Primary Effectiveness Measure Research Articles

Intradermal Injection of Tranexamic Acid for the Treatment of Adult Melasma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Melasma is a chronic skin pigmentation disorder, and intradermal injection of tranexamic acid (TXA) is an effective treatment option for melasma with limited comparative efficacy studies. Objectives: To compare the effectiveness of TXA injections with other treatment modalities for patients with melasma, as measured by Melasma Area and Severity Index (MASI). Methods: A total of 17 eligible randomized controlled trials were included in the meta-analysis. The MASI and the modified MASI served as the primary outcome measures of treatment effectiveness. Patient satisfaction was also evaluated. Results: Among the various administration routes for TXA, intradermal injection and microneedling demonstrated superior effectiveness, followed by oral administration and topical application. As for patient satisfaction, oral administration outperformed the injection method, whereas topical administration significantly underperformed injection. Furthermore, TXA injections were more effective than the majority of non-TXA standard treatments for melasma. Conclusions: This meta-analysis and systematic review suggested that intradermal TXA injection is an effective alternative for melasma treatment, with potential advantages over other administration routes.

Exploring dysregulated miRNAs in ALS: implications for disease pathogenesis and early diagnosis.

Amyotrophic lateral sclerosis(ALS) is a progressive neurodegenerative disease marked by motor neuron degeneration, leading to muscle weakness and paralysis, with no effective treatments available. Early diagnosis could slow disease progression and optimize treatment. MicroRNAs(miRNAs) are being investigated as potential biomarkers due to their regulatory roles in cellular processes and stability in biofluids. However, variability across studies complicates their diagnostic utility in ALS. This study aims to identify significantly dysregulated miRNAs in ALS through meta-analysis to elucidate disease mechanisms and improve diagnostic strategies. We systematically searched PubMed, Google Scholar, and the Cochrane Library, following predefined inclusion and exclusion criteria. The primary effect measure was the standardized mean difference (SMD) with a 95% confidence interval, analyzed using a random-effects model. Additionally, we used network pharmacology to examine the targets of dysregulated miRNAs and their roles in ALS pathology. Analysing 34 studies, we found significant upregulation of hsa-miR-206, hsa-miR-133b, hsa-miR-23a, and hsa-miR-338-3p, and significant downregulation of hsa-miR-218, hsa-miR-21-5p, and hsa-let-7b-5p in ALS patients. These miRNAs are involved in ALS pathophysiology, including stress granule formation, nuclear pore complex, SMCR8 and Sig1R dysfunction, histone methyltransferase complex alterations, and MAPK signaling perturbation, highlighting their critical role in ALS progression. This study identifies several dysregulated miRNAs in ALS patients, offering insights into their role in the disease and potential as diagnostic biomarkers. These findings enhance our understanding of ALS mechanisms and may inform future diagnostic strategies. Validating these results and exploring miRNA-based interventions are crucial for improving ALS diagnosis and treatment outcomes.

Cost Effectiveness of Tremelimumab Plus Durvalumab for Unresectable Hepatocellular Carcinoma in the USA.

Treating unresectable hepatocellular carcinoma (uHCC) is challenging. Clinical trials have shown that Single Tremelimumab Regular Interval Durvalumab (STRIDE) offers clinical benefits as a first-line treatment for uHCC, but its cost effectiveness remains unknown in the USA. We aimed to assess the cost effectiveness of STRIDE (tremelimumab plus durvalumab) versus sorafenib and durvalumab monotherapy as the first-line treatment for uHCC in the USA. A partitioned survival model was constructed to assess the cost effectiveness of STRIDE compared to sorafenib and durvalumab monotherapy as the first-line treatment for uHCC from the US societal perspective. The time horizon was 48 months with 1-month cycles. Seven parametric survival functions replicated survival curves from clinical trials, with the best-fitting model used to calculate survival probabilities. Costs, health utilities, and adverse events were included, with quality-adjusted life-years (QALYs) as the primary effectiveness measure. Both costs and effectiveness were discounted at 3%. In the base-case analysis, the incremental cost-effectiveness ratio was compared to a willingness-to-pay threshold of $150,000 per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to examine the uncertainty of the model. In the base-case analysis, STRIDE was cost effective compared to sorafenib, with an incremental cost-effectiveness ratio of $97,995.51 per QALY gained, based on a willingness-to-pay threshold of $150,000 per QALY gained. However, STRIDE was not cost effective compared to durvalumab monotherapy at the same threshold, with an incremental cost-effectiveness ratio of $754,408.92 per QALY gained. Deterministic sensitivity analyses were consistent with the base-case analysis. A probabilistic sensitivity analysis indicated that STRIDE was more likely to be cost effective than sorafenib and durvalumab monotherapy when the willingness-to-pay exceeded $101,000 and $713,000, respectively. The STRIDE regimen appears to be cost effective compared to sorafenib but not compared to durvalumab for first-line uHCC treatment in the USA. However, durvalumab has not yet been approved for uHCC in the USA. Future research should focus on long-term data and economic evaluations of other recommended biologics.

