Treatment Success Rate Research Articles

Comparative Effectiveness of Regenerative Endodontic Treatment Versus Apexification for Necrotic Immature Permanent Teeth With or Without Apical Periodontitis: An Umbrella Review.

The evidence related to the superiority of the recommended treatment protocols for necrotic immature permanent teeth is unclear. We aimed to compare the clinical, radiographic, and overall success rates of apexification and regenerative endodontic treatment (RET), assess the methodological quality, and assess the strength of evidence for outcomes. A search was performed in PubMed, Scopus, LILACS, EMBASE, Web of Science, and the Cochrane Library. The titles, abstracts and full texts of systematic reviews (SRs) comparing RET and apexification were screened. The quality and strength of evidence were analyzed via AMSTAR-2, ROBIS, and modified Kohler's criteria. Twelve SRs were included, with nine having meta-analytic outcomes. The quality of only one study was high, and the risk of bias was low in two studies. Comparable success and survival rates for RET and apexification, with no superiority of any treatment, were reported. RET was superior in stimulating root thickness and lengthening. Weak evidence was noted for a higher clinical and radiographic success rate of the apical plug technique and for root lengthening and an increase in root thickness in RET. RET and apexification exhibited comparable success rates of > 85% across all domains. Most comparisons did not reveal significant differences in clinical, radiographic, or overall success. However, the quality of evidence was weak (class IV) for both outcomes, and the majority of systematic reviews exhibited low or critically low quality and high risk of bias.

Inequalities in tuberculosis control in Ethiopia: A district-level distributional modelling analysis.

Implementation studies indicate that the addition of tuberculosis diagnosis and treatment services into the community health extension workers' tasks-that is 'task-shifting'-improved case detection and treatment outcomes in Ethiopia. Given resource and operational constraints, only a limited number of areas can be targeted by an expanded task-shifting program. Therefore, we mapped the distributional disparities in tuberculosis services across regions and districts and modelled the equity pathways towards optimising national scale-up of this task-shifting intervention in Ethiopia. We used data from various sources including District Health Information Software 2; demographic, geospatial and topographic data; and previously published implementation study findings. We developed methods to integrate these datasets and to calculate the proportion of health facilities with tuberculosis services, the district population to health centre ratio, and the proportion of district population living within 2h walking distance from a health centre. Equity and disparities were then measured in terms of: tuberculosis services coverage; health centre adequacy, that is the district population served by health centres; and spatial access adequacy, that is the district population with health centre access within a two-hour walking distance. Subsequently, districts were ranked according to these measures to allow prioritisation of the health extension worker task-shifting intervention. Tuberculosis services coverage varied from 54% in Afar region to 100% in Harari region, and health centre inadequacy ranged from 10% of districts in Benishangul-Gumuz to 87% in Sidama. After spatial access adjustment, health centre inadequacy ranged from 7% of districts in Sidama to 91% in Somali; and tuberculosis services inadequacy from 7% of districts in Sidama to 97% in Afar. Task-shifting implemented in inadequate districts (55% of all districts) could raise national case detection rate from 66% (currently) to 88% and treatment success rate from 93% to 99%; Benishangul-Gumuz achieving the largest increase of all regions. Access to effective tuberculosis services presents substantial disparities across districts in Ethiopia, due to both health system and tuberculosis-specific factors. Jointly considering both types of factors would enable prioritisation of districts where health extension workers would be most impactful.

Cyclophostin and Cyclipostins analogues counteract macrolide-induced resistance mediated by erm(41) in Mycobacterium abscessus

BackgroundMycobacterium abscessus is an emerging pathogen causing severe pulmonary infections, particularly in individuals with underlying conditions, such as cystic fibrosis or chronic obstructive pulmonary disease. Macrolides, such as clarithromycin (CLR) or azithromycin (AZM), represent the cornerstone of antibiotherapy against the M. abscessus species. However, prolonged exposure to these macrolides can induce of Erm(41)-mediated resistance, limiting their spectrum of activity and leading to therapeutic failure. Therefore, inhibiting Erm(41) could thwart this resistance mechanism to maintain macrolide susceptibility, thus increasing the rate of treatment success. In our previous study, the Erm(41) methyltransferase was identified as a possible target enzyme of Cyclipostins and Cyclophostin compounds (CyC).MethodsHerein, we exploited this feature to evaluate the in vitro activity of CLR and AZM in combination with different CyC via the checkerboard assay on macrolide-susceptible and induced macrolide-resistant M. abscessus strains selected in vitro following exposure CLR and AZM.ResultsOur results emphasize the use of the CyC to prevent/overcome Erm(41)‑induced resistance and to restore macrolide susceptibility.ConclusionThis work should expand our therapeutic arsenal in the fight against a antibioticresistant mycobacterial species and could provide the opportunity to revisit the therapeutic regimen for combating M. abscessus pulmonary infections in patients, and particularly in erm(41)-positive strains.

