Primary Effectiveness Measure Research Articles

Cost-effectiveness of central automated unit dose dispensing with barcode-assisted medication administration in a hospital setting.

Central automated unit dose dispensing (cADD) with barcode-assisted medication administration (BCMA) has been shown to reduce medication administration errors (MAEs). Little is known about the cost-effectiveness of this intervention. To estimate the cost-effectiveness of cADD with BCMA compared to usual care. An economic evaluation was conducted alongside a prospective before-and-after effectiveness study in a Dutch university hospital. The primary effect measure was the difference between the rate of MAEs before and after implementation of cADD with BCMA, obtained by disguised observation in six clinical wards and subsequent extrapolation to the entire hospital. The cost-analysis was conducted from a hospital perspective with a 12-month incremental costing approach. The total costs covered the pharmaceutical service, nurse medication handling, wastage, and materials related to cADD. The primary outcome was the cost-effectiveness ratio expressed as costs per avoided MAE, obtained by dividing the annual incremental costs by the number of avoided MAEs. The secondary outcome was the cost-effectiveness ratio expressed as costs per avoided potentially harmful MAE (i.e. MAEs with the potential to cause harm). The intervention was associated with an absolute MAE reduction of 4.5% and a reduction of 2.7% for potentially harmful MAEs. Based on 2,260,870 administered medications in the entire hospital annually, a total of 102,210 MAEs and 59,830 potentially harmful MAEs were estimated to be avoided. The intervention was associated with an increased incremental cost of €1,808,600 annually. The cost-effectiveness ratio was €17.69 per avoided MAE and €30.23 per avoided potentially harmful MAE. The implementation of cADD with BCMA was associated with a reduced rate of medication errors, including harmful ones, at higher overall costs. The costs per avoided error are relatively low, and therefore, this intervention could be an important strategy to improve patient safety in hospitals.

BeatPain Utah: study protocol for a pragmatic randomised trial examining telehealth strategies to provide non-pharmacologic pain care for persons with chronic low back pain receiving care in federally qualified health centers

IntroductionAlthough evidence-based guidelines recommend non-pharmacologic treatments as first-line care for chronic low back pain (LBP), uptake has been limited, particularly in rural, low-income and ethnically diverse communities. The BeatPain study...

Evaluating health outcomes in the treatment of hypothyroidism.

Clinical hypothyroidism is defined by the inadequate production of thyroid hormone from the thyroid gland to maintain normal organ system functions. For nearly all patients with clinical hypothyroidism, lifelong treatment with thyroid hormone replacement is required. The primary goal of treatment is to provide the appropriate daily dose of thyroid hormone to restore normal thyroid function for each individual patient. In current clinical practice, normalization of thyrotropin (TSH) level is the primary measure of effectiveness of treatment, however the use of a single biomarker to define adequate thyroid hormone replacement is being reevaluated. The assessment of clinical health outcomes and patient-reported outcomes (PROs), often within the context of intensity of treatment as defined by thyroid function tests (i.e., undertreatment, appropriate treatment, or overtreatment), may play a role in evaluating the effectiveness of treatment. The purpose of this narrative review is to summarize the prominent health outcomes literature in patients with treated hypothyroidism. To date, overall mortality, cardiovascular morbidity and mortality, bone health and cognitive function have been evaluated as endpoints in clinical outcomes studies in patients with treated hypothyroidism. More recent investigations have sought to establish the relationships between these end results and thyroid function during the treatment course. In addition to clinical event outcomes, patient-reported quality of life (QoL) has also been considered in the assessment of adequacy of hypothyroidism treatment. From a health care quality perspective, treatment of hypothyroidism should be evaluated not just on its effectiveness for the individual patients but also to the extent to which patients of different sociodemographic groups are treated equally. Ultimately, more research is needed to explore differences in health outcomes between different sociodemographic groups with hypothyroidism. Future prospective studies of treated hypothyroidism that integrate biochemical testing, PROs, and end result clinical outcomes could provide a more complete picture into the effectiveness of treatment of hypothyroidism.