Oral Cannabis Extract for Secondary Prevention of Chemotherapy-Induced Nausea and Vomiting: Final Results of a Randomized, Placebo-Controlled, Phase II/III Trial.

The aim of this randomized, placebo-controlled, two-stage, phase II/III trial was to determine the efficacy of an oral cannabis extract in adults with refractory nausea and/or vomiting during moderately or highly emetogenic, intravenous chemotherapy despite guideline-consistent antiemetic prophylaxis. Here, we report results of the prespecified combined analysis including the initial phase II and subsequent phase III components. Study treatment consisted of oral capsules containing either tetrahydrocannabinol 2.5 mg plus cannabidiol 2.5 mg capsules (THC:CBD) or matching placebo, taken three times a day from days -1 to 5, in addition to guideline-consistent antiemetics. The primary measure of effect was the difference in the proportions of participants with no vomiting or retching and no use of rescue medications (a complete response) during hours 0-120 after the first cycle of chemotherapy on study (cycle A). We recruited 147 evaluable of a planned 250 participants from 2016 to 2022. Background antiemetic prophylaxis included a corticosteroid and 5-hydroxytryptamine antagonist in 97%, a neurokinin-1 antagonist in 80%, and olanzapine in 10%. THC:CBD compared with placebo improved the complete response rate from 8% to 24% (absolute difference 16%, 95% CI, 4 to 28, P = .01), with similar effects for absence of significant nausea, use of rescue medications, daily vomits, and the nausea scale on the Functional Living Index-Emesis quality-of-life questionnaire. More frequent bothersome adverse events of special interest included sedation (18% v 7%), dizziness (10% v 0%), and transient anxiety (4% v 1%). There were no serious adverse events attributed to THC:CBD. THC:CBD is an effective adjunct for chemotherapy-induced nausea and vomiting despite standard antiemetic prophylaxis, but was associated with additional adverse events. Drug availability, cultural attitudes, legal status, and preferences may affect implementation. Future analyses will evaluate the cost-effectiveness of THC:CBD.

Dosimetry for repetitive transcranial magnetic stimulation: a translational study from Alzheimer's disease patients to controlledin vitroinvestigations.

Objective.Recent studies have indicated that repetitive transcranial magnetic stimulation (rTMS) could enhance cognition in Alzheimer's Disease (AD) patients, but to now the molecular-level interaction mechanisms driving this effect remain poorly understood. While cognitive scores have been the primary measure of rTMS effectiveness, employing molecular-based approaches could offer more precise treatment predictions and prognoses. To reach this goal, it is fundamental to assess the electric field (E-field) and the induced current densities (J) within the stimulated brain areas and to translate these values toin vitrosystems specifically devoted in investigating molecular-based interactions of this stimulation.Approach.This paper offers a methodological procedure to guide dosimetric assessment to translate the E-field induced in humans (in a specific pilot study) intoin vitrosettings. Electromagnetic simulations on patients' head models and cellular holders were conducted to characterize exposure conditions and determine necessary adjustments forin vitroreplication of the same dose delivered in humans using the same stimulating coil.Main results.Our study highlighted the levels of E-field andJinduced in the target brain region and showed that the computed E-field andJwere different among patients that underwent the treatment, so to replicate the exposure to thein vitrosystem, we have to consider a range of electric quantities as reference. To match the E-field to the levels calculated in patients' brains, an increase of at least the 25% in the coil feeding current is necessary whenin vitrostimulations are performed. Conversely, to equalize current densities, modifications in the cells culture medium conductivity have to be implemented reducing it to one fifth of its value.Significance.This dosimetric assessment and subsequent experimental adjustments are essential to achieve controlledin vitroexperiments to better understand rTMS effects on AD cognition. Dosimetry is a fundamental step for comparing the cognitive effects with those obtained by stimulating a cellular model at an equal dose rigorously evaluated.

Assessing the efficacy of Laser pulpotomy versus conventional pulpotomy in primary teeth: A systematic review and meta-analysis of clinical trials.

