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Levodopa is the most effective therapy for Parkinson's disease, but chronic treatment is associated with the development of potentially disabling motor complications. Experimental studies suggest that motor complications are due to non-physiological, intermittent administration of the drug, and can be reduced with continuous delivery. We aimed to assess efficacy and safety of levodopa-carbidopa intestinal gel delivered continuously through an intrajejunal percutaneous tube. In our 12-week, randomised, double-blind, double-dummy, double-titration trial, we enrolled adults (aged ≥30 years) with advanced Parkinson's disease and motor complications at 26 centres in Germany, New Zealand, and the USA. Eligible participants had jejunal placement of a percutaneous gastrojejunostomy tube, and were then randomly allocated (1:1) to treatment with immediate-release oral levodopa-carbidopa plus placebo intestinal gel infusion or levodopa-carbidopa intestinal gel infusion plus oral placebo. Randomisation was stratified by site, with a mixed block size of 2 or 4. The primary endpoint was change from baseline to final visit in motor off-time. We assessed change in motor on-time without troublesome dyskinesia as a prespecified key secondary outcome. We assessed efficacy in a full-analysis set of participants with data for baseline and at least one post-baseline assessment, and imputed missing data with the last observation carried forward approach. We assessed safety in randomly allocated patients who underwent the percutaneous gastrojejunostomy procedure. This study is registered with ClinicalTrials.gov, numbers NCT00660387 and NCT0357994. From baseline to 12 weeks in the full-analysis set, mean off-time decreased by 4·04 h (SE 0·65) for 35 patients allocated to the levodopa-carbidopa intestinal gel group compared with a decrease of 2·14 h (0·66) for 31 patients allocated to immediate-release oral levodopa-carbidopa (difference −1·91 h [95% CI −3·05 to −0·76]; p=0·0015). Mean on-time without troublesome dyskinesia increased by 4·11 h (SE 0·75) in the intestinal gel group and 2·24 h (0·76) in the immediate-release oral group (difference 1·86 [95% CI 0·56 to 3·17]; p=0·0059). In the safety analyses 35 (95%) of 37 patients allocated to the levodopa-carbidopa intestinal gel group had adverse events (five [14%] serious), as did 34 (100%) of 34 patients allocated to the immediate-release oral levodopa-carbidopa group (seven [21%] serious), mainly associated with the percutaneous gastrojejunostomy tube. Continuous delivery of levodopa-carbidopa with an intestinal gel offers a promising option for control of advanced Parkinson's disease with motor complications. Benefits noted with intestinal gel delivery were of a greater magnitude than were those obtained with medical therapies to date, and our study is, to our knowledge, the first demonstration of the benefit of continuous levodopa delivery in a double-blind controlled study. AbbVie.

Solid lipid nanoparticles (SLNs) are very potential formulations for topical delivery of antifungal drugs. Hence, the purpose of this research was to formulate the well-known antifungal agent Fluconazole (FLZ)-loaded SLNs topical gel to improve its efficiency for treatment of Pityriasis Versicolor (PV). FLZ-SLNs were prepared by modified high shear homogenization and ultrasonication method using different concentration of solid lipid (Compritol 888 ATO, Precirol ATO5) and surfactant (Cremophor RH40, Poloxamer 407). The physicochemical properties and the in vitro release study for all FLZ-SLNs were investigated. Furthermore, the optimized FLZ-SLN formula was incorporated into gel using Carpobol 934. A randomized controlled clinical trial (RCT) of potential batches was carried out on 30 well diagnosed PV patients comparing to market product Candistan ® 1% cream. Follow up was done for 4 weeks by clinical and KOH examinations. The results showed that FlZ-SLNs were almost spherical shape having colloidal sizes with no aggregation. The drug entrapment efficiency ranged from 55.49% to 83.04%. The zeta potential values lie between −21 and −33 mV presenting good stability. FLZ showed prolonged in vitro release from SLNs dispersion and its Carbapol gel following Higuchi order equation. Clinical studies registered significant improvement (p < .05) in therapeutic response (1.4-fold; healing%, 4-fold; complete eradication) in terms of clinical cure and mycological cure rate from PV against marketed cream. Findings of the study suggest that the developed FLZ loaded SLNs topical gels have superior significant fast therapeutic index in treatment of PV over commercially available Candistan ® cream.

