Minor Adverse Effects Research Articles

Invasive devices to monitor the intraspinal perfusion pressure in the hemodynamic management of acute spinal cord injury: A systematic scoping review.

Various methods for measuring intrathecal pressure (ITP) after spinal cord injury (SCI) to guide hemodynamic management have been investigated. To synthesize the current literature, this current study conducted a scoping review of the use of intrathecal devices to monitor ITP during acute management of SCI with the aim of understanding the association between ITP monitoring with physiological and clinical outcomes. A systematic review of literature following the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. All eligible studies were screened for inclusion and exclusion criteria. Data extracted included number of patients included, severity of injury, characteristics of the intervention-intrathecal device used to record the ITP, outcomes -hemodynamic parameters observed, changes in the American Spinal Injury Association (ASIA) Impairment Scale (AIS), total motor scores, association of ITP with other physiological variables. The search yielded a total of 1,698 articles, of which 30 observational studies and 2 randomized clinical trials were deemed eligible based on their use of an intrathecal invasive device to monitor spinal cord perfusion pressure (SCPP) in patients with SCI. Of these, 9 studies used a lumbar drain, 23 a Codman pressure probe and 1 study that used both. These studies underscore the crucial interplay between ITP, the SCPP and physiological variables, with neurological outcome. It is still unclear whether monitoring from a lumbar drain is accurate enough to highlight what is occurring at the site of SCI, which is the main advantage of Codman Probe, however, the latter requires specialized personnel that may not be available in most settings. Minor adverse effects were associated with lumbar drain catheters, while cerebrospinal fluid leak requiring repair (~ 7%) is the main concern with Codman Probes. Future investigation of SCPP protocols via lumbar drains and Codman probes ought to involve multi-centered randomized controlled trials and continued translational investigation with animal models.

Curcumin extract improves beta cell functions in obese patients with type 2 diabetes: a randomized controlled trial

BackgroundType 2 diabetes mellitus (T2DM) is a chronic condition characterized by insulin resistance and impaired insulin production, leading to elevated blood glucose levels. Curcumin, a polyphenolic compound from Curcuma longa, has shown potential in improving insulin sensitivity and reducing blood glucose levels, which may help mitigate type 2 diabetes progression.ObjectiveTo assess the efficacy of improving type 2 diabetes (T2DM).Study designThis randomized, double-blind, placebo-controlled trial included subjects (n = 272) with criteria for type 2 diabetes.MethodsAll subjects were randomly assigned to receive curcumin (1500 mg/day) or placebo with blind labels for 12 months. To assess the improvement of T2DM after curcumin treatments body weight and body mass index, fasting plasma glucose, glycosylated hemoglobin A1c, β-cell function (homeostasis model assessment [HOMA-β]), insulin resistance (HOMA-IR), insulin, adiponectin, and leptin were monitored at the baseline and at 3-, 6-, 9-, and 12-month visits during the course of intervention.ResultsAfter 12 months of treatment, the curcumin-treated group showed a significant decrease in fasting blood glucose (115.49 vs.130.71; P < 0.05), HbA1c (6.12 vs. 6.47; P < 0.05). In addition, the curcumin-treated group showed a better overall function of β-cells, with higher HOMA-β (136.20 vs. 105.19; P < 0.01) The curcumin-treated group showed a lower level of HOMA-IR (4.86 vs. 6.04; P < 0.001) and higher adiponectin (14.51 vs. 10.36; P < 0.001) when compared to the placebo group. The curcumin-treated group also showed a lower level of leptin (9.42 vs. 20.66; P < 0.001). Additionally, body mass index was lowered (25.9 4 vs.29.34), with a P value of 0.001.ConclusionsA 12-month curcumin intervention in type 2 diabetes patients shows a significant glucose-lowering effect. Curcumin treatment appeared to improve the overall function of β-cells and reduce both insulin resistance and body weight, with very minor adverse effects. Curcumin intervention in obese patients with type 2 diabetes may be beneficial.Trial registrationThai clinical trials regentrify no.20140303003.