This study systematically reviewed the clinical and radiographic outcomes of laser versus conventional pulpotomy in primary teeth. It also compared the success and effectiveness of different lasers to enhance the understanding and use of laser pulpotomy as an alternative treatment. An electronic search was carried out in PubMed and Cochrane from 1st January 1999 to 31st December 2023. The published articles in the English language were searched using MeSH terms and text words. Only randomized controlled trials with a sample size of more than 10 and follow-ups over 6 months were included. Meta-analysis and forest plots were evaluated by utilizing Review Manager 5.4 software. Two reviewers assessed the risk of bias using the RoB 2 tool and discrepancies were resolved by the third reviewer. The success rates were combined using a random effects model to determine clinical and radiographic outcomes. We used risk ratios with 95% confidence intervals (CI) as the primary effect measures and set the significance level at 0.05. Only 18 studies met the inclusion criteria after an electronic search. Among them, 13 studies evaluated the clinical and radiographic outcomes of laser with formocresol pulpotomy, 2 studies compared with ferric sulfate pulpotomy, and the remaining studies with Mineral trioxide aggregate (MTA) pulpotomy. The various studies showed different levels of bias. There was no significant difference in the clinical success rate (p = 0.47; RR: 1.01; 95% CI 0.98-1.04; I2 = 0%; p = 0.70) and radiographic success rate (p = 0.94; RR: 1.00; 95% CI 0.91-1.09; I2 = 64%; p = 0.001) between laser pulpotomy and formocresol. Similarly, there was no significant difference between laser pulpotomy and ferric sulfate or MTA pulpotomy. Diode laser and LLLT can be considered as alternative pulpotomy agents to formocresol in primary teeth. However, high-quality trials are needed to confirm the accuracy and reliability of these findings.

Lasers for the treatment of nail psoriasis: a systematic review.

This systematic review assesses the evidence concerning laser treatments for nail psoriasis (NP), a prevalent condition among individuals with cutaneous psoriasis that notably affects their quality of life. Traditional treatments have limitations in terms of drug delivery and poor patient adherence, leading to interest in laser therapies for their targeted approach, extended treatment intervals, and the potential to enhance topical medication effectiveness. The MEDLINE, Embase, Web of Science, and Cochrane Library databases were searched. English-language randomized and non-randomized controlled trials with full-text availability were included. Data on the laser type, treatment protocol, Nail Psoriasis Severity Index (NAPSI) outcomes, and adverse events were extracted, and nail bed and matrix features and patient satisfaction were assessed. The primary effect measure was a percentage reduction in NAPSI scores from baseline. Nineteen studies involving the pulse dye laser (PDL), long-pulsed neodymium:yttrium aluminum garnet (Nd:YAG) laser and fractional carbon dioxide laser (FCL) were identified. Lasers, particularly those used in conjunction with topical agents, have shown favorable results. PDL effectively lowered NAPSI scores, and the Nd:YAG laser had comparable effectiveness but more discomfort. FCL also shows promise, particularly for topical drug delivery. PDL and Nd:YAG laser treatment were more effective at reducing nail bed features, whereas FCL was effective at reducing both nail bed and matrix features. Overall, lasers are promising treatment alternatives for NP, with similar NAPSI outcomes to topical therapies and intralesional injections.

Cost-effectiveness of Transforaminal epidural steroid injections for patients with ACUTE sciatica: a randomized controlled trial

BackgroundTransforaminal epidural injections with steroids (TESI) are increasingly being used in patients sciatica. The STAR (steroids against radiculopathy)-trial aimed to evaluate the (cost-) effectiveness of TESI in patients with acute sciatica (< 8 weeks). This article contains the economic evaluation of the STAR-trial.MethodsParticipants were randomized to one of three study arms: Usual Care (UC), that is oral pain medication with or without physiotherapy, n = 45); intervention group 1: UC and transforaminal epidural steroid injection (TESI) 1 ml of 0.5% Levobupivacaine and 1 ml of 40 mg/ml Methylprednisolone and intervention group 2: UC and transforaminal epidural injection (TEI) with 1 ml of 0,5% Levobupivacaine and 1 ml of 0.9% NaCl (n = 50). The primary effect measure was health-related quality of life. Secondary outcomes were pain, functioning, and recovery. Costs were measured from a societal perspective, meaning that all costs were included, irrespective of who paid or benefited. Missing data were imputed using multiple imputation, and bootstrapping was used to estimate statistical uncertainty.ResultsNone of the between-group differences in effects were statistically significant for any of the outcomes (QALY, back pain, leg pain, functioning, and global perceived effect) at the 26-weeks follow-up. The adjusted mean difference in total societal costs was €1718 (95% confidence interval [CI]: − 3020 to 6052) for comparison 1 (intervention group 1 versus usual care), €1640 (95%CI: − 3354 to 6106) for comparison 2 (intervention group 1 versus intervention group 2), and €770 (95%CI: − 3758 to 5702) for comparison 3 (intervention group 2 versus usual care). Except for the intervention costs, none of the aggregate and disaggregate cost differences were statistically significant. The maximum probability of all interventions being cost-effective compared to the control was low (< 0.7) for all effect measures.ConclusionThese results suggest that adding TESI (or TEI) to usual care is not cost-effective compared to usual care in patients with acute sciatica (< 8 weeks) from a societal perspective in a Dutch healthcare setting.Trial registrationDutch National trial register: NTR4457 (March, 6th, 2014).

