Continuous Drug Administration Research Articles

Nebulizers.

Nebulizers generate aerosols from liquid-based solutions and suspensions. Nebulizers are particularly well suited to delivering larger doses of medication than is practical with inhalers and are used with a broad range of liquid formulations. When the same drug is available in liquid or inhaler form, nebulizers are applicable for use with patients who will not or cannot reliably use a pressurized metered-dosed inhaler (pMDI) or dry powder inhaler (DPI) due to poor lung function, hand-breath coordination, cognitive abilities (e.g., infants, elderly) or device preference. In a nebulizer, liquid medication is placed in a reservoir and fed to an aerosol generator to produce the droplets. A series of tubes and channels direct the aerosol to the patient via an interface such as mouthpiece, mask, tent, nasal prongs or artificial airway. All nebulizers contain these basic parts, although the technology and design used can vary widely and can result in significant difference in ergonomics, directions for use, and performance. While many types of nebulizers have been described, the three categories of modern clinical nebulizers include: (1) pneumatic jet nebulizers (JN); (2) ultrasonic nebulizers (USN); and (3) vibrating mesh nebulizers (VMN). Nebulizers are also described in terms of their reservoir size. Small volume nebulizers (SVNs), most commonly used for medical aerosol therapy, can hold 5 to 20 mL of medication and may be jet, ultrasonic, or mesh nebulizers. Large volume nebulizers, typically jet or ultrasonic nebulizers, hold up to 200 mL and may be used for either bland aerosol therapy or continuous drug administration.

Metronomic Chemotherapy for Pediatric Refractory Solid Tumors: A Retrospective Single-Center Study.

Metronomic chemotherapy (MC) is based on chronic administration of chemotherapeutic agents at minimally toxic doses without prolonged drug-free breaks, that inhibits tumor angiogenesis and induces tumor dormancy. This study aimed to determine the efficacy of MC for pediatric refractory solid tumors. We retrospectively analyzed the data of pediatric patients with relapsed/refractory solid tumors who received treatment, including low-dose continuous administration of anticancer drugs, at our institute. Of the 18 patients, the disease statuses at the initiation of MC were complete remission (n=2), partial remission/stable disease (n=5), and progressive disease (n=11). The overall survival rate was 61% at 12 months and 34% at 24 months, and the progression-free survival rate was 21% at 12 and 24 months. Although only 5 of the 18 patients showed certain tumor regression or maintained remission, tumors that stabilized, maintained remission/stable disease, and showed certain advantages in terms of overall survival rate, even if limited to progressive disease. Approximately half of the patients demonstrated temporal tumor stabilization and improved survival time. Overall, previous reports and the present study support the conclusion that MC has the potential to play an important role in pediatric cancer treatment during the advanced stage.

Development and characterization of 3D printed ethylene vinyl acetate (EVA) as drug delivery device for the treatment of overactive bladder

The overactive bladder is a condition characterized by a sudden urge to urinate, even with small volumes of urine present in the bladder. The current treatments available for this pathology consist on conservative approaches and the continuous administration of drugs, which when made by conventional methods has limitations related to the first pass metabolism, bioavailability, severe side effects, and low patient adherence to treatments, ultimately leading to low effectiveness. Within this context, the present work proposes the design, manufacture, and characterization of an intravesical implant for the treatment of overactive bladder pathology, using EVA copolymer as a matrix and oxybutynin as a drug. The fabrication of devices through two manufacturing techniques (extrusion and additive manufacturing by fused filament fabrication, FFF) and the evaluation of the implants through characterization tests was proposed. The usability and functionality were evaluated through simulated insertion of the device/prototype in a bladder model through catheter insertion tests. The safety and effectiveness of the devices was investigated from mechanical testing as well as drug release assays. Drug release assays presented a burst release in the first 24 h, followed by a release of 1.8 and 2.8 mg/d, totalizing 32 d. Mechanical tests demonstrated an increase in the stiffness of the specimens due to the addition of the drug, showing a change in maximum stress and strain at break. The released dose was higher than that usually presented when considering the oral administration route, showing the optimization of the development of this implant has the potential to improve the quality of life of patients with overactive bladder.