Estimation of the adverse effects following immunization after SARS-CoV-2 Vaccine (Covishield and Covaxin) in lactating women: A single centre exploratory study from India

ABSTRACT Context: The global COVID-19 pandemic has universally impacted individuals, with lactating women being uniquely susceptible to severe infection. Vaccination plays a critical role in building population immunity, mitigating severe illness and curtailing the health crisis. However, data on adverse effects and vaccine safety in lactating women remains scarce. Aims: To assess the prevalence and types of adverse effects post-COVID vaccination in lactating women. Methods: This study was conducted at a tertiary care hospital’s COVID-19 vaccination centre in North India, and followed a prospective observational design over a specific timeframe. A total of 200 lactating women were surveyed, with specific inclusion and exclusion criteria applied. Telephonic follow-up was conducted for one month after the first dose for 152 participants and after the second dose for 123 participants. Adverse effects following immunization (AEFIs) were recorded and analyzed. Results: Of the study cohort, 45 (29.60%) reported minor adverse effects following the first vaccine dose, with just four (3.25%) experiencing adverse effects after the second dose. Common AEFIs included fever (18.42%) and body aches (9.21%), along with headache, malaise, injection site pain and diffuse abdominal pain. Conclusions: This study provides valuable insights into the adverse effects of COVID-19 vaccines in lactating women, which can help primary physicians and policy maker to improve vaccination policies and guidelines. The study revealed that lactating mothers experienced only mild AEFIs, aligning with current literature. Further broader, multicentre research is needed to reinforce these findings and to assess the long-term safety and efficacy of COVID-19 vaccines in this population.

Energy transitions of declining energy industries: the effect of renewable portfolio standards on the U.S. coal industry

Abstract This study examines the influence of Renewable Portfolio Standards (RPS) on coal industry employment and wages in the top 10 U.S. coal-producing states from 2001 to 2018, with a specific focus on the 2003-2009 RPS adoption period. Employing a difference-in-differences methodology and utilizing data encompassing employment, gas prices, and RPS-related MWh at the quarterly level, our findings reveal that RPS had only temporary and minor adverse effects on coal employment. These effects manifested with a delay of up to four quarters but dissipated within two years. Moreover, RPS had no significant impact on state’s coal sector wages.

Efficacy of botulinum neurotoxin A in persistent idiopathic dentoalveolar pain: a case series.

Persistent idiopathic dentoalveolar pain (PIDP) is a challenging clinical entity associated with both physical and emotional consequences. Currently, the management is symptom-based and includes both topical and/or systemic treatments. More recently, botulinum neurotoxin-A (BONT-A) has been suggested as a treatment option. We present a case series of 9 patients (5 female) with mean age 56 ± 15 diagnosed with PIDP. All patients reported prior experience with systemic drugs without a sufficient pain-relieving effect. BONT-A (BOTOX, Allergan) 100 U diluted with saline solution was used and the dose ranged from 20U to 50U distributed in 3 sites (intraoral and/or extraoral) per session. Patients underwent further injections (50U) monthly if pain severity measured using a Numerical Rating Scale (NRS 0-10) was still > 3 for 3 months. Pain severity and characteristics were recorded at baseline (T0), after 1 month (T1), 2 months (T2) and 3 months (T3). Mean pain intensity at baseline was NRS 6 (4-10). Latency before analgesic effect was at least 5-10 days after injection. Minor adverse effects were sickness and muscular hypotonia. Pain significantly reduced to NRS 4 (0-8) at T1, to NRS 2 (0-8) at T2 and to NRS 2 (NRS 0-8) at T3. Patients' functional variables (discomfort while chewing, talking, swallowing) were also recorded. BONT-A is widely used and although the exact mechanism of action remains unclear, it can be used effectively in reducing pain for a variety of conditions including PIDP. Our results suggest that BONT-A seems to be an alternative therapeutic approach for patients with PIDP.

