히알루론산 연구와 출처

Background Stem cells are specialised precursor cells that can replace aged or damaged cells and thereby maintain healthy tissue function. Stem cell therapy is increasingly used as a treatment for knee osteoarthritis, despite the lack of clarity around the mechanism by which stem cell therapy may slow down disease progression in osteoarthritis, and uncertainty regarding its benefits and harms. Objectives To assess the benefits and harms of stem cell injections for people with osteoarthritis of the knee. A secondary objective is to maintain the currency of the evidence, using a living systematic review approach. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase on 15 September 2023, unrestricted by date or language of publication. We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) for relevant trial protocols and ongoing trials. Selection criteria We included randomised controlled trials (RCTs), or trials using quasi-randomised methods of participant allocation, comparing stem cell injection with placebo injection, no treatment or usual care, glucocorticoid injection, other injections, exercise, drug therapy, surgical interventions, and supplements and complementary therapies in people with knee osteoarthritis. Data collection and analysis Two review authors selected studies for inclusion, extracted trial characteristics and outcome data, assessed risk of bias and assessed the certainty of evidence using the GRADE approach. The primary comparison was stem cell injection compared with placebo injection. The primary time point for pain, function and quality of life was three to six months, and the end of the trial period for participant-reported success, joint structure changes and adverse event outcomes. Major outcomes were pain, function, quality of life, global assessment of success, radiographic joint progression, withdrawals due to adverse events and serious adverse events. Main results We found 25 randomised trials (1341 participants) comparing stem cell injections with placebo injection (eight trials), no treatment or usual care (analgesia, weight loss and exercise) (two trials), glucocorticoid injection (one trial), hyaluronic acid injection (seven trials), platelet-rich plasma injections (two trials), oral acetaminophen (paracetamol) (one trial), non-steroidal anti-inflammatory drugs plus physical therapy plus hyaluronic acid injection (one trial) and stem cell injection plus intra-articular co-intervention versus co-intervention alone (three trials) in people with osteoarthritis of the knee. Trials were predominantly small, with sample sizes ranging from 6 to 252 participants, with only two trials having more than 100 participants. The average age of participants across trials ranged from 51 to 66 years, and symptom duration varied from one to 10 years. Placebo-controlled trials were largely free from bias, while most trials without a placebo control were susceptible to performance and detection biases. Here, we limit reporting to the main comparison, stem cell injection versus placebo injection. Compared with placebo injection, stem cell injection may slightly improve pain and function up to six months after treatment. Mean pain (0 to 10 scale, 0 no pain) was 4.5 out of 10 points with placebo injection and 1.2 points better (2.5 points better to 0 points better) with stem cell injection (I 2 = 80%; 7 studies, 445 participants). Mean function (0 to 100 scale, 0 best function) was 46.3 points with placebo injection and 14.2 points better (25.3 points better to 3.1 points better) with stem cell injection (I 2 = 82%; 7 studies, 432 participants). We are uncertain whether stem cell injections improve quality of life or increase the number of people who report treatment success compared to placebo injection, because the certainty of the evidence was very low. Mean quality of life was 45.3 points with placebo injection and 22.8 points better (18.0 points worse to 63.7 points better) with stem cell injection (I 2 = 96%; 2 studies, 288 participants) at up to six months follow-up. At the end of follow-up, 89/168 participants (530 per 1000) in the placebo injection group reported treatment success compared with 126/180 participants (683 per 1000) in the stem cell injection group (risk ratio (RR) 1.29, 95% CI 1.10 to 1.53; I 2 = 0%; 4 trials, 348 participants). We downgraded the evidence to low certainty for pain and function due to indirectness (as the source, method of preparation and dose of stem cells varied across studies), and suspected publication bias (up to three larger RCTs have been conducted but withdrawn prior to reporting of results). For quality of life and treatment success, we further downgraded the evidence to very low certainty due to imprecision in addition to indirectness and suspected publication bias. We are uncertain of the potential harms associated with stem cell injection, as there were very low event rates for serious adverse events. At the end of follow-up, 5/219 participants (23 per 1000) in the placebo injection group experienced serious adverse events compared with 4/242 participants (16 per 1000) in the stem cell injection group (RR 0.72, 95% CI 0.20 to 2.64; I 2 = 0%; 7 trials, 461 participants) and there were no reported withdrawals due to adverse events. We downgraded the evidence to very low certainty due to indirectness, suspected publication bias and imprecision. Radiographic progression was not assessed in any of the included studies. Authors' conclusions Compared with placebo injections and based upon low-certainty evidence, stem cell injections for people with knee osteoarthritis may slightly improve pain and function. We are uncertain of the effects of stem cell injections on quality of life or the number who report treatment success. Although the putative benefits of stem cell therapies for osteoarthritis include potential regenerative effects on damaged tissues, particularly articular cartilage, we remain uncertain of the effect of stem cell injections on structural progression in the knee (measured by radiographic appearance). There is also uncertainty regarding the safety of stem cell injections. Serious adverse events were infrequently reported, although all invasive joint procedures (including injections) carry a small risk of septic arthritis. The risk of other important harms, including potential concerns related to the use of a therapy with the theoretical capacity to promote cell growth, or to the use of allogeneic cells, remains unknown.

Objective To stablish whether combined arthrocentesis with platelet-rich plasma, fibrin-rich plasma, hyaluronic acid, corticosteroids and non-steroidal anti-inflammatory drugs is more effective than exclusive arthrocentesis in patients with temporomandibular joint osteoarthritis. Study design A bibliographic search was conducted in Pubmed, Web of Science, Embase and Scopus in July 2024. RCTs were included. The PRISMA checklist was followed. The study is registered with PROSPERO, number CRD42024542631. Results Six RCTs were included with a total of 179 patients. For the variable of maximum oral opening, a better response was observed in the combined arthrocentesis group than in the arthrocentesis group at 6 months (P = .011) and at 12 months (P Conclusion Combined arthrocentesis techniques show significant improvements in maximum mouth opening at six and twelve months and in pain at twelve months pos-treatment. However, the lack of protocol development and the scarcity of similar studies highlight the heterogeneity of the results.

Background Ageing is a degenerative process that affects the entire body. Skin ageing is characterised by a decrease in the levels of collagen, elastin fibre, and hyaluronic acid (HA), resulting in a loss of skin elasticity and hydration. Prior studies suggest that oral collagen supplements can help increase collagen, elastin, and HA levels, ultimately improving skin health. Objective To assess the impact of collagen-based supplements on the signs of skin ageing and determine the effective dosage. Methods This systematic review and meta-analysis utilized PubMed, Clinical Key, ProQuest, and Cochrane Library databases to identify studies published from 2010 to 2021. It includes ten randomised controlled trials (RCTs) with a total of 646 participants. Results The findings indicate that collagen supplements were statistically effective in increasing skin hydration (SMD 1.25 (CI: 0.77-1.74)) and elasticity (SMD 0.61 (CI: 0.21-1.02)). The most commonly administered dose was 4 g/day, with a median dose of 3.5 g/ day. Limitations Most of the studies could not control for weather-related factors. The findings are more applicable to females. Moderate heterogeneity (I2 = 55.5-56.5%) may limit generalisability. The risk of bias was generally unclear, and publication bias could not be assessed due to the small number of studies. Conclusion Oral administration of collagen supplement in a dose ranging from 1-10 g/day was statistically effective in increasing the skin hydration and elasticity.

