Treatment Period Research Articles

Early Improvements With Atogepant for the Preventive Treatment of Migraine: Results From 3 Randomized Phase 3 Trials.

Three phase 3 trials demonstrated the efficacy and safety of atogepant in episodic migraine (EM) and chronic migraine (CM) across 12-week treatment periods. This analysis evaluates improvements in efficacy and functional outcomes in the first 4 weeks of treatment with the oral calcitonin gene-related peptide receptor antagonist, atogepant, for the preventive treatment of migraine. ADVANCE, ELEVATE, and PROGRESS were phase 3, multicenter, randomized, double-blind, placebo-controlled 12-week trials. ADVANCE and ELEVATE included participants aged 18-80 years with >1 year history of EM and 4-14 monthly migraine days (MMDs). ELEVATE required previous treatment failures to 2-4 classes of oral preventives. PROGRESS included participants aged 18-80 years with >1 year history of CM, ≥15 monthly headache days, and ≥8 MMDs. This analysis reports the atogepant 60 mg once daily (QD) and placebo treatment arms. Outcomes included efficacy endpoints (reporting a migraine day on day 1, change from baseline in weekly migraine days [WMDs] at weeks 1-4, and in MMDs in the first 4 weeks) and functional endpoints evaluated by the Activity Impairment in Migraine-Diary (AIM-D) at weeks 1-4 and the European Quality-of-Life 5-Dimension 5-Level (EQ-5D-5L) at weeks 1-2 and 4. The modified intent-to-treat population included the ADVANCE (atogepant, n = 222; placebo, n = 214), ELEVATE (atogepant, n = 151; placebo, n = 154), and PROGRESS (atogepant, n = 256; placebo, n = 246) studies. Atogepant-treated participants had greater reductions in the proportion of participants with a migraine day on day 1. The odds ratio compared with placebo was 0.39 (95% CI 0.23-0.67; p = 0.0006) in ADVANCE, 0.53 (95% CI 0.29-0.94, p = 0.031) in ELEVATE, and 0.63 (95% CI 0.43-0.93, p = 0.021) in PROGRESS. Atogepant treatment reduced WMDs at weeks 1-4 and MMDs in the first 4 weeks, and improved AIM-D and EQ-5D-5L at all assessed timepoints for weeks 1-4 compared with placebo. Atogepant 60 mg QD demonstrated superiority to placebo in efficacy and functional measures in the first 4 weeks of treatment across 3 preventive studies, 2 in EM and 1 in CM. ClinicalTrials.gov NCT03777059; NCT04740827; NCT03855137. Submitted: 12/13/2018; 02/02/2021; 02/25/2019. First patient enrolled: 12/14/2018; 03/05/2021; 03/11/2019 clinicaltrials.gov/ct2/show/NCT03777059. clinicaltrials.gov/ct2/show/NCT04740827 clinicaltrials.gov/ct2/show/NCT03855137. This study provides Class II evidence that atogepant 60 mg QD reduces migraine frequency and improves functional outcomes within 4 weeks of initiation in patients with EM and patients with CM.

Long-Term Safety of Ixekizumab Treatment in Patients with Psoriasis, Psoriatic Arthritis, or Axial Spondyloarthritis: a PostHoc Analysis of Cerebro-Cardiovascular Events.

Psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) may confer an increased risk for cardiovascular (CV) disease, including major adverse cerebro-cardiovascular events (MACE), deep vein thrombosis (DVT), and pulmonary embolism (PE). Patients with these conditions are often exposed for extended time periods to biologics, such as ixekizumab (IXE). Therefore, understanding the risk of CV events, especially MACE, in patients with PsO, PsA, and axSpA exposed to IXE is important. The incidence of MACE (i.e., adjudicated cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), DVT, and PE was assessed in adults who received ≥ 1 dose of IXE across 25 randomized clinical trials (17 PsO, 4 PsA, 4 axSpA). Rates of CV events were analyzed for pooled studies by indication and analyzed from treatment initiation up to the end of the study program. Exposure-adjusted incidence rates per 100 patient-years (IR/100PY) are reported. This integrated safety analysis included 6892 patients with PsO, 1401 with PsA, and 932 with axSpA. The median duration of IXE exposure was 478.5days (1.3years) for patients with PsO, 504.5days (1.4years) for patients with PsA, and 981.0days (2.7years) for patients with axSpA. The incidence of adjudicated MACE was low (IR/100PY: PsO = 0.5; PsA = 0.5; axSpA = 0.3) and stable over the treatment periods. The most common types of MACE reported were non-fatal myocardial infarction (IR/100PY: PsO = 0.3; PsA = 0.3; axSpA = 0.3), followed by non-fatal stroke (IR/100PY: PsO = 0.1; PsA = 0.2; axSpA = 0.0), and cardiovascular death (IR/100PY: PsO = 0.1; PsA = 0.1; axSpA = 0.0). The incidences of DVT (IR/100PY: PsO = 0.1; PsA = 0.1; axSpA = 0.1) and PE (IR/100PY: PsO = 0.1; PsA = 0.0; axSpA = 0.0) were low. This integrated safety analysis of 25 randomized clinical trials showed that the incidence of adjudicated MACE was low among adult patients with PsO, PsA, and axSpA and that the rates did not increase with increasing IXE exposure. The supplementary TableS1 provides a comprehensive list of clinical trials and their registration numbers.

Efficacy of complement inhibition with pegcetacoplan in children with C3 glomerulopathy.

C3 glomerulopathy (C3G) is a rare kidney disease due to a dysregulation of the alternative complement pathway, orphan of specific treatment. Pegcetacoplan is an inhibitor of the third complement component C3, currently on a phase III registration protocol in C3G. Here we describe our experience with the off-label use of pegcetacoplan in pediatric patients with C3G. This retrospective, observational study evaluated the efficacy and safety of pegcetacoplan in five pediatric patients, not eligible in the registration protocol, over a 12-week treatment period. The drug was given subcutaneously, twice a week for the first month, then weekly. The change in urinary protein-to-urinary creatinine ratio (mean of three samples) was the primary endpoint. We also evaluated the changes in serum C3, albumin, sC5-b9, creatinine, and urinary erythrocytes (number/µL). At baseline, median proteinuria/creatininuria ratio (mean of three samples) was 4.97mg/mg (3.53-7.69), and after 12weeks of treatment with pegcetacoplan, it decreased to less than 30% of baseline (p = 0.043) as did erythrocyturia (p = 0.043). C3 levels increased more than 600% of baseline (p = 0.043), whereas the levels of sC5-b9 decreased to normal range (p = 0.043). Three of four patients with impaired kidney function showed an improvement in eGFR. No adverse event was recorded. In C3G patients, pegcetacoplan therapy improves clinical and laboratory features during a 12-week treatment. The present study, although small and with a limited follow-up, supports the use of complement-targeted therapy in C3G. Further studies with a larger number of patients and longer follow-up are needed.

Effectiveness and safety of finerenone in membranous nephropathy patients: a retrospective, real‑world study.

We aimed to conduct a retrospective analysis to assess the efficacy and safety of finerenone in patients with membranous nephropathy (MN). This study conducted a retrospective analysis of patients with MN who were treated with finerenone for follow-up period ranging from 3 to 6months. The study compared the estimated glomerular filtration rate (eGFR), urine total protein-to-creatinine ratio (PCR), urine albumin-to-creatinine ratio (ACR), serum creatinine concentration (SCr), blood pressure and serum potassium (K+) during the follow-up period. In this study, 20 patients with MN were treated with finerenone for a follow-up period of 3 to 6months. Prior to treatment, the average eGFR was 65.15mL/min/1.73m2, the average PCR was 3643.63mg/g, and the average ACR was 2489.44mg/g. After 3months of treatment, 80% of patients experienced a decrease in PCR. The median decrease percentages in PCR and ACR are 24.49% and 28.82%, respectively. After 6months of treatment, the median decrease percentages in PCR and ACR are 42.03% and 43.66%, respectively while the eGFR remained stable with little variation from baseline. During the treatment period, there were minimal changes in serum potassium levels and serum creatinine levels and no treatment discontinuations or hospitalizations due to hyperkalemia were observed. Blood pressure decreased by about 10mmHg in 6 patients (30%), while there was no difference before and after the addition of finerenone in the remaining 14 (70%) patients. The retrospective analysis indicates that finerenone treatment led to significant reductions in PCR and ACR in patients with membranous nephropathy over a 3 to 6-month period, with minimal impact on eGFR, SCr, and K+ levels, highlighting its capacity as a therapeutic option for MN patient group.