Effects of Melatonin on Sleep Quality and Patient-Reported Outcomes After Arthroscopic Rotator Cuff Surgery: A Prospective Randomized Controlled Trial.

Sleep disturbance is a significant symptom associated with both rotator cuff tears and arthroscopic rotator cuff repair. Melatonin has been shown to be safe and effective in managing multiple sleep disorders, including secondary sleep disorders, with relatively minor adverse effects and lack of addictive potential. To investigate the effects of oral melatonin on postoperative sleep quality after arthroscopic rotator cuff repair. Randomized controlled trial; Level of evidence, 1. This was a prospective randomized clinical trial evaluating patients undergoing arthroscopic rotator cuff repair. Exclusion criteria included history of alcohol abuse, current antidepressant or sedative use, revision rotator cuff repair, severe glenohumeral arthritis, and concurrent adhesive capsulitis. Patients were randomly assigned in a 1:1 ratio to 1 of 2 groups: 5-mg dose of melatonin 1 hour before bedtime or standard sleep hygiene (≥6 hours per night, avoiding caffeine and naps in the evening). Patients in the melatonin group took their assigned melatonin dose for 6 weeks beginning the day of surgery. Patient-reported outcome assessments, including the Pittsburgh Sleep Quality Index (PSQI), the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), and the Single Assessment Numeric Evaluation (SANE), and pain medication charts were collected preoperatively as well as at 2 weeks, 6 weeks, 3 months, 4 months, and 6 months postoperatively. Numeric variables were analyzed using paired and unpaired t tests, with significance set at P < .05. Eighty patients were included for final analysis (40 in the control group, 40 in the melatonin group). Patient characteristics such as age, sex, race, body mass index, and laterality did not differ significantly (P≥ .05). Preoperative ASES, SANE, and PSQI scores did not differ between groups (P≥ .055). PSQI scores were significantly lower (better quality sleep) in the melatonin group at the 6-week postoperative period (P = .036). There was a positive correlation between how patients rated the intensity of their pain and the PSQI at the 6-week postoperative period (0.566). The PSQI question regarding sleep quality was found to be significantly lower in the melatonin group at the 3-month, 4-month, and 6-month postoperative periods (P = .015, P = .041, and P≤ .05, respectively). SANE scores were significantly lower in the melatonin group (P = .011) at 6 weeks and then higher in the melatonin group (P = .017) at 6 months. ASES scores were significantly higher in the melatonin group at 4 and 6 months (P = .022 and P = .020, respectively). Lastly, patients who were randomized into the melatonin group were found to use significantly less narcotic medication at the 4-month postoperative period (P = .046). Melatonin use after arthroscopic rotator cuff repair led to improved sleep quality (PSQI) in the early postoperative period as well as improved functional outcomes (ASES and SANE scores) and decreased narcotic use in the later postoperative period. Patients with significant sleep disturbances associated with rotator cuff repairs may benefit from the use of melatonin. NCT04278677 (ClinicalTrials.gov identifier).

Efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) in anejaculation: A randomized controlled trial.

Anejaculation represents significant psychological distress and sexual and reproductive challenges among male individuals and couples. Effective fertility management options are available to address the reproductive challenges associated with anejaculation. However, there is a lack of methods to reverse the condition itself. This study aims to assess the effectiveness and safety of repetitive transcranial magnetic stimulation (rTMS) in patients suffering from anejaculation. A total of 94 patients with anejaculation individuals were randomly assigned to receive high-frequency (HF) stimulation on the left dorsolateral prefrontal cortex (DLPFC), low-frequency (LF) stimulation on the right DLPFC, and sham stimulation for 4 weeks, with daily sessions of stimulation occurring on five consecutive weekdays each week. After 4 weeks of rTMS treatment, the patients in both the HF and LF groups exhibited a similar reduction in their male sexual health questionnaire for ejaculatory dysfunction bother/satisfaction score, Hamilton Anxiety Scale score, Hamilton Depression Scale score, and Pittsburgh Sleep Quality Inventory score, which were statistically significant compared with sham treatment. Additionally, there were no significant differences observed in erectile function and cognitive function across the three groups. However, there were notable disparities in the cure rates between HF- and LF-group patients (16.1% vs. 54.8%, p=0.001). Additionally, it is worth noting that only two HF group patients and one LF group patient experienced spontaneously resolving minor adverse effects during the treatment process. At the 8-week follow-up, among patients who initially responded to the treatment, only one from the HF group experienced a relapse. The findings of this study demonstrate that rTMS represents a secure and efficacious remedy for anejaculation patients.

