BACKGROUND: Sarcopenia and undernutrition are crucial in the cycle of frailty in patients requiring hemodialysis therapy, and their deleterious clinical consequences are well documented. However, little attention has been directed towards examining their combined impact on clinical outcomes.
OBJECTIVE: This study aimed to elucidate the effects of concomitant sarcopenia and undernutrition on clinical outcomes in patients undergoing hemodialysis.
METHODS: This prospective cohort study recruited outpatients undergoing hemodialysis from four facilities. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia, 2019. Undernutrition was determined using the Geriatric Nutritional Risk Index, with a score of <92 classified as undernutrition. Patients were classified into four groups according to the presence or absence of sarcopenia and undernutrition. Cox proportional hazards analysis was used to assess the independent association between concomitant sarcopenia and undernutrition, all-cause mortality, and cardiovascular (CV) events after adjusting for baseline characteristics.
RESULTS: We included 450 patients in this analysis. Of the 450 patients, 69 (15.3%) had concomitant sarcopenia and undernutrition. The mean follow-up period was 1067 days, and there were 61 deaths and 60 CV events. The cumulative survival rate was significantly lower in the sarcopenia with undernutrition group (P = 0.011). The overlap of sarcopenia and undernutrition was significantly associated with a risk of mortality (hazard ratio 2.10; 95% confidence interval 1.05-4.21; P = 0.037). However, no association was observed between the co-occurrence of sarcopenia and undernutrition and the risk of CV events.
CONCLUSIONS: Concomitant sarcopenia and undernutrition were significantly associated with an increased mortality risk among patients undergoing hemodialysis. This finding reaffirms the importance of managing sarcopenia and undernutrition in patients undergoing hemodialysis in daily clinical practice.

UNASSIGNED: Injectable extended-release formulations of luteinizing hormone-releasing hormone agonists (LHRHa) have simplified the treatment of prostate cancer with a satisfactory level of androgen castration. This study aims to determine the percentage of patients whose initial LHRHa prescription was renewed during follow-up, how many changed formulation and how their quality of life evolved.
UNASSIGNED: This is an observational, prospective, multicentre study of men with prostate cancer who were to receive treatment with LHRHa (triptorelin every 3 or 6 months, leuprorelin every 3 or 6 months, or goserelin every 3 months) for 24 months. The treatment used was recorded and quality of life was assessed (QLQ-PR25 questionnaire) at four follow-up visits.
UNASSIGNED: A total of 497 men (median age 75 years) were evaluated. The median exposure to LHRHa was 24 months. The initial prescription was renewed in 95.7% at follow-up 1 and 75% at follow-up 4. The main reason for changing from a 6-month to a 3-month formulation was a preference for sequential treatment (according to the investigator) and to see the physician more frequently (according to the patient). The main reason for switching from the 3-month to 6-month formulation was simplification of treatment (according to the investigator) and for convenience (according to the patient). Findings in the QLQ-PR25 questionnaire revealed no changes in urinary or bowel symptoms, though an improvement in sexual activity was reported. Practically all investigators and patients were satisfied/very satisfied with the treatment.
UNASSIGNED: Changes in formulation were scarce and generally justified by convenience factors or personal preferences. Patients maintained a good health status, with a high rate of retention of LHRHa treatment.
UNASSIGNED: Study number: A-ES-52014-224.A plain language summary is provided as supplementary material (available at: https://www.drugsincontext.com/wp-content/uploads/2024/05/dic.2024-2-2-Suppl.pdf).