Elimination of transmission of onchocerciasis (river blindness) with long-term ivermectin mass drug administration with or without vector control in sub-Saharan Africa: a systematic review and meta-analysis

WHO has proposed elimination of transmission of onchocerciasis (river blindness) by 2030. More than 99% of cases of onchocerciasis are in sub-Saharan Africa. Vector control and mass drug administration of ivermectin have been the main interventions for many years, with varying success. We aimed to identify factors associated with elimination of onchocerciasis transmission in sub-Saharan Africa. For this systematic review and meta-analysis we searched for published articles reporting epidemiological or entomological assessments of onchocerciasis transmission status in sub-Saharan Africa, with or without vector control. We searched MEDLINE, PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, African Index Medicus, and Google Scholar databases for all articles published from database inception to Aug 19, 2023, without language restrictions. The search terms used were "onchocerciasis" AND "ivermectin" AND "mass drug administration". The three inclusion criteria were (1) focus or foci located in Africa, (2) reporting of elimination of transmission or at least 10 years of ivermectin mass drug administration in the focus or foci, and (3) inclusion of at least one of the following assessments: microfilarial prevalence, nodule prevalence, Ov16 antibody seroprevalence, and blackfly infectivity prevalence. Epidemiological modelling studies and reviews were excluded. Four reviewers (NM, AJ, AM, and TNK) extracted data in duplicate from the full-text articles using a data extraction tool developed in Excel with columns recording the data of interest to be extracted, and a column where important comments for each study could be highlighted. We did not request any individual-level data from authors. Foci were classified as achieving elimination of transmission, being close to elimination of transmission, or with ongoing transmission. We used mixed-effects meta-regression models to identify factors associated with transmission status. This study is registered in PROSPERO, CRD42022338986. Of 1525 articles screened after the removal of duplicates, 75 provided 282 records from 238 distinct foci in 19 (70%) of the 27 onchocerciasis-endemic countries in sub-Saharan Africa. Elimination of transmission was reported in 24 (9%) records, being close to elimination of transmission in 86 (30%) records, and ongoing transmission in 172 (61%) records. I2 was 83·3% (95% CI 79·7 to 86·3). Records reporting 10 or more years of continuous mass drug administration with 80% or more therapeutic coverage of the eligible population yielded significantly higher odds of achieving elimination of transmission (log-odds 8·5 [95% CI 3·5 to 13·5]) or elimination and being close to elimination of transmission (42·4 [18·7 to 66·1]) than those with no years achieving 80% coverage or more. Reporting 15-19 years of ivermectin mass drug administration (22·7 [17·2 to 28·2]) and biannual treatment (43·3 [27·2 to 59·3]) were positively associated with elimination and being close to elimination of transmission compared with less than 15 years and no biannual mass drug administration, respectively. Having had vector control without vector elimination (-42·8 [-59·1 to -26·5]) and baseline holoendemicity (-41·97 [-60·6 to -23·2]) were associated with increased risk of ongoing transmission compared with no vector control and hypoendemicity, respectively. Blackfly disappearance due to vector control or environmental change contributed to elimination of transmission. Mass drug administration duration, frequency, and coverage; baseline endemicity; and vector elimination or disappearance are important determinants of elimination of onchocerciasis transmission in sub-Saharan Africa. Our findings underscore the importance of improving and sustaining high therapeutic coverage and increasing treatment frequency if countries are to achieve elimination of onchocerciasis transmission. The Bill & Melinda Gates Foundation and Neglected Tropical Diseases Modelling Consortium, UK Medical Research Council, and Global Health EDCTP3 Joint Undertaking. For the Swahili, French, Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Varicella-associated disseminated intravascular coagulation secondary to Henoch-Schönlein purpura with renal and gastrointestinal system involvement in a child: A case report.