Neonatal hypoglycemia is common and can cause brain injury. Buccal dextrose gel is effective for treatment of neonatal hypoglycemia, and when used for prevention may reduce the incidence of hypoglycemia in babies at risk, but its clinical utility remains uncertain. We conducted a multicenter, double-blinded, placebo-controlled randomized trial in 18 New Zealand and Australian maternity hospitals from January 2015 to May 2019. Babies at risk of neonatal hypoglycemia (maternal diabetes, late preterm, or high or low birthweight) without indications for neonatal intensive care unit (NICU) admission were randomized to 0.5 ml/kg buccal 40% dextrose or placebo gel at 1 hour of age. Primary outcome was NICU admission, with power to detect a 4% absolute reduction. Secondary outcomes included hypoglycemia, NICU admission for hypoglycemia, hyperglycemia, breastfeeding at discharge, formula feeding at 6 weeks, and maternal satisfaction. Families and clinical and study staff were unaware of treatment allocation. A total of 2,149 babies were randomized (48.7% girls). NICU admission occurred for 111/1,070 (10.4%) randomized to dextrose gel and 100/1,063 (9.4%) randomized to placebo (adjusted relative risk [aRR] 1.10; 95% CI 0.86, 1.42; p = 0.44). Babies randomized to dextrose gel were less likely to become hypoglycemic (blood glucose < 2.6 mmol/l) (399/1,070, 37%, versus 448/1,063, 42%; aRR 0.88; 95% CI 0.80, 0.98; p = 0.02) although NICU admission for hypoglycemia was similar between groups (65/1,070, 6.1%, versus 48/1,063, 4.5%; aRR 1.35; 95% CI 0.94, 1.94; p = 0.10). There were no differences between groups in breastfeeding at discharge from hospital (aRR 1.00; 95% CI 0.99, 1.02; p = 0.67), receipt of formula before discharge (aRR 0.99; 95% CI 0.92, 1.08; p = 0.90), and formula feeding at 6 weeks (aRR 1.01; 95% CI 0.93, 1.10; p = 0.81), and there was no hyperglycemia. Most mothers (95%) would recommend the study to friends. No adverse effects, including 2 deaths in each group, were attributable to dextrose gel. Limitations of this study included that most participants (81%) were infants of mothers with diabetes, which may limit generalizability, and a less reliable analyzer was used in 16.5% of glucose measurements. In this placebo-controlled randomized trial, prophylactic dextrose gel 200 mg/kg did not reduce NICU admission in babies at risk of hypoglycemia but did reduce hypoglycemia. Long-term follow-up is needed to determine the clinical utility of this strategy. ACTRN 12614001263684.

One mechanism of action for the anticaries effect of topical fluoridation is through precipitation of CaF 2 . In this in vitro study energy-dispersive x-ray spectroscopy (EDX) is used as a semiquantitative method to detect enamel fluoride-precipitation under the influence of acidic and neutral pH-value and absence or presence of a salivary pellicle. Crowns of 30 human caries-free third molars were quartered into four specimens and the enamel surface ground flat and polished. Two specimens each were stored in human saliva (120 minutes pellicle formation). Teeth were randomly allocated into 6 treatment groups: NaF_a (experimental acidic sodium fluoride; 12500 ppmF − , pH 4.75); NaF_n (experimental neutral sodium fluoride; 12500 ppmF − , pH 7.0); GB_a (acidic gel base; 0 ppmF − , pH 4.75); GB_n (neutral gel base; 0 ppmF − , pH 7.0); AmF-NaF_a (experimental acidic amine/sodium fluoride; 12500 ppmF − , pH 4.75); EG_a (acidic amine/sodium fluoride; Elmex Geleé, CP-GABA GmbH; 12500 ppmF − , pH 4.75). Each gel was applied for 60 seconds to one specimen with and one specimen without pellicle. Two specimens served as controls (no gel, without/with pellicle). Atomic percent (At%) of O, F, Na, Mg, P, Ca was measured by EDX. ∆At% and Ca/P-ratios were calculated. EDX could semi-quantify superficial enamel fluoride-precipitation. Only specimens treated with acidic fluoride gels showed fluoride-precipitation, a salivary pellicle tended to decrease At%F.