Epidemiological trends in TB during a technical assistance project, Zambia, 2015-2018.

Three health facilities: Chongwe Health Centre (CHC), Chongwe District Hospital (CDH), and Ngwerere Health Centre (NHC) in Chongwe District, Lusaka Province, Zambia. To describe the epidemiological trend of TB in 2015-2018, with the 2014 data as baseline. This was an observational study. At CHC, CDH, and NHC, 457, 851 and 85 cases, respectively, of all types of TB were registered in 2014-2018. The numbers of patients with presumptive TB at CHC and CDH increased from 606 and 406, respectively, in 2014 to 1068 and 1848, respectively, in 2018. The proportion of patients with bacteriologically positive TB among patients with presumptive TB decreased at CHC and CDH from over 10% in 2014 to less than 5% in late 2018. The treatment success rates decreased at CHC and CDH in 2017 from respectively 93.7% and 93.0% in 2014 to 69.1% and 73.0% in 2017. GeneXpert equipment was installed at CHC in 2016 and CDH in 2017. After introducing GeneXpert equipment at CHC and CDH, the proportion of bacteriologically-positive TB among presumptive TB significantly decreased because of the high number of patients with presumptive TB screened; however, it may have also caused treatment success rates to have stumbled.

Success Rates and Prognostic Factors in the Management of Keratoconus: A 10-Year Retrospective Cohort Study at Siriraj Hospital

Objective: To evaluate the success rates of different treatment modalities, identify prognostic factors associated with treatment outcomes and factors influencing disease progression in keratoconus patients. Materials and Methods: A retrospective cohort study of keratoconus patients at Siriraj Hospital during January 2013 to December 2023 was done. Patient characteristics, symptoms and signs related to keratoconus, outcomes of corneal topography, treatment modalities, and best-corrected visual acuity (BCVA) before and after treatment were recorded. Treatment outcome was defined as a “success” when the BCVA post-treatment was equal to or better than 6/12. Progression of keratoconus was based on the Belin ABCD progression criteria. Results: Total 119 patients (231 eyes) were analyzed. The mean age at diagnosis was 28.0 ± 9.5 years. Two hundred and sixteen eyes (93.5%) were clinical keratoconus. The overall success rate of all treatment modalities was 87.4%. Contact lenses were the most frequent treatment modality (147 eyes, 72.4%) with the highest success rate (90.5%). A worse initial BCVA, high keratometric reading and thinner cornea were risk factors for treatment failure in this group. Of 133 eyes disease progression could be evaluated (median follow-up time; 33 months) and 58 eyes(43.6%) met criteria for disease progression (median survival time; 8.8 years). No significant factors were found to be associated with disease progression. Conclusion: Success rate in keratoconus treatment at Siriraj Hospital was 87.4%. Contact lenses were most frequently applied 72.4%. Factors associated with treatment failure were found in this group but for disease progressionremained unclear due to limitations of the study.

TB programme outcomes in South Fly District, Papua New Guinea, were maintained through COVID-19.

An established response to an outbreak of drug-resistant TB (DR-TB) on Daru Island, South Fly District (SFD), Western Province, Papua New Guinea (PNG). To describe and evaluate the trends in TB case notification disaggregated by demographic and clinical characteristics, programmatic interventions for TB and COVID-19 and treatment outcomes in 2017-2022. A cohort study of routinely collected programmatic data of all patients registered for TB treatment in SFD comparing pre-COVID (2017-2019) to COVID (2020-2022) periods. Of the 3,751 TB cases registered, 19.6% had DR-TB, and the case notification rate was 1,792/100,000 for Daru and 623/100,000 for SFD. There was a 29.2% reduction in case notifications from 2019 to 2021, with recovery in 2022. During COVID, the healthcare workforce was adversely impacted, and active TB case-finding was stopped. During COVID, compared to pre-COVID, bacteriological confirmation increased (62.3% to 71.9%), whereas rates of child TB notifications (11.6% to 9.1%), pulmonary TB (60.8% to 57.4%) and DR-TB (20.7% to 18.6%) decreased. High rates of treatment success were maintained for both drug-susceptible (86.5%) and DR-TB (83.6%). Health systems strengthening and community engagement before COVID likely contributed to resilience and mitigated potential impacts on TB in this remote and resource-limited setting. Case notifications remain very high, and additional interventions are needed to interrupt transmission.

