Safety Of Long-term Treatment Research Articles

Efficacy and safety of long-term treatment with elobixibat in hemodialysis patients with chronic constipation: an observational study

BackgroundConstipation is a common complication in hemodialysis patients and can impact their quality of life. Elobixibat selectively inhibits ileal bile acid transporter to suppress bile acid reabsorption, increase the amount of bile acid entering the colonic lumen, and promote water secretion and colonic motility in the large intestine. While the efficacy and safety of elobixibat in hemodialysis patients up to 12 weeks after administration have been reported, the long-term efficacy and safety of elobixibat in hemodialysis patients with chronic constipation are yet to be elucidated. This study evaluates the efficacy and safety of long-term treatment with elobixibat in hemodialysis patients with chronic constipation.MethodsThis was a single-center observational study. A total of 54 patients who had received elobixibat for at least 24 weeks were enrolled. Data on the frequency of spontaneous bowel movements (SBM), Bristol stool form scale (BSFS), patient satisfaction, constipation scoring system (CSS), interdialytic weight gain, laboratory values including blood electrolyte levels, controlling nutritional status (CONUT) score, and adverse events were collected and retrospectively compared between baseline and the last observation.ResultsLong-term elobixibat treatment in the 54 hemodialysis patients with chronic constipation significantly increased (p < 0.05) the frequency of SBM and mean stool form score assessed as per the BSFS at the last observation (duration of treatment, 24.4 to 240.0 weeks). Patient satisfaction and CSS also improved (p < 0.05). Mean serum phosphorus levels decreased (p < 0.05). The treatment was well tolerated.ConclusionsLong-term treatment with elobixibat maintained good bowel movement status and patient satisfaction in hemodialysis patients with chronic constipation. Improved dialysis-related laboratory levels were also demonstrated.Trial registration: UMIN Clinical Trials Registry, UMIN000049865, 22 December 2022, retrospectively registered.

European randomized controlled trial evaluating differential target multiplexed spinal cord stimulation and conventional medical management in subjects with persistent back pain ineligible for spine surgery: 24-month results.

Differential target multiplexed spinal cord stimulation (DTM SCS) was shown to be superior to conventional SCS for treating chronic low back pain (CLBP) in subjects with persistent spinal pain syndrome with previous spinal surgery (PSPS-T2) or ineligible for it (PSPS-T1). This study reports 24-month efficacy and safety of DTM SCS vs. conventional medical management (CMM) in PSPS-T1 subjects across four European countries. This is a prospective, multicenter, open-label, randomized, controlled trial with optional crossover. Subjects randomized 1:1 to DTM SCS or CMM. Primary endpoint was responder rate (% subjects reporting ≥50% CLBP relief) at 6 months. A superiority test compared responder rates between treatments. CLBP and leg pain levels, functional disability, quality of life (QoL), patient satisfaction and global impression of change were evaluated for 24 months. A Composite Responder Index (CRI) was obtained using CLBP relief, disability and QoL. Incidence of study-related adverse events evaluated safety. A total of 55 and 57 subjects were randomized to DTM SCS and CMM respectively. DTM SCS was superior, with CLBP responder rates ≥80% and CLBP relief >5.6 cm (>70% reduction) through the 24-month follow-up. Improvements with DTM SCS in other outcomes were sustained. The CRI was >80% for DTM SCS through 24 months. Opioid medication intake decreased in subjects treated with DTM SCS. Most patients treated with DTM SCS felt satisfied and improved at the end of the study. Safety was congruent with other studies. DTM SCS is efficacious and safe during 24 months for the treatment of CLBP and leg pain in PSPS-T1 patients ineligible for spine surgery. This randomized controlled trial shows that Differential Target Multiplexed SCS (DTM SCS) is an effective and safe long-term treatment for PSPS type 1 patients suffering from axial low back pain with or without leg pain and who are ineligible for spinal surgery. Currently, CMM treatments are their only option and provide limited benefits. Besides superior pain relief, DTM SCS provides significant improvements in functional disability, quality of life, high levels of satisfaction and perceived impression of change.

