Intravenous Research Articles

Oritavancin Versus Daptomycin for Osteomyelitis Treatment After Surgical Debridement.

Weekly intravenous (IV) oritavancin and daily daptomycin were compared in an outpatient setting following extensive surgical debridement for treating patients with osteomyelitis. This was a retrospective, observational study of patients diagnosed with acute osteomyelitis. Exclusion criteria were the use of Gram-negative antibiotic therapy, use of antibiotics for more than 48h prior to oritavancin or daptomycin or prior use of > 2 doses of oritavancin or more than 4weeks of daptomycin. Clinical success was resolution or improvement of symptoms and no further treatment. Data were analyzed with Chi-square test or Fisher's exact test. Consecutive outpatients (n = 150) with acute osteomyelitis who were treated with oritavancin or daptomycin (1:1) following extensive surgical debridement were identified. Staphylococcus aureus was the most common pathogen (n = 117). No patient in either group received prior antibiotic therapy (previous 30days) or was hospitalized within 90days prior to surgical debridement. Twenty-one (28%) patients prescribed oritavancin had chronic kidney disease, seven of whom were receiving hemodialysis or peritoneal dialysis. Compared to oritavancin, patients prescribed daptomycin had higher rates of all-cause readmission [odds ratio (OR) 2.89; p < 0.001], more infection-related readmission (OR 3.19; p < 0.001), and greater likelihood of receiving antibiotics post-discontinuation of initial therapy (OR 2.13; p < 0.001). Repeat surgical debridement was required for 68.0% with daptomycin vs. 23.1% with oritavancin (p < 0.001). Oritavancin demonstrated a significantly higher rate of clinical success compared to daptomycin, with lower all-cause and infection-related readmissions, reduced need for repeat surgical debridement, and fewer additional antibiotic requirements.

A review on transdermal drug delivery system

Drugs that are applied topically are delivered using transdermal drug delivery devices. These are pharmaceutical preparations of varying sizes, containing one or more active ingredients, intended to be applied to the unbroken skin in order to deliver the active ingredient after passing through the skin barriers, and these avoid first pass metabolism. Today about 74% of drugs are taken orally and are not found effective as desired. To improve efficacy transdermal drug delivery system was emerged. A notable advantage of transdermal drug delivery compared to other methods like oral, topical, intravenous (IV), and intramuscular (IM) administration is its controlled release of medication into the patient's system. This controlled release is achieved either by using a porous membrane enclosing a medication reservoir or by utilizing the patient's body heat to melt thin layers of medication embedded in the adhesive. Despite its benefits, transdermal drug delivery has certain limitations due to the skin's effective barrier function. Only molecules with small sizes can efficiently permeate the skin and consequently be delivered through this method.

Change in neurocognitive functioning in patients with treatment-resistant depression with serial intravenous ketamine infusions: The Bio-K multicenter trial

This nonrandomized, multicenter, open-label clinical trial explored the impact of intravenous (IV) ketamine on cognitive function in adults (n = 74) with treatment-resistant depression (TRD). Patients received three IV ketamine infusions during the acute phase and, if remitted, four additional infusions in the continuation phase (Mayo site). Cognitive assessments using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were conducted at baseline, end of the acute phase, and end of the continuation phase (Mayo site). Results showed a significant 53 % (39/74) remission rate in depression symptoms after the acute phase. In adjusted models, baseline language domain score was associated with a higher odd of remission (Odds Ratio, 1.09, 95 % CI = 1.03–1.17, p = 0.004) and greater improvement in MADRS at the end of the acute phase (β =-0.97; 95 % CI, -1.74 to -0.20; P = 0.02). The likelihood of remission was not significantly associated with baseline immediate or delayed memory, visuospatial/constructional, or attention scores. In the continuation phase, improvements in immediate and delayed memory and attention persisted, with additional gains in visuospatial and language domains. Limitations included an open-label design, potential practice effects, and ongoing psychotropic medication use. Overall, the study suggests cognitive improvement, not deterioration, associated with serial IV ketamine administrations for TRD. These findings encourage future studies with larger sample sizes and longer follow-up periods to examine any potential for deleterious effect with recurrent ketamine use for TRD.Trial Registration: ClinicalTrials.gov: NCT03156504

An mHealth application for chronic vascular access: A multi-method evaluation.