Impact of financial support on treatment outcomes of multidrug-resistant tuberculosis: A population-based, retrospective cohort study in Shanghai, China

BackgroundTo date, the prolonged treatment duration and expensive second-line anti-tuberculosis drugs (SLDs) for multidrug-resistant tuberculosis (MDR-TB) can impose a significant financial burden, which may negatively impact treatment outcomes. This study examines the effect of a subsidy policy on treatment outcomes of MDR-TB patient.. MethodsWe collected demographic and drug resistance data of all registered MDR-TB patients between April 2011 and December 2019 in Shanghai, China. Documentation of financial support received was routinely maintained until December 2021. We employed multivariate logistic regression to assess the association between financial support and treatment outcomes, estimating odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). ResultsOf the 865 patients, 70.6% (611/865) achieved treatment success. The median amount compensated under the subsidy policy was 2359 United States dollar (USD), with an interquartile range from 1116 to 5652 USD. A positive association was found between benefiting from the subsidy policy and higher rate of treatment success, with an adjusted OR of 2.95 (95% CI, 2.03–4.28). Among the 641 patients covered by the policy, the adjusted OR comparing those with higher versus lower reimbursement was 1.74 (95% CI, 1.16–2.61). ConclusionsFinancial support policies for MDR-TB patients demonstrate a positive influence on treatment outcomes.

Endovascular treatment of non-acute symptomatic anterior circulation distal medium artery disease

Objective: To examine the clinical effect of endovascular treatment for patients with non-acute symptomatic anterior circulation distal medium artery disease (aDMAD). Methods: This is a retrospective case series study.Retrospective analysis was conducted on the clinical data of 28 patients(29 lesions) with non-acute symptomatic aDMAD who underwent endovascular treatment at the Department of Neurosurgery,Beijing Hospital from May 2018 to March 2024. There were 15 males and 13 females,with an age of (63.4±10.2) years (range:36 to 82 years). The course of disease were more than 72 hours of all the patients. Confirmed by digital subtraction angiography,the lesion was located in distal anterior circulation and (or) medium arteries. Among them, 21 lesions (72.4%) located at middle cerebral artery and 8 lesions (27.6%) located at anterior cerebral artery.The median degree of stenosis before surgery (M(IQR)) was 90%(23%) (range:70% to 100%).After standardized drug treatment,there was still a transient ischemic attack or cerebral infarction in the vascular related area.The therapeutic effects and complications were analyzed,and the differences in the occurrence of target vessel restenosis under different interventional treatment methods were collected. Results: A total of 28 patients with 29 lesions underwent endovascular treatment, with a treatment success rate of 96.6% (28/29). The course of disease was 60(66)days (range:9 to 210 days). Simple plain balloon angioplasty was performed in 12 cases (13 lesions), drug-coated balloon (DCB) angioplasty in 7 cases (7 lesions), and stent placement in 9 cases (9 lesions). The median degree of stenosis after surgery was 20%(39%) (range:0 to 50%). There was no new cerebral infarctions,cerebral hemorrhages,or other complications during the perioperative period.Imaging follow-up was conducted on 23 lesions for 12(15)months(range:3 to 34 months),with 10 cases (43.5%) of restenosis,3 cases (13.0%) of symptomatic restenosis,and 4 cases (17.4%) of re-treatment. There were no new cases of cerebral hemorrhage or death during the follow-up process.The restenosis rate was 6/10 for the conventional balloon group,1/6 for the DCB group, and 3/7 for the stent group; the rate of symptomatic restenosis was 1/10 for the conventional balloon group,0/6 for the DCB group, and 2/7 for the stent group. Conclusions: Endovascular treatment for non-acute symptomatic aDMAD is relatively effective,but there is a high rate of restenosis postoperatively. DCB may reduce the occurrence of postoperative restenosis.