Efficacy and safety of combining short-course neoadjuvant chemoradiotherapy with envafolimab in locally advanced rectal cancer patients with microsatellite stability: A phase II PRECAM experimental study.

Conventional neoadjuvant chemoradiotherapy (nCRT) yields a pathologic complete response (pCR) rate of 15%-30% for locally advanced rectal cancer (LARC). This study ventures to shift this paradigm by incorporating short-course nCRT with immunotherapy, specifically Envafolimab, to achieve improved treatment efficacy and possibly redefine the standard of care for LARC. The PRECAM study is a prospective, single-arm, phase 2 clinical trial for LARC in patients with microsatellite stable (MSS) tumors. Participants received short-course radiotherapy (25Gy/5f), followed by two cycles of CAPEOX chemotherapy and six weekly doses of Envafolimab, a PD-L1 antibody, before total mesorectal excision surgery. The primary endpoint was the pCR rate. From April to December 2022, 34 patients were enrolled, of whom 32 completed the study, each diagnosed with an MSS rectal adenocarcinoma. All patients underwent preoperative CRT combined with Envafolimab. Remarkably, a pCR rate of 62.5% (20/32) was attained, and a significant pathologic response rate of 75% (24/32) was achieved. Additionally, 21 of 32 participants achieved a neoadjuvant rectal (NAR) score below 8, suggesting an effective treatment response. Common adverse events included tenesmus (78.1%), diarrhea (62.5%), and leukocyte decrease (40.6%). Two Grade 3 adverse events were noted, one related to liver function abnormality and the other to a decrease in platelet count. Surgical procedures were performed in all cases, with minor complications, including ileus, infections, and anastomotic leakage. As of this report, there have been no reported cases of recurrence or death during the follow-up period, ranging from 12 to 20 months. In LARC patients exhibiting MSS tumors, combining short-course nCRT with Envafolimab demonstrated favorable efficacy, leading to a significant pCR rate. Minor adverse effects and surgical complications were observed. These preliminary but promising results underscore the potential of this approach and call for further exploration and validation through a randomized controlled trial.

Efficacy and Safety of BoozLiv™ as an add on therapy in patients with alcoholic liver disease: An open-label, randomized controlled trial

BackgroundAlcoholic Liver Disease (ALD) poses a significant global health threat, contributing to millions of deaths each year. Despite the well-established link between chronic alcohol consumption and liver damage, treatment options remain limited, emphasizing the need for innovative approaches. MethodsAn open-label, randomized controlled trial was conducted in India, involving 68 adult ALD patients over a 12-week period. The patients were randomized into two groups: one receiving standard therapy and the other receiving standard therapy along with BoozLiv™ syrup. Liver function tests, Model for End-Stage Liver Disease (MELD) scores, and safety parameters were assessed at various intervals. ResultsThe study demonstrated that BoozLiv™ syrup, as an add-on therapy, significantly reduced total bilirubin, direct bilirubin, SGOT, SGPT, ALP, and GGT levels compared to standard therapy alone (p ​< ​0.05). The MELD score, indicative of liver function, showed a substantial improvement in the BoozLiv™ group (p ​< ​0.01). Safety analysis revealed that BoozLiv™ was well-tolerated, with only minor adverse effects such as nausea and vomiting reported. ConclusionBoozLiv™ syrup, used in conjunction with standard therapy, showed promising results in improving liver function and reducing liver damage markers in ALD patients. The safety profile was favorable and no patient has withdrawn their consent due to adverse events. Further long-term studies in larger populations are warranted to validate these findings and establish BoozLiv™ as a potential therapeutic option for ALD.