Healthcare consumers require diverse resources to assist their navigation of complex healthcare interactions, however, these resources need to be fit for purpose. In this study, we evaluated the utility, usability and feasibility of children, families and adults requiring long-term intravenous therapy using a recently developed mobile health application (App), intravenous (IV) Passport. Multi-site, parallel, multi-method, prospective cohort study. A multi-site, multi-method study was carried out in 2020-2021, with 46 participants (20 adults, 26 children/family) reporting on their experiences surrounding the use of the IV Passport for up to 6 months. Overall, utility rates were acceptable, with 78.3% (N = 36) using the IV Passport over the follow-up period, with high rates of planned future use for those still active in the project (N = 21; 73%), especially in the child/family cohort (N = 13; 100%). Acceptability rates were high (9/10; IQR 6.5-10), with the IV Passport primarily used for documenting new devices and complications. Thematic analysis revealed three main themes (and multiple subthemes) in the qualitative data: Advocacy for healthcare needs, Complexity of healthcare and App design and functionality. Several recommendations were made to improve the end-user experience including 'how to' instructions; and scheduling functionality for routine care. The IV Passport can be safely and appropriately integrated into healthcare, to support consumers. Patient-/parent-reported feedback suggests the Intravenous Passport is a useful tool for record-keeping, and positive communication between patients/parents, and clinicians. Not applicable. Consumers reported their experiences surrounding the use of the IV Passport for up to 6 months.

A phase 1b study of zilovertamab in combination with paclitaxel for locally advanced/unresectable or metastatic HER2-negative breast cancer

BackgroundZilovertamab is a humanized monoclonal antibody targeting ROR1, an onco-embryonic antigen expressed by malignant cells of a variety of solid tumors, including breast cancer. A prior phase 1 study showed that zilovertamab was well tolerated and effective in inhibiting ROR1-signaling, which leads to activation of ERK1/2, NF-κB, and NRF2 target genes. This phase 1b study evaluated the safety and tolerability of zilovertamab with paclitaxel in patients with advanced breast cancer.Patients and methodsEligible patients had locally advanced, unresectable, or metastatic HER2− breast cancer with Eastern Cooperative Group performance status of 0–2 and without prior taxane therapy in the advanced setting. Study treatment included 600 mg of zilovertamab administered intravenously (IV) on Days 1 and 15 of Cycle 1 and then Day 1 of each 28-day cycle along with paclitaxel weekly at 80 mg/m2 IV.ResultsStudy patients had received a median of 4 prior therapies (endocrine therapy + chemotherapy) for locally advanced, unresectable, or metastatic disease. No patient discontinued therapy due to toxicity ascribed to zilovertamab. Adverse events were consistent with the known safety profile of paclitaxel. Of 16 patients, 6 (38%) had a partial response, and 6/16 (38%) patients had stable disease as best tumor response.ConclusionThe combination of zilovertamab and paclitaxel was safe and well tolerated in heavily pre-treated advanced breast cancer patients. Further evaluation of ROR1 targeting in breast cancer patients with zilovertamab is warranted.Trial Registration: NCT02776917. Registered on ClinicalTrials.gov on 05/17/2016.

A comparative analysis of opioid-free and opioid-sparing anaesthesia techniques for laparoscopic ovariectomy in healthy dogs

