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Purpose To evaluate the clinical effect of the warming step for subcutaneous (SC) injection on injection site pain (ISP). Methods A single center, randomized, partially blinded, crossover study in 44 healthy participants was conducted. Participants self-injected with autoinjectors (1 mL) with either high pain (citrate/sodium chloride (NaCl)) or low pain (mannitol) formulations at refrigerated temperature or warmed to room temperature (RT) according to the instructions for use (IFU). The ISP was recorded using visual analog scale (VAS) and injection site reactions (ISRs) were captured using severity scores. Results The average VAS scores were clinically different between high pain and low pain formulation but not affected by the warming step. While the average VAS was not affected by injectate temperature, some individual participants reported bidirectional VAS responses to injectate temperature. A post injection questionnaire showed that most participants were not bothered by the cold sensation of the injected solution. The clinical results are consistent with modeling that indicates rapid temperature equilibration of subcutaneously injected solutions. Conclusion Formulation composition was the dominating factor contributing to ISP as compared to solution temperature due to transient thermal equilibrium of the injected solution in SC tissue. While injection temperature may be a lever for improving the injection experience for some patients, the warming step is unlikely to reduce ISP for most patients. Although this study was conducted with 1 mL injection of two representative formulations, this finding of lack of correlation between ISP and solution temperature is likely extrapolatable to most small volume (e.g., ≤ 2 mL) injections of subcutaneous formulations.

Optimal bowel preparation is vital for the efficacy and safety of colonoscopy. The inconvenience, discomfort, required consumption of large volumes of product, and potential adverse effects associated with some bowel preparations deter patients from colonoscopy and may provide inadequate cleansing. A dual-action, non-phosphate, natural orange-flavored, low-volume preparation containing sodium picosulfate and magnesium citrate (P/MC) is currently being reviewed for bowel cleansing. This was a phase 3, randomized, multicenter, assessor-blinded, prespecified non-inferiority, head-to-head study to investigate the efficacy, safety, and tolerability of day-before administration of P/MC vs. 2L polyethylene glycol solution and two 5-mg bisacodyl tablets (2L PEG-3350 and bisacodyl tablets (HalfLytely and Bisacodyl Tablets Bowel Prep Kit)) in adult patients preparing for colonoscopy (SEE CLEAR II Study). The primary objective of the study was to demonstrate the non-inferiority of P/MC to 2L PEG-3350 and bisacodyl tablets in overall colon cleansing using a modified Aronchick scale. In addition, efficacy in the ascending, mid (transverse and descending), and recto-sigmoid segments of colon was evaluated using a modified Ottawa scale. Patient acceptability and tolerability of the bowel preparations were assessed via a standard questionnaire. Safety was assessed based on the monitoring of adverse events (AEs) and meaningful findings on clinical evaluations including physical examinations, vital sign measurements, and electrocardiograms (ECGs). A total of 603 patients were randomized to receive either P/MC (n = 300) or 2L PEG-3350 and bisacodyl tablets (n = 303). Based on the Aronchick scale, successful overall cleansing was similar in patients receiving P/MC (83.0%) and patients receiving 2L PEG-3350 and bisacodyl tablets (79.7%). P/MC demonstrated non-inferiority to 2L PEG-3350 and bisacodyl tablets in overall cleansing of the colon, as measured by the Aronchick scale. Similarly, the efficacy of P/MC, as measured by the Ottawa scale, was non-inferior to 2L PEG-3350 and bisacodyl tablets in cleansing the ascending, mid, and recto-sigmoid segments of the colon. Patient-reported acceptability and tolerability for each item examined on the questionnaire was significantly greater for P/MC compared with 2L PEG-3350 and bisacodyl tablets (P<0.0001).Treatment-emergent AEs related to the bowel preparation reported by 1% of patients receiving P/MC or 2L PEG-3350 and bisacodyl tablets were nausea (3.0% vs. 4.3%), vomiting (1.4% vs. 2.0%), and headache (2.7% vs. 1.7%). No clinically meaningful changes were noted in either treatment arm in data collected from physical examinations, vital sign measurements, and ECGs. When administered as a day-before dose, the bowel cleansing effects of P/MC were non-inferior compared with 2L PEG-3350 and bisacodyl tablets using the clinician-rated Aronchick and Ottawa scales. Treatment acceptability was significantly more favorable in patients receiving P/MC than in patients receiving 2L PEG-3350 and bisacodyl tablets.

