Probability Of Treatment Success Research Articles

Determinants of successful methadone maintenance treatments in two groups of patients: a first study

Background: drug abuse is a social and public health problem, with high costs to society. It is, therefore, important to develop effective treatments for this problem, and evaluate these by identifying determinants of successful outcomes in order to plan more efficient public health interventions.The methadone maintenance treatment (MMT), at an appropriate dosage, is recognized as the most effective therapy for opiate addiction, but it is very important to consider the motivation and stage of change of patients for reaching treatment success. These must also be considered when investigating the determinants of MMT success. The aim of this study is to identify the determinants of successful MMT given to “heroin-addicts" attending the drug addiction Services of the Local Health unit of the Italian autonomous Province of Trento in two groups of patients, as outlined below. Methods: a retrospective cohort study was conducted. 393 heroin addicted patients, admitted for the first time to a MMT program in the drug addiction Services of Trento Local Health unit between the years 2000-2008, were considered. Patients were divided into 2 groups on the basis of the objective of treatment suggested by the clinical team and negotiated with the patient: group a labelled high evolution, group B low evolution.High evolution corresponds to a clinical situation in which, by opinion of the operators, the patient has the ability to pursue goals of change. In these cases, the methadone treatment is aimed at reaching a drug free condition and the goal/outcome is opioid abstinence (negative urine results in 90%-100%). Low evolution is characterized by little or no compliance to the assessment and/or therapeutic proposal aimed at achieving change. In these cases, the methadone treatment is aimed at achieving two or more of the following objectives: retention in treatment regimens, improvement of health and/or psychological distress, reduction of criminal activity, of overdose risk, of risk behavior and increase of work.The probability of successful treatment was estimated by means of a multivariate logistic model. The odds ratios and 95% confidence intervals were calculated. Results: for group a, the absence of previous admissions into rehabilitation centres, and social therapy associated with MMT were associated to an overall successful treatment.For the group B, the determinants of successful MMT were: having started treatment after 35 years, having a low educational level, not having previous imprisonments and not assuming the substance more than once a week. Conclusions: the “program" related factors usually considered (like for instance: previous admissions into rehabilitation centres, social therapy) and “individual" ones (like for instance: having started treatment after 35 years, having a low educational level, not having previous imprisonments and not assuming the substance more than once a week ), influenced the effectiveness of MMT in a different way: if for patients in high evolution group the determinants of success were more associated to “program-related" factors, in the case of the low evolution group, the positive outcome seemed to be mostly related to “individual" factors....

Small intestinal submucosa graft bulbar urethroplasty is a viable technique: results compared to buccal mucosa graft urethroplasty after propensity score matching.

Small intestinal submucosa (SIS) graft urethroplasty has been employed to decrease buccal mucosa morbidity and facilitate the procedure. The first published series had a short follow-up, inhomogeneous patient selection, and a lack of a control group. Our purpose is to report treatment outcomes at 13years in a propensity score-matched cohort comparing bulbar urethroplasty with SIS (SISU) or buccal mucosa (BMU). From our institutional database of 1132 bulbar urethroplasties, we used propensity score matching with the nearest-neighbor method without replacement to generate a study sample of 25 BMU and 25 SISU. Failure was defined as any treatment after urethroplasty. Survival analyses were used to analyze treatment failure occurrence with data censored at 156mo. Matching resulted in a complete correction of bias between the two samples except for the follow-up duration, which was slightly longer in the SIS group. The cumulative treatment success probability of BMU and SISU at 156mo was 83.4% and 68%, respectively. At multivariable Cox regression, SIS graft, previous urethrotomy, stricture length, and lower postoperative Qmax (within 2mo after catheter removal) were predictors of failure. Stricture length had a more remarkable effect in SISU, with estimated survival probabilities from the Cox model lower than 80% in strictures > = 3cm. SIS has poorer outcomes compared to BM but may still be useful when BM grafting is not possible. The best candidates for SISU, with similar success to BMU, are patients with strictures shorter than 3cm, preferably without a history of DVIU.

