Adjunctive Agents Research Articles

Implications of opioid-sparing medications in critically ill patients: A scoping review

ObjectiveThe purpose of this scoping review was to evaluate literature involving opioid-sparing medications in critically ill patients with a focus on clinically meaningful outcomes. DesignScoping review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. SettingIntensive care unit. Patients or participantsAdult patients in an intensive care unit setting. InterventionsNone. Main variables of interestPubMed and Cochrane Library were searched from October 1, 2019 to June 1, 2023. Inclusion criteria consisted of randomized controlled trials evaluating adjunctive analgesic use in adult patients in an intensive care unit setting. ResultsThere were 343 citations and titles identified in the initial search, with 328 remaining after removal of duplicates, 294 excluded at title and abstract screening, 34 available for full text review, and six included in the scoping review. Most studies reported modest reductions in opioid use as a secondary endpoint. Improvement in clinical outcomes such as reduction in duration of mechanical ventilation or delirium were reported in two trials with dexmedetomidine. ConclusionsIn recently published trials of adjunctive agents in critically ill patients, opioid-sparing effects were small. Data to support improvements in clinical outcomes remains limited.

A Critical Review of Postbiotics as Promising Novel Therapeutic Agents for Clostridial Infections.

Clostridial infections, known for their severity and rapid progression, present significant challenges in both clinical and veterinary fields. These bacteria, which can survive without oxygen and produce protective spores, cause many diseases, ranging from simple gastrointestinal disorders to severe and potentially fatal infections including botulism, tetanus, and gas gangrene. The rising occurrence of antibiotic-resistant strains and the repetitive character of some Clostridial illnesses, including Clostridioides difficile infections (CDI), highlight the immediate need for alternate treatment approaches. Postbiotics, which are metabolites derived from probiotics, are showing great potential as effective agents against these diseases. The current study offers a comprehensive investigation of the potential of postbiotics as therapeutic agents for treating Clostridial infections, including C. difficile, Clostridium perfringens, Clostridium botulinum, and Clostridium tetani. It also examines the processes by which postbiotics exert their effects. Preliminary investigations have shown that postbiotics have promising antibacterial and antibiofilm properties, indicating their potential as adjunct agents in methods for controlling microbial growth. Nevertheless, more study is required to thoroughly demonstrate their medicinal uses.

Major considerations of maxillary/mandible osteonecrosis caused by bisphosphonates in the dental implant scenario: a systematic review

Introduction: The literature has shown that several patients with a history of bisphosphonate treatment appear to be at risk for medication-related osteonecrosis of the jaw (MRONJ) osteonecrosis of the jaw. Objective: It was analyzing the use of BP associated with dentistry. Because it is a possible alternative for the reduction of loss and increase in bone density, as well as for the possibility of osteonecrosis, which requires therapeutic and preventive measures in the involvement of invasive practices such as dental implants. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from April to June 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: 85 articles were founded, and 54 articles were evaluated and 30 were included in this systematic review. Considering the Cochrane tool for risk of bias, the global assessment resulted in 24 studies with a high risk of bias and 18 studies that did not meet GRADE and AMSTAR-2. Most studies showed homogeneity in their results, with X2 =81.9% >50%. It was concluded that osteoporosis is a metabolic condition that affects alveolar bone density, but does not present problems for the installation of osseointegrated implants, as long as there is sufficient bone mass in the region where the tooth will be implanted. It suggests to the dental surgeons the knowledge of the diagnosis so that it makes a careful evaluation, directing the professional to observe the quality of the bone through routine image examinations. Further, alendronate sodium is used to decrease bone resorption, the drug should be considered as an adjunctive therapeutic agent for the treatment of osteoporosis.

A Three-Month Clinical Trial on the Efficacy of Hyaluronic Acid Adjunctive Non-Surgical Therapy for Periodontitis in Patients with Type 2 Diabetes Mellitus.