Post-switch Effectiveness of Etanercept Biosimilar Versus Continued Etanercept in Rheumatoid Arthritis Patients with Stable Disease: A Prospective Multinational Observational Study.

To better inform clinicians about the use of etanercept biosimilar (SB4) in patients with rheumatoid arthritis (RA), COMPANION-B, a prospective real-world observational study, evaluated the effectiveness of the voluntary switch from originator (etanercept, ETN) to SB4 in patients with stable RA (low-disease activity/remission). The study recruited adult patients (18years or older) with RA (2010 American College of Rheumatology criteria) prescribed ETN as their first or second biologic for at least 6months across 14 sites in Canada and five in Australia. Patients had stable disease (Disease Activity Score-28 using erythrocyte sedimentation rate [DAS28-ESR] less than 3.2) at enrollment with no evidence of flare within the previous 3months. Concomitant disease-modifying antirheumatic drugs (DMARDs) were permitted. Patients could elect to continue ETN or voluntarily switch to SB4 in consultation with their doctors. The primary effectiveness measure was the proportion of patients with disease worsening (defined as a DAS28-ESR increase of at least 1.2 from baseline and minimum score of at least 3.2 or a defined modification in RA treatment) during 12months of follow-up. The secondary effectiveness measure was the proportion of patients with disease worsening at month6. Serious adverse events (SAEs) and non-serious adverse reactions (NSARs) were recorded. Of 163 patients enrolled, 109 elected to continue on ETN and 54 switched to SB4; 65.8% of patients received non-biologic DMARD(s), 52.6% methotrexate, and 10.5% oral corticosteroid(s). At month12, the proportion of patients with disease worsening was comparable in the ETN group (22.8% [95%CI 15.0-32.2]) and SB4 group (17.6% [95%CI 8.4-30.9]). Similarly, the proportions of patients with disease worsening were also comparable at month6 (ETN: 7.9% [95%CI 3.5-15.0]; SB4: 7.8% [95%CI 2.2-18.9]). SAEs were low and similar across both groups (ETN: 8.7%; SB4: 5.7%). NSARs were slightly higher in the SB4 vs. ETN group (13.2% vs. 2.9%). SB4 demonstrated comparable effectiveness to ETN over 12months in patients with stable RA who voluntarily switched to the biosimilar in a real-world setting.