Immunocompromised patients who developed varicella-zoster virus (VZV)-associated disseminated intravascular coagulation (DIC) previously included recipients of bone marrow, hematopoietic stem cell, or organ transplantations, patients with primary nephropathy receiving corticosteroid therapy, cancer patients receiving chemotherapy, and patients with human immune deficiency virus infection. The case reported here is novel because, to our knowledge, there has been no report of VZV-associated DIC after the onset of Henoch-Schönlein purpura (HSP). To report the successful treatment of a novel pediatric case with VZV-associated DIC secondary to HSP. An 8-year-old girl developed VZV-associated DIC 24 days after diagnosis of HSP with renal and gastrointestinal involvement. She was treated with methylprednisolone at a local hospital for 19 days, and suddenly developed fever starting from day 4 in our hospital. Her fever persisted with vesicular skin rashes on her back, strong abdominal and lower back pain, epistaxis, hematochezia, erosion and bleeding on her lips, in her mouth and at puncture sites on day 5. She was diagnosed with DIC with the laboratory evidence of dramatically decreased platelet count and fibrinogen, prolonged activated partial thromboplastin time and prothrombin time, and increased fibrin degradation products including d-dimers. She also developed multiple organ dysfunction syndrome. On day 7, the patient VZV nucleic acid result turned out to be positive. Methylprednisolone treatment was discontinued, and she was given a multi-modality therapy including medications of acyclovir and antibiotics, intravenous gamma-immunoglobulin, various blood product transfusions, continuous renal replacement therapy, plasma exchange, and administration of liver and gastrointestinal system protection drugs. The patient multi-organ function damage gradually recovered. After VZV control, the patient was treated with oral methylprednisolone again for HSP with nephritis. Urine analysis was normal 1 year later, and oral hormone was discontinued. No complication or relapse occurred during 2 years of follow-up. This case report, for the first time, adds HSP treated with corticosteroids to the spectrum of clinical conditions that progressed to life-threatening secondary varicella-associated DIC. Early identification of varicella infection and DIC, combined with timely antiviral, immunoglobulin transfusion, plasma exchange, and other combined therapies are essential for saving patients' lives.

Application of surface-layer matrix-assisted laser desorption/ionization mass spectrometry imaging to pharmaceutical-loaded poly(ester urea) films

Polymer thin films are often used in transdermal patches as a method of continuous drug administration for patients with chronic illness. Understanding the drug segregation and distribution within these films is important for monitoring proper drug release over time. Surface-layer matrix-assisted laser desorption/ionization mass spectrometry imaging (SL-MALDI-MSI) is a unique analytical technique that provides an optical representation of chemical compositions that exist at the surface of polymeric materials. Solvent-free sublimation is employed for application of matrix to the sample surface, so that only molecules in direct contact with the matrix layer are detected. Here, these methodologies are utilized to visualize variations in drug concentration at both the air and substrate interface in pharmaceutical-loaded polymer films.

From Innovation to Implementation: The Evolution of HIV Pre-Exposure Prophylaxis and Future Implications.

Pre-exposure prophylaxis (PrEP) is a highly effective HIV-prevention strategy that involves the continuous administration of antiretroviral drugs to HIV-negative individuals with a substantial risk of contracting an HIV infection. The use of PrEP has shown a reduction in the risk of HIV acquisition through sexual intercourse by up to 99%. Despite its effectiveness, PrEP uptake remains low among populations at high risk of HIV infection. This highlights the need for further research in strategies to enhance awareness and uptake of PrEP amongst these specific populations. This article presents a comprehensive overview of the existing literature on the effectiveness of PrEP in reducing HIV transmission rates. Additionally, we examine the obstacles related to PrEP implementation and uptake and put forward potential strategies to raise awareness and improve its use among populations at an increased risk of contracting HIV.