Background/Objectives: Conventional periodontal treatment for patients with diabetes has shown promising results, primarily focusing on glycated hemoglobin (HbA1c) levels as an endpoint measure. The properties of hyaluronic acid (HA) have been harnessed in various periodontal therapies, and it is a promising agent also in a non-surgical approach. The aim of this clinical trial was to assess the efficacy of hyaluronic acid in a local adjunctive non-surgical treatment for periodontitis in patients with type 2 diabetes. Methods: Eighty adult participants with well-controlled type 2 diabetes (HbA1c 7% (53 mmol/mol) or less) took part in the trial. The clinical parameters of periodontitis as well as the glycated hemoglobin (HbA1c) levels were evaluated, and an analysis of the potential differences between the control (placebo) and intervention (HA) groups was performed. Results/Conclusions: A decrease in all the clinical values of periodontitis after treatment was observed in the vast majority of patients in both groups. Differences in the clinical parameters were observed 12 weeks after the intervention between the patients in the placebo and HA therapy groups. Bleeding on probing (BoP) was reduced in the control group to 15-25% and was approximately 5.5% more in the intervention group (9.5-18.25%). The clinical attachment level (CAL) decreased 1 mm more in the HA therapy group (1-2 mm) than in the no adjunctive treatment group (2-3 mm). The probing depth (PD) was reduced similarly in both groups (3-3.75 mm). Due to the bilateral relationship between diabetes and periodontitis, healthcare professionals seek advancements in managing periodontal inflammation. The results of this study indicate that non-surgical periodontal treatment with HA as an adjunctive agent is worth considering in the therapy for patients with diabetes.

Multifunctional Indomethacin Conjugates for the Development of Nanosystems Targeting Cancer Treatment.

It is well known that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin (IND) exhibits significant anticancer potential reported not only by in vitro and in vivo studies, but also in clinical trials. Despite promising results, IND is not widely used as an adjunctive agent in cancer therapy due to the occurrence of several gastrointestinal side effects, primarily after oral administration. Therefore, this study aimed to develop a nanosystem with reduced toxicity and risk of side effects for the delivery of IND for cancer treatment. IND was encapsulated in nanostructured lipid carriers (NLC) in the form of a phospholipid conjugate, where a covalent bond exists between the drug and phosphatidylcholine skeleton. For this purpose, seven new hybrid molecules were synthesized, and subsequently evaluated as anticancer agents in an in vitro model against selected cancer cell lines. Biological studies demonstrated that the synthesized conjugates possessed excellent antiproliferative effects, exhibiting a 2.7-fold to even 100-fold higher activity against selected cancer cells, while remaining non-toxic to healthy cells. Based on biological studies and molecular calculations, heterosubstituted phosphatidylcholine containing IND and oleic acid (IND-OA-PC) in the sn-1 and sn-2 positions, respectively, was identified as the most potent molecule. Subsequently, IND-OA-PC was encapsulated in nanostructured lipid carriers (IND-OA-PC-NLC). The results revealed that IND-OA-PC-NLC has a spherical shape with an average diameter of 155 nm and a negatively charged surface (-17.4 ± 0.49 mV). In this study, it was proven that the encapsulated conjugate of indomethacin with PC exhibits high activity against triple-negative (TNBC, Her2-, PR-, and ER-) breast cancer cells MDA-MB-468. While free IND was active at a concentration of 270.5μM, in the form of the phospholipid conjugate (IND-OA-PC), it inhibited the growth of cancer cells at 67.5μM and after conjugate encapsulation (IND-OA-PC-NLC) it was effective at only 10.3μM. Our study revealed that the conjugation of NSAID with phosphatidylcholine and its combination with nanotechnology techniques create opportunities to repurpose well-known drugs from this group for new therapeutic applications.

