REKOVER study protocol: a pRospective patient treatment rEgistry of tramadol and dexKetoprofen trometamol oral fixed-dose combination (SKUDEXA) in mOderate to seVere acutE pain in Real-world setting in Asia.

INTRODUCTION: Satisfactory management of acute pain remains a major medical challenge despite the availability of multiple therapeutic options including the fixed-dose combination (FDC) drugs. Tramadol and dexketoprofen trometamol (TRAM/DKP) 75/25 mg FDC was launched in 2018 in Asia and is widely used in the management of moderate to severe acute pain. There are limited data on its effectiveness and safety in Asian patients, and therefore, a need to better understand its usage patterns in clinical practice. We aim to understand the usage pattern of TRAM/DKP FDC, its effectiveness and tolerability in patients with moderate to severe acute pain in Asia. METHODS AND ANALYSIS: REKOVER is a phase-IV, multicountry, multicentre, prospective, real-world observational study. A total of 750 postsurgical and non-surgical patients (male and female, aged 18-80 years) will be recruited from 13 tertiary-care hospitals (15 sites) in Singapore, Thailand, the Philippines and Malaysia. All patients prescribed with TRAM/DKP FDC and willing to participate in the study will be enrolled. The recruitment duration for each site will be 6 months. The severity of pain will be collected using Numeric Pain Rating Scale through the treatment period from day 1 to day 5, while satisfaction with the treatment will be evaluated using Patient Global Evaluation Scale at the end of treatment. Any adverse event reported during the study duration will be recorded for safety analysis (up to day 6). The study data will be entered into the ClaimIt portal and mobile application (app) (ObvioHealth, USA). All the inpatient data will be entered into the portal by the study site and for outpatient it will be done by patients through an app. ETHICS AND DISSEMINATION: The study has been approved by the local ethics committee from each study sites in Singapore, Thailand, the Philippines and Malaysia. Findings will be disseminated through local and global conference presentations, publications in peer-reviewed scientific journals and continuing medical education.

From Waterloo to the Great Wall: A retrospective, multicenter study on the clinical practice and cultural attitudes in the management of premature ejaculation, in China.

Premature ejaculation (PE), despite its wide prevalence, is largely underdiagnosed and undertreated. Being a multifactorial dysfunction with strong cultural characteristics, PE requires skillful attitudes in the psychosexological support, necessary to manage the patient's and the couple's expectations, as well as in the medical treatment. Dapoxetine is a short-acting selective serotonin reuptake inhibitor approved for use in lifelong and acquired PE in a number of countries. Opinions, not always generated by the evidence-based medicine, impacted the attitudes of Western andrologists, as a nocebo effect which produced a drug's Waterloo, characterized by low prescription rates much more built on the patients' and doctors' expectations than on costs, side effects, and efficacy. In the present study, we retrospectively reviewed real-life data from eight Andrology and Sexual Medicine Public Centers in China to assess the prevalence of PE among attending patients, its association with erectile dysfunction, its subtype, and the proposed treatments. In 2019, among 156,486 patients coming to the centers, 32,667 visits having PE as the chief complaint were performed (20.9%). Almost all patients received treatment prescriptions (32,641 patients, 99.92%); 23,273 patients came back for a follow-up visit in the subsequent 12 months (71.2% of those who initially received treatment). Dapoxetine, either alone or in combination with another therapy, was the most prevalent treatment, prescribed to 22,767 patients (69.7% of treated patients), followed by traditional Chinese medicine (TCM) (39.4%). At follow-up, 8174 patients were unsatisfied with treatment, and a new treatment was proposed (35.12%). Dapoxetine was the best treatment, with an overall 27.1% switching rate when used either alone or in combination: Although the switching rate for Dapoxetine alone was 44.2%, the association of the same drug with psychotherapy resulted in much lower rates (19.5%) and reached a minimum of 12% when also combined with TCM demonstrating how cultural aspects and medical attitudes may dramatically impact on the therapy of a multifaceted, complex, and culture-grounded sexual symptom such as PE. In conclusion, taking switching rates as surrogate markers of treatment failure, this real-life study-the largest in the field-shows that in a more patient-oriented (as in Chinese medical culture), and less symptom-oriented (as in Western medical attitudes), Dapoxetine is a successful treatment for PE patients, with higher reliability when used alone or as part of combined and integrated therapies.