ObjectiveTo compare the perioperative analgesic effects of an opioid-free (OFA) and an opioid-sparing (OSA) anaesthetic protocol in dogs undergoing laparoscopic ovariectomy. Study designProspective, randomized, blinded, clinical trial. AnimalsA group of 28 client-owned dogs. MethodsDogs were allocated to one of two groups. The OFA group was administered intramuscular (IM) dexmedetomidine 5 μg kg–1 and ketamine 1 mg kg–1, followed by two intraoperative constant rate infusions (CRIs) of dexmedetomidine (3 μg kg–1 hour–1) and lidocaine (1 mg kg–1 loading dose, 2 mg kg–1 hour–1). The OSA group was administered IM dexmedetomidine 5 μg kg–1, ketamine 1 mg kg–1 and methadone 0.2 mg kg–1, followed by two intraoperative saline CRIs. In both groups, anaesthesia was induced with intravenous (IV) propofol 2 mg kg–1 and diazepam 0.2 mg kg–1 and maintained with isoflurane. Rescue dexmedetomidine (0.5 μg kg–1) was administered IV if there was a 20% increase in cardiovascular variables compared with pre-stimulation values. Ketorolac (0.5 mg kg–1) was administered IV when the surgery ended. Postoperative analgesia was evaluated using the Short Form-Glasgow Composite Measure Pain Scale and methadone (0.2 mg kg–1) was administered IM if the pain score was ≥ 6/24. Statistical analysis included mixed analysis of variance, Chi-square test and Mann–Whitney U test. ResultsThere were no significant differences in the intraoperative monitored variables between groups. The OFA group showed a significantly lower intraoperative rescue analgesia requirement (p = 0.016) and lower postoperative pain scores at 3 (p =0.001) and 6 (p < 0.001) hours. No dogs were administered rescue methadone postoperatively. Conclusions and clinical relevanceAlthough both groups achieved acceptable postoperative pain scores with no need for further intervention, the analgesic efficacy of the OFA protocol was significantly superior to that of the OSA protocol presented and was associated with a lower intraoperative rescue analgesia requirement and early postoperative pain scores.

MDSC-targeted liposomal all-trans retinoic acid suppresses mMdscs and improves immunotherapy in HBV infection

ABSTRACT Background Myeloid-derived suppressor cells (MDSCs) are evolving as a prominent determinant in cancer occurrence and development and are functionally found to suppress T cells in cancer. Not much research is done regarding its involvement in viral infections. This research was designed to investigate the role of MDSCs in hepatitis B virus (HBV) infection and how targeting these cells with our novel all-trans retinoic acid encapsulated liposomal formulation could improve immunotherapy in C57BL/6 mice. Methods Ten micrograms (10 μg) of plasmid adeno-associated virus (pAAV/HBV 1.2, genotype A) was injected hydrodynamically via the tail vein of C57BL/6 mice. An all-trans retinoic acid encapsulated liposomal formulation (L-ATRA) with sustained release properties was used in combination with tenofovir disoproxil fumarate (TDF), a nucleotide analog reverse transcriptase inhibitor (nRTI) to treat the HBV infection. The L-ATRA formulation was given at a dose of 5 mg/kg intravenously (IV) twice a week. The TDF was given orally at 30 mg/kg daily. Results Our results revealed that L-ATRA suppresses MDSCs in HBV infected mice and enhanced T-cell proliferation in vitro. In vivo studies showed higher and improved immunotherapeutic effect in mice that received L-ATRA and TDF concurrently in comparison with the groups that received monotherapy. Lower HBV DNA copies, lower concentrations of HBsAg and HBeAg, lower levels of ALT and AST and less liver damage were seen in the mice that received the combination therapy of L-ATRA + TDF. Conclusions In effect, targeting MDSCs with the combination of L-ATRA and TDF effectively reduced mMDSC and improved immunotherapy in the HBV infected mice. Targeting MDSCs could provide a breakthrough in the fight against hepatitis B virus infection.

Effect of continuous 2MHz transcranial ultrasound as an adjunct to tenecteplase thrombolysis in acute anterior circulation ischemic stroke patients: an open labeled non-randomized clinical trial.

The treatment of acute ischemic stroke has improved in last few decades. While meta-analyses of several trials have established the safety and efficacy of Intravenous (IV) Tenecteplase thrombolysis, concomitant continuous transcranial doppler (TCD) ultrasound administration has not been assessed in any clinical trial. The aim of this study was to determine the effects of continuous 2MHz TCD ultrasound during IV Tenecteplase thrombolysis for Middle cerebral artery (MCA) stroke. A total of 19 patients were included, 13 received TCD ultrasound and 6 sham TCD with IV Tenecteplase. TCD spectrum and difference in Pre and post TCD parameters were measured. Asymptomatic hemorrhagic transformation of infarct wasseen in two patients. There was no mortality or clinical worsening in thesonothrombolysis group as against sham sonothrombolysis group. Median of peak systolic velocity wasincreased in both thesonothrombolysis (P = 0.0002) and sham sonothrombolysis group (P-value = 0.001). The difference in change in mean flow velocity between two groups, sonothrombolysis (11cm/sec)and sham sonothrombolysis (3.5cm/sec) were also significantly different (P = 0.014). This pilot work has established safety of continuous 30min TCD application along with IV Tenecteplase thrombolysis and it concludes thatconcomitant 2MHz TCD ultrasound administration significantly increased the MCA blood flow compared to chemothrombolysis alone.CTRI Registered Number: CTRI/2021/02/031418.