Autogenous soft tissue grafting in aesthetic peri-implant surgical reconstruction

Introduction. Autogenous soft tissue grafting in aesthetic peri-implant surgical reconstruction is an effective technique for augmenting the tissues surrounding dental implants, contributing to their longterm success. This method involves harvesting soft tissue from the patient and placing it around the implant to enhance peri-implant thickness, stability, and aesthetics. Objective of the study. The study aims to evaluate the effectiveness of autogenous soft tissue grafting in peri-implant augmentation compared to other techniques and identify the factors contributing to the procedure’s success. Material and methods. The analysis was based on scientific articles published in the last five years, selected from PubMed, Scopus, and Cochrane Library. Randomized clinical trials, systematic reviews, and cohort studies comparing autogenous grafting with other methods were included. Studies with fewer than 10 patients were excluded. A total of 1,150 articles were identified, of which 20 were included in the analysis. Results. The reviewed studies demonstrated that autogenous grafting improves soft tissue thickness and reduces the incidence of gingival recession compared to other augmentation techniques. Most studies reported a significant increase in soft tissue stability following this procedure. Conclusions. Autogenous soft tissue grafting is a gold standard method for aesthetic peri-implant reconstruction, showing superior effectiveness in improving soft tissue stability and aesthetics. The success of the intervention depends on appropriate patient selection and the application of rigorous surgical techniques. The integration of adjunctive biological agents and minimally invasive techniques can further enhance the efficiency and predictability of long-term outcomes.

POST‐UK (Adjunctive Intra‐Arterial Urokinase After Successful Endovascular Thrombectomy in Patients With Large‐Vessel Occlusion Stroke): Study Protocol of a Multicenter, Prospective, Randomized, Open‐Label, Blinded‐End Point Trial

BACKGROUND Intra‐arterial infusion of an adjunctive thrombolytic agent after macrovascular recanalization by endovascular thrombectomy was regarded as a promising strategy to promote outcomes of patients with stroke. Given the characteristics of urokinase as an affordable, available, and widely applied medication, especially in Eastern countries, this trial aims to assess the safety and efficacy of intra‐arterial urokinase as adjunct to endovascular thrombectomy in improving outcomes among patients with anterior large‐vessel occlusion stroke after excellent to complete reperfusion. METHODS The POST‐UK (Adjunctive Intra‐Arterial Urokinase After Successful Endovascular Thrombectomy in Patients With Large Vessel Occlusion Stroke) trial is a multicenter, prospective, randomized, open‐label, blinded‐end point trial conducted in China. The planned sample size is 498. Those eligible patients with anterior circulation large‐vessel occlusion stroke and achieving excellent to complete reperfusion by endovascular thrombectomy are planned to be consecutively randomized in a 1:1 ratio to the experimental group (a single dose of intra‐arterial urokinase) or to standard of care. RESULTS The primary outcome is a freedom from disability (modified Rankin Scale score of 0–1) at 90±7 days. The safety outcomes are mortality within 90±7 days and symptomatic intracranial hemorrhage within 48 hours. CONCLUSION The POST‐UK trial will provide valuable insight of efficacy and safety of intra‐arterial urokinase in patients with large‐vessel occlusion stroke after achieving excellent to complete reperfusion by endovascular thrombectomy.

A study of intracoronary thrombolytic agents in high thrombotic burden lesions during primary PCI