Prevalence, treatment outcomes and determinants of TB/HIV coinfection: A 4-year retrospective review of national tuberculosis registry in a country in a MENA region

BackgroundThe co-occurrence of tuberculosis (TB) and AIDS (HIV) has emerged as a significant public health challenge. This study investigated the epidemiological factors and treatment outcomes of TB in individuals based on their HIV status in Iran. MethodsThe current study was a descriptive-analytical cross-sectional study that focused on new patients diagnosed with TB in Iran between 2018 and 2021. Patients’ data were sourced from the National Tuberculosis Registry database of Iran. A multiple logistic regression model was used to investigate the relationship between the most important influencing factors and TB/HIV coinfection. ResultsOver a 4-year period, a study was conducted on 25,011 new TB patients out of 30,762 registered in the national database. TB and HIV were coinfected in 672 cases (2.68%). The highest number of coinfection cases were found in patients with smear-negative pulmonary tuberculosis (249 patients, 37.05%) and extrapulmonary tuberculosis (123 patients, 18.19%). TB patients with coinfection had a median TB treatment duration of three months longer than others. The success rate of TB treatment was lower in patients with coinfection (437 patients, 65.02%) than in non-coinfection patients (20,302 patients, 83.41%). Treatment success probability in smear-positive pulmonary tuberculosis patients with and without coinfection was lower than other types of TB. Logistic regression analysis showed that having a TB risk factor was the strongest predictor of coinfection, with an odds ratio of 29.73 (95% CI: 22.05–40.07), followed by having an HIV risk factor with an odds ratio of 17.52 (95% CI: 13.68–22.45). ConclusionsThe findings of this research offer significant insights into the potential causes of HIV coinfection in individuals with TB, which could be used to inform the development of policies and strategies aimed at enhancing the identification and treatment of TB patients who are at risk of TB/HIV coinfection and to promote optimal health status for patients with TB.

Factors associated with the outcome of root canal treatment-A cohort study conducted in a private practice.

To investigate the association of various pre-, intra- and post-operative factors on root canal treatment outcome. In this cohort study, primary or secondary root canal treatment of mature permanent teeth was performed by a single endodontist in a private practice over 13 years, and followed 1-4 years after treatment. Treatment details and clinical and radiographic data were collected. The proportion of successfully treated teeth and roots based on strict radiographic (periapical index (PAI) ≤2) and clinical criteria (absence of pain, swelling or sinus tract) was estimated. To evaluate joint associations of prognostic factors and treatment success probability, 44 pre, intra- and post-operative factors were investigated using bivariate associations, and a multiple logistic regression model was fitted using Generalized Estimating Equations. 1259 teeth (2445 roots, 3149 canals) were assessed with a recall rate of 91%. The proportion of successfully treated teeth was 79.9% [95% confidence interval 77.7-82.1]. Eleven prognostic factors were identified that significantly reduced the odds ratio (OR) for treatment success at tooth level. Six were preoperative: injury history (OR = 0.05[0.01-0.24]), root PAI (OR = 0.29[0.20-0.42], 0.21[0.13-0.34] and 0.22[0.12-0.42] for PAI = 3, 4 and 5, respectively, against PAI = 1), lesion diameter (OR = 0.30[0.21-0.43] and 0.24[0.16-0.37] for diameters of 1-5 mm and ≥6 mm, respectively, against no lesion), tooth type (OR = 0.51[0.27-0.97] and OR = 0.45[0.24-0.83] for premolars and molars, respectively, against incisors or canines), tenderness to periapical palpation (OR = 0.64[0.43-0.94]) and two canals per root (OR = 0.67[0.54-0.83]). Four factors were intraoperative: root filling of unsatisfactory quality (OR = 0.18[0.08-0.40]) or extending beyond or shorter than 2 mm from the apex (OR = 0.44[0.26-0.75] and 0.62[0.40-0.97] respectively), resin sealer (OR = 0.58[0.39-0.87] against bioceramic sealer) and single visit treatment (OR = 0.40[0.21-0.75] against multiple visits). One factor was post-operative: defective coronal restoration (OR = 0.35[0.21-0.56]). The following factors were associated with unsuccessful root canal treatment: (i) history of injury, apical periodontitis with increased severity (larger lesion, higher PAI, tenderness to periapical palpation), or complicated anatomic conditions (premolar or molar, two canals in a single root); (ii) technically suboptimal root filling (of unsatisfactory quality or not ending within 2 mm of radiographic apex) performed in a single-visit, or use of resin sealer instead of novel bioceramic sealer; (iii) suboptimal quality coronal restoration.

Efficacy and Health-Related Quality of Life Impact of Fecal Microbiota, Live-jslm: A Post Hoc Analysis of PUNCH CD3 Patients at First Recurrence of Clostridioides difficile Infection.