Role of radiofrequency ablation in the treatment of symptomatic distant metastasis of thyroid cancer.

To evaluate the effectiveness and safety of radiofrequency ablation (RFA) for the treatment of symptomatic distant metastasis of differentiated thyroid carcinoma. The medical records of 12 patients who underwent RFA for the palliative treatment of 18 symptomatic distant metastases from thyroid cancer between January 2008 and December 2020 were analyzed. All patients were assessed for their degree of discomfort and underwent periodical evaluations as outpatients, including clinical examination, imaging, and serologic markers. Among the 18 tumors treated, nine were soft tissue, and nine were bone metastases. The mean size of the treated tumors was 5.3cm (range, 1.7-10.7cm). All patients complained of pain, discomfort and/or bulging of the metastatic mass before RFA. After RFA, 11 out of the 18 patients with metastatic tumors (61.1%) reported a subjective improvement in symptoms. Nine out of 18 tumors decreased in size, with a mean size reduction ratio of 43% ± 22%. Although symptom improvement was achieved in 61.1% of the tumors, after a mean follow-up duration of 37.4months, five patients experienced progression of the tumor, four patients had a stable tumor status, and three patients died from pneumonia. There were no major adverse events related to RFA during the treatment or follow-up period. RFA can be used as palliative therapy to relieve the symptoms caused by metastatic tumors; however, it has a limited role in improving the overall prognosis in patients with distant metastasis from thyroid cancer.

Testing an integrated approach for managing roof rats in citrus orchards.

Roof rats (Rattus rattus) are a substantial pest throughout citrus crops, yet little is known about efficacious, cost-effective strategies to manage this rodent. Therefore, we developed two integrated pest management (IPM) programs that incorporated elevated bait stations containing diphacinone-treated oats and trapping, and we compared those programs to a bait-station only approach to determine which strategies were most practical for the management of roof rats in citrus orchards. Bait applications substantially reduced rat activity within orchards. However, our initial IPM approach that used a combination of baiting, snap trapping and Goodnature® A24 traps were not successful at keeping rats from rapidly repopulating. A second IPM strategy that relied on baiting and more extensive snap trapping was effective at reducing rat activity up to, and likely beyond, a 6-month treatment period. Although baiting by itself was less expensive than IPM plots, the difference in cost between baiting and the IPM approach that used only baiting and snap trapping should be minimal during long-term management programs. The high efficacy of a management program that incorporates an initial bait application, followed by a long-term snap-trapping program, should yield effective management of roof rats in citrus orchards. © 2025 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Management of Chronic Post-Endodontic Pain with a Standardized Gabapentin Pyramid Protocol: A Case Series and Clinical Guidelines.

Persistent post-endodontic pain following endodontic therapy is a rare but substantial clinical challenge. Mechanisms that mediate peripheral neuropathy and/or central sensitization likely play a pivotal role in its development and chronification. The objective of this case series is to describe a management plan for persistent post-endodontic pain and provide prescription guidelines using a standardized "Gabapentin Pyramid Protocol" for clinical practice. Four cases of persistent post-endodontic pain are presented. A peripheral etiology for pain was eliminated in all four cases. All patients were also refractory to conventional analgesics. Patients received the "Gabapentin Pyramid Protocol". Three of the four cases experienced complete resolution of symptoms within the prescribed treatment period. In one case, symptoms were greatly reduced but recurred upon discontinuation of the drug. The "Gabapentin Pyramid Protocol" represents an effective treatment option for persistent post-endodontic pain, demonstrating significant symptom relief and potential for complete resolution.

Performance improvements and increased ruminal microbial interactions in Angus heifers via supplementation with native rumen bacteria during high-grain challenge