Safety and efficacy of Testosterone in woman

Introduction: The aim of this study is to evaluate the benefits and risks associated with testosterone treatment for postmenopausal women. Menopause is a natural phase in a woman's life marked by a decline in the production of female hormones like estrogen and progesterone. However, testosterone is also a hormone naturally produced by women, and it should be replenished when its production decreases. Although testosterone is not yet available for women due to lack of approval from the FDA (United States Food and Drug Administration), both research and clinical work have indicated its efficacy in addressing various symptoms of testosterone deficiency, including a diminished interest in sexual activity and weight gain. The objective of this article is to assess the benefits and risks of testosterone therapy in postmenopausal women by reviewing research and clinical studies that explore its use, as well as the associated side effects and risks. Materials and Methods: A systematic review was conducted, involving searches in databases such as PubMed and Google Scholar, using filters related to the topic. Initially, 42 published works were identified. Additional criteria, such as "prospective cohort studies" and "randomized clinical trials," were then applied to refine the results. The search had no language restrictions or time limitations, yielding 9 potentially relevant articles for the review. Results: However, this analysis utilized eight articles of the clinical trial or randomized trial type, retrieved from PUBMED and Google Scholar databases, highlighting the safety and effectiveness of testosterone in women. Conclusions: Following the conducted search, it was concluded that testosterone proves to be an effective treatment for postmenopausal women experiencing decreased sexual activity. Nevertheless, it is acknowledged that further research is imperative to validate its effectiveness in treating premenopausal women, as well as ensuring its safety in long-term treatment

Efficacy and safety of nemolizumab and topical corticosteroids for prurigo nodularis: results from arandomized double-blind placebo-controlled phase II/III clinical study in patients aged ≥ 13 years.

Prurigo nodularis (PN), a chronic inflammatory skin condition, adversely affects the quality of life of affected individuals. Current treatment options for PN in Japan are limited. To evaluate the optimal dose, efficacy and safety of long-term treatment with nemolizumab in patients with PN in Japan. In a 16-week double-blind phase II/III study, patients aged ≥ 13 years with PN were randomly assigned (1 : 1 : 1) to nemolizumab 30-mg, 60-mg or placebo groups, with concomitant topical corticosteroids, every 4 weeks. The primary efficacy endpoint was the percentage change in the weekly mean Peak Pruritus Numerical Rating Scale (PP-NRS) score (range 0-10, with higher scores indicating worse itching) from baseline to week 16. Secondary efficacy endpoints assessed the impact of treatment on pruritus, PN severity, sleep and quality of life. At week 16, the least-squares mean percentage change from baseline in the PP-NRS score was -61.1% in the nemolizumab 30-mg group (n = 77), -56.0% in the 60-mg group (n = 76), and -18.6% in the placebo group (n = 76). Differences between both nemolizumab groups and placebo were significant; the difference between the 30-mg and placebo groups was -42.5% [95% confidence interval (CI) -51.9 to -33.1; P < 0.0001], and between the 60-mg and placebo groups was -37.4% (95% CI -46.7 to -28.1; P < 0.0001). Patients treated with nemolizumab also had greater improvements in the number and severity of prurigo nodules, and in sleep and quality of life compared with the placebo group. Both nemolizumab doses were well tolerated. Improvements in PN were greater following nemolizumab treatment, despite continuation of topical corticosteroids in both groups.

Updated guidelines for prescribing opioids to treat patients with chronic non-cancer pain in Korea: developed by committee on hospice and palliative care of the Korean Pain Society.

There are growing concerns regarding the safety of long-term treatment with opioids of patients with chronic non-cancer pain. In 2017, the Korean Pain Society (KPS) developed guidelines for opioid prescriptions for chronic non-cancer pain to guide physicians to prescribe opioids effectively and safely. Since then, investigations have provided updated data regarding opioid therapy for chronic non-cancer pain and have focused on initial dosing schedules, reassessment follow-ups, recommended dosage thresholds considering the risk-benefit ratio, dose-reducing schedules for tapering and discontinuation, adverse effects, and inadvertent problems resulting from inappropriate application of the previous guidelines. Herein, we have updated the previous KPS guidelines based on a comprehensive literature review and consensus development following discussions among experts affiliated with the Committee on Hospice and Palliative Care in the KPS. These guidelines may assist physicians in prescribing opioids for chronic non-cancer pain in adult outpatient settings, but should not to be regarded as an inflexible standard. Clinical judgements by the attending physician and patient-centered decisions should always be prioritized.

Efficacy and safety of epidural block with lidocaine for refractory severe plaque psoriasis: An open-label pilot study in real world setting.