Background Recurrent aphthous stomatitis (RAS) is a common oral mucosal condition affecting over 2.5 billion people worldwide. Although 0.1% triamcinolone acetonide is a standard treatment, its comparative efficacy remains uncertain. Objective To evaluate and compare systematically the efficacy of 0.1% triamcinolone acetonide with those of alternative therapies for RAS management. Methods A systematic review and meta-analysis were conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. From December 2024 to April 2025, PubMed and the Cochrane Central Register of Controlled Trials, Semantic Scholar, and ScienceDirect were searched for randomized controlled trials (RCTs) evaluating 0.1% triamcinolone acetonide in minor RAS treatment. Eligible studies reported the outcomes of pain reduction, ulcer size, or healing time. Risk of bias was assessed by using the Cochrane Risk of Bias Tool, and meta-analysis pooled estimates were calculated by employing a random effects model. Results Twenty-five RCTs involving 1474 participants were included. Thyme honey, sumac gel, and laser therapies were significantly more effective than 0.1% triamcinolone acetonide in reducing pain and ulcer size. CBD oil, hyaluronic acid, curcumin, amlexanox, and nanoformulated triamcinolone exhibited comparable efficacies as 0.1% triamcinolone acetonide. The outcomes under chamomile, acemannan, and doxycycline benzocaine gel treatments were less favorable than those under 0.1% triamcinolone acetonide treatment. Laser therapy, sumac gel, and Punica granatum extract significantly reduced healing time compared with 0.1% triamcinolone acetonide. The meta-analysis demonstrated that 0.1% triamcinolone acetonide was significantly more effective than thyme honey, Rhus coriaria gel, and nanobased triamcinolone in reducing ulcer size and shortened healing time compared with Salvizan and P. granatum gels. However, no significant effect was observed in pain reduction when 0.1% triamcinolone acetonide was compared with either other treatments or the placebo, and no significant difference in healing time was found when 0.1% triamcinolone acetonide was compared with the placebo. Conclusion Natural agents, such as honey, sage, and sumac gel, show promise as effective, safe alternatives to 0.1% triamcinolone acetonide in the treatment of minor RAS, especially in patients intolerant to corticosteroids. While 0.1% triamcinolone acetonide significantly reduced ulcer size and shortened healing time compared with several alternative treatments, it demonstrated no significant advantage in pain reduction or healing time over the placebo. The results of this work should be interpreted with caution because of the limited number of placebo-controlled trials and the moderate-to-high risk of bias in the included studies. Registration We registered our review protocol in PROSPERO under the ID CRD42024573362.

Skin aging, driven by intrinsic and extrinsic factors, leads to wrinkles and dryness, primarily due to reduced levels of collagen and hyaluronic acid. Agastache rugosa extract (Agatri ® , AG) and a complex of A. rugosa , Ficus carica , and Lycium barbarum extracts (AGEs Blocker™, AB) have been suggested to support skin health in previous studies. Based on preclinical evidence supporting AB's superior efficacy compared to AG, we aimed to investigate whether these effects could also be observed in humans. To this end, we directly compared the effects of AG and AB on skin parameters in a randomized, double-blind, placebo-controlled trial. Forty-five participants were randomized to receive AG (1000 mg/day), AB (500 mg/day), or maltodextrin tablets for 12 weeks. After 8 and 12 weeks of supplementation, both AG and AB significantly reduced wrinkle size and transepidermal water loss compared to placebo. The skin moisture content, dermal density, and elasticity were also improved by supplementation with AG and AB. Notably, AB demonstrated greater efficacy than AG in enhancing these skin parameters. Taken together, this study provides the first clinical evidence that both AG and AB supplementation improves multiple features of skin aging, with AB demonstrating superior efficacy. These findings suggest that AG and AB may serve as promising candidates for the development of dietary supplements targeting skin health.

PURPOSE: This randomized, double-blind, placebo-controlled trial investigated the effects of Curcuma longa extract (CLE) supplementation on vascular, redox-inflammatory biomarkers, and neuropathy symptoms in adults with type 2 diabetes mellitus (T2DM). METHODS: Seventy-six adults with T2DM were randomized to receive CLE (1200 mg/day) or placebo for three months. Plasma concentrations of hyaluronic acid (HA), syndecan-1 (SDC1), syndecan-4 (SDC4), matrix metalloproteinases (MMP-2 and MMP-9), thioredoxin-1 (Trx1), thioredoxin-binding protein-2 (TBP2), sirtuin-1 (SIRT1), nuclear factor erythroid 2–related factor 2 (Nrf2), and the p65 subunit of nuclear factor kappa B (NF-κB p65) were measured at baseline and post-intervention. Neuropathy symptoms were assessed using a validated questionnaire. RESULTS: Baseline characteristics were comparable between groups. After 3 months, CLE supplementation resulted in a significant reduction in neuropathy symptom score compared with placebo (P = 0.048). CLE significantly reduced markers of endothelial glycocalyx shedding, including SDC1 (66.5 vs. 113.0 ng/mL; P = 0.001), SDC4 (155.1 vs. 225.5 pg/mL; P = 0.040), and HA (259.8 vs. 371.7 ng/mL; P = 0.002), as well as MMP-2 (198.4 vs. 233.3 ng/mL; P < 0.001) and MMP-9 (1.2 vs. 2.0 ng/mL; P < 0.001). In parallel, CLE increased antioxidant/redox markers Trx1, SIRT1, and Nrf2 (all P < 0.05) and reduced TBP2 and NF-κB p65 levels (both P < 0.001), indicating coordinated modulation of vascular, redox, and inflammatory pathways. CONCLUSION: Short-term supplementation with CLE was associated with favorable modulation of vascular and redox-inflammatory biomarkers and improvement in neuropathy symptoms in adults with T2DM. These findings support the role of CLE as a promising bioactive nutritional supplement for the prevention and management of vascular and neuropathic complications associated with diabetes.