Clostridioides difficile infection (CDI) causes symptoms of varying severity and negatively impacts patients' health-related quality of life (HRQL). Despite antibiotic treatment, recurrence of CDI (rCDI) is common and imposes clinical and economic burdens on patients. Fecal microbiota, live-jslm (REBYOTA [RBL]) is newly approved in the USA for prevention of rCDI following antibiotic treatments. We analyzed efficacy and HRQL impact of RBL vs. placebo in patients at first rCDI using data from the phase3 randomized, double-blind placebo-controlled clinical trial, PUNCH CD3. This post hoc analysis included patients at first rCDI fromPUNCH CD3. Treatment success (i.e., absence of diarrhea within 8weeks post-treatment) was analyzed adjusting for baseline patient characteristics. HRQL was measured using the Clostridioides difficile Quality of Life Survey (Cdiff32); absolute scores and change from baseline in total and domain (physical, mental, and social) scores were summarized and compared between arms. Analyses were conducted for the trial's blinded phase only. Among 86 eligible patients (32.8% of the overall trial population, RBL 53 [61.6%], placebo 33 [38.4%]), RBL-treated patients had significantly lower odds of recurrence (i.e., greater probability of treatment success) at week8 vs. placebo (odds ratio 0.35 [95% confidence interval 0.13, 0.98]). Probability of treatment success at week8 was 81% for RBL and 60% for placebo, representing 21% absolute and 35% relative increases for RBL (crude proportions 79.2% vs. 60.6%; relative risk 0.53, p = 0.06). Additionally, RBL was associated with significantly higher Cdiff32 total (change score difference 13.5 [standard deviation 5.7], p < 0.05) and mental domain (16.2 [6.0], p < 0.01) scores vs. placebo from baseline to week8. Compared to placebo, RBL demonstrated a significantly higher treatment success in preventing further rCDI and enhanced HRQL among patients at first recurrence, establishing RBL as an effective treatment to prevent further recurrences in these patients. ClinicalTrials.gov Identifier NCT03244644.

Efficacy of pegylated interferon α-2b plus entecavir therapy and predictors of treatment success in children with chronic hepatitis B.

Interferon therapy, used in the treatment of chronic hepatitis B (CHB), is one of the means by which patients can achieve a functional cure. Pegylated interferon is currently used in the treatment of CHB. There are two main types of pegylated interferon: α-2b and α-2a. This study explored the efficacy, safety, and predictors of treatment response for α-2b plus entecavir among children in a real-world setting. The study included 76 patients aged 3-18 years, all of whom were treated with interferon α-2b plus entecavir. The mean duration of treatment was 401.99 days, and 31.6% (24/76) of patients achieved HBsAg clearance. Competing risk model analyses showed that children with baseline HBsAg <1500 IU/mL (subdistribution hazard ratio [sHR]=2.643, P=0.022) and a higher baseline alanine aminotransferase (ALT) level (sHR=1.005, P=0.000) had a higher probability of achieving HBsAg clearance during treatment. Conversely, children with a higher hepatitis B virus loading level (sHR=0.835, P=0.043) and age ≥10 years (sHR=0.243, P=0.002) had a lower probability of achieving HBsAg clearance during treatment. A decrease of >1 log10 in HBsAg level (sHR=3.479, P=0.001) at 12 weeks of treatment was associated with a higher probability of achieving surface antigen clearance. These results indicated that interferon plus entecavir therapy is a promising means of achieving HBsAg clearance in children with CHB. Moreover, HBsAg, ALT, virus loading, and age are indicators of treatment success probability.

Comparison of Long-Term Effects Following Phacoemulsification Combined with Goniosynechialysis and Trabeculectomy in Patients with Primary Angle-Closure Glaucoma and Cataract.