Epidural block using lidocaine, a non-selective blocker of voltage-gated sodium channels (Nav), has demonstrated efficacy in the treatment of severe plaque psoriasis in a limited number of cases. This study aimed to evaluate the effectiveness and safety of epidural lidocaine block in adult patients with severe, treatment-resistant plaque psoriasis. This was an open-label pilot study. Patients with severe plaque-type psoriasis unresponsive to at least one systemic treatment were enrolled for a 1-week epidural lidocaine block and followed up for 48 weeks. Thirty-six patients participated, with 32 completing the study. At the 12-week mark, there was a remarkable 59% improvement in the mean Psoriasis Area Severity Index (PASI) score (P < 0.001). By week 48, 28 out of 32 patients (87%) achieved PASI 75, while 18 out of 32 (56%) reached PASI 90. Within 7 days, 20 out of 21 patients (95%) reported a reduction in itch, with a mean itch reduction of 82% at day 1 and 94% at day 7. Notably, no severe side effects were observed. Epidural lidocaine block proved to be an effective and safe long-term treatment option for individuals with refractory severe plaque psoriasis.

Long Term Outcome of Percutaneous Coronary Intervention in Patients with Unprotected Left Main Disease

Background: The management of unprotected left main coronary artery disease (LM CAD) poses a significant clinical challenge. Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) have been extensively compared, with PCI emerging as a viable option for specific patient subsets. Advancements in interventional cardiology, including drug-eluting stents and intravascular ultrasound, have improved PCI outcomes, yet long-term efficacy remains a subject of investigation. Objective: This study aims to evaluate the long-term outcomes of PCI in patients with unprotected LM CAD, focusing on all-cause mortality, cardiac deaths, myocardial infarction, revascularization, and stroke. Methods: A descriptive cross-sectional study was conducted at the Peshawar Institute of Cardiology, KPK, from November 2022 to October 2023. A total of 120 patients aged 55-70 years with LM disease undergoing PCI were included. Long-term outcomes were assessed after five years. Data analysis was performed using SPSS version 23, focusing on frequency and association of outcomes with gender. Results: The study observed all-cause mortality in 15.0% (n=18) of the patients, cardiovascular mortality in 6.7% (n=8), myocardial infarction in 7.5% (n=9), revascularization in 14.2% (n=17), and stroke in 4.2% (n=5). Gender analysis revealed no significant difference in all-cause mortality (P=0.73), with a notable gender disparity in cardiovascular mortality favoring females (P=0.04). Revascularization and stroke rates did not significantly differ by gender. Conclusion: PCI presents a favorable and safe long-term treatment option for patients with unprotected LM CAD, with significant outcomes in terms of mortality, myocardial infarction, revascularization, and stroke. The study supports the continued use of PCI in clinical practice, highlighting the necessity for further comparative research with CABG to optimize patient outcomes.

Phentermine in the Modern Era of Obesity Pharmacotherapy: Does It Still Have a Role in Treatment?

This review provides an overview of the history, mechanism of action, and expected treatment effects of the anti-obesity medication (AOM), phentermine. It also includes a summary of recent research and practical guidance for prescribing clinicians. Recent research on phentermine is sparse and consists primarily of observational studies with methodologic limitations. These studies suggest that phentermine use is associated with clinically significant weight loss in adults and that the medication is generally well tolerated. Large-scale observational studies evaluating phentermine's safety have not identified an increased risk of cardiovascular events or elevations in blood pressure. There is no data to support the notion that phentermine is addictive. Although it remains the most commonly prescribed AOM in the USA, phentermine has little rigorous research to support its efficacy and safety in long-term treatment, which creates a dilemma with guideline-recommended chronic use of AOMs. While we await forthcoming conclusive data on this front, clinicians may consider using phentermine long-term in selected patients, if such prescribing is consistent with local regulatory statutes.

Long-term efficacy and safety of dupilumab for moderate-to-severe atopic dermatitis: a prospective real-world cohort study in China.

Dupilumab has demonstrated remarkable efficacy and safety in clinical trials for moderate-to-severe atopic dermatitis (AD). However, long-term real-world evidence, especially in the Chinese population, remains limited. To investigate the long-term efficacy and safety of dupilumab for moderate-to-severe AD in a real-world clinical setting in China and analyze factors that may influence its long-term treatment outcomes. This prospective, observational real-world study included moderate-to-severe AD patients from the AD cohort of the dermatology department of Chongqing Hospital of Traditional Chinese Medicine who received dupilumab treatment for≥52 weeks. Efficacy and adverse events were assessed at baseline, weeks 4, 16, 24, and 52. Multivariate logistic regression analysis was used to identify predictive factors for achieving EASI 50 and EASI 75 at week 52. A total of 124 patients were included. At week 52, EASI, SCORAD, IGA, NRS, and DLQI scores were significantly improved compared to baseline. The proportions of patients achieving EASI-50/75 were 50.81%/29.84%, 72.58%/42.74%, 75%/53.23%, and 67.74%/41.94% at weeks 4, 16, 24 and 52, respectively. Female sex, absence of atopic comorbidities, higher baseline EASI, and medication compliance were positive predictive factors for 52-week EASI-50/75. Eosinophil elevation predicted lower EASI-50 attainment. Nineteen adverse events occurred during the 52-week period (incidence rate: 14.52%), mostly mild and manageable. Dupilumab demonstrated significant efficacy and a low incidence of adverse events over 52 weeks in Chinese patients with moderate-to-severe AD, making it an effective and safe long-term treatment option. Predictive factors were identified to guide treatment optimization.

Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis

BackgroundAn unmet need exists for focal segmental glomerulosclerosis (FSGS) treatment. In an 8-week, phase 2 trial, sparsentan, a dual endothelin–angiotensin receptor antagonist, reduced proteinuria in patients with FSGS. The efficacy and safety of longer-term treatment with sparsentan for FSGS are unknown.MethodsIn this phase 3 trial, we enrolled patients with FSGS (without known secondary causes) who were 8 to 75 years of age; patients were randomly assigned to receive sparsentan or irbesartan (active control) for 108 weeks. The surrogate efficacy end point assessed at the prespecified interim analysis at 36 weeks was the FSGS partial remission of proteinuria end point (defined as a urinary protein-to-creatinine ratio of ≤1.5 [with protein and creatinine both measured in grams] and a >40% reduction in the ratio from baseline). The primary efficacy end point was the estimated glomerular filtration rate (eGFR) slope at the time of the final analysis. The change in eGFR from baseline to 4 weeks after the end of treatment (week 112) was a secondary end point. Safety was also evaluated.ResultsA total of 371 patients underwent randomization: 184 were assigned to receive sparsentan and 187 to receive irbesartan. At 36 weeks, the percentage of patients with partial remission of proteinuria was 42.0% in the sparsentan group and 26.0% in the irbesartan group (P=0.009), a response that was sustained through 108 weeks. At the time of the final analysis at week 108, there were no significant between-group differences in the eGFR slope; the between-group difference in total slope (day 1 to week 108) was 0.3 ml per minute per 1.73 m2 of body-surface area per year (95% confidence interval [CI], −1.7 to 2.4), and the between-group difference in the slope from week 6 to week 108 (i.e., chronic slope) was 0.9 ml per minute per 1.73 m2 per year (95% CI, −1.3 to 3.0). The mean change in eGFR from baseline to week 112 was −10.4 ml per minute per 1.73 m2 with sparsentan and −12.1 ml per minute per 1.73 m2 with irbesartan (difference, 1.8 ml per minute per 1.73 m2; 95% CI, −1.4 to 4.9). Sparsentan and irbesartan had similar safety profiles, and the frequency of adverse events was similar in the two groups.ConclusionsAmong patients with FSGS, there were no significant between-group differences in eGFR slope at 108 weeks, despite a greater reduction in proteinuria with sparsentan than with irbesartan. (Funded by Travere Therapeutics; DUPLEX ClinicalTrials.gov number, NCT03493685.)

Long-term results after EUS gallbladder drainage in high-surgical-risk patients with acute cholecystitis: A 3-year follow-up registry.

Background and study aims Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has become the favorite drainage option for high surgical-risk patients with acute cholecystitis. However, data on long-term outcomes regarding efficacy and security over 1 year are scarce. Patients and methods We performed a retrospective review of a prospectively maintained database to analyze the 3-year long-term outcomes of EUS-GBD with lumen apposing metal stents (LAMS) in high-surgical-risk patients with acute cholecystitis. Results Fifty patients with acute cholecystitis who underwent EUS-GBD with LAMS and 3-year follow-up or until death were included in this study. No endoscopic revisions were scheduled unless an adverse event (AE) or suspected LAMS dysfunction occurred. AEs occurred in 18%, 20%, and 26% of patients in the first, second, and third years, respectively. Thirteen patients developed at least one AE, and six presented with a second AE during follow-up. Recurrence of cholecystitis occurred in two patients (4%). Seven stent migrations (14%) occurred but all were asymptomatic. Symptomatic LAMS-related AEs (LAMS-RAEs) (37.5%) were related to gastric location of the stent compared with duodenal location (66.7% vs. 12.5%, P = 0.03). No stent-related bleeding or stent-related mortality was observed. Conclusions EUS-GBD with LAMS without scheduled removal is an effective and safe long-term treatment in high-surgical-risk patients with acute cholecystitis. Late LAMS-RAEs tend to be more asymptomatic over time. Symptomatic LAMS-RAEs are associated with gastric location, and overall, AEs tend to recur.