Effectiveness, cost-effectiveness and return on investment of individual placement and support compared with traditional vocational rehabilitation for individuals with severe mental illness in the Netherlands: a nationwide implementation study

ObjectivesTo assess the effectiveness, cost-effectiveness and return on investment of individual placement and support (IPS) implemented through a reimbursement strategy on a nationwide scale compared with traditional vocational rehabilitation (TVR)...

Cost-effectiveness analysis of margin-controlled surgery for vulvar Paget’s disease

ObjectivesTo determine the cost of two surgical treatment approaches for vulvar Paget’s disease and model the cost-effectiveness considering differences in recurrence and reoperation over time. MethodsWe assessed cost-effectiveness between excision guided by Mohs micrographic surgery (MMS-E) and traditional wide local excision (WLE). We examined billing data from patients with vulvar Paget’s disease who underwent MMS-E (cases, n = 24, 2018–2022) or WLE (controls, n = 64, 1990–2020). We created typical treatment bundles incorporating physician-administered services and facility costs standardized to Medicare reimbursements in 2022 United States Dollars (USD). The primary measure of effectiveness was disease-free years of life. A secondary analysis estimated quality-adjusted life years (QALY). A Markov model simulated treatment pathways over a 10-year time horizon. Transition probabilities were based on institutional recurrence rates (3-year RR 6.7 % for MMS-E vs 34.1 % for WLE). We used a willingness-to-pay threshold of 100,000 USD per QALY. ResultsThe cost of a single surgical episode was 34,664 USD for MMS-E and 14,969 USD for WLE. In the setting of lower recurrence rates with MMS-E, the incremental cost was 12,789 USD per disease-free year gained. A secondary analysis incorporating QALY showed an incremental cost of 72,820 USD per QALY. ConclusionsMMS-E appears to be a cost-effective treatment for vulvar Paget’s disease compared to historic standard of care. Our ability to estimate quality of life gained by avoiding disease recurrence was limited by scant data for this rare condition; thus, future studies incorporating health utility values are needed to facilitate a more comprehensive analysis.

Digitally augmented, parent-led CBT versus treatment as usual for child anxiety problems in child mental health services in England and Northern Ireland: a pragmatic, non-inferiority, clinical effectiveness and cost-effectiveness randomised controlled trial

Anxiety problems are common in children, yet few affected children access evidence-based treatment. Digitally augmented psychological therapies bring potential to increase availability of effective help for children with mental health problems. This study aimed to establish whether therapist-supported, digitally augmented, parent-led cognitive behavioural therapy (CBT) could increase the efficiency of treatment without compromising clinical effectiveness and acceptability. We conducted a pragmatic, unblinded, two-arm, multisite, randomised controlled non-inferiority trial to evaluate the clinical effectiveness and cost-effectiveness of therapist-supported, parent-led CBT using the Online Support and Intervention (OSI) for child anxiety platform compared with treatment as usual for child (aged 5-12 years) anxiety problems in 34 Child and Adolescent Mental Health Services in England and Northern Ireland. We examined acceptability of OSI plus therapist support via qualitative interviews. Participants were randomly assigned (1:1) to OSI plus therapist support or treatment as usual, minimised by child age, gender, service type, and baseline child anxiety interference. Outcomes were assessed at week 14 and week 26 after randomisation. The primary clinical outcome was parent-reported interference caused by child anxiety at week 26 assessment, using the Child Anxiety Impact Scale-parent report (CAIS-P). The primary measure of health economic effect was quality-adjusted life-years (QALYs). Outcome analyses were conducted blind in the intention-to-treat (ITT) population with a standardised non-inferiority margin of 0·33 for clinical analyses. The trial was registered with ISRCTN, 12890382. Between Dec 5, 2020, and Aug 3, 2022, 706 families (706 children and their parents or carers) were referred to the study information. 444 families were enrolled. Parents reported 255 (58%) child participants' gender to be female, 184 (41%) male, three (<1%) other, and one (<1%) preferred not to report their child's gender. 400 (90%) children were White and the mean age was 9·20 years (SD 1·79). 85% of families for whom clinicians provided information in the treatment as usual group received CBT. OSI plus therapist support was non-inferior for parent-reported anxiety interference on the CAIS-P (SMD 0·01, 95% CI -0·15 to 0·17; p<0·0001) and all secondary outcomes. The mean difference in QALYs across trial arms approximated to zero, and OSI plus therapist support was associated with lower costs than treatment as usual. OSI plus therapist support was likely to be cost effective under certain scenarios, but uncertainty was high. OSI plus therapist support acceptability was good. No serious adverse events were reported. Digitally augmented intervention brought promising savings without compromising outcomes and as such presents a valuable tool for increasing access to psychological therapies and meeting the demand for treatment of child anxiety problems. Department for Health and Social Care and United Kingdom Research and Innovation Research Grant, National Institute for Health and Care (NIHR) Research Policy Research Programme, Oxford and Thames Valley NIHR Applied Research Collaboration, Oxford Health NIHR Biomedical Research Centre.