IntroductionContinuous renal replacement therapy (CRRT) is a critical therapeutic intervention for patients with severe acute kidney injury in intensive care. However, premature filter clotting remains a significant challenge during CRRT, impacting treatment efficacy, costs and patient outcomes. Anticoagulation is essential to maintain circuit patency, with regional citrate anticoagulation (RCA) emerging as a preferred strategy due to its favourable bleeding profile. The standard target for post-filter ionised calcium (iCa) concentration during RCA-CRRT is set between 0.25 and 0.35 mmol/L, although evidence supporting this range is limited. We hypothesise that a higher post-filter iCa target (0.35–0.45 mmol/L) can provide comparable circuit patency while potentially reducing adverse effects associated with citrate administration.Methods and analysisThis multicentre randomised controlled non-inferiority trial will compare a low post-filter iCa target (0.25–0.35 mmol/L) with a higher post-filter iCa target (0.35–0.45 mmol/L) in patients undergoing RCA-CRRT in the intensive care unit. A total of 412 CRRT sessions will be randomised with a 1:1 ratio into these two groups. The primary outcome is the incidence of filter clotting. Secondary outcomes include filter lifespan, post-filter iCa levels, citrate infusion rates, the occurrence of metabolic adverse effects, financial costs and blood loss.Ethics and disseminationThe study has obtained approval from the ethics committee (Ethics Committee Est III, Nancy, France) and patients will be included after providing informed consent. The results will be disseminated at academic conferences and in peer-reviewed publications. All procedures were developed in order to assure data protection and confidentiality.Trial registration numberNCT05814341.

Oral magnesium for leg cramps treatment in pregnancy is a controversial issue according to recent Cochrane systematic review. This study aims to evaluate the efficacy of Mg++ supplementation in leg cramps treatment in pregnancy. This observational clinical trial studied 132 pregnant women with leg cramps in the first trimester of pregnancy. At baseline, 74 (56.3%) had two leg cramps episodes per week, 28 (21.1%) three episodes, 13 (9.8%) four episodes and 9 (6.8%) five or more episodes. They were randomized 1:1 to 300 mg/day of oral Mg++ citrate (n = 66) or placebo (n = 66). The primary outcome was the frequency of leg cramps episodes per week reported by pregnant women. Secondary outcomes were the ocurrence of leg cramps and oral magnesium side effects. 130 pregnant women completed the study and the two groups were comparable according to some sociodemographic and clinical characteristics. After 4 weeks of intervention it was observed a 28.4% (39/132) (CI 95%: 20.9-37.0) reduction of leg cramps in all participants and no difference between the two groups was found; reduction of 27.2% (18/66) (CI 95%: 17.0-39.6) in Mg++ group and 32.8% (21/66) (CI 95%: 21.6-45.7) in the placebo group. The OR of leg cramps was 1.3 (CI 95%: 0.6-2.9), p = 0.527, taking the placebo group as reference. Among pregnant women who remained with leg cramps the mean of leg cramps episodes per week showed no significance difference between the Mg++ and placebo groups; t-student test: p = 0.408. Four pregnant women showed gastrointestinal side effects; 2 in each group had nauseas and diarrhoea. Oral magnesium supplementation during pregnancy did not reduce the ocurrence and frequency of episodes of leg cramps.