Bacterial vaginosis (BV) is associated with an elevated vaginal pH and the presence of abnormal offensive discharge. It is common, often recurrent, and the most effective treatment regimen is unknown. 'Metronidazole Versus lactic acId for Treating bacterial vAginosis' (VITA) is a UK-based randomised controlled trial assessing clinical and cost-effectiveness of topical lactic acid gel compared to oral metronidazole antibiotic for treating second and subsequent BV episodes. Few BV trials report on women's preferences for treatment in the context of their own experiences. This qualitative study investigated the acceptability and tolerability of the two treatments. During the trial, semi-structured telephone interviews were undertaken between January-May 2018. A total of 33 women diagnosed with BV were consecutively sampled then interviewed from six sites across England. Thematic analysis was guided by the acceptability of health interventions framework. Potential causes of BV and its impact on women's lives were explored in addition to women's treatment preference and perceived treatment effectiveness. Although women felt antibiotics treat BV effectively, and were associated with longer time periods between episodes, they generally preferred using the lactic acid gel because of ease of use, once daily application and less side-effects. Women would recommend the lactic acid gel to others for mild cases of BV but to take antibiotics when more severe. The risk of antibiotic drug resistance was a common concern. Self-help medicating or self-decision to not treat was also evident due to prior experience of poor outcomes from treatment. Triggers of BV were attributed to personal hygiene habits-soaps used to wash the vagina and sexual practices such as unprotected sex. Acceptability and preference for topical lactic acid gel or oral metronidazole tablets in the treatment of recurrent BV was affected by personal choice relating to affective attitude, burden, ethicality, intervention coherence, opportunity costs, and self-efficacy. These differed depending on ease of use, tolerability and past experiences, but not necessarily based on perceived drug effectiveness. Knowledge of a patient preference for topical lactic acid gel therapy despite lower perceived effectiveness may be useful for clinicians when making treatment decisions.

Background and Objectives Midazolam rectal gel is a novel rectal formulation that may be a promising and potential alternative to oral administration for pediatric sedation. The objective of this study was to evaluate the safety, pharmacokinetics, pharmacodynamics, and absolute bioavailability of midazolam rectal gel in healthy Chinese subjects. Methods An open-label, single-dose, randomized, two-period, two-treatment, crossover clinical study was conducted in 22 healthy subjects (16 males and six females), each receiving 2.5 mg intravenous midazolam in one period and 5 mg midazolam rectal gel in another period (the dosages here were calculated as active midazolam). Safety, pharmacokinetic, and pharmacodynamic assessments were conducted throughout the study. Results All of the subjects completed both treatment periods. The formulation of rectal gel was well tolerated, with no serious adverse events occurring. After a single rectal dose of 5 mg midazolam rectal gel, it was absorbed rapidly with a median value of time to peak concentration ( T max ) of 1.00 h, and mean values of the peak concentration ( C max ) and area under the concentration–time curve (AUC 0– t ) of 37.2 ng/mL and 137 h·ng/mL, respectively. The absolute bioavailability of rectal gel was 59.7%. The rectal gel exhibited a relatively delayed onset but a more stable sedative effect and a longer duration when compared with intravenous midazolam. Conclusion Midazolam rectal gel may be a feasible alternative with a high level of acceptance in pediatric sedation and enhanced bioavailability compared to an oral formulation. The modeling results may help to disclose out the exposure-response relationship of midazolam rectal gel and support the design of an escalating-doses study and pediatric extrapolation study. Clinical trial registration The study was registered at http://www.chinadrugtrials.org.cn (No. CTR20192350).

Background Hypertrophic scars, resulting from alterations in the normal processes of cutaneous wound healing, are characterized by proliferation of dermal tissue with excessive deposition of fibroblast-derived extracellular matrix proteins, especially collagen, over long periods, and by persistent inflammation and fibrosis. The present study aim to compare the efficacy of silicone gel versus combination of a 577-nm pro- yellow laser and silicone gel in the treatment of post-surgery hypertrophic scar. Methods This study is a randomized comparative study In the period from 14 January 2021 up to the end of January 2023. 30 patients with post-surgery hypertrophic scar divided into two groups: A: one half of scar was managed with 577 nm diode laser 3 sessions monthly combined with application of silicone gel at home. A + B: the entire scar was treated with silicone gel within six months who admitted to the Laser unit of the Dermatology and Andrology Department at Al-Azhar University Hospital, Assiut during the study period. Results Significant improvement in pigmentation, pliability, height and total Vancouver score. By comparing between silicone gel and combination of silicone gel and a 577 nm diode laser, the combination shows significant improving than silicone gel alone. The scar in the lip and breast area showed a significant higher improvement rate with yellow laser plus silicone gel compared to the other site. Conclusion Combination of silicone gel and yellow laser has significant effect in making surgical scars less distinct.