Purpose This study aimed to evaluate whether adjunctive low-level laser therapy (LLLT) provides additional clinical benefit over an optimized arthrocentesis protocol with hyaluronic acid in patients with ADDwoR. Materials and methods From December 2022 to December 2023, a single-blinded prospective randomized clinical trial was conducted at The British University in Egypt's Department of Oral and Maxillofacial Surgery. The study involved 40 female participants diagnosed with Anterior Disc Displacement without Reduction (ADDwoR). Following TMJ arthrocentesis, subjects were assigned to one of two parallel cohorts: Group A received ten subsequent sessions of low-level laser therapy (LLLT), while Group B served as the control, receiving arthrocentesis alone. Treatment efficacy was evaluated based on pain intensity measured via a Visual Analogue Scale (VAS) and maximum mouth opening (MMO). Clinical assessments were performed at 2-week intervals over a 12-week follow-up period. Results No significant age-related differences were detected when comparing the intervention group to the control group (p = 0.087). No significant intergroup differences were observed in maximum mouth opening (MMO) or pain scores (VAS) at any follow-up time point (p > 0.05). Over the 12-week period, both study arms demonstrated significant clinical enhancement in terms of MMO and pain intensity (p Conclusion While both TMJ arthrocentesis alone and arthrocentesis supplemented with LLLT significantly improved maximum mouth opening and reduced pain, LLLT did not provide a significant incremental benefit over arthrocentesis with hyaluronic acid. These findings suggest that clinical improvements are primarily driven by the main intervention and may reflect a possible therapeutic ceiling effect, beyond which adjunctive LLLT does not confer measurable short-term benefit. Clinical trial number Not applicable.

Aim The intricate architecture of multirooted teeth challenges access to the furcation for treatment. This study aimed to assess the clinical and radiographic efficacy of oxygen-releasing oral gel and 0.8% hyaluronic acid gel along with hydroxyapatite bone graft to treat Class II furcation defects. Methodology Overall, 45 (one site per participant, aged from 20 to 60 years) mandibular molars with periodontitis (stage II and stage III, grade A and B) and class II buccal furcation defects were treated in this study. Selected sites were randomly divided into three groups. In group 1, placebo gel was placed after open flap debridement (OFD), in group 2- 0.8% hyaluronic acid gel + hydroxyapatite bone graft was placed after OFD, and, in group 3, oxygen-releasing oral gel + hydroxyapatite bone graft was placed after furcation defect OFD. Clinical parameters such as gingival index, plaque index, relative vertical clinical attachment level, relative horizontal clinical attachment level, and probing pocket depth were recorded at baseline and six months later. Radiographic measurements-intra bony defect & % bone fill-were measured and calculated by cone beam computed tomography. Results: The mean reduction in intra bony defect was highest in Group 3 (1.433±0.594), followed by Groups 2 (1.000 ± 0.000) and 1 (0.700±0.414). Group 1 showed the lowest mean bone fill (34.69%±12.14), which was significantly lower than in Groups 2 (46.87%±4.71) and 3 (50.93%±4.62), with p-values of (p Conclusion Within the limitations of this study, its results imply that oxygen-releasing gel along with hydroxyapatite bone graft in surgical periodontal therapy to treat class II furcation defects has shown superior regenerative potential. Clinical Trial Register: CTRI/2025/02/081311.

Purpose We aimed to evaluate in a double-blind randomized placebo-controlled trial (RCT) the effectiveness of two citrate-based products in preventing ureteral stent encrustation in patients with severe urinary system damage requiring long-term stent placement and frequent replacements to prevent complications. Methods Men and women aged 50-80, with severe urinary system damage were randomized to Product 1, Product 2 or Placebo. Efficacy points included encrustation prevention analyzed by mean normalized Kidney, Ureter and Bladder (KUB) score, ease of stent removal, and rate of emergency room (ER) visits. Results Of 142 patients randomized (Product 1, n = 37; Product 2, n = 62; Placebo, n = 43) 142 received treatment and 138 reached 9 months of follow-up. At 3 months Product 1 was associated with significant improvements vs. Product 2 by means of mean normalized KUB (mnKUB) score (W = - 5.75, p Conclusion This study emphasises the efficacy of a combination of potassium and magnesium citrates, Phillantus niruri, Ceterach officinarum and hyaluronic acid (Product 1) in managing long-term ureteral stent dependency, enhancing clinical outcomes and improving patient quality of life (QOL).

Oral hyaluronan has been reported to improve various aspects of skin physiology, but existing trials often lack methodological rigor, comprehensive outcome assessment, and diverse populations. This randomized, double-blind, placebo-controlled trial evaluated the effects of sodium hyaluronate (SH) supplementation at two daily doses on skin parameters in healthy Caucasian adults. A total of 150 participants were randomized to receive SH (1.8 MDa) at 60 mg/day (SH60), 120 mg/day (SH120), or placebo for 12 weeks. Facial hydration, transepidermal water loss (TEWL), sebum, elasticity, wrinkle depth, skin gloss, colorimetric parameters, epidermal thickness, dermal density, red areas, and pore size were assessed at baseline and monthly. Subjective skin condition was evaluated every two weeks, and components of natural moisturizing factor (NMF) in forearm skin were quantified by LC-MS/MS. SH120 significantly enhanced skin hydration and elasticity, while reducing TEWL, sebum, and periorbital wrinkle depth versus placebo. It also improved skin structure by increasing epidermal thickness, dermal density, and NMF levels. SH60 showed similar but more modest effects. No changes were observed for colorimetric parameters, red areas, pore size, or gloss. In conclusion, oral SH supplementation improved multiple aspects of skin physiology, supporting its use as a functional food ingredient with measurable benefits for skin health and healthy aging.Trial registration: ClinicalTrials.gov, NCT07065110 (retrospectively registered on 15 Jul 2025); EFSA (European Food Safety Authority) registry: EFSA202400027979 (prospectively filed on 06 Jun 2024).

Objective To evaluate the efficacy and safety of Zhangyanming Tablets (ZYMT) combined with 0.1% sodium hyaluronate eye drops for dry eye disease (DED). Methods A stratified, randomized, doubleblind, placebo-controlled multicenter trial was conducted from June 2022 to August 2024, enrolling 144 patients with DED from 3 centers. Participants were randomized 1:1 to either the ZYMT group (ZYMT + 0.1% sodium hyaluronate, n=72) or the control group (placebo + 0.1% sodium hyaluronate, n=72). Participants received the study tablets (2 tablets orally, 3 times daily) concurrently with the eye drops (1 drop, 5 times daily) for 8 weeks. The primary outcome was the mean change from baseline in the ocular surface disease index (OSDI) score. The secondary outcomes included the efficacy rate, the mean change from baseline in the tear film breakup time (TFBUT), Schirmer's test, corneal fluorescein staining (CFS) and Chinese medicine (CM) syndrome score. Safety was assessed by monitoring adverse events, vital signs, and laboratory parameters (hematology, urinalysis, liver and kidney functions, and electrocardiogram). Results A total of 119 patients completed this study, among which 58 were in the ZYMT group and 61 were in the control group. After 8 weeks of treatment, the mean change from baseline in the OSDI score in the ZYMT group was significantly greater than those in the control group in week 8 [absolute difference -5.66, 95% confidence interval (CI), -9.56 to -1.76]. The efficacy rate was 62.1% (36/58) in the ZYMT group versus 42.6% (26/61) in the control group (relative risk: 1.46, 95% CI, 1.02 to 2.08). The mean changes from baseline in TFBUT and CM symptom score were significantly greater in the ZYMT group than those in the control group at week 8 (P 0.05). Conclusion ZYMT combined with 0.1% sodium hyaluronate eye drops can significantly alleviate the ocular symptoms, improve tear film, and demonstrate a good safety. (Registration No. ChiCTR2200061479).