Comparison of block characteristics and outcomes in opioid-free and opioid-based thoracic continuous spinal anaesthesia in patients undergoing major abdominal surgery: A double-blinded randomised controlled trial.

Thoracic continuous spinal anaesthesia (TCSA) is emerging as the sole anaesthetic for major abdominal surgery due to its better perioperative outcomes. This study was designed to evaluate block characteristics and outcomes in 'opioid-free' and 'opioid-based' TCSA. After ethical approval, trial registration and written informed consent, 50 adult patients undergoing major abdominal surgery were randomised into 'opioid-free' (bupivacaine alone) and 'opioid-based' (bupivacaine with fentanyl) groups. After confirmation of T4-L1 dermatome level of spinal anaesthesia, sedation by intravenous (IV) midazolam (0.02-0.05 mg/kg), ketamine (0.25 mg/kg) and dexmedetomidine (bolus dose of 1 µg/kg IV over 10 min followed by 0.2-0.7 µg/kg/h infusion) were started. The primary outcome measured was postoperative pain scores for 72 h in both groups. The secondary objectives were rescue opioid requirement, and the dose of bupivacaine required to achieve T4 level. Data were compared using the two-sided Student t-test, Mann-Whitney and Fisher's exact tests. The 'opioid-based' group performed significantly better compared with the 'opioid-free' group concerning pain scores at rest at 0 h (P = 0.023), 18 h (P = 0.023) and 24 h (P = 0.016) postoperatively, decreased intrathecal bupivacaine requirement [(induction (P = 0.012) and maintenance (P = 0.031)], postoperative rescue fentanyl requirement (P = 0.018) and patient satisfaction (P = 0.032) at the cost of increased postoperative nausea and vomiting (P = 0.049). The 'opioid-based' TCSA provided better postoperative analgesia with significantly lesser postoperative pain scores when compared to the 'opioid-free' group in patients undergoing major abdominal surgery.

Adeno-Associated Virus-Mediated Dorsal Root Ganglion Toxicity in the New Zealand White Rabbit.

Recombinant adeno-associated virus (AAV)-mediated degeneration of sensory neurons in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) has been observed in non-human primates (NHPs) following intravenous (IV) and intrathecal (IT) delivery. Administration of recombinant AAV encoding a human protein transgene via a single intra-cisterna magna (ICM) injection in New Zealand white rabbits resulted in histopathology changes very similar to NHPs: mononuclear cell infiltration, degeneration/necrosis of sensory neurons, and nerve fiber degeneration of sensory tracts in the spinal cord and of multiple nerves. AAV-associated clinical signs and incidence/severity of histologic findings indicated that rabbits were equally or more sensitive than NHPs to sensory neuron damage. Another study using human and rabbit transgene constructs of the same protein demonstrated comparable changes suggesting that the effects are not an immune response to the non-self protein transgene. Rabbit has not been characterized as a species for general toxicity testing of AAV gene therapies, but these studies suggest that it may be an alternative model to investigate mechanisms of AAV-mediated neurotoxicity and test novel AAV designs mitigating these adverse effects.

Intravenous tranexamic acid reduces complications following surgical treatment of pathologic fractures of the lower extremity.

This study aimed to evaluate the postoperative complications associated with administering intravenous (IV) tranexamic acid (TXA) in patients undergoing surgical fixation for neoplastic pathologic fractures of the lower extremities. Patients ≥18 years old who underwent surgical intervention for neoplastic pathologic lower extremity fractures from 2015 to 2021 were identified using the Premier Healthcare Database. This cohort was divided by TXA receipt on the index surgery day. Patient demographics, hospital factors, patient comorbidities, and 90-day complications were assessed and compared between the cohorts. From 2015 to 2021, 4497 patients met inclusion criteria (769 TXA[+] and 3728 TXA[-]). Following propensity score matching, patients who received TXA had a significantly shorter length of stay than those who did not (7.6 ± 7.3 days vs. 9.0 ± 15.2, p = 0.036). Between the two cohorts, there were no significant differences in comorbidities. Regarding differences in postoperative complications, TXA(+) patients had significantly decreased odds of deep vein thrombosis (DVT) (1.87% vs. 5.46%; odds ratio [OR]:0.33; 95% confidence interval: 0.17-0.62; p = 0.001). Administration of IV TXA may be associated with a decreased risk of postoperative DVT without an increased risk of other complications. Orthopedic surgeons should consider the utilization of IV TXA in patients treated surgically for neoplastic pathologic fractures of the lower extremity.