Abstract Objectives High thrombus burden during Primary PCI begets worst possible outcomes, studies on adjunctive intracoronary thrombolytic agents show heterogeneous1,2 results & have limited long term follow-up. Although early studies support mechanical thrombectomy devices, larger randomized trial show that they are not able to reduce the MACE3, 4. There is no randomised clinical data for sustained mechanical thrombectomy devices till now. Purpose of the study The main purpose of this study is to analyse long term outcomes of low bleeding risk group patients undergoing Primary PCI with high thrombus burden, receiving intracoronary thrombolytic agents as an adjunctive therapy. Methods In this prospective observational single centre study, we analysed one year follow-up data of 108 consecutive primary PCI patients with high thrombus burden (G4, G5) and low bleeding risk, who were stratified into two groups basing on whether they receive intracoronary thrombolytic agent as an adjunctive agent before stent implantation. The primary outcome was NACE (Net Adverse Clinical Events, which include MACE, Death, ST/MI, major bleeding events), secondary outcomes include the individual components of the primary outcomes when analysed separately. Results The primary outcome events occurred in 21 patients (26%) in Primary stent group(PS, n=80), whereas it occurred in 2 patients(6%) in primary intra coronary thrombolysis group(PIT, n=28). Log-Rank (Mantel Cox) NACE curves show that PS group has high events when compared to PIT group(26% Vs 7%, p value – 0.042, Hazard ratio - 2.56; 95% CI - 0.76 – 8.57), there is no statistically significant difference in all other key secondary outcome event curves. Conclusion In patients presenting with STEMI, undergoing primary PCI, with high thrombus burden & low bleeding risk group, those receiving intracoronary thrombolytic agent as the adjunctive therapy before stent implantation, are able to reduce the NACE event rates during the one year of follow-up.Fig1:Log Rank (Mantel Cox) NACE curve

Artemisia argyi polysaccharide alleviates osmotic diarrhea by enhancing intestinal barrier protection and anti-inflammation

Artemisia argyi polysaccharide (AAP) is a homogeneous polysaccharide with a molecular weight of 16 kDa, displaying anti-inflammatory, antioxidant, and anti-tumorigenic properties, and potential protective effects on intestinal barrier function. It is anticipated to serve as an efficient component in diarrhea treatment. This study aims to examine the impact of AAP on diarrhea severity, intestinal barrier function, and inflammation in diarrhea-induced rats. The results demonstrated that AAP treatment notably decreased the incidence of diarrhea, reduced its severity, and lowered the disease activity score in rats, while also increasing body weight. Oral administration of AAP augmented goblet cell counts and elevated mucin-2 expression, aiding in the restoration of the mucus barrier. Additionally, AAP treatment enhanced colonic microbial diversity by increasing the abundance of S24–7 and Lactobacillus, while decreasing the levels of Bacteroides, Clostridium, and Sutterella. Moreover, the AAP administration elevated the levels of steroid hormones, prostaglandins, and their derivatives. By inhibiting the TLR4/MyD88/NF-κB pathway, AAP mitigated the release of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and increased the secretion of anti-inflammatory factor (IL-10). Overall, oral AAP administration effectively combats osmotic diarrhea by fortifying mucus barrier integrity and exerting anti-inflammatory effects, suggesting its potential use as an adjunctive agent in oral rehydration therapy.

Evaluation of Anti-Proliferative and Apoptosis-Inducing Activities of the New Ciprofloxacin Derivative on Human Leukemia NB4 Cells

Backgrounds:: Leukemic stem cells are considered to be the main cause of treatment failure and disease recurrence due to their resistance to most common therapies. Apoptosis induction is one of the highly effective methods for treating cancer. Ciprofloxacin is among the compounds whose antitumor effects have been confirmed. Objectives: In this study, we investigated the anti-proliferative effect and induction of apoptosis by one of the derivatives of this family called 1-Cyclopropyl-6-fluoro-7-[4-(2-{[(1R,2S,5R)- 2- isopropyl-5-methylcyclohexyl]oxy}-2-oxoethyl)-piperazin-1-yl]-4-oxo-1,4-dihydroquinoline-3- carboxylic acid (ICH-CP) on NB4 cell line as an in vitro model of Acute promyelocytic leukemia (APL). NB4 cells were treated using the ICH-CP combination in various concentrations. Methods: The viability of NB4 cells was evaluated by MTT assay, and their morphology of apoptosis was examined by fluorescence microscopy. Flow cytometry and Annexin V/PI staining were used to quantify apoptosis. Finally, the expression of three genes, Bax, Bcl-2, and Survivin was inquired by real-time PCR. Results: According to the results, ICH-CP was able to destroy about 60% of NB4 cells in a dose and time-dependent manner. Light microscopy and fluorescence microscopy studies on treated cells confirmed the induction of apoptosis. Also, the real-time PCR analysis showed that ICH-CP induces apoptosis in the NB4 cell line via the down-regulation of Survivin and Bcl-2, in contrast to the up-regulation of the Bax gene. Conclusion: Based on the present data, it seems that the novel compound can be a good candidate for the treatment of acute myeloid leukemia. Furthermore, it is recommended to evaluate the qualification of ICH-CP as an adjunctive agent for other cancer cell lines.