The goal of this clinical trial is to evaluate whether hyaluronic acid (HA) improves periodontal healing in people with periodontal disease who smoke. Moreover, the effects of HA on biomolecules and bacteria levels will be assessed during the follow up period. The main questions it will answer are: Will periodontal sites treated with HA gel after non-surgical periodontal treatment (NSPT) lead to better outcomes in clinical parameters compared to the sites treated with NSPT only in smokers? Will adjunctive use of HA gel reduce oxidative stress markers and bacteria levels during follow-up? Researchers will compare periodontal sites receiving NSPT with adjunctive HA gel application to sites receiving NSPT alone to determine whether HA provides additional clinical, biochemical and microbiological benefits. Participants will: * first receive full-mouth NSPT then, randomization will be performed in selected jaw to determine the test sites. These two interproximal test sites will additionally receive HA gel application. * attend follow-up visits at 1, 3 and 6 months for clinical periodontal measurements and to provide gingival crevicular fluid samples (GCF) and subgingival samples. The GCF samples will be evaluated for Metallothionein (MT) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and subgingival samples for periodontal pathogens. This study is a split-mouth study that investigates the clinical, biochemical and microbiological efficacy of Hyadent BG® gel application in periodontal pockets after non-surgical periodontal treatment (NSPT) in smoking patients. The study will include 23 smokers with periodontitis who applied to the Department of Periodontology, Faculty of Dentistry, Marmara University. Eligible participants will receive detailed information regarding study procedures, and written informed consent will be obtained prior to enrollment. Treatment Procedures Two days before NSPT, radiographic and full mouth clinical evaluations will be carried out to determine which jaw will be included for the study. The intraoral photographs will be taken, and impressions of the related jaw will be taken for stent fabrication. One day before NSPT, clinical measurements of the related sites with the stent will be repeated. NSPT will be completed in three sessions within two weeks. Before starting NSPT, baseline pooled gingival crevicular fluid (GCF) samples then pooled subgingival microbiological samples will be collected sequentially from the related sites of the selected jaw. Then oral hygiene instructions will be provided, followed by full-mouth supragingival and subgingival scaling using ultrasonic and hand instruments within two weeks. At the last session of NSPT, test sites (non-adjacent sites with ≥ 6mm pocket depth) for adjunctive use of HA gel will be randomly determined by coin toss from the selected jaw, and HA will be applied subgingivally. All patients will be followed up at 1-, 3-, and 6-month intervals. Periodontal Clinical Measurements At baseline and at 1-, 3-, and 6-month, full-mouth clinical measurements will be performed. Periodontal clinical measurements will be recorded at six sites per tooth-mesiobuccal, midbuccal, distobuccal, mesiolingual, midlingual, and distolingual-using a Williams periodontal probe (Hu-Friedy). Plaque Index (PI): Dental plaque accumulation will be assessed after air drying the teeth using a periodontal probe and visual inspection, according to the PI system developed by Silness and Löe. Gingival Index (GI): The gingival inflammatory status will be assessed using the GI developed by Löe and Silness. Probing Depth (PD): PD will be measured as the distance from the free gingival margin to the base of the periodontal pocket by inserting the periodontal probe to the pocket base. Clinical Attachment Level (CAL): CAL will be recorded by measuring the distance from the cemento-enamel junction to the base of the pocket. Bleeding on Probing (BOP) (%): BOP will be assessed 25-30 seconds after pocket probing. Sites showing bleeding will be recorded as positive (+), while those without bleeding will be recorded as negative (-). Collection of GCF and Subgingival Microbiological Samples At baseline, both GCF and pooled subgingival microbiological samples will be collected after clinical measurements from test and control sites, but at follow-up visits (1st, 3rd, and 6th months) prior to clinical measurements. Before sampling, supragingival plaque will be carefully removed, then the test (n=2) and control (n=2) sites will be isolated from saliva using cotton rolls and dried. First, GCF samples will be collected. Periopaper strips will be inserted 1-2 mm into the periodontal pocket and left in place for 30 seconds at the selected sites. GCF volume will be measured. Following GCF sampling, subgingival microbiological sampling will be carried out by inserting sterile paper points (#30) to the base of the periodontal pockets and keeping them in place for 10 seconds. All GCF samples and the subgingival microbiological samples will be stored at -80°C until analysis day. GCF samples will be analyzed by using commercially available Enzyme-Linked Immunosorbent Assay kits for metallothionein (MT) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Quantification of A. actinomycetemcomitans, F. nucleatum, P. gingivalis, T. forsythia, and P. intermedia in subgingival microbiological samples will be performed using Real-Time Polymerase Chain Reaction. Statistical Analysis Statistical analyses will be performed using IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY, USA). A confidence level of 95% will be adopted for all analyses, and a p-value of less than 0.05 will be considered statistically significant. Due to the split-mouth study design, test and control sites within the same individual will be treated as paired samples. Descriptive statistics for clinical parameters (PI, GI, BOP, PD, and CAL) and biochemical markers (MT and 8-OHdG) will be expressed as mean ± standard deviation, median, and minimum-maximum values. The normality of data distribution will be assessed using the Shapiro-Wilk test. For normally distributed variables, within-group comparisons over time (baseline, 1 month, 3 months and 6 months) will be analyzed using one-way repeated measures analysis of variance (ANOVA). When a statistically significant difference is detected, pairwise comparisons will be performed using the Tukey post hoc test. Comparisons between test and control sites will be conducted using the paired samples t-test. For variables that do not follow a normal distribution, within-group comparisons over time will be analyzed using the Friedman two-way analysis of variance. When significant differences are observed, pairwise comparisons will be performed using the Wilcoxon signed-rank test. Between-group comparisons for non-normally distributed variables will be performed using the Mann-Whitney U test. Correlations between clinical, biochemical, and microbiological variables will be evaluated using Spearman's correlation analysis. Variables found to be significant will be further analyzed using multiple linear regression to assess their independent effects. PROCEDURE: Scaling and Root Planing: Scaling and root planing is a conventional gold-standard treatment for periodontitis. As part of this procedure, subgingival plaque and tartar are removed and root surfaces are planed. DEVICE: Hyaluronic Acid (HYADENT BG): Hyaluronic acid will be locally applied to periodontal pockets as an adjunct to non-surgical periodontal treatment, aiming to support periodontal healing. After completion of scaling and root planing, the material will be delivered subgingivally to designated test sites.