86. Long-term cost-effectiveness of full endoscopic vs open discectomy: two-year results of a RCT

<h3>BACKGROUND CONTEXT</h3> Open microdiscectomy is a frequently performed surgical procedure for sciatica caused by lumbar disc herniation. Percutaneous transforaminal endoscopic discectomy (PTED) has been introduced as a less invasive alternative and 1-year results show non-inferiority in leg pain reduction and dominancy in cost-effectiveness. <h3>PURPOSE</h3> To compare the long-term cost-effectiveness of PTED with open microdiscectomy among patients with sciatica caused by lumbar disc herniation as measured at two years. <h3>STUDY DESIGN/SETTING</h3> Randomized controlled trial at four clinics in the Netherlands which ran from February 2016 to April 2019. <h3>PATIENT SAMPLE</h3> Patients were aged from 18 to 70 years and had at least 6 weeks of radiating leg pain caused by lumbar disc herniation. The trial included a predetermined set of 125 PTED patients who were the early cases performed by three surgeons who had not performed PTED before the trial. Eventually 304 patients were allocated to PTED and 309 to open microdiscectomy. <h3>OUTCOME MEASURES</h3> Primary effect measures included leg pain as measured on the VAS for leg pain and health-related quality of life (QALYs). Costs were measured from a societal perspective. <h3>METHODS</h3> An economic evaluation was conducted alongside the PTED trial. A cost-effectiveness analysis and a cost-utility analysis were conducted. The primary analysis was conducted according to the intention-to-treat approach. All missing data were imputed using multiple imputation by chained equations (MICE), stratified by treatment group. Predictive mean matching was used to create 10 complete datasets. Disaggregate cost differences were analyzed using linear regression models, both adjusted and unadjusted for confounders. Differences in total costs and effects between treatment groups were obtained from a system of seemingly unrelated regressions (SUR) that accounted for the potential correlation between costs and effects. These total cost and effect differences were adjusted for baseline and confounders. Incremental cost-effectiveness ratios were calculated by dividing incremental costs by incremental effects. Uncertainty was estimated by bootstrapping and presented using Cost-effectiveness Planes and Cost-Effectiveness Acceptability Curves. <h3>RESULTS</h3> At 24 months, 92% of the follow-up data were available. Statistically significant differences in leg pain and QALYs were found in favor of PTED at 24-month follow-up (leg pain: 7.3; QALYs: 0.043). Surgery costs were higher for PTED than for open microdiscectomy (ie, €4,500/patient vs €4,095/patient). All other disaggregate costs as well as total societal costs were lower for PTED than for open microdiscectomy, namely primary care, secondary care, medication, informal care, absenteeism, presenteeism and productivity loss. Per performed PTED procedure, €138 in health care costs and €2787 in societal costs are saved. Cost-effectiveness acceptability curves indicated that the probability of PTED being cost-effective compared with open microdiscectomy (meaning on average less costly and more effective) was 99.4% for leg pain and 99.2% for QALYs, regardless of the willingness-to-pay. <h3>CONCLUSIONS</h3> Results suggest that PTED is less costly and more effective, and therefore cost-effective compared with microdiscectomy for patients with sciatica from the societal perspective. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

SP1.2.9 Stylish surgical writing: the state of the art surveyed

Abstract Introduction Glaring gaps exist between what most readers consider proficient writing and what academics typically publish. This study aimed to assess the writing styles of the 13 journals held in the highest esteem by 11 surgical specialties. Methods The first 1,000 words of the initial 10 articles published in January 2018 from the 11 journals affiliated with surgical specialty associations were assessed as well as the BMJ and Lancet. The primary effect measures were Flesch-Kincaid Readability Ease (FRES, range zero (difficult) to 100 (easy)) and Flesch-Kincaid Grade Level (FGL, range -3.40 to infinity), related to journal Impact Factor and article citations. Results FRES median was 18.2 (1.4–38.2) and FGL 16.3 (12–26.2). FRES was directly related to the use of be verbs (p=0.004), but inversely proportional to numbers of common abstract nouns, words per sentence, characters per word, authors, references, level of evidence, and Journal Impact Factor (all p&amp;lt;0.04). Citations were inversely related to FRES (rho -0.292, p&amp;lt;0.001; critical value 14.5 (OR 0.20 p&amp;lt;0.001)) and directly proportional to FGL (rho 0.279, p=0.001; critical value of 15.5 (OR 5.04 p=0.05)). The journal with the highest FRES (most readable) was the British Journal of Oral &amp; Maxillo-Facial Surgery (median 30.4; total citations 5). Conclusion Big differences in writing style and readability were plain with FRES varying 28- and FGL two-fold. No journals had a FGL of &amp;lt;12 (reading age of &amp;gt;17 yr.). Superior Journal prestige, Impact Factor, and citations were not associated with better Flesch-Kincaid reading ease.