In vitro test methods for evaluating high molecular weight polyethylene oxide polymer induced hemolytic and thrombotic potential

To combat opioid abuse, the U.S. Food and Drug Administration (FDA) released a comprehensive action plan to address opioid addiction, abuse, and overdose that included increasing the prevalence of abuse-deterrent formulations (ADFs) in opioid tablets. Polyethylene oxide (PEO) has been widely used as an excipient to deter abuse via nasal insufflation. However, changes in abuse patterns have led to unexpected shifts in abuse from the nasal route to intravenous injection. Case reports identify adverse effects similar to thrombotic thrombocytopenic purpura (TTP) syndrome following the intravenous (IV) abuse of opioids containing PEO excipient. Increased risk of IV opioid ADF abuse compared to clinical benefit of the drug led to the removal of one opioid product from the market in 2017. Because many generic drugs containing PEO are still in development, there is interest in assessing safety consistent with generic drug regulation and unintended uses. Currently, there are no guidelines or in vitro assessment tools to characterize the safety of PEO excipients taken via intravenous injection. To create a more robust excipient safety evaluation tool and to study the mechanistic basis of HMW PEO-induced TMA, a dynamic in vitro test system involving blood flow through a needle model has been developed.

Severe pain management in the emergency department: patient pathway as a new factor associated with IV morphine prescription.

Across the world, 25-29% of the population suffer from pain. Pain is the most frequent reason for an emergency department (ED) visit. This symptom is involved in approximately 70% of all ED visits. The effective management of acute pain with adequate analgesia remains a challenge, especially for severe pain. Intravenous (IV) morphine protocols are currently indicated. These protocols are based on patient-reported scores, most often after an immediate evaluation of pain intensity at triage. However, they are not systematically prescribed. This aspect could be explained by the fact that physicians individualize opioid pain management for each patient and each care pathway to determine the best benefit-risk balance. Few data are available regarding bedside organizational factors involved in this phenomenon. This study aimed to analyze the organizational factors associated with no IV morphine prescription in a standardized context of opioid management in a tertiary-care ED. A 3-month prospective study with a case-control design was conducted in a French university hospital ED. This study focused on factors associated with protocol avoidance despite a visual analog scale (VAS) ≥60 or a numeric rating scale (NRS) ≥6 at triage. Pain components, physician characteristics, patient epidemiologic characteristics, and care pathways were considered. Qualitative variables (percentages) were compared using Fisher's exact test or the chi-squared tests. Student's t-test was used to compare continuous variables. The results were expressed as means with their standard deviation (SD). Factors associated with morphine avoidance were identified by logistic regression. A total of 204 patients were included in this study. A total of 46 cases (IV morphine) and 158 controls (IV morphine avoidance) were compared (3:1 ratio). Pain patterns and patient's epidemiologic characteristics were not associated with an IV morphine prescription. Regarding NRS intervals, the results suggest a practice disconnected from the patient's initial self-report. IV morphine avoidance was significantly associated with care pathways. A significant difference between the IV morphine group and the IV morphine avoidance group was observed for "self-referral" [adjusted odds ratio (aOR): 5.11, 95% CIs: 2.32-12.18, p < 0.0001] and patients' trajectories (Fisher's exact test; p < 0.0001), suggesting IV morphine avoidance in ambulatory pathways. In addition, "junior physician grade" was associated with IV morphine avoidance (aOR: 2.35, 95% CIs: 1.09-5.25, p = 0.03), but physician gender was not. This bedside case-control study highlights that IV morphine avoidance in the ED could be associated with ambulatory pathways. It confirms the decreased choice of "NRS-only" IV morphine protocols for all patients, including non-trauma patterns. Modern pain education should propose new tools for pain evaluation that integrate the heterogeneity of ED pathways.