The goal of this randomized clinical trial was to learn whether low-level laser therapy or hyaluronic acid application improves healing after free gingival graft surgery in adults with insufficient keratinized gingival tissue in the mandibular lower teeth region. The main questions it aimed to answer were: * Do low-level laser therapy and hyaluronic acid application reduce shrinkage of the gingival graft? * Do these treatments reduce postoperative pain and pain medication use and improve wound healing, clinical outcomes, appearance, and oral health-related quality of life? Researchers compared three groups: free gingival graft surgery alone, free gingival graft surgery with low-level laser therapy and free gingival graft surgery with hyaluronic acid application. Participants underwent free gingival graft surgery and were followed for six months. During follow-up, researchers measured graft size and shrinkage, periodontal clinical measurements, pain at the donor and recipient sites, pain medication use, wound healing, esthetic outcomes, and oral health-related quality of life. This randomized controlled clinical trial evaluated the effects of low-level laser therapy and hyaluronic acid application on graft shrinkage, postoperative morbidity, wound healing, clinical outcomes, esthetic results, and oral health-related quality of life following free gingival graft surgery. Adult participants with insufficient keratinized gingival tissue in the mandibular anterior region were randomly assigned to one of three parallel groups: free gingival graft surgery alone as the control group, free gingival graft surgery combined with low-level laser therapy, or free gingival graft surgery combined with hyaluronic acid application. All participants underwent a standardized free gingival graft procedure. In the low-level laser therapy group, an 810-nm diode laser was applied at 0.1 W in continuous-wave mode for 60 seconds on the day of surgery and on postoperative days 1, 3, 7, and 14. In the hyaluronic acid group, 0.8% hyaluronic acid gel was applied in addition to the surgical procedure, while the control group received no additional treatment. Postoperative pain at the donor and recipient sites was assessed using a visual analog scale during the first seven postoperative days, and analgesic consumption was recorded. Donor-site epithelialization and early wound healing were evaluated on postoperative days 7, 14, and 21. Clinical periodontal measurements, including recession depth, recession width, vestibular depth, keratinized tissue width, probing depth, plaque index, gingival index, and bleeding on probing, were recorded at baseline and at the 1-, 3-, and 6-month follow-up visits. Graft dimensions and shrinkage were assessed using standardized clinical photographs and digital image analysis, while esthetic outcomes were evaluated during the 3- and 6-month follow-up periods. Oral health-related quality of life was assessed at baseline and at 6 months. DEVICE: Topical Hyaluronic Acid Gel: A 0.8% hyaluronic acid gel was applied directly to the recipient bed immediately before placement and stabilization of the free gingival graft. The gel was also applied topically to the palatal donor site immediately after surgery. Participants were prescribed the same gel and instructed to apply it to the palatal donor site three times daily for 14 days. DEVICE: Low-Level Laser Therapy: Low-level laser therapy was administered to the palatal donor site and the recipient site using an 810-nm diode laser at 0.1 W in continuous-wave mode for 60 seconds. Laser applications were performed immediately after free gingival graft surgery and repeated on postoperative days 1, 3, 7, and 14. PROCEDURE: Free Gingival Graft Surgery: A standardized free gingival graft was harvested from the palatal donor site and placed and stabilized at the recipient site in the mandibular anterior region to increase the width of keratinized gingiva.

The device´s intended use is to treat defects and/or lesions of the oral mucosa, e.g. oral mucositis.To prove safety of the device in terms of clinical results. This is an multi-centre, open-label, first-in-man prospective study. Up to 60 patients in total will be involved in the open-label trial of new medical device - Mucopad HA. Eligible patients will be undergoing treatment with the device for up to 10 weeks, after which it is expected that there should be significant improvement in the healing process of oral mucositis after radiotherapy. It is considered as an improvement when there is a significant reduction or complete resolution of the mucositis. Mucositis will be assessed as a WHO scale. Quality of life will be assessed by Oral Mucositis Daily Questionnaire (OMDQ) provided by FACIT. The FACIT and all related works are owned and copyrighted by, and the intellectual property of David Cella, Ph.D. Permission for use of the OMDQ questionnaire is obtained by contacting Dr. Cella at information@facit.org. List of investigational sites is in appendix 7. DEVICE: Mucopad HA: The product is a Class III Medical Device incorporating a medicinal substance (antiseptics-octenidine) within the composition made of sodium hyaluronate polysacharide stabilised by calcium chloride. Device is administered directly onto the area affected by mucositis.

This is a Randomized Clinical Trial to compare two interventions for reducing knee pain and improving knee function of patients with knee osteoarthritis. Sixty participants will be randomly allocated to one of the intervention groups, either a knee educational program or a combination of knee educational program and medical interventions. Participants will be assessed primarily on function and pain, as well as other secondary outcomes at baseline, at the end of the interventions, and three months after the end of the interventions. OTHER: Clinical treatment and Knee educational program: Three weekly medical interventions, according to the patient's need as observed at baseline. 1. 3ml paraspinal infusion of 1% Lidocaine (segmental spinal level); 2. 5,000 impulses of Radial Shockwave Therapy (pneumatic generator, 0.16mJ/mm² of energy and 20Hz of frequency) at the most painful spot of the knees; 3. \*6,000 pulses of Focused Shockwave Therapy (electromagnetic generator) at four sites of the painful knee. For those with knee pain of 7 or above in Visual Analogue Scale after the treatments above, the interventions below will be delivered in the order they appear: 4. Ultrasound guided genicular nerve block: infusion of up to 10ml 0.50% Levobupivacaine without vasoconstrictor; 5. Hydrodissection of superficial and deep plane nerves: infusion of 10ml 5% dextrose diluted in water (D5W); 6. Intra-articular Infusion of Hyaluronic Acid: ultrasound guided infusion of 2.5ml of sodium hyaluronate at the knee joint. * Four weekly applications. OTHER: Knee educational program: Three weekly 60-minute educational program sessions with the following services: Stretching and strengthening exercises for specific muscle groups (hip flexors, extensors, and abductors; knee flexors and extensors; plantar flexors; and abdominal muscles), using one's own body and gravity resistance. Patients will be encouraged to practice them at home at least twice a week after the end of the sessions. Nutritional guidance: Instructions on the importance of adequate weight management, healthy food consumption, and the adequate intake of nutrients. Physical activities: Counseling on home-based physical activities, according to their physical capacities, to protect knee joints. General health: psychology counseling, encouraging participants to apply strategies and self help conduct to improve their general health; Occupational Therapy: Activities of Daily Living strategies to protect knee joints; Nursing: Counseling on strategies for improving healthy sleeping habits.