Comparison of efficacy and safety of tofacitinib and azathioprine in patients with alopecia areata and variants: a double-blind, randomized controlled trial.

Alopecia areata (AA) is an autoimmune pathology manifested by loss of hair. To evaluate and compare the efficacy and safety of tofacitinib and azathioprine in patients with AA and variants. In this double-blind randomized controlled trail (RCT) carried out at the Department of Dermatology, Medical Teaching Institute-Lady Reading Hospital (MTI-LRH), Peshawar, Pakistan, patients aged ≥ 12 years diagnosed with AA, alopecia totalis (AT) or alopecia universalis (AU) with minimum 50% scalp hair loss for a period ≥ 06 years were included. Patients were randomly assigned to receive oral tofacitinib 5mg twice daily (Group I) or oral azathioprine 2mg/kg body weight once daily (Group II). The primary endpoint was Severity of Alopecia Tool (SALT) score, evaluated at baseline and 06 months follow-up. Safety was consistently assessed during the study. A total of 104 patients underwent random allocation into either the tofacitinib group (n = 52) or the azathioprine group (n = 52). The mean (SD) age of patients was 20.23 (7.14) years and 22.26 (8.07) years, while the mean (SD) disease duration was 6.59 (4.01) years and 7.98 (4.40) years in in Group I and II, respectively. Overall, 40 (38.5%) patients were adolescents while 70 (67.3%) were male. 52 (50%) had AA, 37 (35.5%) had AT and 15 (14.5%) had AU. Mean baseline SALT score in tofacitinib group was 91.02 ± 10.21 and azathioprine group was 91.02 ± 10.63, which at 06 months follow-up improved to 14.1 ± 24.6 and 63.9 ± 33.9, respectively (difference, 11.5 points; 95% confidence interval, 38.3-61.3, p < 0.0001). Overall, no major adverse effects and no difference among the minor adverse effects in the two groups (04 adverse events for tofacitinib group and 08 for azathioprine group: p = 0.23) was observed. Efficacy of tofacitinib was significantly higher than azathioprine, whilst both drugs were well-tolerated in patients with AA and variants.

Relationship between Male Sexual Dysfunction, Fertility Power and Heart Function: Avicenna’s Standpoint

Honey has been used since ancient times to treat various diseases such as gynecological diseases. The current study aims to investigate clinical trials related to the therapeutic effects of honey on women’s diseases. Databases including Web of Sci- ence, Scopus, PubMed, Google scholar, and SID were investigated for clinical studies focusing on honey in gynecological diseases up to 31 June 2022. Eligibility was checked based on selection criteria. Twenty-five clinical trials met the inclusion criteria. Therapeutic properties of honey and its compounds as a systemic and/or local treatment on vulvovaginal candidiasis, cervicitis, dysmenorrhea, premenstrual syndrome, labor pain, episiotomy and cesarean wounds, nipple fissure, breast cancer and intrauterine insemination (IUI), with the mechanisms of action of antibacterial, antifungal, anti-inflammatory, wound healing, analgesic, antioxidant and anticancer activities have been proven. It was also found that phenolic compounds includ- ing flavonoids and phenolic acids are the main ones responsible for most of these therapeutic effects of honey. This study supports the healing properties of honey in gynecological diseases at reproductive age. Also, in the current studies, honey proved safe with minor adverse effects. Of course, to achieve definitive conclusions about the effectiveness and safety of honey, it is necessary to conduct more clinical trials with a larger sample size, appropriate intervention duration, and optimal doses in future studies.