Cost-effectiveness analysis of adding tuberculosis household contact investigation on passive case-finding strategy in Southwestern Uganda.

The standard passive case-finding strategy implemented by most developing countries is inadequate to detect new cases of Tuberculosis. A household contact investigation is an alternative approach. However, there is limited cost-effectiveness data to support planning and implementation in low and middle-income countries. The study aimed to evaluate the cost-effectiveness of adding household contact investigation (HCI) to the passive case-finding (PCF) strategy in the Tuberculosis control program in Southwestern Uganda. We conducted an economic evaluation using a retrospective study approach and bottom-up costing (ingredients) techniques. It was a synthesis-based evaluation of existing data extracted from the District Health Information System (DHIS 2), TB registers, and a primary cost survey. The study compared two methods of Tuberculosis (TB) case finding (PCF and HCI) strategies. Regarding PCF, patients either self-reported their signs and symptoms or were prompted by healthcare workers. At the same time, HCI was done by home visiting and screening contacts of TB patients. Patients and household contacts presumed to have Tuberculosis were requested to produce samples for analysis. We applied a static decision-analytic modeling framework to examine both strategies' costs and effectiveness. The study relied on cost and probability estimates from National Tuberculosis (TB) program data, activity costs, and published literature. It was performed from the societal and provider perspectives over 1.5 years across 12 facilities in Ntungamo, Sheema, and Rwampara Districts. The primary effectiveness measure was the number of TB cases detected (yield) and the number needed to screen (NNS). The TB yield was calculated from the number of patients screened during the period under study. The incremental cost-effectiveness ratio (ICER) was expressed as cost in 2021 US$ per additional TB case detected. We did not apply a discount rate because of the short analytic time horizon. The unit costs of detecting a Tuberculosis case were US$ (United States dollar) 204.22 for PCF and US$ 315.07 for HCI. Patient and caregiver costs are five times more in PCF than in HCI [US$26.37 Vs. US$ 5.42]. The ICER was US$ 3,596.94 per additional TB case detected. The TB screening yields were 0.52% (1496/289140) for passive case finding and 5.8% (197/3414) for household contact investigation. Household contact investigation yield among children 0-14 Vs. 15+ years [6.2% Vs.5.4%] P = 0.04. The Yield among People living with HIV (PLHIV) Vs. HIV-negative [15.8% Vs.5.3%] P = 0.03 in HHCI. The PCF yield in men Vs. Women [1.12% Vs.0.28%] P<0.01. The NNS in PCF was 193 [95% CI: 186-294] and 17 [95% CI: 14-22] in HCI. Our baseline assumptions and the specific implementations of adding HCI to existing PCF programs in the context of rural African settings prove to be not cost-effective, rather than HCI as a strategy. HCI effectively identifies children and PLHIV with TB and should be prioritized. Meanwhile, the Passive case-finding strategy effectively finds men with TB and costs lower than household contact investigation.

Efficacy of the ExVent Accessory for the O2Vent Optima Oral Appliance in the Treatment of Obstructive Sleep Apnea

Study Objectives: An optional accessory for the O2Vent Optima mandibular advancement device, the ExVent, provides oral expiratory positive airway pressure (EPAP). Similar to nasal EPAP, oral EPAP results in passive airway dilatation, reducing flow limitation. The present study was conducted to evaluate the safety and efficacy of the ExVent accessory for the treatment of mild to moderate obstructive sleep apnea (OSA). Methods: This prospective, multicenter, open-label, single-arm study enrolled participants diagnosed with mild to moderate OSA (defined as apnea–hypopnea index [AHI] 5–29). During the Home Use Phase, study participants logged their hours of O2Vent Optima + ExVent usage at home over 3 months. Participants were then evaluated by in-laboratory polysomnogram while using the O2Vent Optima + ExVent. The primary effectiveness measure was a change in AHI relative to baseline while using the O2Vent Optima + ExVent. Results: Treatment with the O2Vent Optima + ExVent improved AHI by 62% on average, from 15.3 (interquartile range [IQR]: 11.5–19.5) to 5.8 (IQR: 3.9–6.8; p&lt;0.001). Mean oxygen saturation improved from 93.5%±1.2% to 94.6%±1.34% (p=0.006). The lowest oxygen saturation increased from 85% (IQR: 83%–87%) to 90% (IQR: 89%–95; p&lt;0.001). The overall treatment success rate (AHI&lt;5) was 66%, and the treatment response rate (&gt;50% reduction in AHI) was 77%. No excessive adverse events or device malfunction events were reported. Conclusions: Use of the O2Vent Optima with the ExVent oral EPAP accessory successfully reduced AHI in mild to moderate OSA with no significant adverse effects.