The Role of Adjunctive Triamcinolone Acetonide in Post-traumatic Vitreoretinal Surgery: Current Insights and Future Perspectives.

Post-traumatic vitreoretinal surgery is pivotal for repairing damage to the retina and vitreous body, commonly resulting from blunt or penetrating ocular trauma. Incorporating adjunctive pharmacological agents, particularly triamcinolone acetonide (TA), has gained considerable prominence in optimizing surgical outcomes. TA, a potent corticosteroid, is applied intraoperatively to improve the visualization of vitreous structures and epiretinal membranes, enabling surgeons to perform more precise maneuvers. Furthermore, its anti-inflammatory properties are instrumental in reducing postoperative complications such as macular edema and proliferative vitreoretinopathy (PVR), conditions that could hinder recovery and compromise visual acuity. TA use during vitrectomy enhances surgical precision and contributes to a smoother postoperative recovery. However, concerns surrounding potential side effects, such as steroid-induced ocular hypertension and cataract formation, necessitate careful patient selection and close monitoring throughout its use. Looking ahead, innovations in sustained-release formulations and combination therapies may further augment TA efficacy while reducing associated risks. This review provides current insights into TA application in post-traumatic vitreoretinal surgeries and highlights emerging trends poised to enhance its therapeutic role.

Associations between C-reactive protein and individual symptoms of depression in a lower-middle income country.

Data on associations between inflammation and depressive symptoms largely originate from high income population settings, despite the greatest disease burden in major depressive disorder being attributed to populations in lower-middle income countries (LMICs). We assessed the prevalence of low-grade inflammation in adults with treatment-resistant depression (TRD) in Pakistan, an LMIC, and investigated associations between peripheral C-reactive protein (CRP) levels and depressive symptoms. This is a secondary analysis of two randomised controlled trials investigating adjunctive immunomodulatory agents (minocycline and simvastatin) for Pakistani adults with TRD (n = 191). Logistic regression models were built to assess the relationship between pre-treatment CRP (≥ or <3 mg/L) and individual depressive symptoms measured using the Hamilton Depression Rating Scale. Descriptive statistics and regression were used to assess treatment response for inflammation-associated symptoms. High plasma CRP (≥3 mg/L) was detected in 87% (n = 146) of participants. Early night insomnia (odds ratio 2.33, 95% CI 1.16-5.25), early morning waking (odds ratio 2.65, 95% CI 1.29-6.38) and psychic anxiety (odds ratio 3.79, 95% CI 1.39-21.7) were positively associated, while gastrointestinal (odds ratio 0.38, 95% CI 0.14-0.86) and general somatic symptoms (odds ratio 0.34, 95% CI 0.14-0.74) were negatively associated with inflammation. Minocycline, but not simvastatin, improved symptoms positively associated with inflammation. The prevalence of inflammation in this LMIC sample with TRD was higher than that reported in high income countries. Insomnia and anxiety symptoms may represent possible targets for personalised treatment with immunomodulatory agents in people with elevated CRP. These findings require replication in independent clinical samples.