DRESS, una reacción alérgica no mediada por IgE

DRESS (drug reaction syndrome with eosinophilia and sys¬temic symptoms) is a rare drug-induced multisystemic hy-persensitivity response that can induce a severe cutaneous adverse reaction that is difficult to diagnose and treat. It fre-quently manifests as an extensive skin rash, systemic symp¬toms, lymphadenopathy, visceral organ involvement, and hematological alterations, mainly leukocytosis, eosinophilia, and sometimes atypical lymphocytosis that manifest 2 to 8 weeks after continuous administration of the responsible drug. The most prevalent drugs related with this syndrome are phenytoin, carbamazepine, allopurinol, and abacavir. Some specific human leukocyte antigen (HLA) alleles have been identified that are associated with hypersensitivity to these drugs. The pathophysiology of DRESS syndrome is not yet fully understood; the main hypothesis is a T-cell me¬diated hypersensitivity response when interacting with the major histocompatibility complex receptor in individuals with genetic susceptibility factors. The criteria of the European Registry of Severe Cutaneous Adverse Reactions to Drugs (RegiSCAR) are the most commonly used for the diagnosis of DRESS syndrome. Drug-induced hypersensitivity syndrome (DiHS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP) should be considered for any rash that appears following the administration of any drug. Therapy of this condition includes the elimination of the causative agent as soon as possible, as well as systemic corticosteroids which remain the mainstay of treatment of DRESS with in-ternal organ involvement. Steroid-sparing agents such as cyclosporine, intravenous immunoglobulins (IVIGs), and other immunosuppressive agents have been used successfully to contribute to treatment. Keywords: DRESS; drug hypersensitivity syndrome; adverse drug reactions; hypersensitivity reaction; eosinophilia.

Metronomic Chemotherapy Based on Topotecan or Topotecan and Cyclophosphamide Combination (CyTo) in Advanced, Pretreated Ovarian Cancer.

Patients with advanced ovarian cancer (OC) have a detrimental prognosis. The options for systemic treatment of advanced OC in later lines of treatment are limited by the availability of active therapies and their applicability to often fragile, exhausted patients with poor performance status. Metronomic chemotherapy (MC) is a concept of a continuous administration of cytotoxic drugs, which is characterized by multidirectional activity (anti-proliferative, anti-angiogenic, and anti-immunosuppressive) and low toxicity. We have performed a retrospective analysis of consecutive, advanced, chemo-refractory OC patients treated with MC based on single-agent topotecan (1 mg p.o. q2d) or on a topotecan (1 mg q2d) and cyclophosphamide (50 mg p.o. qd) combination (CyTo). Metronomic chemotherapy demonstrated promising activity, with 72% and 86% of patients achieving biochemical or objective disease control and 18% and 27% of patients achieving a biochemical or objective response, respectively. The median PFS in the whole population was 3.65 months, but the median PFS in patients with a biochemical response to MC (18.2% of patients) reached 10.7 months. The study also suggested that overweight or obese patients had significantly better outcomes on MC than patients with BMI <25 kg/m2. This article is the first report in the literature on metronomic chemotherapy based on a topotecan + cyclophosphamide combination (CyTo). The CyTo regimen demonstrated safety, clinical activity, and potential broad clinical applicability in advanced OC patients and will be evaluated in a forthcoming clinical trial.

The Effect of Acupressure Therapy on Blood Pressure At Hypertension Patient

Introduction: Hypertension is a chronic disease characterized by an increase in systolic and diastolic blood pressure above 140/100 mmHg. Hypertension with not controlled management will have an impact on the emergence of various complications including stroke, kidney failure, heart disease. Currently conventional therapy for hypertension uses drugs such as captopril, but continuous drug administration can cause adverse side effects from the drug. Acupressure therapy is a relatively inexpensive complementary therapy and tends not to have side effects like chemical drugs.&#x0D; Objective: This study aims to identify the effect of acupressure therapy on blood pressure in hypertensive clients.&#x0D; Methods: The research method used is pre-experimental. Respondents who participated in this study were 12 respondents who were residents at Kelurahan Utama, Kecamatan Cimahi Selatan. Acupressure therapy is given by massage using fingers at points ST 36, LR 3, Li 4 for 30 minutes with a massage strength of 3 kg. Furthermore, the data were analyzed using the wilcoxon test.&#x0D; Results: The results showed that the mean systolic and diastolic blood pressure before treatment was 153.33/94.17 mmHg, systolic and diastolic blood pressure after treatment was 142.83/88.50 mmHg. Conclusion: There is an effect of acupressure therapy on reducing blood pressure (p value = 0.006) in hypertensive clients. It is recommended for hypertensive clients to continue acupressure therapy in an effort to reduce high blood pressure

