Real-world persistence of multiple sclerosis disease-modifying therapies.

BACKGROUND AND PURPOSE: Treatment persistence is the continuation of therapy over time. It reflects a combination of treatment efficacy and tolerability. We aimed to describe real-world rates of persistence on disease-modifying therapies (DMTs) for people with multiple sclerosis (pwMS) and reasons for DMT discontinuation. METHODS: Treatment data on 4366 consecutive people with relapse-onset multiple sclerosis (MS) were pooled from 13 UK specialist centres during 2021. Inclusion criteria were exposure to at least one MS DMT and a complete history of DMT prescribing. PwMS in blinded clinical trials were excluded. Data collected included sex, age at MS onset, age at DMT initiation, DMT treatment dates, and reasons for stopping or switching DMT. For pwMS who had received immune reconstituting therapies (cladribine/alemtuzumab), discontinuation date was defined as starting an alternative DMT. Kaplan-Meier survival analyses were used to express DMT persistence. RESULTS: In 6997 treatment events (1.6 per person with MS), median time spent on any single maintenance DMT was 4.3 years (95% confidence interval = 4.1-4.5 years). The commonest overall reasons for DMT discontinuation were adverse events (35.0%) and lack of efficacy (30.3%). After 10 years, 20% of people treated with alemtuzumab had received another subsequent DMT, compared to 82% of people treated with interferon or glatiramer acetate. CONCLUSIONS: Immune reconstituting DMTs may have the highest potential to offer a single treatment for relapsing MS. Comparative data on DMT persistence and reasons for discontinuation are valuable to inform treatment decisions and in personalizing treatment in MS.

Delay to elective colorectal cancer surgery and implications for survival: a systematic review and meta-analysis.

AIM: The Covid-19 pandemic has delayed elective colorectal cancer (CRC) surgery. The aim of this study was to see whether or not this may affect overall survival (OS) and disease-free survival (DFS). METHOD: A systematic review was carried out according to PRISMA guidelines (PROSPERO ID: CRD42020189158). Medline, EMBASE and Scopus were interrogated. Patients aged over 18 years with a diagnosis of colon or rectal cancer who received elective surgery as their primary treatment were included. Delay to elective surgery was defined as the period between CRC diagnosis and the day of surgery. Meta-analysis of the outcomes OS and DFS were conducted. Forest plots, funnel plots and tests of heterogeneity were produced. An estimated number needed to harm (NNH) was calculated for statistically significant pooled hazard ratios (HRs). RESULTS: Of 3753 articles identified, seven met the inclusion criteria. Encompassing 314 560 patients, three of the seven studies showed that a delay to elective resection is associated with poorer OS or DFS. OS was assessed at a 1 month delay, the HR for six datasets was 1.13 (95% CI 1.02-1.26, p = 0.020) and at 3 months the pooled HR for three datasets was 1.57 (95% CI 1.16-2.12, p = 0.004). The estimated NNH for a delay at 1 month and 3 months was 35 and 10 respectively. Delay was nonsignificantly negatively associated with DFS on meta-analysis. CONCLUSION: This review recommends that elective surgery for CRC patients is not postponed longer than 4 weeks, as available evidence suggests extended delays from diagnosis are associated with poorer outcomes. Focused research is essential so patient groups can be prioritized based on risk factors in future delays or pandemics.

The impact of the introduction of selective screening in the UK on the epidemiology, presentation, and treatment outcomes of developmental dysplasia of the hip.

Aims: Developmental dysplasia of the hip (DDH) can be managed effectively with non-surgical interventions when diagnosed early. However, the likelihood of surgical intervention increases with a late presentation. Therefore, an effective screening programme is essential to prevent late diagnosis and reduce surgical morbidity in the population. Methods: We conducted a systematic review and meta-analysis of the epidemiological literature from the last 25 years in the UK. Articles were selected from databases searches using MEDLINE, EMBASE, OVID, and Cochrane; 13 papers met the inclusion criteria. Results: The incidence of DDH within the UK over the last 25 years is 7.3/1,000 live births with females making up 86% of the DDH population (odds ratio 6.14 (95% confidence interval 3.3 to 11.5); p < 0.001). The incidence of DDH significantly increased following the change in the Newborn and Infant Physical Examination (NIPE) guidance from 6.5/1,000 to 9.4/1,000 live births (p < 0.001). The rate of late presentation also increased following the changes to the NIPE guidance, rising from 0.7/1,000 to 1.2/1,000 live births (p < 0.001). However, despite this increase in late-presenting cases, there was no change in the rates of surgical intervention (0.8/1,000 live births; p = 0.940). Conclusion: The literature demonstrates that the implementation of a selective screening programme increased the incidence of DDH diagnosis in the UK while subsequently increasing the rates of late presentation and failing in its goal of reducing the rates of surgical intervention for DDH.

The cost effectiveness of potential risk factors for developmental dysplasia of the hip within a national screening programme.

Early detection of developmental dysplasia of the hip (DDH) is associated with improved outcomes of conservative treatment. Therefore, we aimed to evaluate a novel screening programme that included both the primary risk factors of breech presentation and family history, and the secondary risk factors of oligohydramnios and foot deformities. A five-year prospective registry study investigating every live birth in the study's catchment area (n = 27,731), all of whom underwent screening for risk factors and examination at the newborn and six- to eight-week neonatal examination and review. DDH was diagnosed using ultrasonography and the Graf classification system, defined as grade IIb or above or rapidly regressing IIa disease (≥4o at four weeks follow-up). Multivariate odds ratios were calculated to establish significant association, and risk differences were calculated to provide quantifiable risk increase with DDH, positive predictive value was used as a measure of predictive efficacy. The cost-effectiveness of using these risk factors to predict DDH was evaluated using NHS tariffs (January 2021). The prevalence of DDH that required treatment within our population was 5/1,000 live births. The rate of missed presentation of DDH was 0.43/1000 live births. Breech position, family history, oligohydramnios, and foot deformities demonstrated significant association with DDH (p < 0.0001). The presence of breech presentation increased the risk of DDH by 1.69% (95% confidence interval (CI) 0.93% to 2.45%), family history by 3.57% (95% CI 2.06% to 5.09%), foot deformities by 8.95% (95% CI 4.81% to 13.1%), and oligohydramnios nby 11.6% (95 % CI 3.0% to 19.0%). Primary risk factors family history and breech presentation demonstrated an estimated cost-per-case detection of £6,276 and £11,409, respectively. Oligohydramnios and foot deformities demonstrated a cost-per-case detected less than the cost of primary risk factors of £2,260 and £2,670, respectively. The inclusion of secondary risk factors within a national screening programme was clinically successful as they were more cost and resource-efficient predictors of DDH than primary risk factors, suggesting they should be considered in the national guidance.