Vaccine Adverse Effects Following Covishield among Health-care Workers in Central India

Abstract Introduction: This study aims to analyze common adverse effects following immunization that are temporally associated after receiving the above 2 doses of ChAdOx1 nCoV-19 Vaccine (Covishield) COVID-19 vaccines among health-care worker from January 2021 to April 2021, in the central region of India in a tertiary care hospital. Materials and Methods: A surveillance-based study was conducted between January 2021 and April 2021 among the health-care worker of the tertiary care hospital in the central part of India. The study was designed to identify the adverse effects reported after receiving a ChAdOx1 nCoV-19 Vaccine (Covishield) COVID-19 vaccination and demographic details were collected. Results: Within 48 h of the initial immunization dose, 651 mild adverse effects in all participants were documented. Headache (n = 168, 16%), fever (n = 105, 10%), fatigue (n = 115, 11%), and muscular discomfort (n = 115, 10%) were among the frequent side effects. One hundred and five minor adverse effects were reported between 3 and 7 days. No major adverse effects were observed after the first and second doses of vaccine. Conclusion: The first 48 h were the most common observational period for the short-term adverse effects of both dosages. After 15 days of both doses, the incidence declined for consecutive weeks until it was completely absent. The symptoms were transient and of a minor in nature. There were no documented severe vaccine-related side effects. Our research demonstrated that the vaccination had a decreased adverse event profile, was safe, and was well-tolerated.

Nitrogen-functionalized catalyst synthesized using spent coffee ground biochar-cobalt hybrid for oxygen reduction reaction via pyrolysis and ball-milling

In this work, oxygen reduction reaction (ORR) catalysts were developed from a precursor of spent coffee ground-based biochar. Nitrogen doping was achieved via urea addition preceding a pyrolysis synthesis process, yielding nitrogen-doped biochar (NDB). Cobalt was deposited onto the NDB surface using a non-conventional ball-milling procedure. The microstructure of the synthesized samples was studied through Scanning Electron Microscopy (SEM), where a rather distorted surface, highlighted by prominent wrinkles (which doubled the surface area at 50.58 m2/g), was shown for nitrogen-doped samples. Moreover, the high energy ball-milling technique shows an almost perfect coverage of cobalt nanoparticles on the biochar surface through SEM/EDS and Raman results. Additionally, electrochemical testing was conducted using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Cyclic voltammetry measurements conducted under nitrogen (inert) and oxygen-saturated alkaline solution (0.1 M KOH) conditions showed that nitrogen doping enhances the oxygen reduction reaction current (-1 vs -0.59 mA.cm−1 at -0.3 V vs Hg/HgO) and slightly reduces the onset potential compared to pristine biochar. Depositing cobalt onto the NDB surface had a minor adverse effect on the onset potential, but significantly increased the oxygen reduction reaction current, reaching a value of -2.09 mA.cm−2 at -0.3 V vs Hg/HgO. All catalysts were compared to a commercial carbon supported platinum catalyst (Pt10%C) to showcase the potential room of improvement for the developed catalysts.

Efficacy of transcutaneous electrical nerve stimulation combined with mirabegron therapy compared with mirabegron monotherapy for overactive bladder: a prospective randomized controlled study.

The objective was to evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) combined with mirabegron therapy compared with mirabegron monotherapy in the treatment of female patients with overactive bladder (OAB). In this randomized controlled study, 100 female outpatients with OAB were screened. Among these patients, 86 who met the inclusion criteria were randomly divided into the TENS combined with mirabegron treatment group and mirabegron monotherapy treatment group, with 43 patients in each group. The voiding diary, Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Symptom Bother Score (OAB-q SBS), total health-related quality of life (OAB-q HRQoL), and treatment satisfaction-visual analog scale (TS-VAS) score before and after treatment were recorded to evaluate the efficacy of OAB treatment. Seventy-nine of the 86 patients (40 in the TENS plus mirabegron group and 39 in the mirabegron monotherapy group) completed 12 weeks of treatment. TENS combined with mirabegron therapy was superior to mirabegron monotherapy in improving the primary endpoints, including the daily number of micturition episodes and the daily MVV/micturition and secondary endpoints, including the daily number of urgency episodes, the OABSS, the OAB-q SBS, the HRQoL score and TS-VAS score. There were no statistically significant differences in urgency urinary incontinence and nocturia between the groups. Some minor adverse effects were observed, including muscle pain, local paresthesia and constipation. The combination of TENS and mirabegron was more effective than mirabegron alone in the treatment of female patients with OAB. ChiCTR2400080528 (31.01.2024, retrospectively registered).