Efficacy and safety of long-term use of low molecular weight heparins in patients with systemic lupus erythematosus and antiphospholipid syndrome

To date, the management of patients with antiphospholipid syndrome (APS) with ineffectiveness and/or intolerance to vitamin K antagonists and direct oral anticoagulants remains controversial. One of the treatment strategies is the administration of low molecular weight heparins (LMWH) over a long period of time. Objective: to evaluate the efefficacy and safety of long-term treatment with LMWH in patients with APS. Material and methods. The study included 15 patients (13 women and 2 men) with APS. In 2 of them APS was isolated, in 12 it was combined with systemic lupus erythematosus (SLE), and in 1 – with SLE and psoriatic arthritis. The mean age of patients was 44 ± 12 years, and the mean duration of disease was 12 [6; 18] years. All patients were repeatedly examined in the V. A. Nasonova Research Institute of Rheumatology during hospitalizations and continued outpatient care in the clinical diagnostic center of the Institute. Results and discussion. Ten (67 %) patients received nadroparin, 5 (33 %) patients received enoxaparin. The median duration of therapy was 4 [1; 10] years. Indications for the use of LMWH were inefficacy and intolerance of oral anticoagulants (n = 12, 100 %) and vascular involvement such as thromboangiitis obliterans with the development of chronic arterial insufficiency, ulcers and necrosis of the toes (n = 6, 40 %). During therapy, 13 (86 %) of 15 patients showed clinical improvement: healing of ulcers and necrosis, reduction in the stage of arterial insufficiency, recanalization of venous blood clots. During the entire treatment period with LMWH, one patient experienced a relapse of thrombosis due to an insufficient dose of the drug. No hemorrhagic complications occurred in any case. Other adverse events, including elevated liver aminotransferases, osteoporosis, and thrombocytopenia, were also not observed. Conclusion. The results obtained suggest that long-term therapy with LMWH may be safe and effective in patients with APS.

FRI442 Ongoing Clomiphene Treatment For Men With Hypogonadotropic Hypogonadism

Abstract Disclosure: S.R. Smith: None. Context: Male hypogonadism is becoming recognized with increasing frequency. Testosterone products remain the only approved medical therapy, although highly problematic in men with hypogonadotropic hypogonadism because of inconvenient routes of administration, high cost, and unavoidable suppression of the hypothalamic-pituitary-gonadal axis. There is a need for effective and safe alternative medication. Objective: The purpose of this study was to evaluate the use of clomiphene long term in men with hypogonadotropic hypogonadism. Methods: Thirty-one men with non-congenital hypogonadotropic hypogonadism were treated with clomiphene citrate on an ongoing basis for up to 20 years. Seven patients were treated for &amp;gt; 12 years; 20 patients were treated for &amp;gt; 4 years. Initial age range was from 23 to 74 years, with a mean of 52. Serum testosterone and LH levels were monitored periodically. Clomiphene dose was adjusted at each office visit as required to achieve and maintain normal testosterone levels and improvement in hypogonadal symptoms in each individual patient. Patients were monitored for adverse effects. Data generated were analyzed retrospectively with Microsoft Excel statistical programs. Results: Improvement in hypogonadal symptoms occurred in nearly all patients. All 31 men experienced increases in serum testosterone and LH levels into the normal range, and statistical analysis showed these increases to be highly significant. Testosterone levels increased from 226 +/- 12 to 542 +/- 35 (mean +/- SEM) ng/dl through the period of treatment (P &amp;lt; .0001). LH levels increased from 3.6 +/- 0.4 to 10.0 +/- 1.6 mIU/ml (P &amp;lt; .0002). Clomiphene dose required to achieve and maintain appropriate responses was highly variable within the group of patients, ranging from 3.57 to 200 mg daily, with a mean dose of 54.4 mg daily. There was evidence of diminishing returns with dosage increases to &amp;gt; 100 mg daily. However, response to adjusted clomiphene dose, once established, was generally quite stable for each patient over extended periods of time, up to 20 years. No major adverse effects were encountered. Conclusions: Clomiphene is an effective and safe long-term treatment for men with non-congenital hypogonadotropic hypogonadism. It should be made available as an alternative to testosterone products for this group of men. Presentation: Friday, June 16, 2023

Effect of Intratrigonal Botulinum Toxin in Patients with Bladder Pain Syndrome/Interstitial Cystitis: A Long-Term, Single-Center Study in Real-Life Conditions.