Background Skin incision scars are cosmetically displeasing; the effects of current treatments are limited, and new methods to reduce scar formation need to be found. Objective We sought to determine whether immediate postoperative injection of stromal vascular fraction gel (SVF-gel) could reduce scar formation at skin incision sites. Methods A prospective, randomized, double-blind, self-controlled trial was conducted in patients who underwent breast reduction. SVF-gel was intradermally injected into the surgical incision on one randomly selected side, with the other side receiving saline as a control. At the 6-month follow-up, the incision scars were evaluated using the Vancouver scar scale (VSS) and visual analog scale (VAS). Antera 3D camera was used for objective evaluation. Results The VSS score and VAS score were significantly different between the SVF-gel-treated side (3.80 ± 1.37, 3.37±1.25) and the control side (5.25 ± 1.18, 4.94 ± 1.28). Moreover, the SVF-gel-treated side showed statistically significant improvements in scar appearance, based on evidences from Antera 3D camera. Limitations This was a single-center, single-race, and single-gender study. Furthermore, the results were available only for the 6-month interim follow-up period. Conclusion Postoperative immediate SVF-gel injection in surgical incisions can reduce scar formation, and exert a preventive effect on scars. Level of Evidence I Evidence obtained from at least one properly designed randomized controlled trial. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Background Scar formation is undesirable both cosmetically and functionally. It shows that silicone gel is effective in preventing and improving scars formed due to a wound formation after injury. Objectives This study investigates whether a silicone gel composition based on a novel concept of infusing a biologically active material such as hyaluronic acid and/or salts with various polysiloxane derivatives in a specific proportion to achieve desired viscosity range and their action has a synergistic beneficial effect on skin scar after injury. Methods We have developed a topical gel utilizing a combination of emulsifiers, sodium hyaluronate, polysiloxane, and its derivatives. The method of preparation comprises mixing of aqueous phase dispersion and polysiloxanes blend under stirring at room temperature. Results It results in the formation of a homogenous smooth gel formulation. The developed topical gel formulation was characterized for physicochemical properties, rheology, stability, and anti‐scar activity in Wistar rats. It was found that the developed formulation system consists of desirable attributes for skin applications. In vivo investigation of developed polysiloxane gel formulation for anti‐scar activity shown promising outcomes compared to marketed product (Kelo‐cote scar gel). Furthermore, a histopathology study of healed skin tissues observed the formation of microscopic skin structures compared to the Kelo‐cote scar gel. Conclusions It indicates that the combination of polysiloxanes and sodium hyaluronate resulting an improvement in anti‐scar activity compared to the marketed product containing polysiloxanes alone.

Sodium taurodeoxycholate (TDCA) gel is a novel candidate for the treatment of atopic dermatitis and is currently under clinical development. TDCA is a taurine‐conjugated bile acid derivative that acts as a G protein‐coupled bile acid receptor agonist and modulates immune responses. This phase 1 study aimed to investigate the safety, tolerability, and pharmacokinetic profile of sodium TDCA after single and multiple topical administrations of sodium TDCA gel in healthy male subjects. Subjects were randomized to receive a single topical administration of sodium TDCA 5, 10, 30, and 50 mg (0.05%, 0.1%, 0.3%, and 0.5% of 10 g) gel or placebo in the single‐ascending dose (SAD) study (N = 32), and sodium TDCA 10, 30, and 50 mg (0.1%, 0.3%, and 0.5% of 10 g) gel or placebo for 28 days (N = 24) in the multiple‐ascending dose (MAD) study. Safety profiles were assessed based on adverse events (AEs), global irritation score (GIS), and numerical pain rating scale (NPRS). Serial blood samples were collected for 24 h at baseline and up to 168 h post‐dose in the SAD study and for 72 h at baseline and up to 240 h post‐dose at steady state in the MAD study. No serious AEs were reported and all AEs were mild in severity for both SAD and MAD studies. The plasma concentrations of TDCA did not increase significantly after topical administrations. Changes in the plasma concentrations of TDCA likely reflected the circadian rhythm rather than the administration of sodium TDCA gel.