UNASSIGNED: To evaluate the safety and tolerability of rimegepant 75 mg for the acute treatment of migraine in participants concurrently using a preventive migraine medication.
UNASSIGNED: This long-term, open-label safety study (NCT03266588) enrolled adults with a history of 2-14 moderate or severe migraine attacks per month. Participants self-administered rimegepant 75 mg (1) up to once daily as needed for 52 weeks to treat attacks of any pain intensity or (2) every other day plus as needed for 12 weeks. Preventive migraine medications were allowed if dosing was stable for ≥2 months prior to the baseline visit.
UNASSIGNED: Of 1800 rimegepant-treated participants, 243 (13.5%) took a concomitant preventive medication. The most common preventive medication was topiramate (26.3%). Rimegepant exposure was comparable in both groups (mean [SD] number of doses per 4 weeks was 7.8 [4.5] in those taking preventives and 7.7 [4.7] in those not taking preventives). The proportion of participants experiencing ≥1 on-treatment adverse event (AE) was 68.7% among those using preventive medication and 59.2% among those not using preventives. Serious AEs occurred in 4.5% of those using preventive medication and 2.3% of those who were not using preventives. AEs leading to study drug discontinuation occurred in 4.5% of those taking preventive medication and 2.4% of those not taking preventives. AEs occurring in ≥5% of participants in either cohort (with preventives vs without preventives) were upper respiratory tract infection (7.4% vs 9.0%), nasopharyngitis (7.8% vs 6.6%), sinusitis (7.0% vs 4.8%), urinary tract infection (5.3% vs 3.6%), and back pain (5.3% vs 2.8%).
UNASSIGNED: Acute treatment of migraine with rimegepant 75 mg for up to 52 weeks was well tolerated and had a favorable safety profile in adults who were concomitantly using preventive migraine medication.

UNASSIGNED: Pituitary neuroendocrine tumors (PitNETs) are a diverse group of benign neoplasms that account for a significant proportion of intracranial tumors (13%). The coexistence of PitNET with other intracranial lesions, such as meningiomas and intracranial aneurysms, has been constantly reported in the literature; yet, the pathophysiological mechanisms remain unknown, and the appropriate management is controversial. This study aims to describe the clinical characteristics, surgical treatment, and outcomes of patients with PitNET with coexisting intracranial lesions in a single healthcare center.
UNASSIGNED: A retrospective analysis was conducted on 12 patients who underwent surgical treatment for PitNET and another intracranial lesion at our single tertiary referral center over 15 years from January 2008 to May 2023.
UNASSIGNED: Among these coexisting lesions, aneurysms were the most commonly found (41.67%), followed by meningiomas (33.33%). Surgical intervention for both lesions was performed in a single-stage procedure for most cases (75%), employing transcranial, endoscopic endonasal, and combined approaches. We found low preoperative Karnofsky Performance Scale scores in three patients, with significant differences in functional outcomes.
UNASSIGNED: These findings contribute to the limited knowledge about PitNET coexisting with other intracranial lesions and emphasize the importance of patient-tailored, multidisciplinary management in these unusual scenarios.

Purpose of the study The current study had two goals: first, it compared the radiological and functional results of the ipsilateral shaft and proximal femur fractures treated by using two different methods, i.e., single implant vs dual implants. The second goal was to devise a clinical algorithm for guiding and managing such fractures. Methods This study was conducted in a level 1 trauma center and included 34 patients with concomitant ipsilateral fractures of the proximal femur and shaft of the femur. The patients were divided into two groups as per our clinical algorithm. Group I, comprising of 16 patients, were treated with a single implant like the proximal femoral nail (PFN) or proximal femoral nail antirotation (PFNA2). Group II of dual implants, comprising of 18 patients, were treated with two types of implants separately for proximal and shaft fracture. Results All patients were followed at monthly intervals up to six months, then at three monthly intervals up to one year, with a minimal follow-up of one year of every patient. On clinical evaluation by Friedman-Wyman criteria, in group I, seven patients had a fair outcome, eight patients had a good outcome, and one patient had a poor outcome, while in group II, eight patients had a fair outcome, nine patients had a good outcome, and one patient had a poor outcome. No patient developed non-union or avascular necrosis of the femoral head in any of the groups. Conclusion For concurrent ipsilateral diaphyseal and proximal femur fractures, both dual and single implants are equally effective alternatives if properly applied as per our clinical algorithm. Implant selection primarily depends on the pattern of injury, and our clinical algorithm can be a suitable guide for guiding the selection of implants.