Background. Uric acid (UA) renal lithiasis has a high rate of recurrence and a prevalence ranging from 10% and 15%, depending on the population. The most important etiological factor is persistence of urinary pH below 5.5 and one of the most common treatments is alkalization with citrate. Recent studies demonstrated that theobromine, which is abundant in chocolate and cocoa, is a potent inhibitor of UA crystallization. Aim. The aim was to compare the efficacy of citrate versus citrate + theobromine as treatment for UA lithiasis. Methods. This randomized cross-over trial investigated the efficacy of two treatments in 47 patients with UA renal lithiasis. Urine volume, pH, UA excretion, theobromine excretion, and risk of UA crystallization (RUAC) at baseline and at the end of each intervention period were measured. Results. Each treatment significantly reduced the risk of UA crystallization compared to basal values. The RUAC after citrate + theobromine was lower than the RUAC after citrate, although this difference was not statistically significant. Conclusion. The combined consumption of citrate and theobromine may be a promising strategy for the prevention of UA kidney stones.

Bowel cleansing is essential for a successful colonoscopy, but the ideal clearing agent and the volume have yet to be determined. A small-volume cleanser is important for patient compliance. This study aimed to compare the bowel cleansing efficacy, safety, tolerability, and acceptability of a 300-mL small-volume sodium picosulfate/magnesium citrate (PSMC) preparation-Bowklean with one 2-L polyethylene glycol (PEG)/bisacodyl-Klean-Prep/Dulcolax preparation under identical dietary recommendations. This multicenter, randomized, parallel-group, pre-specified noninferiority study enrolled 631 outpatients scheduled to undergo colonoscopy (Bowklean = 316 and Klean-Prep/Dulcolax = 315). After bowel preparation, an independent evaluator blinded to the subject’s treatment allocation rated the quality of the colon cleansing. Efficacy was evaluated using the Aronchick Scale and Ottawa Bowel Preparation Scale (OPBS). Safety was assessed by monitoring adverse events. Tolerability and acceptability were measured via a patient questionnaire. Bowklean was non-interior to Klean-Prep/Dulcolax in overall colon cleansing but was associated with significantly better preparation quality. Notably, Bowklean was associated with significantly greater tolerability and acceptability of bowel preparations than Klean-Prep/Dulcolax. Safety profiles did not differ significantly between the groups. Our data indicate that Bowklean is a more effective and better-tolerated bowel cleansing preparation before colonoscopy than Klean-Prep/Dulcolax. Bowklean may therefore increase positive attitudes toward colonoscopies and participation rates.

Purpose The effect of SAM vaginal gel, a medical device containing adsorptive silicon dioxide and antioxidative sodium selenite and citric acid, on histologically-proven cervical intraepithelial neoplasia type 2 (CIN2) as well as p16 positive CIN1, and on the presence of the onco-marker p16 was investigated. Methods 216 women aged 25–60 years were randomized to either receive an intravaginal daily dose of SAM gel for three 28-day periods, or be followed-up without intervention. The primary endpoint was efficacy, defined as a combined histological and cytological regression. At baseline and after 3 months participants had: a guided biopsy including p16 immunohistochemical (IHC) staining, only if a lesion was visible at colposcopy; a cervical smear for cytology, high-risk human papillomavirus (hr-HPV) and a p16/Ki-67 test. At 6 months a further cytology and p16/Ki-67 test was performed. Results Regression of CIN lesions was observed in 78 out of 108 patients (72.2%) in the SAM gel arm and in 27 out of 108 patients (25.0%) in the control arm. Similarly, the change in the p16/Ki-67 cytological test status was significantly in favor of the treatment arm. The prevalence of hr-HPV decreased significantly ( p  < 0.001) in the treatment arm, from 87.0% to 39.8%, while it slightly increased in the control arm, from 78.7% to 83.3%. At 6 months the cytological regression in the treatment group and the highly significant effect on p16/Ki-67 was still present. Conclusion SAM vaginal gel enhances the regression of cervical lesions and clears hr-HPV and p16/Ki-67 in smears significantly, thus offering an active non-destructive management to prevent cervical cancer. Trial registration number ISRCTN11009040, date of registration: 10/12/2019; https://doi.org/10.1186/ISRCTN11009040 ; retrospectively registered.