A clinical study to evaluate the efficacy and safety of a mouthwash containing Hydrogen Peroxide, Sodium Hyaluronate and Glycine in the healing of post-extraction sites of wisdom teeth by film forming action. 57 subjects, with an indication for a third molar extraction, will be enrolled in the study. Participants selection will take place at the IRCCS "Ca" Granda Ospedale Maggiore Policlinico of Milan - UOC Surgery Maxillo Facial and Dentistry where the internship activity of the Degree Course in Dentistry and Dental Prosthetics, Dental Hygiene and the School of Specialization in Orthodontics of the University of Milan is held. Subsequently, subjects will be equally divided and randomly assigned into the test or control groups. Assessment of outcomes will be carried out at a distance of 7 days. DRUG: Filming Formulation of Hydrogen Peroxide and Hyaluronic Acid: The enrolled subjects will be examined and treated by specialized medical personnel. The extraction will be carried out by an experienced operator and will follow the standard guidelines for the extraction of impacted teeth. Once the tooth has been removed, a suture with detached stitches using silk thread 3/0 will be applied. From a pharmacological point of view, the patient will be prescribed antibiotic therapy (Amoxicillin 1g) to be administered twice daily for seven days, analgesic/anti-inflammatory therapy with NSAIDs (e.g. Synflex 550 mg/Brufen 800 mg) are to be used for a maximum of twice daily. The treatment to be evaluated involves mouth rinsing with 10 ml of BMG0703 three times daily, after meals and after normal oral hygiene procedures, for one week (date of the follow-up visit). Patients with allergic reactions or hypersensitivity to the product will be advised to discontinue its use, and seek medical advice. DRUG: Chlorhexidine mouthwash: The enrolled subjects will be examined and treated by specialized medical personnel. The extraction will be carried out by an experienced operator and will follow the standard guidelines for the extraction of impacted teeth. Once the tooth has been removed, a suture with detached stitches using silk thread 3/0 will be applied. From a pharmacological point of view, the patient will be prescribed antibiotic therapy (Amoxicillin 1g) to be administered twice daily for seven days, analgesic/anti-inflammatory therapy with NSAIDs (e.g. Synflex 550 mg/Brufen 800 mg) are to be used for a maximum of twice daily. Subjects in this group are to use Chlorhexidine 0.2% mouthwash as an active comparator; 10 ml three times daily, after meals and after normal oral hygiene procedures, for one week (date of the follow-up visit). Patients with allergic reactions or hypersensitivity to Chlorhexidine will be advised to discontinue its use, and seek medical advice. OTHER: Placebo product: The enrolled subjects will be examined and treated by specialized medical personnel. The extraction will be carried out by an experienced operator and will follow the standard guidelines for the extraction of impacted teeth. Once the tooth has been removed, a suture with detached stitches using silk thread 3/0 will be applied. From a pharmacological point of view, the patient will be prescribed antibiotic therapy (Amoxicillin 1g) to be administered twice daily for seven days, analgesic/anti-inflammatory therapy with NSAIDs (e.g. Synflex 550 mg/Brufen 800 mg) are to be used for a maximum of twice daily. Subjects in this group are to use a placebo product, and will be instructed to use 10 ml for mouth rinsing three times daily, after meals and after normal oral hygiene procedures, for one week (date of the follow-up visit). Patients with allergic reactions or hypersensitivity to the product will be advised to discontinue its use, and seek medical advice.

Assessment of the efficacy of BMG0703 in the treatment of periodontitis and control of supragingival plaque, compared to Chlorhexidine and a placebo product The enrolled subjects will be examined and treated by specialized medical personnel. Patients will undergo a professional oral hygiene session (causal therapy) and will be instructed to perform proper oral hygiene manoeuvres at home. Next, subjects will be divided into three groups: after the causal therapy, the treatment of the pockets will be performed by probing, between 3 and 7 mm, with the test product, active comparator or placebo, with the aid of a dedicated sterile syringe. The application will be repeated after approx. 5 minutes. One bottle of the product (test, comparative or placebo) will then be given to the patient who will be instructed to use it 3 times a day, after meals and after normal oral hygiene procedures, for at least one week. The subjects will then be re-evaluated after 3 days and after a week. During these check-ups, new samples will be collected at the level of the initial sampling sites and will be reassessed on the basis of the selected clinical indices (in particular plaque, bleeding and probing depth). Patients with allergic reactions or hypersensitivity due to the use of the products will be advised to discontinue the use of the products and seek medical advice. DRUG: Hydrogen Peroxide and Hyaluronic acid filming formulation: Patients will undergo a professional oral hygiene session (causal therapy) and will be instructed to perform proper oral hygiene manoeuvres at home. After the causal therapy, the treatment of the pockets will be performed by probing, between 3 and 7 mm, with BMG0703 by means of a dedicated sterile syringe. The application will be repeated after approx. 5 minutes. One bottle of BMG0703 will then be given to the patients who will be instructed to use it 3 times a day, after meals and after normal oral hygiene procedures, for at least one week. The subjects will then be re-evaluated after 3 days and after a week. During these check-ups, new samples will be collected at the level of the initial sampling sites and will be reassessed on the basis of the selected clinical indices (in particular plaque, bleeding and probing depth). DRUG: Chlorhexidine 0.2%: Patients will undergo a professional oral hygiene session (causal therapy) and will be instructed to perform proper oral hygiene manoeuvres at home. After the causal therapy, the treatment of the pockets will be performed by probing, between 3 and 7 mm, with Chlorhexidine 0.2% by means of a dedicated sterile syringe. The application will be repeated after approx. 5 minutes. One bottle of Chlorhexidine 0.2% will then be given to the patients who will be instructed to use it 3 times a day, after meals and after normal oral hygiene procedures, for at least one week. The subjects will then be re-evaluated after 3 days and after a week. During these check-ups, new samples will be collected at the level of the initial sampling sites and will be reassessed on the basis of the selected clinical indices (in particular plaque, bleeding and probing depth). DRUG: Placebo: Patients will undergo a professional oral hygiene session (causal therapy) and will be instructed to perform proper oral hygiene manoeuvres at home. After the causal therapy, the treatment of the pockets will be performed by probing, between 3 and 7 mm, with a placebo product by means of a dedicated sterile syringe. The application will be repeated after approx. 5 minutes. One bottle of the placebo product will then be given to the patients who will be instructed to use it 3 times a day, after meals and after normal oral hygiene procedures, for at least one week. The subjects will then be re-evaluated after 3 days and after a week. During these check-ups, new samples will be collected at the level of the initial sampling sites and will be reassessed on the basis of the selected clinical indices (in particular plaque, bleeding and probing depth).