Melatonin as an add-on anti-seizure medication in children with epilepsy: An open-label randomized controlled trial

Objectives: The primary objective of this study is to measure the effect of melatonin in decreasing seizure frequency in intervention group as compared to controls in children with drug-resistant epilepsy. Materials and Methods: An open-label randomized controlled trial was conducted from July 2020 to June 2022 in children between 2 and 14 years with drug-resistant epilepsy attending Pediatric and Neurology outpatient department and inpatient department. After noting down baseline seizure frequency, children were randomized into the melatonin group and control group. In the melatonin group, add-on melatonin was added to the existing ASM, and in the control group, ASMs were continued. The primary and secondary outcomes were measured after 3 months of follow-up. Results: The percentage change in the seizure frequency between both groups at the end of 3 months of follow-up was not statistically significant, but the percentage reduction of seizure frequency was more than 50% in the melatonin group. Melatonin was well tolerated in our children except for 4 (22%) who developed minor adverse effects. Conclusion: Add-on melatonin decreases seizure frequency to some extent which was not statistically significant with no major side effects. Further studies are needed to assess add-on melatonin’s long-term effectiveness and safety in children with drug-resistant epilepsy.

Feasibility, acceptability, and safety of a novel device for self-collecting capillary blood samples in clinical trials in the context of the pandemic and beyond.

Home blood self-collection devices can enable remote monitoring, but their implementation requires validation. Our objectives were to explore (i) the impact of sampling sites and topical analgesia on capillary blood volume and pain perception and (ii) the safety, acceptability, and failure of capillary self-collection among adults and children using the Tasso-SST device. We conducted a two-phase study. The investigational phase consisted of two on-site cross-sectional studies in healthy adult participants (≥ 12 years) and children (1-17 years) with their accompanying parent. Adults received 4 capillary samplings, where puncture sites and topical analgesia were randomized in a factorial design, and a venipuncture; children (and one parent) had one capillary sampling. The two co-primary outcomes were blood volume and pain. The implementation phase was conducted in two multicentre trials in participants choosing remote visits; blood volume, collection failure, adverse events, and satisfaction were documented. In the investigational phase, 90 participants and 9 children with 7 parents were enrolled; 15 adults and 2 preschoolers participated in the implementation phase. In the adult investigational study, the device collected a median (25%, 75%) of 450 (250, 550) μl of blood with no significant difference between the puncture site, topical analgesia, and its interaction. Using topical analgesia reduced pain perception by 0.61 (95% CI: 0.97, 0.24; P <0.01) points on the 11-point scale; the pain reduction varied by puncture site, with the lower back showing the most significant decrease. Overall, combining all studies and phases, the median volume collected was 425 (250, 500) μl, and the device failure rate was 4.4%; minor adverse effects were reported in 8.9% of the participants, all were willing to use the device again. Capillary blood self-collection, yielding slightly less than 500 μl, proves to be a safe and relatively painless method for adults and children, with high satisfaction and low failure rates. The puncture site and topical analgesia do not affect blood volume, but topical analgesia on the lower back could reduce pain.

Early Non-Surgical Treatment For Microtia Types 1 and 2.