Social and health factors associated with unfavourable treatment outcomes in children and adolescents with drug-sensitive tuberculosis in Brazil: a national retrospective cohort study

Although tuberculosis (TB) poses a significant global health threat to children and adolescents, there is limited information on the factors associated with TB treatment outcomes in this group. This study investigated the social and health factors associated with unfavourable treatment outcomes in children and adolescents with TB in Brazil, a high TB burden country. We conducted a population-based national retrospective cohort study of children (0-9 years) and adolescents (10-17 years) with TB in Brazil notified to the national Sistema de Informação de Agravos de Notificação (Sinan) from Jan 1, 2001, to Dec 31, 2022. Unfavourable treatment outcomes were defined as loss to follow-up, treatment failure, and death. Logistic regression and multinomial models examined the association between social and health factors, unfavourable treatment outcomes overall, and loss to follow-up and death, respectively. A total of 88,270 children and adolescents with TB were included of whom 25,600 (30.6%) had healthcare worker-supervised directly observed therapy (DOT). Of these, 9303 (10.5%) individuals experienced unfavourable TB treatment outcomes. For children, HIV infection (adjusted Odds Ratio 2.4, 95% confidence interval 1.9-3.1) and did not receive DOT (2.3, 1.9-2.7) were associated with unfavourable treatment outcomes. For adolescents, alcohol use (1.6, 1.2-2.0), illicit drug use (4.2, 3.4-5.1), tobacco use (1.6, 1.3-2.1), HIV infection (2.7, 2.2-3.4), and not receiving DOT (2.6, 2.3-2.9) were associated with unfavourable TB treatment outcome. Receiving social protection through government cash transfers protected against death (0.5, 0.3-0.9). In Brazil, TB treatment success rates were comparable to WHO End TB Strategy targets (90%). Substance use, HIV infection, and the absence of supervised treatment were the main factors associated with unfavourable treatment outcomes. Strategies to improve equity of TB treatment outcomes in this vulnerable group, including integrated HIV-TB services, DOT in healthcare facilities or communities, and holistic, person-centred healthcare and social protection, should be evaluated. Department of Health and Social Care (DHSC), the Foreign, Commonwealth & Development Office (FCDO), the Medical Research Council (MRC) and Wellcome, UK.

A 10-Year Follow-Up of Reconstructive Treatment of Peri-Implantitis Using Mineralized Dehydrated Allograft and Resorbable Membrane: A Retrospective Case Series.

To evaluate the 10-year clinical and radiographic outcomes of peri-implantitis intrabony defects treated with mineralized dehydrated bone allograft (MDBA) and resorbable membrane in patients undergoing a regular supportive peri-implant/periodontal therapy (STP). The original study participants were 34 (34 defects). After mechanical debridement and chemical decontamination of implant surfaces, intrabony defects were filled with MDBA and covered by a resorbable membrane. Patients were enrolled in a maintenance program with a recall interval of 6 months. The primary outcome was the absence of additional marginal peri-implant bone loss ≥ 1.0 mm after surgery. The composite outcome was no additional marginal peri-implant bone loss ≥ 1.0 mm and the absence of probing depth (PD) ≥ 5 mm, bleeding on probing and suppuration. Of the original 34 implants, 20 completed the 10-year follow-up, and three failed. Related to the primary outcome, the mean peri-implant marginal bone level changed from 4.78 mm (SD 1.84) at baseline to 3.10 mm (SD 1.73) after surgery and 3.71 mm (SD 1.78) at the follow-up end point. According to the composite outcome for disease resolution, 19 of the 34 original implants were successfully treated at the 10-year follow-up with a statistically significant difference between 1 (31/34 implants) and 5 years (20/34 implants) (p = 0.003) and 1 and 10 years (p = 0.001) but not between 5 and 10 years (p = 1.000). Ten years after the reconstructive treatment, followed by regular SPT, the cumulative successful treatment rate, according to the primary and the composite outcomes, was 58% (20/34 implants) and 53% (19/34) implants, respectively.

Clinical Success of Pulpotomies Using Intermediate Restorations and Preformed Metal Crowns in the Context of a Developing Country: A Retrospective Questionnaire-Based Investigation

Background: Dental caries is one of the most prevalent dental illnesses in children. Untreated severe caries can damage teeth, requiring pulpotomy to save them. Objective: To evaluate the clinical success rate of treatments involving pulpotomies + IRM (Intermediate Restorative Material, composed of reinforced zinc oxide–eugenol polymers) + preformed metal crowns (PMCs) in primary teeth of children treated at a public university in Mexico. Materials and Methods: A cross-sectional ambispective study was conducted on children aged 10 years or younger, treated at a public university in Mexico. A total of 1281 medical records from February 2018 to June 2023 were reviewed, yielding a sample of 199 children treated with pulpotomy + IRM + PMC. Information was collected via telephone interviews with parents/caregivers to inquire about any symptoms following the pulpotomy and metal crown treatments. Success was defined as the absence of pain, inflammation, or infection. Results: During the study period, the number of teeth treated with pulpotomy + IRM + PMC was 414, with follow-ups ranging from 6 to 69 months. Most participants were girls (54.3%), while 45.7% were boys. Out of the 167 pulpotomy + IRM + PMC treatments included in the study, the clinical success rate was 98.2%. Conclusions: The clinical success rate of primary teeth treated with pulpotomy + IRM + PMCs was high, close to 100%, based on evidence and symptom reports from parents/caregivers. It would be beneficial to implement its use in public health institutions in countries such as Mexico.