Cost and cost-effectiveness analysis of mass drug administration compared to school-based targeted preventive chemotherapy for hookworm control in Dak Lak province, Vietnam

School-based targeted preventive chemotherapy (PC), the main strategy for soil-transmitted helminths (STH) control, excludes other at-risk populations including adults and preschool children. Mass drug administration (MDA), covering all age groups, would bring additional health benefits but also requires greater investment. This cost survey and cost-effectiveness analysis compared MDA with school-based targeted PC for STH control in Dak Lak, Vietnam, where STH are endemic. A cost survey was conducted in 2020 to estimate the total and per person economic and financial cost of each strategy. Monte Carlo simulation accounted for uncertainty in cost estimates. The primary effectiveness measure was hookworm-related disability-adjusted life years (DALYs) averted, and secondary measures were hookworm infection-years averted and moderate-to-heavy intensity hookworm infection-years averted. A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of MDA compared to school-based targeted PC using a government payer perspective and a ten-year time horizon. One-way and probabilistic sensitivity analyses (PSA) were performed. Costs are reported in 2020 USD ($). The economic cost per person was $0.27 for MDA and $0.43 for school-based targeted PC. MDA in Dak Lak will cost $472,000 per year, while school-based targeted PC will cost $117,000. Over 10 years, MDA is estimated to avert an additional 121,465 DALYs; 4,019,262 hookworm infection-years, and 765,844 moderate-to-heavy intensity hookworm infection-years compared to school-based targeted PC. The ICER was $28.55 per DALY averted; $0.87 per hookworm infection-years averted, and $4.54 per moderate-to-heavy intensity hookworm infection-years averted. MDA was cost-effective in all PSA iterations. In areas where hookworm predominates and adults suffer a significant burden of infection, MDA is cost effective compared to school based targeted PC and is the best strategy to achieve global targets. The project was funded by the National Health and Medical Research Council (NHMRC) of Australia (Project Grant APP1139561) and JPCDT was supported by a UNSW Scientia PhD Scholarship.

Effectiveness and cost-effectiveness of a multimodal, physiotherapist-led, vocational intervention in people with inflammatory arthritis: study protocol of the Physiotherapy WORKs trial

BackgroundAlthough reduced work ability is a substantial problem among people with inflammatory arthritis (IA), work ability is an underexposed area in clinical practice. Evidence on vocational interventions in IA is limited, but favourable results of delivery by a physiotherapist (PT) warrant the need for further research. Therefore, we aim to evaluate the (cost-)effectiveness of a multimodal, PT-led, vocational intervention in (self-)employed people with IA compared to usual care.MethodsThis randomized controlled trial will include 140 people with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) who are (self-)employed and have reduced work ability (Work Ability Index – Single Item Scale (WAS) ≤ 7/10) and/or RA/axSpA related sick leave (≤ 6 months). Participants will be randomized 1:1 to the intervention or control condition (usual care). The intervention, delivered by primary care PTs, will be personalized to each patient, consisting of 10 to 21 sessions over 12 months. The intervention will be multimodal, comprising of 1) exercise therapy and a physical activity plan, 2) education/self-management support, 3) work-roadmap to guide participants in finding relevant other care, with optionally 4) online self-management course and 5) workplace examination. Assessments will be performed at baseline and after 3, 6, and 12 months. The primary outcome measure of effectiveness is work ability, as measured with the WAS at 12 months. For the cost-effectiveness analysis, the EuroQol (EQ-5D-5L), self-reported healthcare use, sick leave and productivity while at work will be used to estimate the trial based cost-utility from a societal perspective. A process evaluation, including assessments of adherence and treatment fidelity, will be undertaken using the registrations of the PTs and semi-structured interviews at 12 months follow-up in a random sample of the intervention group.DiscussionThe results of this study will provide insights in the (cost-)effectiveness of a multimodal, PT-led, vocational intervention in people with IA and a reduced work ability.Trial registrationThis study is registered in the International Clinical Trial Registry Platform (ICTRP) under number NL9343.