Effect of Furosemide on Prevertebral Soft Tissue Swelling after Anterior Cervical Fusion: A Comparative Study with Dexamethasone.

Retrospective cohort study. This study aimed to investigate the effect of furosemide on prevertebral soft tissue swelling (PSTS) after anterior cervical fusion (ACF) and compare it with the effect of dexamethasone. Postoperative PSTS is a common complication of ACF. Dexamethasone has been used for its treatment; however, its efficacy remains controversial. Furosemide may reduce PSTS if it is soft tissue edema; however, no studies have demonstrated the effect of furosemide on PSTS after ACF. The symptomatic PSTS group received intravenous (IV) administration of dexamethasone or furosemide. The asymptomatic PSTS group did not receive any medication. Patients were divided into the control (no medication, n=31), Dexa (IV dexamethasone, n=25), and Furo (IV furosemide, n=28) groups. PSTS was checked daily with simple radiographs and medication-induced reductions in PSTS from its peak or after medication. The peak time (postoperative days) of PSTS in the control (2.27±0.47, p<0.05) and Dexa (1.91±0.54, p<0.01) groups were significantly later than that in the Furo group (1.38±0.74). PSTS was significantly lower in the Furo group than in the Dexa group from postoperative days 4 to 7 (p<0.05). PSTS reduction after the peak was significantly greater in the Furo group than in the control (p<0.01) and Dexa (p<0.01) groups. After starting the medication therapy, the Furo group showed a significantly greater reduction in PSTS than the Dexa group (p<0.01). No difference was found in symptom improvement among the three groups. If furosemide is used to reduce PSTS after ACF, it can effectively reduce symptoms.

Design and baseline characteristics of SALT-HF trial: hypertonic saline therapy in ambulatory heart failure.

Hypertonic saline solution (HSS) plus intravenous (IV) loop diuretic appears to enhance the diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this therapy in the ambulatory setting have not been evaluated. We aimed to describe the design and baseline characteristics of the SALT-HF trial participants. 'Efficacy of Saline Hypertonic Therapy in Ambulatory Patients with HF' (SALT-HF) trial was a multicenter, double-blinded, and randomized study involving ambulatory patients who experienced worsening heart failure (WHF) without criteria for hospitalization. Enrolled patients had to present at least two signs of volume overload, use ≥ 80mg of oral furosemide daily, and have elevated natriuretic peptides. Patients were randomized 1:1 to treatment with a 1-h infusion of IV furosemide plus HSS (2.6-3.4% NaCl depending on plasmatic sodium levels) versus a 1-h infusion of IV furosemide at the same dose (125-250mg, depending on basal loop diuretic dose). Clinical, laboratory, and imaging parameters were collected at baseline and after 7days, and a telephone visit was planned after 30days. The primary endpoint was 3-h diuresis after treatment started. Secondary endpoints included (a) 7-day changes in congestion data, (b) 7-day changes in kidney function and electrolytes, (c) 30-day clinical events (need of IV diuretic, HF hospitalization, cardiovascular mortality, all-cause mortality or HF-hospitalization). A total of 167 participants [median age, 81years; interquartile range (IQR), 73-87, 30.5% females] were randomized across 13 sites between December 2020 and March 2023. Half of the participants (n=82) had an ejection fraction >50%. Most patients showed a high burden of comorbidities, with a median Charlson index of 3 (IQR: 2-4). Common co-morbidities included diabetes mellitus (41%, n=69), atrial fibrillation (80%, n=134), and chronic kidney disease (64%, n=107). Patients exhibited a poor functional NYHA class (69% presenting NYHA III) and several signs of congestion. The mean composite congestion score was 4.3 (standard deviation: 1.7). Ninety per cent of the patients (n=151) presented oedema and jugular engorgement, and 71% (n=118) showed lung B lines assessed by ultrasound. Median inferior vena cava diameter was 23mm, (IQR: 21-25), and plasmatic levels of N-terminal-pro-B-type natriuretic peptide (NTproBNP) and antigen carbohydrate 125 (CA125) were increased (median NT-proBNP 4969pg/mL, IQR: 2508-9328; median CA125 46U/L, IQR: 20-114). SALT-HF trial randomized 167 ambulatory patients with WHF and will determine whether an infusion of hypertonic saline therapy plus furosemide increases diuresis and improves decongestion compared to equivalent furosemide administration alone.