TU3.6 Surgical training salvage during COVID-19: a hospital quality perspective

IntroductionVicissitudes including re-deployment, elective cancellations, and remote educational events have restricted training opportunities during the COVID pandemic. This study aimed to analyse COVID's impact on global Higher Surgical Trainee (HST) performance metrics including hospital adaptability and variance.Materials and MethodIntercollegiate Surgical Curriculum Programme (ISCP) portfolios of 50 HSTs (median age 36 (range 29–46) yr., female 15, male 35), including 191 six-month rotational placements, were analysed over two years (March 2019 to 2021). Primary effect measures were: operative logbook numbers, index procedures validated against curriculum requirements and Work Based Assessments (WBA).ResultsDuring COVID-19, operative experience per placement declined 26.1% (median 211 vs. 156, p<0.010), with a 32.1% decline in trainee primary surgeon experience (162 vs. 110, p<0.010). Regarding index procedures: cholecystectomy declined 45.5% (11 vs. 6, p=0.027) and inguinal hernia 62.5% (8 vs. 3, p<0.010). WBAs were similar (17 vs. 13, p=0.364). Despite relative equivalence before COVID, median total number of operative procedures performed in District General Hospitals (DGH, n=65) were 40.9% fewer than Tertiary Hospitals (TH, n=110, p<0.010). Radar plots of composite metrics ranged from 11.1 to 75.6% coverage before (p=0.011) vs. 13.3 to 68.9% after COVID (p=0.015).DiscussionHospital training metrics varied over five-fold, a difference likely amplified by COVID, with THs more adaptable to existential shared lessons.

VYC-20L is Safe and Effective for Improving Volume and Aesthetic Appearance of the Nose in Chinese Adults

PurposeSoft tissue filler injection is less invasive than surgical approaches for facial aesthetic improvement. This study evaluated the safety and effectiveness of the soft tissue filler VYC-20L (Juvéderm Voluma® XC) for improvement of volume and aesthetic appearance of the nose in Chinese subjects.Patients and MethodsIn a prospective, multicenter, no-treatment–controlled study in China, adult subjects were randomized 3:1 to receive VYC-20L (treatment group) or have optional treatment delayed by 24 weeks (control group). The treatment group received VYC-20L on day 1 plus optional touch-up at week 8 for suboptimal improvement. The primary effectiveness measure was mean change in nose area volume from baseline to week 24 by digital analysis of three-dimensional (3D) images. Multiple secondary effectiveness and safety measures were assessed.ResultsOf 164 subjects randomized, 162 were treated, and 157 comprised the modified intent-to-treat population (mean age, 31 years; 94% female). In the treatment group, mean VYC-20L volume injected was 1.18 mL (initial treatment) and 0.67 mL (touch-up; n = 46 [38.3%]). VYC-20L achieved significantly larger changes in nose area volume than control at week 24 (2.032 vs ‒0.005 cm3, respectively; p < 0.0001) and greater improvements on the Global Aesthetic Improvement Scale (investigator and subject), Nose Satisfaction Scale, and other 3D measures. No treatment-related adverse events occurred. Most injection site responses were mild/moderate, resolving within 14 days. Mean initial/touch-up treatment procedural pain ratings were less than 3 (0‒10 scale; higher = worse pain).ConclusionVYC-20L is safe and effective for nose augmentation in Chinese adults.

Harnessing new mHealth technologies to Strengthen the Management of Multidrug-Resistant Tuberculosis in Vietnam (V-SMART trial): a protocol for a randomised controlled trial

IntroductionMultidrug-resistant tuberculosis (MDR-TB) remains a major public health problem globally. Long, complex treatment regimens coupled with frequent adverse events have resulted in poor treatment adherence and patient outcomes. Smartphone-based mobile...

Differential attainment in higher surgical training: scoping pan-specialty spectra.