WTP6.4 Influence of Annual Record of Competence Progression panel profile on Differential Attainment

Abstract Introduction Differential Attainment (DA) refers to divergent achievements when related to protected traits. Annual Review of Competency Progression (ARCP) panels play a key role which compositions should reflect, yet no guidance exists on panel profile related to protected traits. This study aimed to evaluate the influence of panel profile on DA. Methods Anonymised ARCPs numbering 1090 in a UK Statutory Education Body (SEB) were examined and primary effect measure was ARCP Outcome (ARCPO) with satisfactory ARCPO classified as 1, 2 or 6, and unsatisfactory as 3 or 4. Results Satisfactory ARCPOs numbered 1005 and unsatisfactory 85. Median panel number was 7 (range 1-15, p&amp;lt;0.001). Median female percentage consultant representation was 18.2% (0% (Urology, Plastic &amp; Paediatric Surgery) to 40% (Core Surgery) and median ethnicity (BME) consultant representation 14.3% (0% (Vascular &amp; Neurosurgery) to 80% (Cardiothoracic Surgery). Multivariable analysis revealed: Trainee seniority (OR 0.800, p&amp;lt;0.001), SAC Liaison Member gender (OR 0.720, p=0.013) and Panel gender balance (N ARCP panel females, OR 10.695, p=0.003) to be independently associated with adverse ARCPO. Discussion Important two to five-fold variance in ARCP panels were found related to gender and ethnicity profile respectively with apparent significant impact on DA.

Comparison of COVID-19 Preprint and Peer-Reviewed Versions of Studies on Therapies for Critically Ill Patients.

Significant increases in the volume of preprint articles due to the COVID-19 pandemic, we examined the reliability of preprint articles compared to their peer-reviewed publications. Preprint articles evaluating experimental studies of select treatment options (anticoagulation, dexamethasone, hydroxychloroquine, remdesivir, and tocilizumab) for COVID-19 in the critically ill, available in a peer-reviewed publication were screened for inclusion within Altmetric (n = 2040). A total of 40 articles met inclusion criteria, with 21 being randomly selected for evaluation. The primary outcome of this evaluation was a change in a study's reported primary outcome or statistical significance between preprint and peer-reviewed articles. Secondary outcomes included changes in primary/secondary outcome effect size and change in study conclusion. One article (4.8%, 95% CI 0.12%-23.8%) had a change in the primary outcome. Seven articles (33.3%, 95% CI 14.6%-57.0%) had a change in the primary outcome's effect measure. Five studies (23.8%, 95% CI 8.2%-47.2%) had changes in statistical significance of at least one secondary outcome. Four studies (19.0%, 95% CI 5.4%-41.9%) had a change in study conclusion. In preprint articles of COVID-19 treatments, the provided primary outcome is generally reliable, while interpretation of secondary outcomes should be made with caution, while awaiting completion of the peer-review process.

Different efficacy of pembrolizumab in overall survival between Asians and non-Asians with advanced cancers: A systematic review and meta-regression analysis.

e13597 Background: Immune checkpoint inhibitors have revolutionized the treatment landscape of malignancy. However, disproportionate enrollment among different races/ethnicities in global trials placed the generalizability in doubt. This meta-analysis aimed to estimate the relative efficacy of pembrolizumab between Asians and non-Asians with advanced cancers. Methods: A systematic review was conducted in PubMed, Cochrane Library, Embase, and Web of Science. The meta-analysis included phase 3 randomized controlled trials investigating pembrolizumab in advanced cancers with available subgroup analysis for Asians and non-Asians. The experimental strategies involved monotherapy versus standard-of-care (SOC) or best supportive care, an add-on to SOC, and combined with multikinase inhibitor versus standard chemotherapy, regardless of the setting. The primary and secondary effect measures were the mean difference (MD) in the natural logarithm (i.e., log) of the hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) between the two subgroups [MD=log(HRAsians)−log(HRNon-Asians)=log(HRAsians/HRNon-Asians)]. We used the random-effects meta-analysis to calculate the pooled ratio of HRs (i.e., exp(MD)) and implemented a meta-regression analysis to identify significant covariates. The heterogeneity among the selected studies was evaluated using the Chi-squared Q test and the I2 statistic. Results: A total of 17 and 11 trials were selected in the meta-analysis for OS and PFS, respectively. These trials reported available subgroup results on Asians and non-Asians (patient numbers 2,732 [25.49%] and 7,000 [65.32%] for OS; 1,438 [22.50%] and 4,129 [64.61%] for PFS). The pooled ratio of HRs for OS was 0.87 (95% confidence interval [CI], 0.76−0.99; p = 0.0391; Chi-squared Q test Χ2 = 20.84, p = 0.29; I2 = 23.9%), favoring Asians, and no significant difference was found in PFS (the pooled ratio of HRs 0.93; 95% CI, 0.82−1.07; p = 0.2391; Chi-squared Q test Χ2 = 7.37, p = 0.77; I2 ≈ 0%). Both linear meta-regression analyses revealed an open-label design as an important covariate accounting for the observed difference, favoring non-Asians (estimated ratios of HR, 1.6318 for OS [95% CI, 1.1442-2.3273]; 1.3429 for PFS [95% CI, 1.0007−1.8020]). The sensitivity analysis showed that the percentage of subsequent treatment or post-progression programmed cell death 1 (PD-1)/ligand 1 (PD-L1) inhibitors had no significant impact. Conclusions: Asians receiving pembrolizumab for advanced cancers may have a superior OS advantage than non-Asians. Although the results warranted further exploration, this meta-analysis provided insight into clinical research design.