Determinants of an unfavorable treatment outcome among tuberculosis patients in the Jimma Zone, Southwest Ethiopia.

Tuberculosis (TB) is a major public health challenge in Ethiopia. TB treatment outcomes were suboptimal compared to the expected target of the national TB control Program. The provision of standard anti-TB treatment is the primary component of the directly observed treatment, short-course strategy. The aim of this study was to assess the TB treatment outcomes and the determinants of an unfavorable treatment outcome. The study used a cross-sectional study design at baseline and record review to identify treatment outcomes. A total of 1,161TB patients were recruited from eight randomly selected districts and one town administration in the Jimma Zone, Ethiopia. Treatment outcomes were grouped into favorable and unfavorable. Of the total participants, 86.9% had a favorable treatment outcome, and 5.7% an unfavorable treatment outcome. The rest were transferred out and not recorded cases. Women were more likely to experience an unfavorable treatment outcome [adjusted odds ratio (AOR) = 1.96, 95% CI 1.06, 3.64]. Patients who were perceived to not be stigmatized were less likely to have an unfavorable treatment outcome (AOR = 0.32, 95% CI 0.15, 0.73). Patients who had a monthly income of > 3,500 Ethiopian birr were less likely to have an unfavorable outcome than patients who did not have a regular income (AOR = 0.04, 95% CI 0.01, 0.45). The observed treatment success rate is lower than the World Health Organization's target of successfully treating > 90% of detected TB cases. It is imperative to ensure that information, education and communication/behavior change communication strategies consider the needs of women and patients with perceived TB stigma. Furthermore, designing locally acceptable and affordable interventions may help to address the financial challenges of TB treatment adherence.

Plasma chemistry and hematology of Eastern Mediterranean Sea green turtles undergoing rehabilitation

Plasma chemistry and hematology of Eastern Mediterranean Sea green turtles undergoing rehabilitation

Efficacy of p62-expressing plasmid in treatment of canine osteoarthritis.

Introduction: Osteoarthritis (OA) is a progressive degenerative disease of synovial joints which is highly prevalent in dogs and results in lameness, loss of joint function and mobility, chronic pain, and reduced quality of life. Traditional OA management consist of non-steroidal anti-inflammatory drugs and remains challenging because of significant side effects, thus there is an urgent need for new effective and safe therapeutics for OA. Methods : Here we present the results of our one-arm open-label pilot clinical study of our novel biologics, a DNA plasmid encoding SQSTM/p62, in 17 companion dogs suffering from OA. The dogs were injected intramuscular with p62-plasmid once a week for 10 weeks, and pain relief was measured using the CBPI (canine brief pain inventory) validated scale. Assessment by the owners was done weekly. The 11 parameters of CBPI are grouped in three major domains: pain severity score (PSS), pain interference score (PIS) and overall impression of the quality of life (QoL). Results : Treatment with the p62-plasmid improved all 11 parameters of CBPI as well as PSS, PIS and QoL: mean PSS score after the treatment decreased from 5.25 to 3.25, PIS score - from 7.0 to 3.27, and number of dogs with excellent and good QoL due to treatment increased from 1 to 12. Overall, the treatment success rate (i.e. a reduction > 1 in PSS and > 2 in PIS) was 90%. Importantly, similar to our previous studies with dogs and humans, no significant side effects of the p62-plasmid during the whole treatment period were observed. Discussion: We believe that anti-inflammatory effects of the p62-plasmid, which we described in our previous works, may play an important role in observed clinical benefits and it is worthy of further studies as a novel OA treatment modality.

A Meta-Analysis and Meta-Regression of Embolisation Outcomes of Pulmonary Arteriovenous Malformations.