Efficacy of vedolizumab during intravenous induction therapy in ulcerative colitis and Crohn's disease: post hoc analysis of patient-reported outcomes from the VISIBLE 1 and 2 studies.

Vedolizumab is an anti-α4β7 integrin antibody used to treat moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). This post hoc analysis of patient-reported outcomes (PROs) from the VISIBLE 1 (NCT02611830) and 2 (NCT02611817) phase 3 studies evaluated onset of treatment effect on patient-reported symptoms during 6-week vedolizumab induction. Patient-reported stool frequency (SF) and rectal bleeding (RB) (UC Mayo score), and SF and abdominal pain (AP) in CD were collected via electronic diary from VISIBLE patients receiving one or more open-label intravenous (IV) vedolizumab induction doses (weeks 0 and 2). PRO data were analyzed using descriptive statistics. Data from 994 patients (UC 383, CD 611) showed mean ratings for all PROs declined consistently week-on-week from baseline through week 6, with early onset of improvement. By week 2, 22% of patients with UC reported RB improvement (≥1-point reduction in RB subscore, 7-day mean), rising to 45% by week 6. By week 6, 18% of patients with UC achieved SF improvement (SF subscore 0; 21% antitumor necrosis factor alpha [anti-TNFα] naive, 13% anti-TNFα experienced). SF improvement in patients with CD (reduction of ≥3 stools, 7-day mean) was achieved by 32% at week 6 (34% anti-TNFα naive, 30% anti-TNFα experienced). Fewer patients with CD reported severe/moderate AP at week 6 (5.1%/28.5%) than baseline (14.6%/61.5%). SF decline appeared greater and faster for anti-TNFα-naive vs. anti-TNFα-experienced patients (UC and CD). Results indicate early onset of patient-reported UC and CD symptom improvement during vedolizumab IV induction in VISIBLE 1 and 2.

A comparative analysis of intravenous infusion methods for low-resource environments.

Intravenous (IV) therapy is a crucial aspect of care for the critically ill patient. Barriers to IV infusion pumps in low-resource settings include high costs, lack of access to electricity, and insufficient technical support. Inaccuracy of traditional drop-counting practices places patients at risk. By conducting a comparative assessment of IV infusion methods, we analyzed the efficacy of different devices and identified one that most effectively bridges the gap between accuracy, cost, and electricity reliance in low-resource environments. In this prospective mixed methods study, nurses, residents, and medical students used drop counting, a manual flow regulator, an infusion pump, a DripAssist, and a DripAssist with manual flow regulator to collect normal saline at goal rates of 240, 120, and 60 mL/h. Participants' station setup time was recorded, and the amount of fluid collected in 10 min was recorded (in milliliters). Participants then filled out a post-trial survey to rate each method (on a scale of 1 to 5) in terms of understandability, time consumption, and operability. Cost-effectiveness for use in low-resource settings was also evaluated. The manual flow regulator had the fastest setup time, was the most cost effective, and was rated as the least time consuming to use and the easiest to understand and operate. In contrast, the combination of the DripAssist and manual flow regulator was the most time consuming to use and the hardest to understand and operate. The manual flow regulator alone was the least time consuming and easiest to operate. The DripAssist/Manual flow regulator combination increases accuracy, but this combination was the most difficult to operate. In addition, the manual flow regulator was the most cost-effective. Healthcare providers can adapt these devices to their practice environments and improve the safety of rate-sensitive IV medications without significant strain on electricity, time, or personnel resources.

Comparison of preemptive and preventive intravenous acetaminophen on opioid consumption in pediatrics undergoing posterior spinal fusion surgery: a randomized controlled trial.