A retrospective cohort study of differential attainment, COVID and Chaos: taking the difference out of a terrible trinity.

This study aimed to evaluate Core Surgical Training (CST) differential attainment related to COVID-19, gender, and ethnicity. The hypothesis was that COVID-19 adversely influenced CST outcomes. A retrospective cohort study of 271 anonymised CST records was undertaken at a UK Statutory Education Body. Primary effect measures were: Annual Review of Competency Progression Outcome (ARCPO), Membership of the Royal College of Surgeons (MRCS) examination pass, and Higher Surgical Training National Training Number (NTN) appointment. Data was collected prospectively at ARCP and analysed with non-parametric statistical methods in SPSS®. CSTs numbering 138 completed training pre- and 133 peri-COVID. ARCPO 1,2&6 were 71.9% pre- vs. 74.4% peri-COVID (P=0.844). MRCS pass rates were 69.6% pre- versus 71.1% peri-COVID (P=0.968) but NTN appointment rates diminished (pre- 47.4% vs. peri- 36.9%, P=0.324); none of the above varied by gender or ethnicity. Multivariable analyses by three models revealed: ARCPO was associated with gender (m: f 1:0.87, OR 0.53, P=0.043) and CST theme (Plastics vs. General OR 16.82, P=0.007); MRCS pass with theme (Plastics vs. General OR 8.97, P=0.004); NTN with the Improving Surgical Training run-through program (OR 5.00, P<0.001). Program retention improved peri-COVID (OR 0.20, P=0.014) with pan University Hospital rotations performing better than Mixed or District General-only rotations (OR 6.63, P=0.018). Differential attainment profiles varied 17-fold, yet COVID-19 did not influence ARCPO or MRCS pass rates. NTN appointment fell by one fifth peri-COVID, but overall training outcome metrics remained robust despite the existential threat.

Competence of Althaeaofficinalis Seed Extract in control of Haemorrhoids in comparison with Daflon

Background: The use of medicinal plants in herbalism has been documented for thousands of years, with evidence dating back to ancient civilizations such as the, Chinese, Greeks and Egyptians1. Extensive clinical studies have demonstrated that Althaeaofficinalis has properties that promote healing of ulcers2. Aim: To evaluate effectiveness of Althaeaofficinalis seed extract compared to Daflon (diosmin plus hesperidin) in treating hemorrhoids. Methods: A double-blind, randomized clinical trial was carried out in Lahore's urban community. Patients with acute hemorrhoids were randomly divided into two parallel groups, each with 60 participants, for a one-week period. The selection of family physicians for the study was done randomly.6,7,8 Interventions: In the beginning, the participants were given either two capsules of 500mg Althaea seed extract or two tablets of Daflonin morning and evening for four days, followed by two capsules/tablets daily for the next three days. The primary measure of effectiveness was the alleviation of symptoms and signs.9,10 Results: Both groups demonstrated similar improvement from first day tolast day. The intensity of symptoms such as itching, tenesmus, and bleeding ,swelling, painetc reduced markedly in both groups, but the reduction was fast in the Althaeaofficinalis seed extract group observed initial days of the trial. Practical Implications: Estimated prevalence of haemorrhoids ranges from 2.9% to 27.9% worldwide.11,12.13 However, due to cultural practices, it is often ignored and left untreated, It is therefore essential to design preventive measures and control strategies for hemorrhoids. Conclusion: Both Althaea and Daflon were found relieving haemorrhoidal signs and symptoms of hemorrhoids. However, the use of Althaea seed extract resulted in quicker relief and it may be used as good alternative to Daflon. Keywords: Haemorrhoids ,Altthaea seed extract, Althaeaofficinalis, double blind, tenesmus, bleeding,