Feedlot cattle may be subjected to digestive disorders, including ruminal acidosis, due to high concentration of grain in their diet. Therefore, novel feeding strategies are required to maximize animal performance and mitigate economic losses in the operation. This study employed a two-period crossover design to assess the effect of direct ruminal administration of native rumen microorganisms (NRM) inoculation on cattle that underwent a high-grain challenge. The NRM inoculation consisted of six microorganisms (1.70 M CFU /day/animal) isolated from the rumen of healthy feedlot cattle: Succinivibrio dextrinosolvens ASCUSBF53, Prevotella albensis ASCUSBF41, Chordicoccus furentiruminis ASCUSBF65, Bacteroides xylanisolvens ASCUSBF52, Clostridium beijerinckii ASCUSBF26, and Syntrophococcus sp. ASCUSBF60. The trial consisted of 16 Angus heifers receiving NRM (n = 8) or a CON (CON = Carrier Buffer; n = 8) inoculation daily for 14-days as pre-challenge while on a high-grain diet and continued daily for a 21-day treatment period. The combined 35 days of microbial supplementation resulted in an improved average daily gain (ADG) of 29% (P = 0.037) and a tendency toward a 19% decrease in the feed efficiency metric, gain to feed ratio (G: F) (P = 0.055). Additionally, administration of NRM to animals on a high-grain diet, improved ruminal microbiome stability (P < 0.001), potentially encouraging the conversion of rumen lactate to propionate over time via the succinate pathway and alleviating metabolic stress.

Taurine protection attenuates bisphenol-A-induced behavioral, neurochemical, and histopathological alterations in male rats.

Due to the continuous exposure to bisphenol-A (BPA), the current study was conducted to evaluate taurine's neuroprotective action against BPA's adverse effect on the brain. Rats were grouped into control, BPA-treated rats, and taurine + BPA-treated rats. At the end of the 35-day treatment period, the memory of the rats was evaluated using the novel object test and the Y-maze test. An open-field test was used to measure motor activity. The changes in monoamines, monoamine oxidase (MAO), acetylcholinesterase (AChE), Na+,K+,ATPase, oxidative stress, caspase-3, and histopathology were evaluated in the cortical and hippocampal tissues of all groups. Data analysis by ANOVA revealed that BPA treatment induced motor hyperactivity and short- and long-term memory impairment. In the cortex, BPA decreased serotonin (5-HT), norepinephrine (NE), MAO, Na+,K+,ATPase, and nitric oxide (NO) and increased dopamine (DA), AChE, lipid peroxidation (MDA), glutathione (GSH), and caspase-3. In the hippocampus, BPA increased 5-HT, DA, NE, MAO, AChE, MDA, NO, GSH, and caspase-3 and decreased Na+,K+,ATPase. These neurochemical changes were accompanied by significant histopathological alterations. Taurine treatment prevented memory impairment and motor hyperactivity induced by BPA. Taurine attenuated the neurochemical changes, oxidative stress, and caspase-3 level. Taurine improved the histopathological change induced by BPA. In conclusion, taurine significantly prevented BPA-induced cognitive deficits, motor coordination impairments, neurotransmitter imbalances, histopathological alterations, oxidative stress, and apoptosis.

Cyto-Genotoxic Assessment of Sulfoxaflor in Allium cepa Root Cells and DNA Docking Studies.

Sulfoxaflor (SFX) is an insecticide that is commonly used for the control of sap-feeding insects. Since SFX is extensively applied globally, it has been implicated in the substantial induction of environmental toxicity. Therefore, in this study, Allium cepa roots have been employed to elucidate the potential cytogenotoxic effects of SFX in non-target cells by examination of mitotic index (MI), chromosomal aberrations (CAs), and DNA damage. Physiological effects of SFX were evaluated by A. cepa root growth inhibition assay, while cytogenotoxic effects were assessed by A. cepa ana-telophase and comet assay. Moreover, DNA binding affinity and binding mode of SFX were examined using molecular docking simulations to shed light on the genotoxic mechanism of action. The half maximal effective concentration (EC50) on the growth of A. cepa cells calculated for SFX was found as 500 mg/L. Moreover, dose- and time-dependent decrease in MI, increase in CAs (disturbed ana-telophase, chromosomal laggards, stickiness, and anaphase chromosome bridge) and DNA damage were observed by the exposure of A. cepa root tips to SFX after 24-, 48-, 72-, and 96-h treatment periods. A 6-bp double-stranded DNA structure containing two intercalation sites (PDB ID: 1Z3F) was used for docking studies. According to DNA docking results, SFX exhibited an energetically more favorable binding affinity with DNA (ΔG = -5.05 kcal/mol) compared with the experimental mutagen methyl methanesulfonate (MMS) (ΔG = -2.94 kcal/mol), and preferentially snugly fits into the minor groove of DNA possessing an intercalation gap, thus, providing valuable mechanistic data into the formation of chromosome aberrations and DNA fragmentation induced by this pesticide in A. cepa.

