 19-Year-Old Woman.

Background: Immunoglobulin A (IgA) vasculitis is common in children and typically resolves spontaneously. However, when presenting in adults, it is more likely to be severe and recurrent. Case Presentation: We present the case of a 19-year-old female patient with recurrent steroid-dependent IgA vasculitis. She had a history of a prolonged episode of IgA vasculitis in childhood. She presented to our hospital with proteinuria and a painful, palpable purpuric rash on her bilateral lower extremities. She was treated with high-dose intravenous steroids. When steroids were tapered, the patient had a recurrence of her painful rash. Over several months, she developed steroid-induced hyperglycemia and worsening proteinuria. Conclusion: Recent studies have shown that corticosteroids have limited effect on long-term outcomes in IgA vasculitis, but steroid-sparing agents have potential for the treatment of recurrent steroid-dependent IgA vasculitis.

Drug Therapy Problems Identified by Clinical Pharmacists at a General Surgery Ward of an Academic Referral Hospital in Jordan.

Introduction: Drug therapy problems (DTPs) continuously occur in hospitalized patients. This study aims to emphasize the role of clinical pharmacists in evaluating the DTP's frequencies, causes, severity ratings, and contributing factors at a general surgery ward in Jordan. Methods: This prospective observational study was conducted at one of the major teaching and referral hospitals in Jordan. Data were collected through clinical pharmacist reviews of paper and electronic medical records as well as patient interviews. DTPs were identified using Cipolle's classification system and rated for severity on a scale of 10. Multiple linear regression was performed to identify factors contributing to DTPs. Drug classes primarily associated with DTPs were specified. Results: During enrollment, a total of 80 patients were recruited in this study. The mean age of the enrolled patients was 52.35 ± 14.82 years, and 49 (61.25%) of them were males. Within the study period, 192 DTPs were identified by clinical pharmacists in 87.5%of the total recruited patients. The mean number of DTPs per patient was 2.40 ± 1.83. The most common categories of DTPs were "needs additional therapy" 46 (23.96%), "unnecessary drug therapy" 45 (23.44%), and "dosage too low" 39 (20.31%). Of the total DTPs, 127 (66.15%) were rated as severe. Multiple linear regression revealed that patients' length of hospital stay and the number of current medications had a statistically significant effect on the number of DTPs identified during hospitalization. Endocrine and metabolic drugs 51 (26.56%) and cardiovascular drugs 36 (18.75%) were the most frequent classes of drugs contributing to DTPs. Conclusion: DTPs are common in the general surgery ward. Clinical pharmacists can provide medication reviews for surgical patients to identify DTPs and rate their severities. Detecting risk factors for DTPs and the most common drug classes associated with them can assist in decision-making relevant to reducing DTPs in the surgical ward.

Safety and efficacy of laser trabeculoplasty compared to drug therapy for the management of open-angle glaucoma: systematic review and meta-analysis study.

BACKGROUND: Intraocular  pressure (IOP) reduction is the approach that is commonly accepted for the control of open-angle glaucoma (OAG). Medical therapy is typically the first-line of treatment. Laser trabeculoplasty (LT) is an alternative therapy; however, whether pharmaco-therapeutic options can be replaced by LT as the first-line is still debatable. METHODS: studies conducted till July 2023 that compared the efficacy of medications and LT for OAG were retrieved from databases such as Embase, PubMed, Cochrane Library, and Web of Science. We completed data extraction for outcomes of interest. The quality of eligible studies was evaluated and random-effects (RE) model was applied for analysis. RESULTS: A total of eighteen trials with 2024 patients were included in the analysis. Overall, there was no statistically significant difference between therapies including laser trabeculoplasty (LT) and drug therapy in terms of successful IOP control (RR:1.30, 95%CI: 0.96, 1.78, P = 0.09, I2 = 96%), and reducing intraocular pressure (IOP) (MD:0.15; 95%CI:-0.55,0.85; P = 0.67, I2 = 62%). A significant reduction in drug therapy need in comparison to the group that received medicine (MD:-1.07; 95%CI;-1.21,-0.93), P < 0.001, with a low heterogeneity level (I2 = 16%). Adverse ocular events were more common in the argon laser group (RR:11.71, 95%CI: 9.93, 23.1; P < 0.001). CONCLUSION: Both LT and topical drug therapy exhibit comparable rates of success and efficacy in reducing intraocular pressure in patients with open-angle glaucoma. Selective LT is considered a safe treatment option with a reduced occurrence of adverse effects on the eyes while eliminating the possible adherence concerns associated with topical medicine and it can be considered a viable initial option for first OAG treatment. KEY MESSAGES: What is known Drug therapy is typically the 1st line of treatment for open-angle glaucoma. Although drugs have been shown to effectively reduce intraocular pressure (IOP), they are associated with a range of ocular and systemic negative effects which contributes to suboptimal adherence to medications. Laser trabeculoplasty (LT) is an alternative therapy; however, whether pharmaco-therapeutic options can be replaced by LT as the first-line is still debatable. What is new In terms of IOP reduction and IOP success rate, LT therapy was comparable in efficacy to drug therapy according to our findings. The safety profile of selective LT was found to be preferable compared to Argon LT.

Practice review: Pharmacological management of severe chronic breathlessness in adults with advanced life-limiting diseases.

BACKGROUND: Severe and refractory chronic breathlessness is a common and burdensome symptom in patients with advanced life-limiting disease. Its clinical management is challenging because of the lack of effective interventions. AIM: To provide practice recommendations on the safe use of pharmacological therapies for severe chronic breathlessness. DESIGN: Scoping review of (inter)national guidelines and systematic reviews. We additionally searched for primary studies where no systematic review could be identified. Consensus on the recommendations was reached by 75% approval within an international expert panel. DATA SOURCES: Searches in MEDLINE, Cochrane Library and Guideline International Network until March 2023. Inclusion of publications on the use of antidepressants, benzodiazepines, opioids or corticosteroids for chronic breathlessness in adults with cancer, chronic obstructive pulmonary disease, interstitial lung disease or chronic heart failure. RESULTS: Overall, the evidence from eight guidelines, 14 systematic reviews and 3 randomised controlled trials (RCTs) on antidepressants is limited. There is low quality evidence favouring opioids in patients with chronic obstructive pulmonary disease, cancer and interstitial lung disease. For chronic heart failure, evidence is inconclusive. Benzodiazepines should only be considered for anxiety associated with severe breathlessness. Antidepressants and corticosteroids should not be used. CONCLUSION: Management of breathlessness remains challenging with only few pharmacological options with limited and partially conflicting evidence. Therefore, pharmacological treatment should be reserved for patients with advanced disease under monitoring of side effects, after optimisation of the underlying condition and use of evidence-based non-pharmacological interventions as first-line treatment.