The study was designed to assess a practical mode of postdilution continuous venovenous hemofiltration (CVVH) with regional citrate anticoagulation (RCA) using a calcium-containing replacement solution, and to compare it with a CVVH mode with no anticoagulation (NA). Both methods were employed in our center for acute kidney injury (AKI) patients at high risk of bleeding. Fifty-six patients were equally allocated into the RCA-CVVH group and the NA-CVVH group. The study displayed no significant differences between groups involving baseline characteristics, severity level, blood gas analysis, hepatic/renal/coagulative functions, electrolytes, hemoglobin concentration, and platelet counts before or after continuous renal replacement therapy (CRRT). Compared to the NA-CVVH group, the RCA-CVVH group had a lower level of transfused packed red blood cells and platelet as well as a longer filter lifespan. The result showed no substantial differences between groups in terms of the mean supporting time and cost involving CRRT per person, the length of ICU and hospital stays, and the ICU survival. Homeostasis was basically preserved at a target range during the RCA post-CVVH procedure. Serious complications did not arise during the RCA process. RCA postdilutional CVVH is a safe and effective mode for application in AKI patients with a high risk of bleeding, and it can extend the filter lifespan and decrease blood loss, compared with the NA mode for CRRT. Further studies are needed to evaluate this mode for CRRT. (Retrospective Registration number ChiCTR1800016462, Registration date 2/6/2018)

Purpose Both 2-L polyethylene glycol with ascorbic acid (2-L PEG/Asc) and sodium picosulfate with magnesium citrate (SP/MC) are low-volume combined agents for colonic preparation. The aim of the current study was to compare the preparation adequacy and patient tolerability of 2-L PEG/Asc and SP/MC. Methods We performed a prospective randomized controlled study in outpatients undergoing daytime colonoscopy at a tertiary academic hospital. We compared preparation adequacy based on the Boston Bowel Preparation Scale (BBPS), polyp and adenoma detection rate (PDR and ADR), compliance, tolerability for ease and palatability, intention to reuse, and patient satisfaction using a questionnaire between 2-L PEG/Asc and three sachets of SP/MC, both given in a split-dose method. Results A total of 388 patients were evaluated based on intention to treat (ITT) and 356 patients per protocol (PP). No significant differences in preparation adequacy were observed in ITT and PP analyses, based on the BBPS ( p  > 0.05). The PDR and ADR were greater than 60 and 40 % in both groups, respectively ( p  > 0.05). Compliance levels were higher in the 2-L PEG/Asc group than in the SP/MC group ( p  < 0.001). Satisfaction (ITT, p  = 0.014; PP, p  = 0.032) and palatability (ITT and PP, p  < 0.001) levels were higher in the SP/MC group than in the 2-L PEG/Asc group, but values for tolerability for ease and intention to reuse were similar in both groups (ITT and PP, p  > 0.05). Conclusions Both 2-L PEG/Asc and SP/MC had adequate bowel cleansing efficacy to satisfy PDR and ADR as quality indicator and had showed similar tolerability.

Purpose The purpose of this study is to compare the efficacy and tolerability of polyethylene glycol (PEG) to sodium picosulfate/magnesium citrate (SPMC) and low-volume polyethylene glycol/ascorbic acid (PEGA) in a single- or split-dose regimen for colonoscopy bowel preparation. Methods This was a prospective, randomized, endoscopist-blinded, multicentre study. Outpatients received either PEG or SPMC or PEGA in a single or a split dose before the colonoscopy. Quality and tolerability of the preparation and complaints during preparation were recorded. Results Nine hundred seventy-three patients were analysed. Satisfactory bowel cleansing (Aronchick score 1 + 2) was more frequent when a split dose was used irrespective of the solution type (PEG 90.1 vs 68.8%, PEGA 86.0 vs 71.6%, SPMC 84.3 vs 60.2%, p  < 0.001). SPMC was the best tolerated followed by PEGA ( p  < 0.006) and PEG as the worst ( p  < 0.001). Tolerability did not correlate with the regimen and amount of the solution used. Female gender is associated with a higher incidence of nausea, vomiting and pain ( p  < 0.029). Conclusions Both PEG, PEGA and SPMC are fully comparable in terms of colonic cleansing when used in similar regimens. The split-dose preparation is more effective in all agents. SPMC and PEGA are better tolerated than PEG. The preparation regimen and/or the volume do not affect tolerability.