Exploring the Potential of Psychedelics in the Treatment of Headache Disorders: Clinical Considerations and Exploratory Insights.

Exploration of the potential of serotonergic psychedelic drugs, such as psilocybin and LSD, as potential treatments for headache disorders. This review addresses the need for well-informed physician guidelines and discusses mechanisms, safety, and efficacy of these treatments. Further research, including the consideration of combination with psychotherapy, is needed. Psychedelics demonstrate promising outcomes as treatments for headache disorders. Recent findings indicated that some patients who underwent brief periods of treatment with psychedelics experienced a reduction in headache attack frequency, severity, or duration. When prescription medications are ineffective at treating headache disorders, or are habit-forming, patients often turn to alternative options. There is anecdotal evidence that psychedelic drugs like LSD and psilocybin can effectively treat and prevent pain in patients with headache disorders, such as migraine or cluster headache. It is vital that physicians treating patients who self-treat with psychedelics be well-informed about the mechanisms and their effects to best advise their patients and coordinate their care well. This is a review assessing the literature on the mechanisms, safety, and efficacy of psychedelic drugs as a headache management intervention. We believe there is evidence that may support further investigation into the clinical use of psychedelic medications to treat cluster headache and migraine, including the consideration of use in conjunction with other interventions like cognitive behavioral therapy or acceptance and commitment training.

Cognitive and behavioral effects of perampanel 4mg daily dose.

The neuropsychological adverse effects of antiseizure medications (ASMs) influence the tolerability, and in turn effectiveness of these medications, which can occur in a dose-dependent fashion. In this study, we examine the neuropsychological effects of perampanel (PER) at 4mg daily as this dose has not been previously assessed with objective cognitive tests. The study was originally designed to assess (1) effects of perampanel at 4mg using different titration rates, and (2) habituation over time. Due to the COVID-19 pandemic, the study was halted, limiting the sample size needed to analyze titration and habituation effects. Therefore, we compared the neuropsychological effects of perampanel 4mg daily from non-drug baseline to the end of drug titration and end of drug maintenance in this randomized double-blind study of healthy volunteers. Treatment period was 6weeks total with 2weeks of variable titration followed by 4-week maintenance. Composite Z-scores were calculated by combining Z-scores from both cognitive (computerized and non-computerized) and behavioral tests. Secondary analyses were conducted on the independent cognitive and behavioral domain Z-scores, and on the raw scores from 19 items in the full battery. The overall composite Z-scores did not differ across baseline, the end of titration, and the end of maintenance. Similarly, individual cognitive and behavioral domain Z-scores did not differ across the three titration rates. Exploratory analyses of the raw scores were marginally significant on only two of the 19 neuropsychological measures. Perampanel 4mg daily was well tolerated with few neuropsychological effects in healthy volunteers.

Effectiveness of a Mobile Health Intervention (DOT Selfie) in Increasing Treatment Adherence Monitoring and Support for Patients With Tuberculosis in Uganda: Randomized Controlled Trial.