OBJECTIVE: The primary objective was to develop a concomitant isocratic ultra-performance liquid chromatographic photo-diode array detection method to estimate Upadacitinib and its process-related impurities: impurity-1 and impurity-2. Further validation was conducted and studied for possible degradants under stress environments.
METHODS: All the chemicals and reagents used were of HPLC (acetonitrile, methanol) and analytical grade (trifluoro acetic acid). The ultra-performance liquid chromatography (Agilent 1290 Infinity II LC system) consists of a quaternary pump, a BEH C18 (50×2.1mm, 1.7μ) column, and photo-diode array detector. The method was developed with acetonitrile: methanol: 0.1% v/v trifluoro acetic acid (50:20:30 v/v/v) mobile phase at 0.2mL/min flow rate within a run time of 5.5min The detection was carried at 231.2nm.
RESULTS: The respective retention times achieved were 2.289min (Upadacitinib), 0.972min (Upadacitinib impurity-1), and 3.508min (Upadacitinib impurity-2). The optimized method was validated further, and the linearity range was best fit at 15.0-180.0μg/mL for Upadacitinib and 1.0-12.0μg/mL for both Upadacitinib impurity-1 and 2 respectively. The detection and quantification limits were 4.50μg/mL, 15.00μg/mL (Upadacitinib) and 0.30μg/mL, 1.0μg/mL (Upadacitinib impurity-1 and 2).
CONCLUSIONS: A fast, isocratic, specific, and reproducible ultra-performance liquid chromatographic method was developed and validated for various parameters according to the ICH Q2 (R1) guidelines studies. Stress studies were conducted exposing the sample dilution to various treatments (acid, alkali, peroxide, HPLC water, heat, and UV light). The degradants were well-separated apart from the peaks of the active substance. The stability indicating nature was observed during the degradation. The optimized method can be applied for the separation and estimation of Upadacitinib and its process-related impurities in pharma sector in tablet dosage forms.

This study presents a unique case of concurrent salmonella and Leptospira meningitis in a 20-year-old woman with no prior medical history. Coinfection with endemic pathogens is plausible, especially in regions like Pakistan. While Salmonella meningitis is uncommon, it presents a significant medical emergency, particularly in immunocompromised adults. Neuroleptospirosis, though rare, can manifest in certain cases. The patient displayed persistent high fever, confusion, irritability, and a single seizure episode. Initial tests, including blood and cerebrospinal fluid (CSF) cultures and serological examinations, detected Salmonella typhi and positive leptospiral antibodies, respectively. Leptomeningeal enhancement was confirmed by an MRI. Treatment with azithromycin, meropenem, and ceftriaxone led to improvement after seven days. She was advised to complete a 28-day course for Salmonella meningitis. This case emphasizes the importance of considering multiple infectious causes, especially in endemic regions. Timely and thorough diagnostic evaluation, followed by appropriate antimicrobial therapy, is essential for effective management. Further research is warranted to enhance understanding of the epidemiology, clinical features, and optimal treatment strategies for such dual infections.

This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three doses of an oral, live, pentavalent rotavirus vaccine (RV5) and three doses of an intramuscular, inactivated poliomyelitis vaccine (IPV) in 400 healthy infants. The primary objective was the non-inferiority of neutralizing antibody (nAb) responses in the concomitant- versus the staggered-use groups. Antibody responses were measured at baseline and 1-month post-dose 3 (PD3). Parents/legal guardians recorded adverse events for 30 or 15 d after study vaccinations in the concomitant-use or staggered-use groups, respectively. At PD3, >98% of participants seroconverted to all three poliovirus types, and the primary objective was met as lower bounds of the two-sided 95% CI for between-group difference in nAb seroconversion percentages ranged from - 4.3% to - 1.6%, for all poliovirus types, p < .001. At PD3, geometric mean titers (GMTs) of nAb responses to poliovirus types 1, 2, and 3 in the concomitant-use group and the staggered-use group were comparable; 100% of participants had nAb titers ≥1:8 and ≥1:64 for all poliovirus types. Anti-rotavirus serotype-specific IgA GMTs and participants with ≥3-fold rise in postvaccination titers from baseline were comparable between groups. Administration of RV5 and IPV was well tolerated with comparable safety profiles in both groups. The immunogenicity of IPV in the concomitant-use group was non-inferior to the staggered-use group and RV5 was immunogenic in both groups. No safety concerns were identified. These data support the concomitant use of RV5 and IPV in healthy Chinese infants.