Biosensor-Integrated Drug Delivery Systems as New Materials for Biomedical Applications.

Biosensor-integrated drug delivery systems are innovative devices in the health area, enabling continuous monitoring and drug administration. The use of smart polymer, bioMEMS, and electrochemical sensors have been extensively studied for these systems, especially for chronic diseases such as diabetes mellitus, cancer and cardiovascular diseases as well as advances in regenerative medicine. Basically, the technology involves sensors designed for the continuous analysis of biological molecules followed by drug release in response to specific signals. The advantages include high sensitivity and fast drug release. In this work, the main advances of biosensor-integrated drug delivery systems as new biomedical materials to improve the patients’ quality of life with chronic diseases are discussed.

Post-treatment evaluation of urogenital schistosomiasis among elementary school children in Erin Osun, a peri-urban community in Irepodun Local Government Area, Osun State.

This study assessed the post-treatment status of urogenital schistosomiasis among school-aged children in Erin Osun in Osun State, Nigeria. A total of 357 children from five elementary schools that had participated in the Osun State Elementary School Feeding and Health Programme (O-MEALS Programme) and received praziquantel as part of the deworming programme were examined for the study. Urine samples were collected and tested for microhaematuria and proteinuria using urinalysis reagent strips. The urine samples were further examined for Schistosoma haematobium ova. A snail survey was conducted in the River Awesin at the water contact points in the community. Out of the 357 participants examined, (4.2%) had S. haematobium infection; males had a higher prevalence (5.5%) than females (2.9%). Christ Apostolic Church Elementary School had the highest (7.2%) prevalence of infection while Ansar-Ud-Deen ‘A’ Elementary School had the least prevalence (1.5%). There was no significant difference (p &gt; 0.05) in the prevalence between gender and between schools. The highest prevalence was recorded among children of age group 13-15years (20.0%) while the least was among the age group 5-8years, and there was a significant difference in the prevalence of infection between age groups (p &lt; 0.05). The overall geometric mean intensity of infection was 1.14 eggs/10mls of urine. There was a high (52.9%) prevalence of proteinuria. However, 47.1% of the participants had no proteinuria, 43.7% had 1+ amount (0.3 g/L) and 1.9% had 3+ amount (5.0 g/L). The low prevalence (4.2%) and intensity (1.14 eggs/10ml) of S. haematobium infection, in this study, suggest a positive impact of the O-Meals programme, which used Praziquantel twice a year to treat the pupils. No snail intermediate host of S. haematobium was encountered during the survey. Continuous drug administration with the feeding initiative and provision of safe drinking water in the community will help sustain the current level of control.

Prevalence of urinary schistosomiasis among school children In Ago Aduloju Community, Ado LGA of Ekiti State, Nigeria