The high percentage of treatment failures seen in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) managed conservatively frequently demands invasive treatment options. We aimed to evaluate the long-term efficacy and adverse events of intratrigonal botulinum toxin injection in such circumstances, as well as to determine possible predictors of response to toxin treatment. A retrospective cohort study included 47 female BPS/IC patients treated with onabotulinum toxin A (OnabotA) in a tertiary hospital between the years 2009 and 2022. All patients received 100 U of OnabotA in ten injections limited to the trigonal area. Patients were divided into three groups based on their treatment response as responders, non-responders and lost to follow-up due to non-medical reasons. The clinical and surgical records of the individuals were retrieved, including the 10-point visual analogue scale (VAS), the number of treatments, the time between injections, and the age at the first injection. A total of 25 patients (>50% of the cohort) were long-term responders, but none of the evaluated parameters was a predictor for this circumstance: age, pain intensity, or duration of improvement following the injection. The time between injections was stable (around 1 year). No severe adverse events were registered. The intratrigonal injection of botulinum toxin in patients with BPS/IC was an effective and safe long-term treatment for patients' refractory to conservative forms of treatment. Age, basal pain intensity, and time to injection request did not predict long-term response to OnaBotA.

P-315 The importance of treatment features beyond pain reduction associated with gonadotropin-releasing hormone analogues from the patient perspective

Abstract Study question Beyond reducing pain, how do women with moderate-severe-endometriosis pain prioritize treatment features and outcomes associated with gonadotropin-releasing hormone (GnRH) analogues? Summary answer Moderate-severe-endometriosis patients prioritized safe long-term treatment, feeling treatment-effects within a few cycles, being able to maintain employment, reducing fatigue, depression, and headaches, and improving libido. What is known already The importance of pain management in endometriosis treatment is well-established. Poor health-related quality of life has been attributed to endometriosis pain, with greater impact as the number of endometriosis symptoms and symptom severity increase. Endometriosis treatment options include analgesics for acute pain episodes and surgery in more severe cases, as well as hormone therapies, including GnRH analogues. The potential risks, benefits, and outcomes associated with currently available GnRH analogues for endometriosis treatment can vary. Data are lacking on the patient perspective with respect to potential treatment features and outcomes beyond just pain reduction. Study design, size, duration Treatment-naïve patients with moderate-severe-endometriosis pain (rating scale ≥4 for menstrual pain) in the United States completed a cross-sectional online survey. Best-worst scaling (BWS) was used to assess preferences for key non-pain treatment attributes that were identified based on the literature. Cognitive pre-test interviews were conducted to confirm content validity of the questionnaire. Data collection for this ongoing survey was initiated in December 2021. Participants/materials, setting, methods Patients (English-speaking, premenopausal, 18-50 years-old) were recruited via healthcare research panel. Eligible patients self-reported laparoscopy-confirmed-endometriosis, no endometriosis/other gynecological surgery in past 3 months, no osteoporosis/bone disease/uterine fibroids history, and healthcare coverage for previous 3 years. Treatment features in the BWS exercise included dosage flexibility, short treatment onset, reversibility of side effects, reducing fatigue, depression, headache, impact on libido, impact on sleep, ability to maintain employment, duration of treatment, and additional need for contraceptive use. Main results and the role of chance Overall, 115 patients (31.1±7.5 years-old) were included in the analyses. On a 0 (no pain) to 10 (pain as bad as you can imagine) scale, the mean worst menstrual and non-menstrual pelvic pain (during past month) were 7.7±1.6 and 5.4±2.7, respectively. The most common endometriosis treatments ever used included over-the-counter pain medications (90.4%) and prescription contraceptives (74.8%). Of 11 BWS features tested, patients prioritized: “You can safely take the treatment for a long period of time” (relative importance=11.4%) “Your ability to get or maintain a job” (11.1%) “When starting a treatment, you will begin to feel the treatment’s effects within the first few menstrual cycles” (10.9%) “You will be less depressed” (10.8%) “Your interest in sex will not be affected” (10.7%) “Any side-effects you may experience are resolved quickly after treatment stops” (10.1%) “You will be less fatigued or tired” (9.5%) “You will have fewer headaches or migraines” (8.6%) Least important to patients were: “Your sleep will not be affected” (6.8%) “Your doctor offers different options for the dose strength and how often you take it, as appropriate to your needs” (5.9%) “You are not required to take additional contraceptives along with the treatment” (4.0%) Limitations, reasons for caution The preferences of patients who participated may differ from those who did not participate, thereby reducing the ability to generalize results. All data were self-reported; diagnosis and treatment could not be independently confirmed. The BWS exercise cannot include all possible attributes and outcomes relevant to patients. Wider implications of the findings Beyond pain reduction, patients most highly valued having safe long-term treatment, feeling treatment effects within a few cycles, rapid resolution of side effects, being able to work, maintaining libido, and reducing fatigue, depression, and headaches. These factors can help physicians to better align endometriosis treatment decision-making with patient preferences. Trial registration number Not applicable