Purpose: To assess the safety and efficacy of Viscotrabeculotomy Versus trabeculectomy with MMC for the management of medically uncontrolled steroid induced glaucoma. Patients and methods: A retrospective review of 86 eyes of 67 patients with medically uncontrolled SIG who underwent either viscotrabeculotomy (VT) or trabeculectomy with MMC (Trab-MMC) at Mansoura Ophthalmic Center (Mansoura, Egypt) between January 2008, and December 2017 was conducted. Keywords: Steroid induced glaucoma, trabeculectomy, trabeculotomy and MMC. Introduction: Steroid induced glaucoma(SIG) is a form of open-angle glaucoma associated with various modalities of corticosteroid administration such as oral, intravenous, inhaled, ocular instilled, intravitreal, and periocular u.Some histologic studies have reported the accumulation of extracellular matrices including basement membrane-like material, fine fibrillar-like material or proteoglycans in the trabecular meshwork (TM) of SIG patients. These observations suggest that such accumulation could lead to an increased resistance to aqueous outflow in the TM of SIG patients.Surgical procedures for intraocular pressure (IOP) reduction in eyes with SIG include trabeculectomy, trabeculotomy,viscocanalostomy and laser trabeculoplasty. Although several case series have shown that these surgeries are effective for IOP reduction, surgical outcomes for SIG are not fully understood due to lack of large case-control studies aiming to investigate the success rates of trabeculotomy in SIG eyes.It has previously been reported that trabeculotomy more effectively reduces IOP in adult Japanese patients with exfoliative glaucoma than in primary open-angle glaucoma (POAG).This IOP lowering effect in eyes with exfoliative glaucoma is thought to be attributable to the relief of abnormally increased outflow resistance that was induced by the accumulation of exfoliative material within the TM. For the same reason, trabeculotomy has been the surgical procedure of choice for adult patients with SIG among Japanese surgeons.Honjo etal previously showed that trabeculotomy helped to reduce IOPs to 21 mm Hg or less in 14 Japanese patients with SIG. However, some questions still without answers for example, whether trabeculotomy with its modifications for SIG offers better IOP management than other surgeries such as trabeculectomy with mitomycin C (MMC), or which characteristics of patients with SIG show better prognosis after trabeculotomy. Therefore the purpose of this retrospective study was to compare the long term surgical outcomes of viscotrabeculectomy(VT) and trabeculectomy with mitomycin C (Trab-MMC) in patients with uncontrolled steroid induced glaucoma. Subjects and methods: A retrospective review of 86 eyes of 67 patients with medically uncontrolled SIG who underwent either viscotrabeculotomy (VT) or trabeculectomy with MMC (Trab-MMC) at Mansoura Ophthalmic Center (Mansoura, Egypt) between January 2008, and December 2017 was conducted. The research conformed to the provisions of the Declaration of Helsinki. The confidentiality of the data was ensured. The VT group included 45 eyes and the Trab-ologen group included 41 eyes. Demographic and clinical data were retrieved from the records such as age at surgery, gender, best-corrected visual acuity (BCVA, LogMAR), intraocular pressure (IOP), gonioscopy, number of glaucoma medications, surgical details and postoperative complications. Steroid-induced glaucoma eyes were defined as open-angle eyes with an IOP elevation of 22 mm Hg or more after the administration of corticosteroid. Glaucoma surgery was performed when IOP was persistently elevated despite maximal tolerated IOP-lowering therapy with potential or actual compromise of optic nerve structure (progressive optic nerve cupping) and/or function (deterioration of visual field testing). All patients were required to sign informed consent forms before surgery. Viscotrabeculotomy (VT) performed in this study involved the creation of a partial thickness (about 50% thickness) quadrangular (4x4 mm) scleral flap, followed by localization of Schlemm's canal by radial incisions straddling the limbus. High viscosity sodium hyaluronate (Healon GV, Pfizer, NY, USA) was then slowly injected into both ends of Schlemm's canal. Trabeculotomy was completed using the standard metal Harm's trabeculotome (Geuder Instruments, Heidelberg, Germany). Rotation of these probes achieved 120-degree opening of the trabecular meshwork. Next, a small amount of sodium hyaluronate was injected through the open ends of the canal of Schlemm and along the trabeculotomy openings. The scleral flap was then secured tightly with interrupted 10/0 Nylon sutures and conjunctival closure ensued. Trabeculectomy technique involved a creation of a limbal-based conjunctival flap, followed by creation of a 3 x 4 rectangular half-thickness sclera flap. MMC was applied in a concentration of 0.03% for 3 minutes through soaked surgical sponge inserted underneath the conjunctival flap and spread of a large surface area posterior to the limbus and planned scleral flap site then thoroughly irrigated by 200mL of sterile normal saline. The procedure was completed in the usual manner with both sclera and conjunctiva closed by 10/0 nylon sutures. Postoperative treatment for both groups consisted of topical steroids (dexamethasone) and antibiotic (ofloxacin) five times a day with gradual taper over a period of 5 weeks. Surgical success was defined at the end of the 4 years of follow up as an IOP between 6 and 21 mmHg and /or IOP reduction greater than 35 % of baseline throughout the entire follow-up period. Absolute success was defined as success being achieved without medications, and qualified success was defined as achieving success with adjunctive medications. Failure was defined as not meeting the above criteria, or any return to the operating theatre for glaucoma reoperation, or loss of vision to no light perception or hypotony (IOP \<6 mmHg on 2 occasions after 3 months from the operation). A minimum follow-up of 3 years was required for inclusion in the study. During the follow up period, eyes that were labelled as "Failure" at any follow up time point were excluded from the data analysis from that follow up time point to the end of the study period (48 months). Follow up was maintained to the patient as part of the patient care service routinely provided by the study setting. The patients' postoperative data was collected from records at day 1, week 1, month 1, month 3, month 6, month 12, month 18, month 24, month 30, month 36 and month 48. PROCEDURE: Viscotrabeculotomy Versus trabeculectomy with "MMC": Viscotrabeculotomy involved the creation of a partial thickness scleral flap, followed by localization of Schlemm's canal by radial incisions.High viscosity sodium hyaluronate was injected into Schlemm's canal.Trabeculotomy was completed using the standard metal Harm's trabeculotome.The scleral flap was then secured and conjunctival closure ensued.Trabeculectomy technique involved a creation of a limbal-based conjunctival flap, followed by creation of a half-thickness sclera flap. MMC was applied underneath the conjunctival flap.The procedure was completed with both sclera and conjunctiva closed by 10/0 nylon sutures.