Goniosynechialysis (Phaco-GSL) is a logical therapeutic approach for patients with primary angle-closure glaucoma (PACG) and cataract. The aim of this study was to compare the long-term effectiveness and safety of Phaco-GSL and trabeculectomy (TRB) in the management of PACG with coexisting cataract. A review was conducted on 96 Chinese patients (96 eyes) with PACG and cataract from Peking Union Medical College Hospital (PUMCH). Among them, 56 patients underwent Phaco-GSL, while 40 underwent TRB. Intraocular pressure (IOP), best corrected visual acuity (BCVA), use of supplemental antiglaucoma medical therapy, surgery success rates, and complications for both procedures were assessed. The average follow-up period was 50.3 ± 18.7months in the Phaco-GSL group and 61.2 ± 15.1months in the TRB group. At the final follow-up, IOP decreased from 27.0 ± 11.1mmHg to 13.5 ± 2.1mmHg in the Phaco-GSL group and in the TRB group IOP decreased from 27.1 ± 7.7mmHg to 16.5 ± 5.5mmHg. The long-term postoperative IOP in the Phaco-GSL group was significantly lower than that in the TRB group. There was a statistically significant reduction in medication usage in both groups, with the TRB group having a higher number of postoperative medications at the final follow-up. The incidence of postoperative complications was significantly higher in the TRB group compared to the Phaco-GSL group. Phaco-GSL is the recommended surgical approach for Chinese patients with primary angle-closure glaucoma (PACG) and cataract. Compared to traditional TRB, eyes undergoing Phaco-GSL show a reduced requirement for antiglaucomatous medications, improved management of IOP, decreased risk of complications, and higher long-term cumulative probability of treatment success for patientswith PACG.

18F-FDG PET/CT Imaging Biomarkers for CAR-T Cell Therapy Outcomes in Large-B-Cell Lymphoma

Introduction: CAR-T cell therapy has transformed the care of patients with large-B-cell lymphoma (LBCL), but disease relapse and toxicities remain clinical challenges, while effective quantitative biomarkers are lacking. Our aim was to determine the role of 18F-FDG PET/CT imaging features as biomarkers in LBCL treated with CD19 CAR-T cell therapy. Methods: 18F-FDG PET/CT scans performed before CAR-T for LBCL were analyzed retrospectively by a board certified radiologist. Metabolic tumor volume (MTV), SUVmax, total lesion glycolysis (TLG), presence of bulky disease, and 106 radiomic features per lesion were recorded using the PET/CT and PyRadiomics plugins for FIJI. Laboratory values including IL-6, IL-10, TNF-α, LDH, ferritin, fibrinogen, and D-dimer pre CAR-T infusion were recorded. Response to CAR-T cell therapy was defined according to Lugano criteria. Cytokine release syndrome (CRS) and neurotoxicity were graded according to ASTCT guidelines. Progression-free survival (PFS) and overall survival (OS) were measured from time of CAR-T cell infusion; PFS events were death, relapse, and disease progression. Association between PET features, markers of inflammation and outcomes were studied with Spearman rank correlations, Cox, and logistic regression models. Multivariable generalized estimating equation models were applied to evaluate differential expression of radiomic features between responders and non-responders, accounting for the dependency structure among ROIs from the same individual. Results: A total of 180 LBCL patients (median age 66 years) treated with autologous CD19 CAR-T (93 axi-cel, 52 tisa-cel, 35 liso-cel) were included. Two time points were considered: 1) pre-apheresis scans (n=161; median SUVmax 19, MTV 56 mL, TLG 427 SUV*mL), and 2) pre-infusion, i.e., latest disease evaluation before CAR-T infusion including post-apheresis/post-bridging, as well as pre-apheresis scans for patients without additional imaging afterwards (n=180; median SUVmax 15, MTV 44 mL, TLG 338 SUV*mL), with a total of 341 PET/CT scans evaluated. At lymphodepletion, MTV was significantly correlated with multiple elevated inflammatory laboratory markers; at latest assessment, all PET and inflammatory markers showed significant correlations. MTV at last assessment before infusion was associated with increased risk of grade ≥ 2 CRS (OR 1.08 [95%CI 1.01-1.20], P=0.031), but not ICANS, in a multivariable logistic regression model adjusted for age, pre-lymphodepletion LDH, CAR-T product, bridging and SUVmax. A higher SUVmax at latest assessment was associated with a lower likelihood of non-complete response (CR) (OR 0.58 [0.41-0.80], P&amp;lt;0.001), while MTV lacked such an association after multivariable model. Increased MTV both before apheresis and at last disease assessment before infusion, but not SUVmax, were associated with decreased PFS (HR 1.11 [1.05-1.17] and HR 1.04 [1.02-1.07], respectively), in a multivariable adjustment. A similar pattern was observed for OS. Notably, the combination of MTV and LDH enabled clear separation of high and low PFS risk groups (P&amp;lt;0.001, Figure 1). Finally, when considering over 100 granular pre-infusion radiomic features ( Figure 2), which are not routinely evaluated in CAR-T patients, multiple novel determinants of CR were discovered, including gray level dependence, run length matrix, and shape-based features (P&amp;lt;0.05). Conclusions: To the best of our knowledge, this represents the most extensive analysis of quantitative 18F-FDG PET/CT features within an LBCL cohort undergoing CAR-T treatment. Our findings indicate that standard PET features (MTV and SUVmax) predict both toxicity and efficacy of CAR-T cell therapy, while also showing correlations with systemic inflammation. Additionally, we present, for the first time, the relevance of granular radiomic features in assessing the probability of treatment success. If confirmed, PET features could serve as effective biomarkers in CAR-T patients and have the potential to guide interventions in high-risk populations.