The Long-Term Effectiveness and Safety of Cannabidiol-Enriched Oil in Children With Drug-Resistant Epilepsy

BackgroundSeveral retrospective studies on pediatric epilepsy reported positive effects of cannabidiol-enriched artisanal cannabis oil and pure cannabidiol oil on seizure reduction. MethodsThis is a retrospective study of children and adolescents with refractory epilepsy caused by various etiologies who were treated with artisanal cannabis oil during January 2014 to June 2019, with at least one year follow-up. ResultsOf 114 patients, 84 (73.3%) reported some improvement in seizure frequency at some point during treatment. Fifty-one (59%) of the 86 patients who continued treatment for at least one year showed >50% improvement in seizure frequency. Seizure etiology, seizure type, and patients' age and sex were not found to be associated with the response to cannabidiol-enriched cannabis oil. Side effects were minor, and positive effects beyond seizure reduction were noted. ConclusionsArtisanal cannabidiol-enriched cannabis may be an effective and safe long-term treatment for refractory epilepsy.

Efficacy and Safety of Long-Term Treatment with Stiripentol in Children and Adults with Drug-Resistant Epilepsies: A Retrospective Cohort Study of 196 Patients.

BackgroundStiripentol is an antiseizure medication with multiple potential mechanisms of action, indicated as adjunctive therapy in people with Dravet syndrome, whose seizures are not adequately controlled with clobazam and valproate. However, there are scattered data on its efficacy in other epilepsy aetiologies and types. We previously reported our single-centre experience on the efficacy of adjunctive stiripentol treatment in a cohort of 132 patients with different types of refractory epilepsies.ObjectiveWe aimed to expand our analysis to a larger cohort of 196 patients with a long-term follow-up.MethodsWe retrospectively evaluated long-term efficacy, tolerability and predictors of treatment response in 196 patients with a long-term follow-up (range 0.5–232.8 months).ResultsAfter an initial median follow-up of 3 months after stiripentol introduction, we observed a responder rate of 53% including seizure freedom in 9%. At subsequent follow-ups at 12 and 24 months, responder rates were 29% and 22%, respectively. Aetiology was associated with sustained response over time, with Dravet syndrome being the aetiology with the highest responder rate (64%) at 48 months compared with syndromes with other genetic causes (13%) or unknown aetiology (38%). A higher responder rate over time was also observed in patients with generalised (44%) and combined focal and generalised epilepsies (28%) than in patients with focal epilepsies (20%). The highest relapse free-survival was observed when stiripentol was initiated at the youngest age (0–4 years) or in adulthood. The retention rate (i.e. proportion of patients who continued stiripentol with no change in either pharmacological or non-pharmacological therapy) was 53% at 12 months and 33% at 24 months.ConclusionsBased on our findings, we suggest that stiripentol is an effective and well-tolerated therapeutic option not only in Dravet syndrome but also in other epilepsy syndromes with or without an established genetic aetiology. Response duration was influenced by age at stiripentol initiation across different aetiologies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-022-00305-7.

Long-term efficacy, safety, and medication compliance of roxadustat on peritoneal dialysis patients with renal anemia affected by the COVID-19 pandemic: a retrospective study.

Current studies have limited data on long-term treatment safety and medication compliance of roxadustat for renal anemia in peritoneal dialysis (PD) patients. We aimed to analyze the long-term efficacy, safety, and medication compliance of roxadustat in the treatment of renal anemia in patients with PD who discontinued recombinant human erythropoietin (rhEPO) treatment due to the corona virus disease 2019 (COVID-19) outbreak. We retrospectively collected patients who were switched from rhEPO to roxadustat in our hospital due to the pandemic. The criteria for subject inclusion: aged >18 years with a dialysis vintage >3 months, without malignant tumor, no severe cardiovascular and cerebrovascular diseases, and not combined hemodialysis. Patients were followed up until the end of December 2021. Hemoglobin (Hb), red blood cell (RBC) and hematocrit (Hct) were recorded at baseline, month 1-12 and month 20, and iron parameters at baseline, 3, 6, 9, 12, and 20 months were collected. The Morisky Medication Adherence Scale-8 (MMAS-8) was used to score medication compliance during rhEPO treatment and roxadustat treatment, and adverse reactions occurred during treatment were collected. The efficacy and medication compliance of roxadustat were analyzed using Wilcoxon rank sum test or t-test. The median follow-up time was 21.1 (20.6, 21.7) months. After 1 month of treatment, the Hb level was significantly increased by 9.4 g/L (95% CI: 6.0-12.8 g/L) compared with the baseline, follow up at 20 months showed the Hb level had remained stable, increased by 20.7 g/L (95% CI: 15.9-25.4 g/L) compared with before treatment. At the beginning of treatment, total iron binding capacity increased, transferrin saturation and serum ferritin decreased, serum iron remained stable during treatment. During roxadustat treatment, no patient discontinued treatment due to the pandemic, and the Morisky score was improved compared with that during rhEPO treatment [5.75 (4.25, 6.00) vs. 6.75 (5.75, 7.00), P=0.000]. There were no serious adverse events associated with roxadustat were observed. Roxadustat can effectively improve anemia and had good tolerance in patients undergoing PD who have difficult using rhEPO, and the medication compliance was better than rhEPO during the COVID-19.