Thalassemics can develop liver fibrosis because of iron overload and hepatitis C infection. The latter is the main risk factor for liver fibrosis in transfusion dependent thalassemics. Excess liver iron is clearly recognized as a co factor for the development of advanced fibrosis in patients with hepatitis virus C infection. Hyaluronic acid serum levels correlate with histological stages of liver fibrosis in hepatitis C patients, so it has a good diagnostic accuracy as a non invasive assessment of fibrosis and cirrhosis.there is evidence that suggests Spirulina may help to protect against liver damage, cirrhosis and liver failure in those with chronic liver disease. Dietary supplement intervention: Spirulina: Spirulina in a dose of 250 mg/kg/day will be given orally for 3 months.

This is a prospective, multicenter, observational clinical study conducted under routine clinical practice conditions aimed at describing adherence to a creatine-based nutritional supplement (Creaticare FEM) in estrogen-depleted adult women. Participants will receive the supplement for 12 weeks, and adherence will be assessed as the percentage of doses consumed and the proportion of participants achieving ≥80% adherence. Secondary outcomes include persistence, satisfaction, tolerability, and adherence to recommended physical activity. Exploratory outcomes include changes in muscle strength, body composition, quality of life, joint pain, and skin health. This is a prospective, multicenter, observational clinical study aimed at evaluating adherence to a creatine-based nutritional supplementation (Creaticare FEM) in estrogen-depleted adult women, including those in menopause or late perimenopause. Creaticare FEM is a multi-ingredient dietary supplement formulated to support musculoskeletal, metabolic, and skin health in this population. The daily dose (10 g) contains creatine monohydrate (3 g), hydrolyzed collagen (5 g), hyaluronic acid (95 mg), beta-alanine (300 mg), magnesium (200 mg), and vitamins A, C, E, and B6. Participants will receive the nutritional supplement for a period of 12 weeks, without any modification of standard clinical practice. The primary objective is to describe adherence to supplementation, defined as the percentage of prescribed doses consumed during the study period and the proportion of participants achieving high adherence (≥80%) at the end of follow-up. Secondary objectives include the assessment of persistence with supplementation, participant-reported acceptability and satisfaction, tolerability through the monitoring of adverse events, and adherence to a general recommendation of physical activity provided as part of routine care. In addition, exploratory analyses will be performed to describe pre-post changes over the 12-week period in selected clinical variables, including muscle strength (handgrip dynamometry), body composition (bioimpedance), quality of life (Cervantes questionnaire), joint pain (visual analog scale), and skin health perception (cosmetic VAS). These exploratory outcomes are descriptive in nature and intended to generate hypotheses for future controlled studies. The study does not involve randomization, control group, or experimental intervention beyond routine supplementation, and therefore is not intended to establish causal relationships or confirm clinical efficacy, but rather to provide real-world evidence on adherence, acceptability, and tolerability of a multimodal nutritional supplement in this population.

With the increase of substance abuse over the world, substance abuse e.g. ketamine and methamphetamine related voiding dysfunction is becoming an important medical problem. However, while the clinical manifestation of the condition is becoming better defined, the underlying pathophysiology is still poorly understood. Moreover, majority of the current treatment is just based on the experience on some small case series and there is no treatment data for larger patient sample or standard recommended treatment in the literature. In order to improve the management of this condition, investigators have formulated a treatment protocol based on the current literatures on the management of voiding dysfunction and also a similar condition, interstitial cystitis / painful-bladder syndrome (IC/PBS). The protocol basically consists of the following modalities: * Basic information and education on the condition, principle of treatment and psychosocial support. * First line treatment will include a course of oral anti-inflammatory drugs (for the control of the inflammation process and pain) and anticholinergic agents (for the irritative urinary symptoms). * If these simple oral medication are found to be not effective, then further treatment will include other oral medications, such as amitriptyline and gabapentin, and some drugs that directly applied into the bladder cavity (hyaluronate) or bladder muscle (botulinum toxin). * For those patients with intractable symptoms and failed all the above treatments, surgical treatment (hydrodistension, augmentation cystoplasty) will be discussed. The purpose of this research is to assess the effectiveness of the above treatment protocol in the management of substance induced voiding dysfunction and also assess any possible adverse events related to the usage of the drugs. With the increase in recreational usage of various soft drugs, such as ketamine, methamphetamine over the world, substance abuse related voiding dysfunction is becoming an important medical problem. However, while the clinical manifestation of the condition is becoming better defined, the underlying pathophysiology is still poorly understood. Moreover, majority of the current treatment is based on the experience on some small case series and there is no treatment data for larger patient sample or standard recommended treatment in the literature. With the rapid increase in patients' demand, there is an urgent need for better clinical study on the effect of various treatment regimes for the condition, to provide more evidence-based recommendation for them. On the other hand, better treatment outcome will also help the rehabilitation of these substance abusers. However, in Hong Kong, due to the limited funding in the tertiary care health system and the poor social support for the patients, some potential treatment options, including COX II inhibitors, intravesical hyaluronate, and botulinum toxin injection, etc, are not readily available for these patients. Therefore, some patients may receive sub-optimal treatment with more side effects or may have limited access to certain therapeutic options. The patients may have to suffer and this also affects the doctors' experience and hence the formulation of ideal treatment for these patients. If extra or adequate funding is available, it may not only widen the potential treatment options for these patients but also provide more clinical experience and data in guiding the formulation of treatment protocols / recommendation and even guide future research direction. Therefore, in this proposal, investigators would like to prospectively study the treatment result of various treatment modalities under a standardized treatment protocol. The results will help to evaluate the effectiveness and also tolerability of various proposed treatment options in substance abused related voiding dysfunction. . Because of the certain similarities in the clinical manifestations and pathology of voiding dysfunction and interstitial cystitis / painful-bladder syndrome (IC/PBS), this treatment protocols (referred to later section) will base on standard recommendations of IC/PBS (including the American Urological Guideline) and literature on voiding dysfunction management. For treatment / medications that are not provided in Hospital Authority formulation, investigators will provide to patient if clinically indicated. Currently, because of the insufficient treatment data and also the behavioural characteristics of these substance abusers, it will be difficult or impractical to perform randomized placebo-controlled clinical trials in this area. As a result, a prospective longitudinal study on a standardized treatment protocol is proposed, which will provide some "Real-life practice" information on the management of these patients. The data gathered from this study may also provide basis for future study. DRUG: First line treatment: oral NSAID and anticholinergic agents: oral NSAID and anticholinergic agents DRUG: Second line treatment: additional treatment for pain control: Gabapentin, tramadol, Lyrica DRUG: Third line treatment: A course of intravesical hyaluronate will be given.: A course of intravesical hyaluronate will be given. PROCEDURE: Fourth line treatment: surgical intervention: Consideration of hydrodistention and augmentation cystoplasty