This study aimed to evaluate differential attainment during higher surgical training (HST; all specialties) related to three ethnic cohorts: White UK (WUKG), Black and Minority Ethnic UK Graduates (BMEUKG), and International Medical Graduates (IMG). Anonymised records of 266 HSTs (126 WUKG, 65 BMEUKG, 75 IMG; 7 years) in a single UK Statutory Education Body were examined. Primary effect measures were Annual Record of Competency Progression Outcome (ARCPO) and Fellowship of the Royal College of Surgeons (FRCS) pass. ARCPOs related to ethnicity and specialty were similar with the exception of general surgery (GS) trainees, four of whom received ARCPO 4 (GS 4.9% (75% BME; p=0.025) vs all other 0%). ARCPO 3 was commoner in women (22/76, (28.9%) than men 27/190 (14.2%), OR 2.46, p=0.006). FRCS pass rates (WUKG vs BMEUKG vs IMG) were 76.9%, 52.9% and 53.9% respectively (p=0.064) but unrelated to gender (M 70.4% vs F 64.3%). On multivariable analyses: ARCPO 3 was associated with Female gender and Maternity Leave (OR 8.05, p=0.001); FRCS pass with ethnicity (OR 0.21, p=0.028) and Hirsch Indices of ≥5 (OR 11.17, p=0.001). Differential attainment was plain with BMEUKG FRCS performance almost a third poorer than WUKG, and women twofold more likely to receive adverse ARCPOs, with return from statutory leave independently associated with training extension. Focused counter measures targeted at non-operative technical skills (including academic reach), Keeping in Touch, Return to Work, and re-induction programmed support are urgently needed for trainees at risk.

Efficacy of monoclonal antibodies in neuromyelitis optica: An updated systematic review with meta‐analysis

Objective This is a critical review of studies aiming to assess the safety and efficacy of monoclonal antibodies as compared with the classical regimen in patients with neuromyelitis optica spectrum disorder. Methods Various electronic databases were searched for original articles reporting results from the use of monoclonal antibodies in neuromyelitis optica spectrum disorder. The Expanded Disability Status Scale and annualized relapse rate score before and after treatment were the primary effect measures. The pooled standardized mean difference with 95% CI was calculated using the random effects model. The heterogeneity of the included studies was calculated using Cochran's Q test and I2 statistics. Results Of 36 included studies, meta-analysis was carried out from 27 studies. The pooled analysis of 1010 patients showed a mean reduction in the mean annualized relapse rate ratio after tocilizumab therapy −2.45 (95% CI −3.13 to −1.77) to be higher compared with rituximab −1.49 (95% CI −1.81 to −1.17). Likewise, the mean reduction in the Expanded Disability Status Scale after tocilizumab was higher −1.10 (95% CI −1.75 to −0.44) compared with rituximab −0.80 (95% CI −1.11 to −0.48). Conclusion Tocilizumab has a greater effect than rituximab in terms of the reduction of the annualized relapse rate and Expanded Disability Status Scale in neuromyelitis optica spectrum disorder patients. The greater efficacy of tocilizumab could result from its multiple dynamic pharmacodynamics (i.e. its effect on interleukin-6-dependent inflammatory processes, involving CD20-negative plasmablasts, pathogenic T cells and regulatory T cells) and to some degree due to heterogeneity in our study. Satralizumab (monotherapy or add-on), eculizumab and inebilizumab (monotherapy) are effective in aquaporin-4-positive cases with good safety profiles. Ublituximab, bortezomib, bevacizumab and C1-esterase inhibitors are both effective and safe add-on drugs.

Effect of Cancer Pain Guideline Implementation on Pain Outcomes Among Adult Outpatients With Cancer-Related Pain