Cost-Effectiveness of Acthar Gel versus Standard of Care for the Treatment of Advanced Symptomatic Sarcoidosis.

Sarcoidosis is a multisystem, inflammatory, systemic granulomatous disease with unknown etiology. Despite the current standard of care (SoC), there is an unmet need for the treatment of advanced symptomatic sarcoidosis. This study assessed the cost-effectiveness of Acthar® Gel (repository corticotropin injection) versus SoC in patients with advanced symptomatic sarcoidosis from the United States (US) payer and societal perspectives over 2 and 3 years. A probabilistic cohort-level state-transition approach was used for this cost-effectiveness analysis. Patients were monitored at the end of a 3-month cycle for the attainment of partial or complete response. Patients in the partial, complete, or no-response state were allowed to transition in each of these states at each 3-month cycle. Following the attainment of response, patients could have a durable response or relapse to a no-response state. Patients in a no-response state received treatment and could transition into a response or no-response state based on the probability of treatment success with the respective treatment. Clinical parameters and health utility data were sourced from the Acthar Gel in Participants with Pulmonary Sarcoidosis (PULSAR) trial (NCT03320070) and healthcare utilization, costs, and disutilities were sourced from the published literature. Base case analysis considered a payer perspective over 2 years. From a payer perspective, Acthar Gel versus SoC results in an incremental cost-effectiveness ratio (ICER) of $134,796 per quality-adjusted life-year (QALY) and $39,179 per QALY over 2 and 3 years, respectively. From a societal perspective, Acthar Gel versus SoC results in an ICER of $117,622 per QALY and $21,967 per QALY over 2 and 3 years, respectively. Sensitivity analysis findings were consistent with the base case. The results from this cost-effectiveness analysis indicate that Acthar Gel is a cost-effective, value-based treatment option for advanced symptomatic sarcoidosis compared to the SoC from the US payer and societal perspectives.

Personalized medicine: consequences for drug research and therapy

In drug research, a serious transformation has taken place. With increasing knowledge gained from molecularmedicine, it became possible to refine and develop new therapies based on the molecular mechanisms of diseases.Medicine and drug development have seen a paradigm shift which can be characterized with the catchword “personalized medicine”, also called “stratified medicine” or “precision medicine”. Personalized medicine is based on definedtandems of therapeutic agents and diagnostic tests. With this addition to the regular medical examination of the patient, specific patient characteristics are determined. The results of such diagnostic tests are then decisive for the choice of therapy or control of the effectiveness of the chosen treatment. The benefit of personalized medicine for the patient is the higher probability of treatment success as well as improved effectiveness and reduced / avoided side effects. Health insurance systems and the public may have the advantage that the health funds can be used more efficiently on this basis. This new paradigm requires also a new debate on the remuneration in health care. In order to bring personalized therapies to patients as quickly as possible, all players in health care should work together to address the challenges associated with personalized medicine.

Treatment success of rescue regimens after dual therapy failure in people living with HIV in a real-life setting