Schistosomiasis is a common neglected tropical disease in sub-Saharan Africa, with the greatest number of infected people residing in Nigeria. Several factors have been shown to facilitate the continuous transmission of schistosomiasis in endemic countries, especially water activity in freshwater bodies where the snail vector lives and socio-economic factors. Available control efforts rely on epidemiological information for better targeting of intervention; however, this information is lacking in some research-naive communities in Ekiti State. Therefore, this study is aimed at determining the prevalence of schistosomiasis in the Ago-Aduloju community. The urine sample was collected from 315 consenting community-based school children and screened for schistosomiasis infection using the filtration technique. Data were gathered utilizing questionnaires and laboratory analysis. 315 participants within the age range of 5-19 years comprising 55.2% males, 44.8% females were examined. The prevalence of schistosomiasis was found to be 6.35% with 4.44% in females and 1.91% in males. Among the participant, the questionnaire revealed 84.1% and 95.6% had received praziquantel and albendazole, respectively. 6.41% of the participant who took praziquantel tested positive for schistosomiasis infection. Haematuria was positive in 0.95% of participants. Although 61.3% of participants are aware of schistosomiasis infection, none of them knew the intermediate host involved in the transmission. The findings showed that there is a significant difference (p&gt;0.05) between respondents that have taken praziquantel and those that are positive for schistosomiasis. Conclusively, the study revealed that schistosomiasis is still of concern among the school children in the Ago-Aduloju community and that continuous Mass Drug Administration and health education is imperative to sensitize and educate the school children on transmission, risk, and prevention of schistosomiasis.

The effects of using a micro-infusion pump without accompanying fluid at a low flow rate on patients undergoing cardiac surgery

BackgroundSince a micro-infusion pump continuously pumps drugs at a low speed, it has the risk of complications including venous blood return, indwelling needle blockage, and the lack of regular delivery of drugs. This study aimed to investigate venous blood return and indwelling needle blockage after cardiac surgery when a micro-infusion pump was used at a very low flow rate of only 2 ml/h without any accompanying fluid. MethodsA total of 215 patients, who were hospitalized at the Second Hospital of Shandong University between May and December 2020, received a continuous intravenous administration of drugs via a micro-infusion pump at 2 ml/h without or with accompanying fluid. These patients were randomly divided into an observation group (108 patients) and a control group (107 patients). In the observation group, drugs were administered at 2 ml/h without any additional fluid. In contrast, the control group received drugs also at 2 ml/h but with a normal saline through an intravenous drip. The venous backflow, blockage of the indwelling needle and catheter, and other adverse reactions were evaluated In addition, the volume of an accompanying fluid as well as the mean of nursing work time and additional costs were calculated. ResultsThe main finding of this analysis showed no statistically significant differences in the number of complications such as venous backflow, blockage of the indwelling needle or catheter, or any adverse reactions between the observational and control groups (P > 0.05). Compared to the control group, the observation group had significantly reduced the amount of fluid intake (P< 0.001). In addition, the 2 ml/h infusion tempo without any additional fluid shortened nursing hours (P < 0.001), and thus reduced costs for the observation group vs. the control group. ConclusionsIt is feasible and safe to administer drugs via a micro-infusion pump at the slow 2 ml/h tempo without any accompanying fluid to patients after surgery requiring minimal volume of fluids.

Conquering multidrug resistant lung cancer by upconversion nanoparticles‐mediated photodynamic therapy and gene silencing

AbstractMultidrug resistance (MDR) problem is a challenging task in cancer treatments. Among various types of cancers, lung cancer is considered incurable, as it is diagnosed very often at the advanced metastatic stage, where surgical operations and radiation treatments become highly ineffective. In addition, lung cancers are multidrug resistant either intrinsically or upon continuous administration and stimulation of chemotherapeutic drugs. To conquer the difficult MDR problem, in this study, we developed a simple and effective therapeutic strategy to achieve complete destruction of multidrug resistant lung cancer by an unprecedented upconversion nanoparticles (UCNPs)‐mediated photodynamic therapy (PDT) combined with effective (~70%) superoxide dismutase 1 (SOD1) gene silencing using ultra‐low doses (320 mW/cm2) of NIR light (980 nm) excitation. To the best of our knowledge, this is the first successful literature example in achieving complete destruction of multidrug resistant cancers. Overall, the current work points out a new direction to the clinicians for the therapeutic design and effective treatments of multidrug resistant cancers.