Real-World Evidence on the Efficacy and Tolerability of Tramadol/Dexketoprofen (TRAM/DKP) Fixed-Dose Combination for the Management of Acute Non-surgical Pain in Asian Patients: A Multicentre Retrospective Case Series.

INTRODUCTION: Multimodal analgesia is key in the effective management of acute pain. Previous clinical trials have demonstrated good results with the use of a fixed-dose combination (FDC) of tramadol 75 mg and dexketoprofen 25 mg (TRAM/DKP) in acute pain management. However, there is a dearth of real-world evidence on the efficacy and safety of this combination in the management of acute non-surgical pain, especially among Asian patients. The case series reported herein investigates the real-world experiences of physicians and Asian patients with the use of TRAM/DKP FDC in the management of acute non-surgical pain. METHODS: Data were collected retrospectively on 11 Asian patients across multiple hospitals who had received a short course of TRAM/DKP FDC for acute non-surgical orthopaedic and non-orthopaedic pain. Data on baseline characteristics, medical history, treatment regimen, clinical outcomes, and patient satisfaction were compiled and shared at a peer-to-peer expert meeting in October 2022. RESULTS: All patients experienced a reduction in pain intensity and were very satisfied with pain management, with a mean satisfaction score of 4.3/5. Five patients (range: 63-74 years) experienced mild adverse events, including nausea, vomiting, and dizziness, which resolved with no need for additional treatment in the majority of cases. No serious adverse events were recorded. CONCLUSION: Asian patients with acute non-surgical orthopaedic and non-orthopaedic pain achieved good pain control with TRAM/DKP FDC. The regimen was well tolerated, and patients reported high levels of satisfaction with the outcomes, indicating that TRAM/DKP FDC is an effective choice for the control of acute non-surgical pain in Asian patients.

Real-world management of abnormal scarring using topical silicone gel: expert consensus and case series from the Asian SCARS Expert Group.

Preventing abnormal scar formation and correcting non-aesthetic mature scars are important to prevent physical and psychosocial consequences of abnormal scarring. Evidence-based guidelines for scar management in Asian patients recommend first-line silicone-based products. Dermatix®* Ultra and Dermatix Ultra Kids are topical silicone gels containing a vitamin C ester that helps lighten scar tissue. Herein, we report a case series including patients with hypertrophic and keloid scars treated with Dermatix, showing that Dermatix is effective for scar treatment and prevention, as well as expert consensus supporting the safe and effective use of Dermatix.

Experience with bilastine in the management of urticaria: Original Real-world cases of Bilastine In Treatment (ORBIT) in Asia.

Urticaria is a disabling condition, resulting in an impaired quality of life and sleep disruption, and can have an adverse impact on work-related or school-related performance and attendance. It is defined according to the presence of unknown (chronic spontaneous urticaria) or known (inducible urticaria) eliciting factors. Guidelines recommend second-generation H1-antihistamines for the first-line treatment of urticaria. Bilastine is indicated in adults, adolescents (aged ≥12 years) and children (aged ≥2 years (Mexico and some African countries), ≥4 years (Canada) or ≥6 years (Europe)) with a body weight of at least 20 kg for the symptomatic treatment of urticaria and allergic rhino-conjunctivitis. The aim of the Original Real-world cases of Bilastine In Treatment (ORBIT) study was to review real-world cases from across the Asia-Pacific region supported by evidence-based literature. Eight diverse, real-world, difficult-to-treat cases with urticaria in people aged 10-75 years are presented. Once-daily bilastine (20 mg (adults/adolescents) or 10 mg (children)) was found to be well tolerated and effective in the long-term management of chronic spontaneous urticaria and inducible urticaria.

N-acetylcysteine as an add-on to Directly Observed Therapy Short-I therapy in fresh pulmonary tuberculosis patients: A randomized, placebo-controlled, double-blinded study.