Few data on the management of two-drug regimen (2DR) failure in people living with human immunodeficiency virus (PLWH) are available. Retrospective study on treatment-experienced PLWH on a 2DR, who underwent virological failure [(VF) two consecutive viral loads (VLs) ≥50 copies/mL, a single VL ≥1000 copies/mL, or an antiretroviral therapy (ART) switch after a single VL ≥50 copies/mL with previous blips] or discontinuation for toxicity (baseline). We included integrase strand transfer inhibitor (INSTI)-based [one INSTI plus one nucleoside reverse transcriptase inhibitor (NRTI) (n=78) or one non-NRTI (n=20)] or boosted protease inhibitor (PI/b)-based [one PI/b plus one NRTI (n=116) or one INSTI (n=12)] 2DRs. Probabilities of treatment success (TS), VF, and discontinuation for any other cause of rescue regimens were estimated by Kaplan-Meier curves. A stepwise Cox model was performed to assess predictors of TS. Overall, 226 PLWH were evaluated: at baseline, 144 individuals discontinued 2DR for toxicity and 82 had VF [median viremia 81 (63-212) copies/mL]; 171 switched therapy (49.7% to a triple-regimen, 40.9% to a different 2DR), while 55 (exclusively among those with VF) maintained their failing regimens. The probabilities of 12- and 24-month TS were 75.6% and 64.7%, respectively. Higher TS probabilities were observed in individuals who switched ART at 2DR failure (p=0.003) and in PLWH who discontinued 2DR for toxicity (p=0.008). A therapy switch was the only predictor of TS (p=0.002). Overall probability of success of rescue regimens introduced after 2DR failure is good; an immediate ART switch is associated with higher efficacy, so this approach should be encouraged.

Adherence and Persistence to Medical Therapy in Glaucoma: An Overview.

Glaucoma is a group of progressive optic neuropathies characterized by loss of retinal ganglion cells and visual field deterioration. Despite the fact that the underlying pathophysiology of glaucoma remains unknown, elevated intraocular pressure (IOP) is a well-established risk factor, and the only factor that can be modified. Robust evidence from epidemiological studies and clinical trials has clearly demonstrated the benefits of IOP control in reducing the risk of glaucoma progression. IOP-lowering therapy by the means of eye drops remains a first-line treatment option. However, like other chronic and asymptomatic conditions, many patients with glaucoma have difficulties in maintaining high rates of adherence persistence to prescribed medications. On average, patients with chronic medical conditions take 30-70% of the prescribed medication doses, and on average 50% discontinue medications in the first months of therapy. The ophthalmic literature shows similarly low rates of adherence to treatment. Indeed, poor adherence is associated with disease progression and increased complication rates, as well as healthcare costs. The present review analyzes and discusses the causes of variability of the adherence to the prescribed drugs. The education of patients about glaucoma and the potential consequences of insufficient adherence and persistence seems fundamental to maximize the probability of treatment success and therefore prevent visual disability to avoid unnecessary healthcare costs.

Pharmacokinetic/Pharmacodynamic Analysis of Oral Calcium Fosfomycin: Are Urine Levels Sufficient to Ensure Efficacy for Urinary Tract Infections?

Urinary tract infections (UTIs) are extremely common and a major driver for the use of antimicrobials. Calcium fosfomycin is an old antibiotic indicated for the treatment of UTIs; however, data about its urine pharmacokinetic profile are scarce. In this work, we have evaluated the pharmacokinetics of fosfomycin from urine concentrations after oral administration of calcium fosfomycin to healthy women. Moreover, we have assessed, by pharmacokinetic/pharmacodynamic (PK/PD) analysis and Monte Carlo simulations, its effectiveness considering the susceptibility profile of Escherichia coli, the main pathogen involved in UTIs. The accumulated fraction of fosfomycin excreted in urine was around 18%, consistent with its low oral bioavailability and its almost exclusively renal clearance by glomerular filtration as unchanged drug. PK/PD breakpoints resulted to be 8, 16, and 32 mg/L for a single dose of 500 mg, a single dose of 1000 mg, and 1000 mg q8h for 3 days, respectively. For empiric treatment, the estimated probability of treatment success was very high (>95%) with the three dose regimens, considering the susceptibility profile of E. coli reported by EUCAST. Our results show that oral calcium fosfomycin at a dose level of 1000 mg every 8 h provides urine concentrations sufficient to ensure efficacy for the treatment of UTIs in women.

Retrospective cohort study to devise a treatment decision score predicting adverse 24-month radiological activity in early multiple sclerosis

Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting about 2.8 million people worldwide. Disease course after the most common diagnoses of relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) is highly variable and cannot be reliably predicted. This impairs early personalized treatment decisions. The main objective of this study was to algorithmically support clinical decision-making regarding the options of early platform medication or no immediate treatment of patients with early RRMS and CIS. Retrospective monocentric cohort study within the Data Integration for Future Medicine (DIFUTURE) Consortium. Multiple data sources of routine clinical, imaging and laboratory data derived from a large and deeply characterized cohort of patients with MS were integrated to conduct a retrospective study to create and internally validate a treatment decision score [Multiple Sclerosis Treatment Decision Score (MS-TDS)] through model-based random forests (RFs). The MS-TDS predicts the probability of no new or enlarging lesions in cerebral magnetic resonance images (cMRIs) between 6 and 24 months after the first cMRI. Data from 65 predictors collected for 475 patients between 2008 and 2017 were included. No medication and platform medication were administered to 277 (58.3%) and 198 (41.7%) patients. The MS-TDS predicted individual outcomes with a cross-validated area under the receiver operating characteristics curve (AUROC) of 0.624. The respective RF prediction model provides patient-specific MS-TDS and probabilities of treatment success. The latter may increase by 5-20% for half of the patients if the treatment considered superior by the MS-TDS is used. Routine clinical data from multiple sources can be successfully integrated to build prediction models to support treatment decision-making. In this study, the resulting MS-TDS estimates individualized treatment success probabilities that can identify patients who benefit from early platform medication. External validation of the MS-TDS is required, and a prospective study is currently being conducted. In addition, the clinical relevance of the MS-TDS needs to be established.

Prognostic factors in major depressive disorder: comparing responders and non-responders to Repetitive Transcranial Magnetic Stimulation (rTMS), a naturalistic retrospective chart review.

Repetitive transcranial magnetic stimulation (rTMS) is widely utilized as an effective treatment for major depressive disorder (MDD) with varying response rates. Factors associated with better treatment outcome remain scarce. This naturalistic retrospective chart review hopes to shed light on easily obtainable and measurable predictive factors for patients referred to rTMS. Protocol parameters, medication, rated scales, rTMS protocols, and treatment outcomes were reviewed for 196 patients with MDD who received rTMS at Saint Boniface Hospital between 2013 and 2019. Logistic regression and marginal effects were used to assess the different predictor variables for response (50% reduction or more on the Hamilton Depression Rating Scale (Ham-D)) and remission (Ham-D of ≤7 by the last session). HamD at 10 sessions was predictive of remission, and Sheehan Disability Scale (SDS) at 10 sessions was predictive of response to rTMS. Ham-D, SDS, and Beck Anxiety Inventory were predictive of remission and response by Beck Anxiety Inventory 20 sessions. High frequency rTMS had a similar response and remission rate to low frequency, but higher response rate to intermittent Theta Burst Stimulation with no difference in remission rate. Positive predictive factors of response were lower age and bupropion use. Negative predictive factors were antipsychotics, anticonvulsants, or benzodiazepine use. For remission, antipsychotics or anticonvulsants use were negative predictors; bupropion use and higher resting motor threshold were positive predictors. Severity of depression as measured by baseline HamD was not associated with different probabilities of treatment success.

Cost-Effectiveness of Acthar Gel Versus Standard of Care for the Treatment of Exacerbations in Moderate-to-Severe Systemic Lupus Erythematosus.

Despite current standard of care (SoC), there is an unmet need for the treatment of active systemic lupus erythematosus (SLE). The study assessed the cost-effectiveness of Acthar® Gel (repository corticotropin injection) versus SoC treatment in patients with active, moderate-to-severe SLE from the US payer and societal perspectives over 2 and 3 years. Cost-effectiveness model was developed using a probabilistic cohort-level state-transition approach. Patients received Acthar Gel in an exacerbation state, and the outcomes were assessed at the end of a 3-month cycle for response achievement based on the probability of treatment success with Acthar Gel. Patients may sustain the response or experience an exacerbation. For the base case scenario, moderate-to-severe SLE was defined as British Isles Lupus Assessment Group (BILAG)-2004 ≥ 20 or SLE Disease Activity Index 2000 (SLEDAI-2K) ≥ 10 and clinical response was based on SLE responder index (SRI)-4. Clinical response, productivity loss, and utility were derived from a phase 4 SLE trial; cost and disutility estimates were sourced from the literature. From a payer perspective, Acthar Gel versus SoC resulted in an incremental cost-effectiveness ratio (ICER) of $133,110 per quality-adjusted life-year (QALY) and $94,818 per QALY over 2 and 3 years, respectively. From a societal perspective, Acthar Gel versus SoC results in an ICER of $70,827 per QALY and $32,525 per QALY over 2 and 3 years, respectively. Results from the sensitivity and scenario analyses are consistent with those of the base case model. Acthar Gel is a cost-effective, value-based treatment option for appropriate patients with moderate-to-severe SLE at a willingness-to-pay threshold of $150,000 over 2-3 years from the US payer and societal perspectives. Acthar Gel results in the reduction of direct medical and indirect costs.