Posterior spinal fusion (PSF), commonly used for adolescent idiopathic scoliosis (AIS), causes severe postoperative pain. Intravenous (IV) administration of acetaminophen has shown promise for opioid-sparing analgesia; however, its analgesic effect and optimal timing for its standard use remain unclear. Our study aimed to evaluate the analgesic effect and optimal timing of IV acetaminophen administration in pediatric and adolescent patients undergoing PSF and requiring adequate pain control. This prospective, randomized, triple-blind trial was conducted in patients aged 11-20 undergoing PSF. Participants were randomized into three groups: the preemptive group (received IV acetaminophen 15 mg/kg after anesthetic induction/before surgical incision), the preventive group (received IV acetaminophen 15 mg/kg at the end of surgery/before skin closure), and the placebo group. The primary outcome was cumulative opioid consumption during the first 24 h postoperatively. Among the 99 enrolled patients, the mean ± standard deviation (SD) amount of opioid consumption during the postoperative 24 h was 60.66 ± 23.84, 52.23 ± 22.43, and 66.70 ± 23.01 mg in the preemptive, preventive, and placebo groups, respectively (overall P = 0.043). A post hoc analysis revealed that the preventive group had significantly lower opioid consumption than the placebo group (P = 0.013). However, no significant differences between the groups were observed for the secondary outcomes. The preventive administration of scheduled IV acetaminophen reduces cumulative opioid consumption without increasing the incidence of drug-induced adverse events in pediatric and adolescent patients undergoing PSF.

An assessment of exposed syringe inner walls as a route of exposure from hazardous drugs.

Maintaining safe working environments for health care personnel, especially for those who regularly handle hazardous drugs (HDs), is of utmost importance. Studies have shown that when closed system transfer devices (CSTDs) are used with standard open barrel syringes, cyclophosphamide (CP), a commonly used HD, is transferred to the syringe plunger during compounding or administration processes. This contamination can then be transferred to the work environment, endangering workers. The purpose of this study was to quantify HD contamination of the inner surface of standard open barrel syringes and to compare contamination levels between three commonly used HDs: 5-fluorouracil (5-FU), CP, and ifosfamide (IF). Each HD was transferred from a vial to an intravenous (IV) bag using a standard open barrel syringe and Becton, Dickinson and Company (BD) PhaSealTM CSTD connectors. Samples were taken from the inner surface of each of the syringe barrels to measure the amount of HD contamination. Each drug was tested 15 times and compared to a positive control. Significant amounts of each drug were transferred to the inner surfaces of the syringes. The average amounts of each drug measured were: 5-FU, 1327.7 ng (standard deviation [SD] = 873.6 ng); CP, 1074.8 ng (SD = 481.6 ng); and IF, 1700.0 ng (SD = 1098.1 ng). There was no statistically significant difference between the three drugs (p = 0.14). This study underscores the presence of HD contamination on standard open barrel syringe inner surfaces after transfer of drug from vial to syringe to IV bag. Such contamination could be spread in the working environment and expose health care workers to harm.

BRASH syndrome with a complete heart block- a case report

IntroductionBRASH syndrome (Bradycardia, Renal failure, Atrioventricular (AV) nodal blocking agent, Shock and Hyperkalemia) is a recently emerging diagnosis that describes the profound bradycardia seen in patients on AV nodal blockers who present with acute kidney injury (AKI) and hyperkalemia.Case presentationWe present a case of a 68 years old female patient with past history of hypertension taking atenolol and Enalapril presented to emergency department with the complaint of loss of consciousness of 02 hours duration. She had 03 days history of fatigue, poor oral intake, decreased urine output, appetite loss, vertigo and global headache. Her vital signs were blood pressure of 60/40 mmHg, absent radial pulse and temperature of 36.4 °C. Her systemic examination was remarkable for dry buccal mucosa; apical heart rate was 22 beats per minute. Glasgow Coma Scale was 13/15. Her laboratory tests showed creatinine of 1.83 mg/dL, blood urea nitrogen of 89 mg/dL and potassium elevated to the level of 6.39 mEq/dL. ECG revealed complete heart block with a normal QT interval and T waves and no U waves with ventricular rate of 22 beats per minute. Her previous medications were discontinued and the patient was resuscitated with intravenous (IV) fluids. She was given 03 doses of 1 mg atropine every 5 minutes but there was no increment in heart rate. She was given 50% dextrose with 10 international units of regular insulin, 1 g of calcium gluconate and Intravenous perfusion of norepinephrine and dopamine. Subsequently, after 14 hours of ICU admission the patient had a cardiac arrest with asystole and resuscitation was attempted but she couldn’t survive.ConclusionBRASH syndrome is largely an under-recognized life threatening clinical diagnosis. Physicians should have high index of suspicion for BRASH when they encounter patients with bradycardia, hyperkalemia, and renal failure, as timely diagnosis is crucial in the management.