Embolisation is a widely utilised therapeutic intervention for pulmonary arteriovenous malformation (PAVM). We conducted a meta-analysis to evaluate outcomes of PAVM embolisation and factors associated with embolisation outcomes. MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from 2000 to July 2022 on studies that assessed embolisation outcomes of PAVM. Immediate technical success rate defined as the complete occlusion of the PAVM at the time of embolisation and treatment success rate defined as ≥ 70% venous sac reduction on follow-up imaging were pooled from included studies with use of random effects proportion meta-analysis. Heterogeneity across studies was assessed with the I2 statistic. Forty-four studies including 1865 patients (604 (32%) males, mean age (range) 45 (24-59) years, 1125 (60%) had hereditary haemorrhagic telangiectasia (HHT)) were included in the meta-analysis. Studies included a total of 4314 PAVMs of which 4047 (94%) were treated. Studies reported morphology of 3074 PAVMs (2519 (58%) simple and 555 (13%) complex). The pooled overall immediate technical success rate for PAVM embolisation was 99%, 95% CI (98-100%) and the treatment success rate was 86%, 95% CI (84-89%). Younger age (p = 0.041), simple PAVM (0.020), and embolisation using plugs (p = 0.001) were associated with higher treatment success. Feeding artery and sac embolisation (p = 0.021) and using coils (p = 0.001) were associated with lower treatment success. There was no significant difference in recanalisation rate between different embolisation agents (OR 0.64, 95% CI -0.09- 1.38). This meta-analysis shows that PAVM embolisation is safe and effective. Higher treatment success rates for PAVM embolisation can be achieved using plugs as the primary embolisation agent. Embolisation agent used had no effect on recanalisation rates.

Fixed-Combination Halobetasol Propionate 0.01% and Tazarotene 0.045% Lotion and Halobetasol Propionate 0.01% Lotion for Plaque Psoriasis on Areas With Body Hair: Maintenance of Treatment Effect

Background: Psoriasis on hair-bearing body areas may be difficult to treat with topical therapy, as hair may reduce penetration of active ingredients.1 Patients may also experience disease rebound following cessation of corticosteroid therapy.2,3 An appropriate vehicle for hair-bearing areas may increase penetration, and a combination of corticosteroid and tazarotene may improve maintenance of treatment effect following cessation.4-6 Fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) and HP 0.01% lotion are indicated for treatment of plaque psoriasis in adults7,8 and contain a vehicle optimized for penetration.6,9 Previously, a post hoc analysis demonstrated the efficacy and safety of HP/TAZ and HP in treating men with plaque psoriasis on the leg, a representative area with body hair.10 Here, we expand on the previous study by reporting maintenance of efficacy following treatment cessation in this population. Methods: In phase 3 trials, participants with moderate-to-severe plaque psoriasis were randomized to treatment or vehicle once daily for 8 weeks (HP/TAZ, n=276; vehicle, n=142; HP, n=285; vehicle, n=145). Participants were assessed at 2-week intervals and at 4 weeks after treatment cessation (week 12).11,12 In this post hoc analysis, treatment success (≥2-grade improvement in investigator’s global assessment score and score of clear or almost clear); erythema, plaque elevation, and scaling success (≥2-grade improvement for each); and safety were assessed in men with psoriasis on the leg treated with HP/TAZ (n=87) or HP (n=91). Maintenance of effect was defined as the proportion of participants who achieved treatment, erythema, plaque elevation, or scaling success at week 8 and maintained success at week 12. Men were assumed to have leg hair. Treatment comparisons were indirect. Results: Four weeks after treatment cessation, HP/TAZ–treated participants exhibited increased rates of treatment success (week 8, 35.3%; week 12, 37.2%) and erythema success (week 8, 37.4%; week 12, 48.4%), whereas HP-treated participants exhibited decreased rates (treatment success: week 8, 35.5%; week 12, 23.1%; erythema success: week 8, 50.6%; week 12, 36.5%). HP/TAZ–treated participants exhibited less attrition in plaque elevation and scaling success after treatment cessation (week 8, 57.4% and 56.3%; week 12, 55.1% and 55.8%, respectively) versus HP-treated participants (week 8, 53.1% and 61.7%; week 12, 39.8% and 41.6%, respectively). For all outcomes, a greater proportion of participants receiving HP/TAZ achieved maintenance of effect from weeks 8 to 12 compared with participants receiving HP (range: HP/TAZ, 74%-85%; HP, 56%-62%). No new safety signals were identified. Conclusions: Following treatment cessation of HP/TAZ, men with plaque psoriasis on the leg experienced further disease improvement and maintained treatment effects at greater rates than those treated with HP, suggesting that tazarotene combined with HP provides prolonged efficacy in hair-bearing areas.