Comparison between Epiretinal Membrane Component in Proliferative Vitreoretinopathy and Other Fibroproliferative Diseases: A Scoping Review

The growth of proliferative vitreoretinopathy epiretinal membrane (PVR-ERM) is a major complication of rhegmatogenous retinal detachment (RRD). Despite surgery, adjunct treatment is necessary to control the aberrant wound healing response that occurs in PVR-ERM to prevent its recurrence. Existing studies on adjunct agents target pathways in the pathogenesis of PVR-ERM. We conducted a scoping review of composition of PVR-ERMs and other fibroproliferative ERMs. After literature search, 12 articles were included into the study. Outcome measured was gene expression, growth factors, extracellular matrix components, and enzymes.Among these studies, 9 compared PVR-ERM with PDR-ERM, 2 compared PVR-ERM with iERM, and 1 compared PVR-ERM with secondary ERM. Higher expression of certain genes or a higher concentration of particular factors can be observed throughout PVR, PDR, iERM, or secondary ERM.TGF-β, MALAT1 gene, and fibronectin are distinct factors that might play a bigger role on the pathogenesis of PVR compared to other fibroproliferative diseases.

Polysaccharide NAP-3 Synergistically Enhances the Efficiency of Metformin in Type 2 Diabetes via Bile Acid/GLP-1 Axis through Gut Microbiota Remodeling.

The polysaccharides of edible mushrooms are excellent phytochemicals for adjuvant treatment of metabolic diseases, but the potential mechanisms of synergistic effects are unclear. In this work, we discovered that NAP-3 enhanced the efficiency of metformin in lipid and glucose metabolism in type 2 diabetic (T2D) mice in a gut microbiome-dependent way. NAP-3 remodeled the intestinal microbial, resulting in the decreased activity of bile salt hydrolases and upregulation of CYP27A1 and CYP7B1 functions in the alternative pathway of bile acid synthesis, which leads to accumulation of the conjugated bile acids in ileum, specifically TβMCA and TUDCA. The accumulated conjugated bile acids either blocked or stimulated the nuclear receptors Farnesoid-X-receptor and TGR5, inducing the release of GLP-1 and ultimately enhanced glucose metabolism in mice. Collectively, our research indicated that edible mushroom polysaccharide NAP-3 may serve as a promising adjunctive oral therapeutic agent for T2D.

Does the Use of Injectable Platelet-Rich Fibrin Following Arthrocentesis for Disc Displacement Without Reduction Alleviate Pain?

The role of adjunctive injection agents at the end of temporomandibular joint (TMJ) arthrocentesis remains controversial. This study aims to compare pain reduction in patients with disc displacement without reduction treated with arthrocentesis alone (AO), arthrocentesis with injectable platelet-rich fibrin (iPRF), and arthrocentesis with hyaluronic acid (HA). A single-center, retrospective cohort study was conducted at the affiliated hospital of Health Sciences University, Hamidiye Faculty of Dentistry. Inclusion criteria were female subjects aged 18-65, who underwent TMJ unilateral arthrocentesis, and diagnosed with disc displacement without reduction. Exclusion criteria were prior use of occlusal splints, accompanying diagnosis of myalgia and bilateral arthralgia which both of the joints exceeds or equal to 50mm visual analogue scale for pain (pVAS) value. The primary predictor variable was the adjunctive injection agent: iPRF, HA, or no injection (AO as control). Primary and secondary outcomes were measured preoperatively (T0), and at 1month (T1) and 6months (T2) postoperatively. The primary outcome was pain (pVAS) at T2. Secondary outcomes were pVAS at T1 and maximum interincisal opening at T1 and T2. Demographics, preoperative and perioperative data were collected. Descriptive, bivariate, and multivariate analyses were conducted. The P value was set at ≤.05. A total of 88 subjects completed the study. The mean age of the subjects in the AO (n=30), HA (n=29) and iPRF (n=29) groups was 36.8 (±10.2), 34.8 (±8.9) and 37.6 (±11.6) respectively (P>.05). The mean pVAS scores at T0 for the AO, HA and iPRF groups were 63.2 (±8.7), 66.7 (±9.6) and 66.2 (±9.6) respectively (P>.05). The mean pVAS scores at T1 were 36.5 (±10.8), 29.0(±11.5) and 35.9 (±9.8) respectively (P<.05). The mean pVAS scores at T2 were 34.8 (±16.3), 24.7 (±12.7) and 25.3 (±13.4) respectively (P<.05). There were no differences in maximum interincisal opening between the groups at any timepoint (P>.05). iPRF and HA injections are associated with greater pain relief compared to AO. No significant difference was observed between iPRF and HA, suggesting that the choice between them can be based on cost-effectiveness.