Directly observed therapy (DOT) is the standard method for monitoring adherence to tuberculosis (TB) treatment. However, implementing DOT poses challenges for both patients and providers due to limited financial and human resources. Increasing evidence suggests that emerging digital adherence technologies, such as video directly observed therapy (VDOT), can serve as viable alternatives. This study aims to evaluate the effectiveness of VDOT compared with usual care directly observed therapy (UCDOT). Between July 2020 and October 2021, we conducted a 2-arm, parallel-group, open-label randomized trial with a 1:1 assignment to receive either the VDOT intervention (n=72) or UCDOT (n=72) for treatment adherence monitoring at public health clinics in Kampala, Uganda. Each group was further stratified to ensure equal numbers of males and females. Eligible patients were aged 18-65 years, had a confirmed diagnosis of TB, and were undergoing daily treatment. The VDOT group was provided with a smartphone equipped with an app, while the UCDOT group followed the routine monitoring practices outlined by the Uganda National TB Program. We tested the hypothesis that VDOT was more effective than UCDOT for monitoring medication adherence. The primary outcome was adherence, defined as having ≥80% of the expected doses observed during the 6-month treatment period. An intention-to-treat analysis was conducted, and multivariable logistic regression was used to estimate the effect of the intervention on adherence monitoring. Adjusted relative risk ratios and their corresponding 95% CIs are presented. Secondary outcomes included treatment completion, loss to follow-up, death, and reasons for missed videos in the intervention group. The intention-to-treat analysis included 142 participants, with 2 excluded due to discontinuation of medication within the first week after enrollment. The median age of participants was 34 (IQR 26-45) years. The median fraction of expected doses observed (FEDO) was significantly higher in the VDOT group compared with the UCDOT group (100, IQR 80-100 vs 30, IQR 10-60, respectively; P<.001). When using a FEDO cutoff of ≥80% to define optimal adherence, 63 of 142 (44%) patients met the threshold, with a significant difference between the VDOT and UCDOT groups (56/71, 79% vs 7/71, 10%, P<.001). After adjusting for confounders, VDOT users were significantly more likely to achieve ≥80% of their expected doses observed compared with UCDOT users (adjusted risk ratio 8.4, 95% CI 4.16-17.0). The most common reasons for failing to submit videos of medication intake were an uncharged phone battery, forgetting to record videos during medication intake, and losing the smartphone. Enhanced VDOT was more effective than UCDOT in increasing adherence monitoring among patients with TB in Uganda. This evidence highlights the potential of digital technologies to improve treatment adherence monitoring and support in high TB burden settings with limited human resources. ClinicalTrials.gov NCT04134689; http://clinicaltrials.gov/ct2/show/NCT04134689.

No Injury Observed in Kidneys Treated with Burst Wave Lithotripsy in Therapeutically Anticoagulated Pigs.

Introduction: Current American Urological Association guidelines recommend that patients with acute obstructive kidney stone requiring continuous anticoagulation/antiplatelet therapy should not be treated by shockwave lithotripsy or percutaneous nephrolithotomy because of the risk of catastrophic renal hemorrhage possible with those techniques. Currently, ureteroscopy is the only recommended surgical treatment. We evaluated if burst wave lithotripsy (BWL) could be used in these cases by treating pigs with BWL while undergoing anticoagulation therapy. Materials and Methods: Six pigs (31-37 kg) were given 200 units/kg porcine heparin, and then the right kidney of each animal was treated with a dose of BWL (18,000 ultrasound pulses at 10 Hz, 20 cycles/pulse, peak positive pressure of 12 MPa) known to fracture kidney stones. The contralateral kidney served as a control. Therapeutic anticoagulation was confirmed by evaluating activated partial thromboplastin time (aPTT). Microhematuria was checked by urine test strips. Kidneys were subsequently evaluated for hemorrhagic injury via MRI. Results: aPTT was significantly elevated (>100 seconds) throughout the entire treatment period (p = <0.001) indicating therapeutic anticoagulation. Gross hematuria was not observed in any of the pigs. After BWL, microhematuria averaged 145.8 red blood cells (RBC)/μL in the BWL-treated kidney and 48 RBC/μL in the control kidneys, and there was no statistically significant difference noted in microhematuria rates between the two groups (p = 0.16). Hemorrhagic injury measured only 0.10 ± 0.02% of the tissue in the BWL-treated kidneys and 0.12 ± 0.04% in the control side, with a paired difference of -0.03 ± 0.05%, showing no significant difference (p = 0.58). Conclusions: A typical clinical dose of BWL causes no hemorrhagic injury to the kidney even during therapeutic anticoagulation therapy. This result suggests that BWL should be safe to use in patients with stone undergoing anticoagulation/antiplatelet therapy.

Correlation between Efficacy and Cardiovascular Adverse Events in Patients with Advanced Solid Cancer Who Received VEGF Pathway Inhibitors: Hypertension within the First Eight Weeks Is Associated with Favorable Outcomes of Patients Treated with VEGF Pathway Inhibitors.