Efficacy and Safety of Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel: Post Hoc Analysis by Baseline Disease Severity

Introduction: Clindamycin phosphate (CLIN) 1.2%/adapalene (ADAP) 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) is the only triple-combination topical treatment approved for acne. These analyses assessed efficacy and safety of CAB gel by baseline acne severity vs component dyads and branded ADAP/BPO gel. Methods: These post hoc analyses used data pooled from two phase 2 and two phase 3, double-blind, 12-week studies (NCT03170388, NCT04892706, NCT04214639, NCT04214652). Eligible participants aged ≥9 years (≥12 years in NCT04892706) were randomized to once-daily CAB or vehicle gel. One phase 2 study included dyad combinations of CAB’s active ingredients: ADAP/BPO, CLIN/BPO, and CLIN/ADAP. The other phase 2 study included a head-to-head comparison of CAB gel and branded ADAP 0.3%/BPO 2.5% gel. Efficacy assessments included least-squares mean percent change from baseline in inflammatory/noninflammatory lesions and treatment success (≥2-grade reduction from baseline in Evaluator’s Global Severity Score [EGSS] and clear/almost clear skin). Safety assessments included treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability. Participants were categorized by baseline disease severity: moderate (EGSS = 3; n=1557) or severe (EGSS = 4; n=230). Results: After 12 weeks, inflammatory lesion reductions in participants with moderate acne were significantly greater with CAB (77.1%) than vehicle (54.1%; P<0.001), the 3 dyads (range, 64.4-69.4%; P≤0.001, all), and branded ADAP/BPO (72.8%; P<0.05). In the severe group, inflammatory lesion reductions with CAB (74.5%) were significantly greater than vehicle (44.4%; P<0.001) and 2 dyads (ADAP/BPO 63.9%, CLIN/BPO 61.3%; P<0.05), and similar to branded ADAP/BPO and CLIN/ADAP (75.4%/73.7%). Reductions in inflammatory lesions were greater than noninflammatory. Over half of CAB-treated participants with moderate disease achieved treatment success at week 12 (53.9% vs 19.5% vehicle; P<0.001), significantly greater than approximately one-third treated with dyads (range, 31.5-35.3%) or branded ADAP/BPO (38.1%; P≤0.001, all). Only CAB and CLIN/ADAP demonstrated significantly greater treatment success rates than vehicle in participants with severe acne at week 12 (30.9% and 34.0% vs 9.0%, respectively, P<0.05). Across all groups, most TEAEs were of mild to moderate severity. Mean cutaneous safety/tolerability scores were ≤1 (1 = mild) across severity groups. Conclusions: CAB gel demonstrated efficacy and safety in participants with both moderate and severe acne. Acne improvements with CAB were superior to the 3 dyads tested and branded ADAP/BPO in participants with moderate acne and generally numerically greater in participants with severe acne. To our knowledge, these analyses of combination topical acne treatments include data from the only double-blind, vehicle-controlled, head-to-head study to date. Funding: Ortho Dermatologics.

Trends of drug-resistant tuberculosis and risk factors to poor treatment-outcome: a database analysis in Littoral region-Cameroon, 2013-2022.

Tuberculosis(TB), currently has limited treatment options, and faces worldwide threat of drug-resistance(DR). In 2022, the DR-TB prevalence in Cameroon was 1.4% among new-cases and 8.3% among retreatment-cases. We analyzed the DR-TB database to descript the trends and DR-TB profile, treatment-outcome and associated risk-factors so-as-to propose measures to enhance program performance in Cameroon. We conducted a retrospective cohort study, analysed the DR-TB database of the Littoral region from 2013 to 2022. We appreciated the data-quality using zero-reporting, completeness, consistency, and validity indicators. We categorized DR-TB into Rifampicin-resistant-TB(RR-TB), multi-drug-resistant-TB(MDR-TB), pre-extensive-drug-resistant-TB(pre-XDR-TB), and XDR-TB and performed descriptive statistics. We assessed DR-TB treatment outcome targeting > 80% cure and/or completed treatment. Multiple logistic regression was used to determine risk factors related to poor treatment outcomes, and adjusted relative risk(RR) was considered significant at p < 0.05. Overall database quality was 93.7% with uniqueness 100%, data-completeness 82.5%, consistency 97% and validity 95.1%. A total of 567 DR-TB cases were reported, with median age of 34 (1-80) years, male-to-female sex ratio (3:2). Cases were classified as 19(3.4%) RR-TB, 536(94.6%) MDR-TB, 7(1.3%) pre-XDR-TB, and 4(0.7%) XDR-TB. Case-reporting increased from 2013, reaching their peak in 2018. The overall treatment refusal rate was 123(11.9%) and treatment outcomes of 270(60.8%) cured, 116(26.4%) completed, 32(7.2%) deaths, 19(4.3%) lost-to-follow-up, and 6(1.4%) failure were recorded. We identified 84 dead (CFR:14.8%) amongst whom 52(62%) refused treatment, 17(20%) occurred during the first month of therapy and 13(15.5%) HIV-TB co-infected. Male gender [p = 0.006, RR = 2.5 (95% CI: 1.3-4.7)], HIV positive status [p = 0.012, RR = 2.1 (95% CI: 1.2-3.7)], and previous DR-TB status [p = 0.02, RR = 3.9 (95% CI: 1.3-12.0)] were statistically associated to poor treatment outcomes. In the Littoral Region-Cameroon, cases of DR-TB increased from 2013, reaching their peak in 2018 befor dropping right up to 2022. RR-TB, MDR-TB, Pre-XDR-TB and XDR-TB represented 3.4%, 94.6%, 1.3% and 0.7% of all reported DR-TB cases. Overall, DR-TB treatment success rate was 87.2%. Male-gender, HIV-positive status, and previous DR-TB are associated with poor TB treatment outcomes. We recommend universal drug susceptibility testing to ensure early/maximum DR-TB case-detection and proper pre-treatment counselling to limit the high death rates and anti-TB treatment refusal rates which are setbacks from achieving end-TB strategies.