An evidence-practice gap exists for cancer pain management, and cancer pain remains prevalent and disabling. To evaluate the capacity of 3 cancer pain guideline implementation strategies to improve pain-related outcomes for patients attending oncology and palliative care outpatient services. A pragmatic, stepped wedge, cluster-randomized, nonblinded, clinical trial was conducted between 2014 and 2019. The clusters were cancer centers in Australia providing oncology and palliative care outpatient clinics. Participants included a consecutive cohort of adult outpatients with advanced cancer and a worst pain severity score of 2 or more out of 10 on a numeric rating scale (NRS). Data were collected between August 2015 and May 2019. Data were analyzed July to October 2019 and reanalyzed November to December 2021. Guideline implementation strategies at the cluster, health professional, and patient levels introduced with the support of a clinical champion. The primary measure of effect was the percentage of participants initially screened as having moderate to severe worst pain (NRS ≥ 5) who experienced a clinically important improvement of 30% or more 1 week later. Secondary outcomes included mean average pain, patient empowerment, fidelity to the intervention, and quality of life and were measured in all participants with a pain score of 2 or more 10 at weeks 1, 2, and 4. Of 8099 patients screened at 6 clusters, 1564 were eligible, and 359 were recruited during the control phase (mean [SD] age, 64.2 [12.1] years; 196 men [55%]) and 329 during the intervention phase (mean [SD] age, 63.6 [12.7] years; 155 men [47%]), with no significant differences between phases on baseline measures. The mean (SD) baseline worst pain scores were 5.0 (2.6) and 4.9 (2.6) for control and intervention phases, respectively. The mean (SD) baseline average pain scores were 3.5 (2.1) for both groups. For the primary outcome, the proportions of participants with a 30% or greater reduction in a pain score of 5 or more of 10 at baseline were similar in the control and intervention phases (31 of 280 participants [11.9%] vs 30 of 264 participants [11.8%]; OR, 1.12; 95% CI, 0.79-1.60; P = .51). No significant differences were found in secondary outcomes between phases. Fidelity to the intervention was low. A suite of implementation strategies was insufficient to improve pain-related outcomes for outpatients with cancer-related pain. Further evaluation is needed to determine the required clinical resources needed to enable wide-scale uptake of the fundamental elements of cancer pain care. Ongoing quality improvement activities should be supported to improve sustainability.

Risk of tuberculosis in patients with rheumatoid arthritis treated with biological and targeted drugs: meta-analysis of randomized clinical trials.

Background:Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs).Methods:A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure.Results:In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36–6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30–6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00–27.31, P = 0.003).Conclusion:This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.

Effectiveness and cost-effectiveness of longstanding exercise therapy versus usual care in patients with axial spondyloarthritis or rheumatoid arthritis and severe limitations: The protocols of two parallel randomized controlled trials.

ObjectivesResearch on effectiveness and cost‐effectiveness of longstanding exercise therapy in patients with axial SpondyloArthritis (axSpA) or Rheumatoid Arthritis (RA) is scarce, and mainly concerned patients with a relatively favorable health status. We aim to evaluate the effectiveness and cost‐effectiveness of longstanding exercise therapy compared to usual care in the subgroup of patients with axSpA or RA and severe limitations in functioning.MethodsIn two separate, parallel randomized controlled trials the effectiveness and cost‐effectiveness of longstanding, active exercise therapy (52 weeks) compared with usual care (1:1) will be evaluated. The longstanding, active exercise therapy will focus on improving individual limitations in daily activities and participation and will be given by a trained physical therapist in the vicinity of the participant. For each diagnosis, 215 patients with severe limitations in activities and participation will be included. Assessments are performed at baseline, 12, 26, and 52 weeks. The primary outcome measure of effectiveness is the individual level of functioning (activities and participation), as measured with the Patient‐Specific Complaints instrument at 52 weeks. For cost‐effectiveness analyses, the EuroQol (EQ‐5D‐5L) and questionnaires on healthcare use and productivity will be administered. The economic evaluation will be a cost‐utility analysis from a societal perspective. After 52 weeks, the patients in the usual care group are offered longstanding, active exercise therapy as well. Follow‐up assessments are done at 104, 156, and 208 weeks.ConclusionThe results of these studies will provide insights in the effectiveness and cost‐effectiveness of longstanding exercise therapy in the subgroup of axSpA and RA patients with severe functional limitations.

Comparative Clinical Effectiveness of Population-Based Atrial Fibrillation Screening Using Contemporary Modalities: A Decision-Analytic Model.