PURPOSE: Pulmonary tuberculosis is associated with increased oxidative stress, enhanced lipid peroxidation, and decreased glutathione (GSH) levels. N-acetylcysteine (NAC) effectively increases GSH levels, improves lipid peroxidation, and decreases reactive oxygen species levels as reported by earlier studies. Hence, we planned to clinically evaluate the effect of NAC as add-on to Directly Observed Therapy Short-I (DOTS-I) regimen on treatment outcome in PTB with the objectives to study the effect of NAC as an add-on to intensive phase of DOTS-I (2 months) on sputum conversion, radiological improvement, GSH peroxidase (GPx) level, and weight and immunological response compared to placebo add-on at the end of 2 and 6 months. MATERIALS AND METHODS: This was a design-prospective, randomized, parallel group, add-on design, placebo-controlled, double-blinded, 24-week study. Parameters studied were sputum acid-fast bacillus examination, radiological improvements, GPx level, weight, and Mantoux response. NAC/placebo was added to DOTS Category I in intensive phase. RESULTS: Totally 48 patients completed the study. In NAC group, 23 patients achieved sputum negativity in 3 weeks while 14 patients in PLACEBO group. There was a significant clearing of infiltration and reduction in cavity size in NAC group compared to placebo at 2 months. At 2 and 6 months, NAC significantly raised GPx level and body weight. In 2 months, the patients with Mix ≤5 became Mx positive (100%) in NAC group while none in placebo group. CONCLUSION: NAC addition to DOTS-I significantly brings about faster sputum negativity, improves radiological response, weight, raises serum GPx level, and rectifies the deregulated immune response. Thus, NAC may be a useful adjuvant to DOTS in PTB.

Efficacy and Safety of Ibrutinib in Indian Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma: Cases from a Named Patient Program.

CONTEXT: This named patient program evaluated the safety and efficacy of ibrutinib, a selective inhibitor of Bruton's tyrosine kinase in Indian patients with relapsed/refractory chronic lymphocytic leukemia (CLL, with/without chromosome 17 deletion [del17p]) and mantle cell lymphoma (MCL). SUBJECTS AND METHODS: The eight enrolled patients (relapsed/refractory CLL: n = 6 [4/6 patients with del17p] and relapsed/refractory MCL: n = 2) had median age of 55 years (range, 52-60) and had received a median of 3 (CLL patients) and 4 (MCL patients) prior therapies. Patients received once-daily dose of ibrutinib (420 mg: CLL, 560 mg: MCL). RESULTS: In CLL patients, the median time to response was 3 months (range, 0.5-7) and five of six patients had partial response (PR) whereas one achieved complete response (CR). Median time on treatment was 11.5 months (range, 8-14); five patients continued treatment and one was recommended stem cell transplantation (SCT). Of the two MCL patients, one achieved PR and one showed CR and advanced to SCT. In CLL patients, the median (range) hemoglobin level improved from 9.8 g/dL (7.2-11) at baseline to 12.0 g/dL (9.5-13.2) and median (range) platelet count improved from 150,000 cells/µL (21,000-195,000) at baseline to 190,350 cells/µL (130,000-394,000) at the time of analysis (July 2016). Most adverse events (AEs) reported were infections (n = 2). No Grade 3-4 or serious AEs, dose reductions, or treatment discontinuation due to AEs were reported. CONCLUSIONS: In this first real-world experience in Indian patients, ibrutinib demonstrated therapeutic efficacy in relapsed/refractory CLL (with/without del17p) and MCL. Safety results were consistent with the current known profile of ibrutinib.

Sodium-Glucose Cotransporter-2 Inhibition and the Glomerulus: A Review.

UNLABELLED: Blood glucose-lowering treatment options generally target insulin action or beta-cell function. In diabetes, expression of the sodium-glucose cotransporter-2 (SGLT2) genes is up-regulated and renal threshold increased, resulting in increased glucose reabsorption from glomerular filtrate, reducing urinary glucose excretion and worsening the hyperglycemic condition. The SGLT2 inhibitors (SGLT2i) are a novel class of anti-diabetic drugs that lower blood glucose levels through the suppression of renal glucose reabsorption thereby promoting renal glucose excretion. The efficacy of SGLT2i is reduced in renal impairment because the ability of glucose-lowering is directly proportional to glomerular filtration rate. On the other hand, ongoing research suggests that SGLT2i may offer potential nephroprotection in diabetes. The SGLT2i have been shown to reduce glomerular hyperfiltration, systemic and intraglomerular pressure and the biochemical progression of chronic kidney disease. Additional mechanisms through which SGLT2i exert nephroprotection may include normalizing blood pressure and uricemia. This review explores this bidirectional relationship of the SGLT2i and the glomerulus. While SGLT2i exhibit reduced efficacy in later stages, they exhibit nephroprotective effects in early stages of renal impairment. FUNDING: Janssen India (Pharmaceutical division of Johnson & Johnson).