OBJECTIVE: Concomitant COVID-19 and influenza vaccination would be an efficient strategy. Although the co-administration of monovalent COVID-19 and influenza vaccinations showed acceptable immunogenicity, it remains unknown whether the bivalent COVID-19 vaccine could intensify immune interference. We aimed to evaluate the immunogenicity and safety of concomitant BA.5-based bivalent COVID-19 and influenza vaccination.
METHODS: An open-label, nonrandomized clinical trial was conducted for 154 age-matched and sex-matched healthy adults between October 2022 and December 2022. Participants received either a concomitant bivalent COVID-19 mRNA booster and quadrivalent influenza vaccination (group C) or separate vaccinations (group S) at least 4 weeks apart. Solicited and unsolicited adverse events were reported up to 6 months postvaccination. Immunogenicity was evaluated by anti-spike (S) IgG electrochemiluminescence immunoassay, focus reduction neutralization test, and hemagglutination inhibition assay.
RESULTS: Group C did not meet the noninferiority criteria for the seroconversion rates of anti-S IgG and neutralizing antibodies against the wild-type SARS-CoV-2 strain compared with group S (44.2% vs. 46.8%, difference of -2.6% [95% CI, -18 to 13.4]; 44.2% vs. 57.1%, difference of -13.0% [95% CI to -28.9 to 2.9]). However, group C showed a stronger postvaccination neutralizing antibody response against Omicron BA.5 (72.7% vs. 64.9%). Postvaccination geometric mean titers for SARS-CoV-2 and influenza strains were similar between groups, except for influenza B/Victoria. Most adverse events were mild and comparable between the study groups.
CONCLUSIONS: Concomitant administration of bivalent COVID-19 mRNA and quadrivalent influenza vaccines showed tolerable safety profiles and sufficient immunogenicity, particularly attenuating immune imprinting induced by previous ancestral vaccine strains.

BACKGROUND: Treating Helicobacter pylori is becoming increasingly difficult with the development of bacterial resistance to many established treatment regimens. As a result, researchers are constantly looking for novel and effective treatments. This trial aims to establish the efficacy of levofloxacin-based sequential treatment regimen and concomitant levofloxacin-based regimen as empirical first-line therapy in the Syrian population.
METHODS: This is an open-label, prospective, single-center, parallel, active-controlled, superiority, randomized clinical trial. The recruitment will target Helicobacter pylori-positive males and females between the ages of 18 and 65 to evaluate the efficacy of empirical first-line therapy in the Syrian population. We are planning to recruit up to 300 patients which is twice the required sample size. One hundred fifty individuals will be randomly assigned to undergo either a sequential levofloxacin-based treatment regimen or a concomitant levofloxacin-based regimen. High-dose dual therapy (proton-pump inhibitor and amoxicillin) will be the rescue therapy in the event of first-line failure. The first-line eradication rate in both groups is the primary outcome, and one of the secondary outcomes is the overall eradication rate of high-dose dual therapy in the event of first-line treatment protocol failure. Intention-to-treat analysis and per-protocol analysis will be used to evaluate the eradication rates of Helicobacter pylori for first-line treatment protocols.
CONCLUSIONS: For the first time in the Syrian population, this randomized controlled trial will provide objective and accurate evidence about the efficacy of a sequential levofloxacin-based treatment regimen.
BACKGROUND: ClinicalTrials.gov NCT06065267 . Registered on October 3, 2023. Prospective registered. Enrollment of the first participant has not started yet.