Esthetic concerns and psychosocial distress often accompany auricular deformities and malformations in both children and their parents. Approximately 30% of newborns are affected by auricular anomalies, with 15% to 20% resulting in permanent defects. While surgical intervention is typically considered the gold standard for malformations, a non-surgical approach, such as splinting, molding, or other non-invasive techniques, can effectively address deformations if promptly administered by a specialist. Microtia, classified into 4 types, presents challenges ranging from fundamental structural anomalies in types 1 and 2 to severe defects in type 3 and complete absence of the external ear in type 4 (anotia). This study introduces a novel non-invasive treatment modality for microtia types 1 and 2. The cohort consisted of 5 newborns treated for microtia types 1 or 2 between 2022 and 2023. Utilizing the EarWell system, treatment was initiated before 3 weeks of age (mean age: 2 weeks), with an average treatment duration of 6.6 weeks, supplemented by molding treatment as needed. Minor adverse effects, such as simple dermatitis, were observed in 2 patients. All parents expressed high satisfaction with the esthetic outcomes, with 60% reporting extreme satisfaction. The prompt initiation of the treatment protocol for microtia types 1 and 2 led to outstanding and timely outcomes in infants, enhancing the quality of life for both parents and their children. Early intervention for subsequent treatment may improve the condition and, in certain cases, serve as a satisfactory alternative for parents hesitant about further surgical intervention for their children.

Calcitriol Treatment Is Safe and Increases Frataxin Levels in Friedreich Ataxia Patients.

Calcitriol, the active form of vitamin D (also known as 1,25-dihydroxycholecalciferol), improves the phenotype and increases frataxin levels in cell models of Friedreich ataxia (FRDA). Based on these results, we aimed measuring the effects of a calcitriol dose of 0.25 mcg/24h in the neurological function and frataxin levels when administered to FRDA patients for a year. 20 FRDA patients where recluted and 15 patients completed the treatment for a year. Evaluations of neurological function changes (SARA scale, 9-HPT, 8-MWT, PATA test) and quality of life (Barthel Scale and Short Form (36) Health Survey [SF-36] quality of life questionnaire) were performed. Frataxin amounts were measured in isolated platelets obtained from these FRDA patients, from heterozygous FRDA carriers (relatives of the FA patients) and from non-heterozygous sex and age matched controls. Although the patients did not experience any observable neurological improvement, there was a statistically significant increase in frataxin levels from initial values, 5.5 to 7.0 pg/μg after 12 months. Differences in frataxin levels referred to total protein levels were observed among sex- and age-matched controls (18.1 pg/μg), relative controls (10.1 pg/μg), and FRDA patients (5.7 pg/μg). The treatment was well tolerated by most patients, and only some of them experienced minor adverse effects at the beginning of the trial. Calcitriol dosage used (0.25 mcg/24 h) is safe for FRDA patients, and it increases frataxin levels. We cannot rule out that higher doses administered longer could yield neurological benefits. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of 177Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, 177Lu-LNC1010, for PRRT. In preclinical studies, 177Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of 177Lu-LNC1010 in patients with advanced/metastatic NETs. 177Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of 177Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Sirolimus is effective for refractory/relapsed idiopathic multicentric Castleman disease: A single-center, retrospective study.

Refractory/relapsed idiopathic multicentric Castleman disease (R/R iMCD) has limited treatment options. With studies showing increased mTOR activation in iMCD patients, sirolimus becomes an attractive and promising therapy for R/R iMCD. Here we report the results of a retrospective study involving 26 R/R iMCD patients treated with sirolimus-containing regimen. The median age at sirolimus initiation was 40.5 years (23-60), with a median prior treatment line of 2 (1-5). 18 patients (69.2%) achieved symptomatic and biochemical response, with a median time to at least overall partial remission of 1.9 months (0.5-14.6). The median follow-up time from sirolimus initiation was 11.7 months (1.6-50.7) and the median time to next treatment (TTNT) was 46.2 months. No patients died at the end of follow-up. Most of the patients in the cohort are in ongoing responses and continue sirolimus therapy. Sirolimus is well tolerated with minor adverse effects. In conclusion, sirolimus is effective for R/R iMCD patients with good tolerance.