Phenobarbital as an adjunctive agent for sedation in pediatric intensive care unit patients: A single-center, retrospective study from Colorado

Abstract Background: Pediatric patients require pharmacological management of pain and agitation associated with mechanical ventilation. Pain and agitation may be refractory to opioids and alpha-2 agonists, prompting the use of adjunctive analgesics and sedatives with alternative mechanisms. The purpose of this study was to describe the use of phenobarbital as an adjunctive agent for refractory agitation in critically ill, mechanically ventilated pediatric patients. Subjects and Methods: This was a single-center, retrospective chart review at a pediatric intensive care unit (PICU) at a pediatric academic medical center in America between 2016 and 2021. Children aged 2 months to 18 years old were admitted to the PICU were mechanically ventilated and received phenobarbital for adjunct sedation. Sixty-three patients had phenobarbital dosing data evaluated, and the 38 patients who were not receiving continuous neuromuscular blockade were included in the primary and secondary outcome analysis of time within the goal sedation score. Descriptive statistics was used to assess baseline characteristics and the primary outcome. Wilcoxon signed-rank tests were used to evaluate secondary outcomes. Results: Patients spent significantly more time within the goal sedation score range after phenobarbital compared to before phenobarbital. The median number of rescue sedative boluses, morphine equivalents (MEs), and benzodiazepine equivalents (BZDE) significantly decreased 2 days after the first phenobarbital dose compared to the 2 days before the first phenobarbital dose. Conclusions: The use of phenobarbital as an adjunct sedative was associated with a statistically significant increase in time spent in the goal sedation score range and decrease in ME, BZDE, and concomitant sedative boluses.

Management of massive haemorrhage in transfusion medicine services in the Middle East and North Africa.

Massive transfusion protocols (MTPs) are critical in managing haemorrhage, yet their utilization varies. There is lack of data on the utilization of MTPs in the Middle East and North Africa (MENA) region. This study aims to assess the degree of utilization of MTPs in the region. We conducted a survey to collect data on MTP use, inviting medical directors of transfusion services from various hospitals. Data were analysed to determine the prevalence of MTP utilization, their compositions, challenges in application and areas of future need. Eighteen respondents participated, representing 11 countries in the region. Thirteen hospitals implemented MTP, and eight included paediatrics. Eleven institutions used more than one definition of massive haemorrhage, with the most common being ≥10 red blood cell (RBC) units transfused for adults and replacement of >50% total blood volume in paediatrics. The majority of sites with MTPs utilized 1:1:1 RBCs:platelets:plasma ratio (70%). Variations were observed in the types and blood groups of components used. Two sites utilized whole blood, while six are considering it for future use. Utilization of adjunctive agents and frequency of laboratory testing varied among the sites. Challenges included the lack of medical expertise in protocol development, adherence and paediatric application. The need assessment emphasized the need for developing regional guidelines, standardized protocols and training initiatives. Although several hospitals have adopted MTPs, variations exist in activation criteria, blood product ratios and monitoring. Challenges include the lack of medical expertise, protocol adherence and addressing paediatric needs. Standardizing protocols, enhancing training and paediatric application are crucial for improving massive transfusion management in the region.

Overweight and Obesity in People Living With Type 1 Diabetes: A Cross-Sectional Analysis of the BETTER Registry.