CURRENT APPROACHES TO CONTROL OF ISONIAZID-RESISTANT TUBERCULOSIS

Isoniazid (H; INH) is an important first-line drug for the treatment of active tuberculosis (TB) and latent TB infection because of its potent early bactericidal activity against Мycobacterium tuberculosis. Currently, TB resistant to INH, alone or in combination with other drugs, is the most common type of drug-resistant TB. Epidemiology of INH-resistant TB, the molecular mechanisms of drug resistance, current methods for diagnosis and therapeutic regimens of this TB form are presented. Studies in the last years have shown that resistance to INH reduces the probability of treatment success and increases the risk of acquiring resistance to other impor­tant first-line drugs. Based on the most recent meta-analyses, the last WHO recommendations for treatment of INH-resistant TB are to include rifampicin (RIF), ethambutol, pyrazinamide and levofloxacin for 6 months, and not to add streptomycin or other injectable agents to the drug regimen. The guideline emphasizes the importance of excluding resistance to RIF before starting the regimen for INH-resistant TB because of the risk for development of multidrug-resistant TB during the treatment course. The WHO recommendations are based on observational studies, not randomized controlled trials, and are thus conditional and based on low certainty in the estimates of effect. There­fore, further work is needed to optimize the treatment and control of INH-resistant TB.

Prostaglandins as a Topical Therapy for Erectile Dysfunction: A Comprehensive Review.

Erectile dysfunction (ED) is a substantial cause of dissatisfaction among many men. This discontentment has led to the emergence of various drug treatment options for this problem. Unfortunately, due to various interactions, contraindications, and side effects, systemic therapies such as phosphodiesterase-5 inhibitors (including sildenafil, tadalafil, vardenafil, avanafil, etc.) are not welcomed in many patients. These problems have led researchers to look for other ways to reduce these complications. This article holistically reviews the efficacy of topical prostaglandins and their role in treating ED. We sought to provide a comprehensive overview of recent findings on the current topic by using the extensive literature search to identify the latest scientific reports on the topic. In this regard, topical and transdermal treatments can be suitable alternatives. In diverse studies, prostaglandins, remarkably PGE1 (also known as alprostadil), have been suggested to be an acceptable candidate for topical treatment. Numerous formulations of PGE1 have been used to treat patients so far. Still, in general, with the evolution of classical formulation methods toward modern techniques (such as using nanocarriers and skin permeability enhancers), the probability of treatment success also increases. Hamzehnejadi M, Tavakoli MR, Homayoun F et al. Prostaglandins as a Topical Therapy for Erectile Dysfunction: A Comprehensive Review. Sex Med Rev 2022;10:764-781.

SP6.1.3 A Decision-Analysis Study of Endoscopic, Surgical and Pharmacological Treatment Options for Chronic Gastro Oesophageal Reflux Disease

Abstract Aims To compare emerging endo-luminal interventions for the treatment of chronic gastro-esophageal reflux disease (GORD) to pharmacological and surgical interventions. Methods An advanced decision-tree model was constructed and populated with data from 19 randomised controlled trials to compare competing treatment pathways that included: Laparoscopic Fundoplication, Stretta, Transoesophageal Incisionless Fundoplication (TIF) and medical management with proton pump inhibitor (PPI). Model transition probabilities were calculated using weighted pooled estimates of proportions calculated using Freeman-Tukey arcsine square root transformation under random effects model to account for heterogeneity. Model uncertainties for all included components were tested with one-way deterministic sensitivity analysis. Monte Carlo Probabilistic Sensitivity Analysis (PSA) was set to 10000 iterations with model probabilities sampled from the entirety of the data distribution of each variable. Results Base-case analysis at 12months follow-up showed that Laparoscopic Fundoplication had the highest probability of treatment success followed by TIF, Stretta and PPI respectively. Conclusion Endo-luminal interventions, although not shown to be superior to surgery, may have an emerging role in the management of GORD, but data on long-term follow-up and cost-effectiveness is lacking.

Cooled and traditional thermal radiofrequency ablation of genicular nerves in patients with chronic knee pain: a comparative outcomes analysis

IntroductionGenicular nerve radiofrequency ablation (GNRFA) is a minimally invasive intervention for patients with chronic knee pain (CKP) not responding to conservative treatments. Few investigations have compared treatment outcomes of cooled-RFA...