Synthesis of 29H,31H-phthalocyanine and chloro (29H,31H-phthalocyaninato) aluminum derivatives showed anti-cancer and anti-bacterial actions

Continuous administration of most chemotherapeutic drugs can induce different types of side effects. There has been growing interest in exploring an alternative approach to synthesizing compounds that are most effective and have fewer side effects. We synthesized 29H,31H-Phthalocyanine, and Chloro (29H,31H- phthalocyaninato) aluminum at low temperatures using lithium in the present study with diisopropylamide as the nucleophile. The physical characteristics of 29H,31H-Phthalocyanine, and Chloro (29H,31H- phthalocyaninato) aluminum were confirmed by FT-IR method, XRD, SEM, and the impact of these compounds on human colorectal carcinoma (HCT-116) and human cervical cells (HeLa) was examined. Treatment with 29H,31H-Phthalocyanine significantly decreased cancer cell growth and proliferation, as determined by MTT and DAPI staining analysis. In contrast, Chloro (29H,31H- phthalocyaninato) aluminum treatment did not show any inhibitory action on colon or cervical cancer cells. We also calculated the inhibitory concentration (IC50) of 29H,31H-Phthalocyanine, which was 30 µg/ml (HCT-116) and 33 µg/ml (HeLa cells). The antibacterial effectiveness of 29H,31H-Phthalocyanine, and chloro (29H,31H- phthalocyaninato) aluminum was studied using Enterococcus faecalis (E. faecalis). The CFU (colony frequency unit) assay confirmed significant activity against the test bacterium after treatment with 29H,31H-Phthalocyanine. However, no activity was seen upon treatment with chloro (29H,31H- phthalocyaninato) aluminum against E. faecalis.

Clinical Efficacy of CT-Guided Continuous Catheterization Drainage for Spinal Tuberculosis with Large Abscesses.

Objective This study aimed to determine the efficacy of computed tomography (CT)-guided local catheterization for the treatment of spinal tuberculosis (TB) with abscess. Methods Clinical data from 22 cases of lumbar TB with abscess receiving treatments from July 2015 to January 2021 were analyzed. Some patients (n = 11) underwent pure surgery (control group) and the others (n = 11) received CT-guided catheterization drainage. The operation and hospitalization time, erythrocyte sedimentation rate (ESR), visual analog scale (VAS), ASIA damage grade, and C-reactive protein (CRP) levels of both groups were compared. Results The operation time, intraoperative blood loss, and hospital stay of the observation group were significantly less than those of the control group (P < 0.05). As the differences in preoperative ESR, CRP, and VAS scores between both groups did not reach significance (P > 0.05), after treatments, the observation group had a lower level of ESR and CRP (P < 0.05); the postoperative VAS scores of the two groups decreased (P > 0.05). Before treatment, the control group comprised 2 cases of ASIA grade A, 1 case of B, 6 cases of C, and 2 cases of D with 3 patients having dyskinesia. After surgery, the motor function of the patients was improved, and there were 3 cases of ASIA D and 8 cases of E. Meanwhile, the preoperative observation group consisted of 9 cases of ASIA D and 2 cases of E. Due to CT-guided catheterization, all patients achieved clinical healing (ASIA E) when the lesions were significantly alleviated, and symptoms such as low back pain and lower extremity pain disappeared. Conclusion CT-guided percutaneous catheter drainage for continuous administration of drugs is effective treatment for spinal TB with abscess, when shortening the operation and hospitalization time and reducing intraoperative blood loss and erythrocyte sedimentation rate. It is worthy of popularization and application.