Cell type specific drug repurposing for breast cancer by integrating single-cell RNA sequencing and molecular docking simulation

Abstract. Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related deaths among women. Despite the widespread use of chemotherapy and radiotherapy, there is an urgent need for novel treatments. This study focuses on drug repurposing for breast cancer using single-cell RNA sequencing (scRNA-seq) data. By analyzing differentially expressed genes across various breast cancer cell types, we identified potential protein targets. We then used Drug2cell to generate top cancer-related drug candidates, followed by molecular featurization of proteins and drugs. Drug-target interactions were analyzed through molecular docking, and the top drug candidates for each cell type were ranked. Our data analysis annotated ten cell types from breast cancer scRNA-seq data. Using the top ten differentially expressed genes, we identified over a hundred protein targets and conducted molecular docking analysis. Fourteen drugs, including doxorubicin and everolimus, were repurposed with supporting clinical evidence for their effectiveness in breast cancer treatment. Overall, this drug-repurposing strategy, combined with scRNA-seq data, identified several cell-type-specific drugs, enhancing therapeutic target discovery and improving treatment success rates for breast cancer.

OGC SO19 - Management and outcomes for Barrett’s oesophagus with dysplasia in a tertiary centre

Abstract Background Barrett’s oesophagus is a premalignant condition. Development of high-grade dysplasia (HGD) formerly was an indication for oesophagectomy, but endoscopic treatment (ET) is now recommended as first-line therapy: radiofrequency ablation (RFA) or endoscopic mucosal resection (EMR). Oesophagectomy is only considered for cases where ET was unsuccessful. Previous review of our institution’s outcomes between 2014 and 2017 showed a 54% complete EMR excision rate and 20% salvage oesophagectomy (n=25). Since then, RFA has been utilised in our institution. We aimed to review our recent data to assess current outcomes. Method Retrospective analysis was performed of patients identified via registration at the Hull University Hospital Trust oesophagogastric MDT between March 2017 and December 2023. Inclusion criteria was confirmed histology of HGD on 2 occasions by 2 specialist pathologists, 6 weeks apart. EMR was performed for focal oesophageal lesions and non-nodular segments were treated by RFA. Patients were included once they had at least one surveillance endoscopy and 6 months had passed following treatment. Patients who were either unfit for ET and managed medically (n=6), and those who were subsequently proven to have more advanced disease and treated surgically (n=4) were excluded. Results 35 patients were identified: 20 underwent EMR, 15 RFA. 55% of EMR patients had successful excision, 9 required additional RFA for residual low-grade dysplasia (LGD). 66% RFA patients had successful ablation. 3 patients required further EMR for residual LGD. Overall 82% had successful ET with no HGD on surveillance. 5 patients had persistent HGD and 1 T1b disease: 4 underwent oesophagectomy, 2 managed oncologically. Barrett’s tended towards being longer in patients where ET failed to eradicate HGD (median 6cm vs 3cm MWU p=0.07). No patient in the series died because of disease-related pathology. 1 patient developed stricture post-RFA requiring dilatation. Conclusion ET for HGD is effective with a high rate of successful treatment. It can be used as a single or dual modality. Salvage oesophagectomy rates are lower than previously reported (8% vs 20%) and complications are low (3% stricture rate). Longer segment Barrett’s may be less likely be responsive to ET, although not reaching significance in our series. ET should continue to be offered as the first-line treatment for oesophageal HGD.