The prevalence and associations of overweight and obesity in Canadian adult people living with type 1 diabetes (PWT1D) are poorly documented. In a cohort of PWT1D patients, this study assesses (i) overweight and obesity frequencies and associated PWT1D clinicodemographic characteristics, (ii) diabetes characteristics, and (iii) the use of noninsulin adjunctive agents. Cross-sectional analysis of self-reported data from the BETTER registry: 1091 adult PWT1D (aged 44.4±15.0years; 32% HbA1c<7% [53mmol/mol]) classified by BMI classes: underweight combined with normal weight, overweight, or obesity. Bivariate analyses were used to identify associations between BMI classes, diabetes characteristics, complications, and treatments. Overweight and obesity affected 34.6% and 19.8% of participants. Compared to underweight+normal weight, PWT1D with overweight/obesity was associated with male sex, higher age, lower education level, longer diabetes duration, and higher total insulin doses and use of cardiorenal therapies (all p<0.001). Compared to other PWT1D, those living with obesity reported higher HbA1c (p<0.05), less frequent hypoglycemia (p<0.05), more cardiovascular diseases (p<0.003), retinopathy, neuropathy, depression treatment as well as noninsulin adjunctive agent use (all p<0.001). Logistic regression showed that living with overweight/obesity was associated with male sex, being treated for cardiorenal therapies, depression, diabetes duration, and total daily insulin doses. Overweight or obesity affects over half of adult PWT1D in the Canadian BETTER registry and is associated with higher HbA1c levels, higher total daily insulin doses, more chronic diabetes complications and noninsulin adjunctive agent use, a worse cardiometabolic profile, and lower hypoglycemia frequency.

Adjunctive Intranasal Esketamine for Comorbid Treatment-Resistant Depression with Suicidal Ideation in Patients Receiving Palliative Care at a Comprehensive Cancer Center: A Case Series.

Background: The psychiatric needs of those with cancer and other advanced illnesses are becoming increasingly recognized. Ketamine is emerging as a promising treatment option for depressive disorders in psychiatric and palliative care. In the palliative care setting, its study has been hindered by lack of consistent administration routes and dosing. Intranasal (IN) esketamine (Spravato®) has recently received U.S. Food and Drug Administration (FDA) approval as an adjunctive agent for treatment-resistant depression (TRD) and major depressive disorder (MDD) with suicidal ideation (SI). Objective: We sought to offer IN esketamine to patients suffering from TRD and SI at a comprehensive cancer center. Methods: We designed and implemented a protocol to administer IN esketamine and describe three cases in which it was provided to patients with TRD and SI at a palliative care clinic in the United States. Results: Following treatment, all three patients had substantial reduction in depression severity and no further suicidalideation. These improvements were maintained for up to a year. No serious adverse events occurred. Conclusions: These cases illustrate the potential utility of IN esketamine in the palliative care setting.

Synergistic Strategies for Castration-Resistant Prostate Cancer: Targeting AR-V7, Exploring Natural Compounds, and Optimizing FDA-Approved Therapies.

Castration-resistant prostate cancer (CRPC) remains a significant therapeutic challenge due to its resistance to standard androgen deprivation therapy (ADT). The emergence of androgen receptor splice variant 7 (AR-V7) has been implicated in CRPC progression, contributing to treatment resistance. Current treatments, including first-generation chemotherapy, androgen receptor blockers, radiation therapy, immune therapy, and PARP inhibitors, often come with substantial side effects and limited efficacy. Natural compounds, particularly those derived from herbal medicine, have garnered increasing interest as adjunctive therapeutic agents against CRPC. This review explores the role of AR-V7 in CRPC and highlights the promising benefits of natural compounds as complementary treatments to conventional drugs in reducing CRPC and overcoming therapeutic resistance. We delve into the mechanisms of action underlying the anti-CRPC effects of natural compounds, showcasing their potential to enhance therapeutic outcomes while mitigating the side effects associated with conventional therapies. The exploration of natural compounds offers promising avenues for developing novel treatment strategies that enhance therapeutic outcomes and reduce the adverse effects of conventional CRPC therapies. These compounds provide a safer, more effective approach to managing CRPC, representing a significant advancement in improving patient care.