Intranasal hydrogel of armodafinil hydroxypropyl-β-cyclodextrin inclusion complex for the treatment of post-traumatic stress disorder

Armodafinil inclusion complex (AIC) hydrogel was prepared and evaluated for its therapeutic effect on Post-traumatic Stress Disorder (PTSD). After computer simulation and physicochemical property investigation, the AIC was formed by lyophilization of armodafinil with ethanol as solvent and hydroxypropyl-beta-cyclodextrin (HP-β-CD) aqueous solution, in which the molar ratio of armodafinil and HP-β-CD was 1–1. The AIC encapsulation efficiency (EE) was (90.98 ± 3.72)% and loading efficiency (LE) was (13.95 ± 0.47)% and it increased the solubility of armodafinil in aqueous solution to 21 times. AIC hydrogel was prepared by adding AIC to methylcellulose (MC) hydrogels (3.33% w/v), and its higher drug release amount and slower release rate were testified by the in-vitro release assay and the rheological test. The mucosa irritation of AIC hydrogel was also evaluated. Healthy group, Model group, Sertraline group with 30 mg/kg sertraline gavage, AIC Hydrogel group with 20 mg/kg AIC hydrogel intranasal administration and AIC Aqueous Solution group with 20 mg/kg AIC aqueous solution gavage were set up for the treatment of mice with PTSD generated from foot shock method. Based on freezing response test in fear-conditioning box and open field test, compared with other groups, PTSD mice in AIC Hydrogel group showed significant improvement in behavioral parameters after 11 days of continuous drug administration and 5 days of drug withdrawal. After sacrifice, the plasma CORT level of PTSD mice in AIC Hydrogel group was elevated compared to Model group. Besides, the western blot (WB) of hippocampal brain-derived neurotrophic factor (BDNF) and amygdala dopamine transporter (DAT) immunohistochemistry sections indicated that AIC hydrogel had a protective effect on the brain tissue of PTSD mice. The brain targeting of intranasal administration was evaluated by fluorescence imaging characteristics of Cy7 hydrogel in the nasal route of drug administration, pharmacokinetics and in-vivo distribution of armodafinil. In short, AIC hydrogel is a promising formulation for the treatment of PTSD based on its high brain delivery and anti-PTSD effect.

Computational modeling of schedule-specific chemotherapy outcomes in mouse tumor model

Despite the rapid development of new innovative strategies in cancer treatment like immunotherapy, chemotherapy still remains a common choice in many cases. Standard protocols of chemotherapeutic administration rely on a maximal tolerated dose paradigm, however there is growing evidence that this approach is not always optimal. Alternative scheduling, like metronomic - low dose continuous drug administration - were recently proved their efficacy. The space of available variants of drug administration protocols is prohibitively large to be explored empirically, and there is an urgent need of predictive mathematical models for rational chemotherapeutic scheduling design. In this work we tested the ability of the minimal pharmacokinetic-pharmacodynamics model to describe schedule-specific tumor volume time evolution in different mouse tumor models.

Effect of anti-diabetic drugs in dialysis patients with diabetes: a nationwide retrospective cohort study

BackgroundType 2 diabetes mellitus is common in patients undergoing dialysis. However, the association between anti-diabetic drug use and survival outcomes is rarely discussed. We aimed to investigate whether continued anti-diabetic medication use affects the survival of diabetic dialysis patients and whether different hypoglycemic drug use influences prognosis.MethodsUsing a nationwide database, we enrolled patients with incident end-stage renal disease under maintenance dialysis during 2011–2015 into the pre-existing diabetes dialysis (PDD), incident diabetes after dialysis (IDD), and non-diabetic dialysis (NDD) groups. The PDD group was further subclassified into patients who continued (PDD-M) and discontinued (PDD-NM) anti-diabetic drug use after dialysis.ResultsA total of 5249 dialysis patients were examined. The PDD-NM group displayed a significantly higher mortality rate than the IDD, PDD-M, and NDD groups (log-rank test P < 0.001). The PDD-M group had a significantly lower risk of death, regardless of insulin (P < 0.001) or oral hypoglycemic agent (OHA) (P < 0.001) use. Initial insulin administration or OHA had no statistically significant effect on overall mortality in the IDD group. But OHA use had better survival trends than insulin administration for the older (P = 0.02) and male subgroups (P = 0.05).ConclusionsFor dialysis patients with diabetes, continuous administration of anti-diabetic drugs after dialysis and choice of medication may affect outcomes.