Objective Many vascular endothelial growth factor (VEGF) pathway inhibitors are used in the treatment of patients with various advanced cancers; however, treatments induce cardiovascular adverse events (CVAEs), such as hypertension, heart failure, arrhythmia, arterial or venous embolism, and hemorrhage. Some studies have suggested a correlation between efficacy and CVAEs; however, further evidence is required. This study evaluated real-world data concerning the frequency and degree of CVAEs and possible associations between CVAEs and efficacy in such patients. Methods We analyzed CVAEs observed in 294 patients with advanced cancer who were treated with ramucirumab, regorafenib, pazopanib, sunitinib, or sorafenib. Results CVAEs of any grade and proteinuria within 8 weeks after the initiation of VEGF pathway inhibitors (early) or during the treatment period (total period) were observed in 72-85% and 77-92% of the patients, respectively. The progression-free survival (PFS) of patients with a CVAE of grade ≥1 in the early period was favorable compared with the PFS of those who had no CVAE (median, 4.9 vs. 3.5 months, p=0.016, log-rank test). Furthermore, the PFS of patients with a CVAE grade ≥3 in the early period was favorable compared to that of those with CVAEs of grades 0-2. Taken together, a higher degree of CVAE was correlated with favorable patient outcomes. Conclusion This study revealed the frequency and degree of CVAEs in patients with solid cancers who received VEGF pathway inhibitors in a real-world setting and added evidence regarding the correlation between CVAEs and efficacy of VEGF pathway inhibitors.

A Novel Treatment for Scabies with Herbal Formulation: A Clinical Safety Assessment Study

Introduction: Scabies, known as Jarb in Unani medicine, is a parasitic infection caused by the mite Sarcoptes scabiei var. Hominis. It is characterized by intense itching, particularly noted by patients at night. In India, this disease affects over three million people, manifesting as papular or vesicular eruptions accompanied by pruritus. Unani physicians have developed comprehensive treatments for scabies, considering its causative factors and various types. Methods: This study was conducted as an open-label, single-arm clinical trial involving 75 patients diagnosed with scabies with male female ration of 1:2.7. The primary objective was to assess the efficacy and safety of a compound Unani formulation. The test group received a Compound Unani formulation Irtifal Shahtra (Fumaria indica Pugsley) at a dose of 5 grams twice daily, Marham Kharish Jadeed (Lawsonia inermis) for topical application twice daily, and Aab-e-Barg-e-Neem (a decoction of Neem leaves) for washing the affected areas before applying Marham twice daily, for a duration of 15 days. Both subjective and objective parameters were evaluated before and after the treatment period. Results: In this study, 94% patients reported a significant reduction in itching after using unani formulation for Scabies. Only 5% patients had mild itching at the end of the study. Regarding cure of the lesions, the reduction in mean values from before to after treatment indicates an improvement in skin lesions. P-value less than 0.05 indicate that the results are statistically significant. Objective parameters such as the skin scraping test, demonstrated a significant reduction (p&lt;0.001). Importantly, no adverse effects were observed with the treatment regimen, further highlighting its effectiveness in alleviating scabies symptoms. Conclusion: This study highlights the safe and effective utilization of Unani formulations in treating one of the most distressing skin disease scabies, without any adverse effects. Keywords: Scabies, Jarb, Itrifal shahtra, Barg neem, Marham Kharish Jadeed, Classical Pharmacopoeial formulations.

Multimodal ultrasound assessment of the injection therapy in lateral epicondylitis: a retrospective observational study

BackgroundAt present, there is a dearth of objective methodologies for assessing the effectiveness of treatments for Lateral Epicondylitis (LE). This study examined 73 patients suffering from tennis elbow using a multimodal ultrasound approach and investigated the correlation between pertinent indicators and clinical scores.Methods73 patients diagnosed with unilateral tennis elbow by interventional ultrasound at Zhejiang Rongjun Hospital were included in the study. Ultrasound data of the extensor tendon, as well as VAS (Visual Analog Scale) and MEPS (Mayo Elbow Performance Score) for the affected elbow, were collected before and after a two-week treatment period. The study aimed to compare the alterations in gray-scale ultrasound features, hemodynamic parameters, and elastography scores pre- and post-treatment, and to analyze the correlation between the changes in ultrasound parameters and pain scores.ResultsFollowing treatment, the effective group exhibited a reduction in both the blood flow grade and elastic score of the extensor tendon. Additionally, the extensor tendon thickness in the effective group diminished to a greater extent than in the ineffective group. The effective group also experienced a higher rate of decrease in blood flow grade and a more pronounced increase in Resistive Index (RI) compared to the ineffective group. The reduction in tendon thickness, the increase in RI, and the improvement in elastic score were all positively correlated with the reduction in VAS scores. Notably, the increase in RI demonstrated the strongest correlation with the decrease in VAS scores.ConclusionsMultimodal ultrasound plays a significant role in the clinical assessment of treatment outcomes for Lateral Epicondylitis.