MO031: Long-term safety of treatment with tolvaptan in patients with autosomal dominant polycystic kidney disease

Abstract BACKGROUND AND AIMS Tolvaptan, a vasopressin antagonist, is a drug that acts by slowing the progression of autosomal dominant polycystic kidney disease (ADPKD). Its administration is not free of side effects. To assess the long-term safety profile of ADPKD patients treated with tolvaptan. METHOD Retrospective observational study was undertaken of ADPKD patients on treatment with tolvaptan. RESULTS Of the 182 ADPKD patients under follow-up in our hospital, 18% (n = 33) started treatment. Of these, 60.6% (n = 20) were male, with an age of 47.64 ± 8.64 years, a baseline Fg of 65.24 ± 20.14 mL/min, TKVh of 1137.45 ± 667.58 mL and a mean follow-up time of 39.85 ± 10.04 months. A total of 72.7% reached the maximum dose (120 mg), the mean maximum dose reached being 108.18 ± 22.42 mg. At the time of the study, 100% of the patients had reached the maximum dose, the mean time to reach it being 5.8 ± 9.3 weeks. A total of 90.9% (n = 30) presented with side effects: 81.8% (n = 27) aquaretic and 12.1% (n = 4) hepatotoxicity. Others being hypernatremia in 9.1% (n = 3) and hyperuricemia in 24% (n = 8). No other side effects were described. A total of 39.4% (n = 13) of the patients temporarily discontinued treatment after 3.01 ± 2.17 months. The reasons were as follows: aquaretic effects 35.7% (n = 5), hepatotoxicity 35.7% (n = 5), 3.03% desire for pregnancy (n = 1), 3.03% cerebral hemorrhage (n = 1) and 3.03% (n = 1) worsening of renal function. Some 30.76% (n = 4) of the patients restarted treatment at 5.5 ± 6.76 months. Therefore, the treatment discontinuation rate was 27.2%. The profile of patients with side effects were mostly male (60%) with mean age of 46 ± 8.65 years and TKVh of 1829.93 ± 1172.83 mL .The maximum dose reached in these patients was 107 ± 23.2 mg with a mean time to reach it of 6.19 ± 9.7 ± weeks. Patients who had more aquaretic side effects were characterized by better baseline prior to renal function and a greater decrease in GFR throughout follow-up. No differences in TRV variations were observed. CONCLUSION Tolvaptan treatment is shown to be safe in the long term. However the patient profile to receive treatment must be considered given that a high percentage present aquaretic effects. Regarding hepatotoxicity, although it is another potentially serious effect to consider, it is easily managed and reversible in our studied sample.

Demonstrating Benefit-Risk Profiles of Novel Therapeutic Strategies in Kidney Transplantation: Opportunities and Challenges of Real-World Evidence.

While great progress has been made in transplantation medicine, long-term graft failure and serious side effects still pose a challenge in kidney transplantation. Effective and safe long-term treatments are needed. Therefore, evidence of the lasting benefit-risk of novel therapies is required. Demonstrating superiority of novel therapies is unlikely via conventional randomized controlled trials, as long-term follow-up in large sample sizes pose statistical and operational challenges. Furthermore, endpoints generally accepted in short-term clinical trials need to be translated to real-world (RW) care settings, enabling robust assessments of novel treatments. Hence, there is an evidence gap that calls for innovative clinical trial designs, with RW evidence (RWE) providing an opportunity to facilitate longitudinal transplant research with timely translation to clinical practice. Nonetheless, the current RWE landscape shows considerable heterogeneity, with few registries capturing detailed data to support the establishment of new endpoints. The main recommendations by leading scientists in the field are increased collaboration between registries for data harmonization and leveraging the development of technology innovations for data sharing under high privacy standards. This will aid the development of clinically meaningful endpoints and data models, enabling future long-term research and ultimately establish optimal long-term outcomes for transplant patients.