Clinical Trial: Study to Investigate the Efficacy and Safety of the Alpha-2-Delta Ligand PD-217,014 in Patients With Irritable Bowel Syndrome.

Despite the emergence of drugs to treat irritable bowel syndrome (IBS), improving abdominal pain can still be challenging. α2δ ligands, such as gabapentin and pregabalin, are sometimes used off-label to tackle this problem. However, evidence for efficacy is limited, and no large-scale studies have been published. To study the efficacy of the α2δ ligand PD-217,014 in IBS. This multi-centre, double-blind, randomised, placebo-controlled, parallel group study randomised participants with Rome II-defined IBS to 150 or 300 mg b.d. of PD-217,014 or placebo b.d. for 4 weeks. The primary efficacy endpoint was responder, defined as having adequate relief of abdominal pain/discomfort for ≥ 50% of the active treatment period. Key secondary endpoints were change from baseline in abdominal pain, bloating, stool frequency/consistency, and global assessment of IBS symptoms. We randomised 330 participants [aged 19-73 years; 209 (65%) female] satisfying Rome II criteria, 322 (98%) were treated, and of whom 271 (84%) completed the study. In this study, 321 satisfied Rome IV criteria. Neither dose of PD-217,014 improved the percentage of participants reporting adequate relief of abdominal pain/discomfort compared with placebo, either using the Rome II-defined total cohort or Rome II and IV IBS bowel habit sub-types. There were similar observations for secondary endpoints, and no association between abdominal pain or anxiety levels at baseline with participant improvement. PD-217,014 was generally well tolerated. This first large, dose-ranging trial examining the efficacy of PD-217,014 showed no significant efficacy in participants with IBS or bowel habit sub-types, irrespective of their pain and anxiety levels.

Extracutaneous sporotrichosis.

SUMMARYSporotrichosis is a subacute-to-chronic infection endemic to tropical and subtropical regions. It usually involves subcutaneous tissue but can occasionally cause extracutaneous infections, especially in hyperendemic areas. Extracutaneous infections are classified based on the anatomic location of the lesion and the route of infection (primary or multifocal). The clinical forms are as follows: (i) pulmonary (primary or multifocal); (ii) osteoarticular (primary or multifocal); (iii) ocular (ocular adnexal lesions including eyelid lesions, conjunctivitis and dacryocystitis, and intraocular infections); (iv) central nervous system; and (v) mucosal (primary or disseminated). Multifocal clinical presentations are observed mainly in immunocompromised individuals. The diagnosis must be confirmed in the laboratory by mycological examination of the clinical samples. Itraconazole and amphotericin B are the most commonly used antifungal agents for treating pulmonary, osteoarticular, ocular, and mucosal forms. Treatment may include surgical excision of the initial lesions in pulmonary and osteoarticular forms. The treatment of neurological involvement is far from optimal and is associated with a high mortality rate despite long treatment periods.

The Appearance of Antiphage Antibodies in Sera of Patients Treated with Phages.

Background: Bacteriophages are neutralized by the sera of patients undergoing phage therapy (PT), particularly during local or concomitant local and oral phage administration in bone infections, soft tissue infections, or upper respiratory tract infections. Methods: The antiphage activity of the sera (AAS) level of 27 patients with bacterial infections such as bone infections, soft tissue infections, or upper respiratory tract infections undergoing PT was performed using the plate phage neutralization test. Results: Our preliminary results suggest that high levels of antiphage antibodies appear late in the treatment period, at the earliest in the 3rd-8th week of PT. Patients with bone infections treated locally with the S. aureus phage Staph_1N and patients with upper respiratory tract infections administered locally and orally with the S. aureus phage Staph_A5L had elevated levels of antiphage antibodies in sera during PT. In parallel to these results, it has been shown that a strong antiphage humoral response does not prevent a positive outcome of phage treatment. Conclusions: The earliest time point at which high levels of antiphage antibodies in sera appear during local and oral PT is day 21 of therapy. We noticed that the high level of antiphage antibodies in sera occurring during local or both local and oral PT was correlated with the type of infection and phage type.