BackgroundAtrial fibrillation (AF) screening is endorsed by certain guidelines for individuals aged ≥65 years. Yet many AF screening strategies exist, including the use of wrist‐worn wearable devices, and their comparative effectiveness is not well‐understood.Methods and ResultsWe developed a decision‐analytic model simulating 50 million individuals with an age, sex, and comorbidity profile matching the United States population aged ≥65 years (ie, with a guideline‐based AF screening indication). We modeled no screening, in addition to 45 distinct AF screening strategies (comprising different modalities and screening intervals), each initiated at a clinical encounter. The primary effectiveness measure was quality‐adjusted life‐years, with incident stroke and major bleeding as secondary measures. We defined continuous or nearly continuous modalities as those capable of monitoring beyond a single time‐point (eg, patch monitor), and discrete modalities as those capable of only instantaneous AF detection (eg, 12‐lead ECG). In total, 10 AF screening strategies were effective compared with no screening (300–1500 quality‐adjusted life‐years gained/100 000 individuals screened). Nine (90%) effective strategies involved use of a continuous or nearly continuous modality such as patch monitor or wrist‐worn wearable device, whereas 1 (10%) relied on discrete modalities alone. Effective strategies reduced stroke incidence (number needed to screen to prevent a stroke: 3087–4445) but increased major bleeding (number needed to screen to cause a major bleed: 1815–4049) and intracranial hemorrhage (number needed to screen to cause intracranial hemorrhage: 7693–16 950). The test specificity was a highly influential model parameter on screening effectiveness.ConclusionsWhen modeled from a clinician‐directed perspective, the comparative effectiveness of population‐based AF screening varies substantially upon the specific strategy used. Future screening interventions and guidelines should consider the relative effectiveness of specific AF screening strategies.

Canakinumab in systemic juvenile idiopathic arthritis: real-world data from a retrospective Italian cohort.

The objective of this study was to use real-world data to evaluate the effectiveness and safety of canakinumab in Italian patients with systemic JIA (sJIA). A retrospective multicentre study of children with sJIA was performed. Clinical features, laboratory parameters and adverse events were collected at baseline, and 6 and 12 months after starting canakinumab. The primary outcome measure of effectiveness was clinically inactive disease (CID) off glucocorticoids (GCs) treatment at 6 months. A total of 80 children from 15 Italian centres were analysed. Of the 12 patients who started canakinumab in CID while receiving anakinra, all maintained CID. Of the 68 with active disease at baseline, 57.4% achieved CID off GCs at 6 months and 63.8% at 12 months. In univariate analysis, the variables significantly related to non-response were number of active joints (NAJs) ≥5, history of macrophage activation syndrome (MAS) and disease duration. Multivariate analysis confirmed the association between non-response and NAJs ≥5 [odds ratio (OR) 6.37 (95% CI: 1.69, 24.02), P = 0.006] and between non-response and history of MAS [OR 3.53 (95% CI: 1.06, 11.70), P = 0.039]. No serious adverse events were recorded in this series. There were two cases of MAS during canakinumab, leading to a rate of 2.9 episodes per 100 patient years. We have confirmed, using real-world data, the efficacy of canakinumab in sJIA in a multicentric cohort. History of MAS and higher NAJ were associated with lower probability of achieving CID.

A randomised feasibility trial of an employer-based intervention for enhancing successful return to work of cancer survivors (MiLES intervention)

BackgroundEmployers express a need for support during sickness absence and return to work (RTW) of cancer survivors. Therefore, a web-based intervention (MiLES) targeted at employers with the objective of enhancing cancer survivors’ successful RTW has been developed. This study aimed to assess feasibility of a future definitive randomised controlled trial (RCT) on the effectiveness of the MiLES intervention. Also preliminary results on the effectiveness of the MiLES intervention were obtained.MethodsA randomised feasibility trial of 6 months was undertaken with cancer survivors aged 18–63 years, diagnosed with cancer < 2 years earlier, currently in paid employment, and sick-listed < 1 year. Participants were randomised to an intervention group, with their employer receiving the MiLES intervention, or to a waiting-list control group (2:1). Feasibility of a future definitive RCT was determined on the basis of predefined criteria related to method and protocol-related uncertainties (e.g. reach, retention, appropriateness). The primary effect measure (i.e. successful RTW) and secondary effect measures (e.g. quality of working life) were assessed at baseline and 3 and 6 months thereafter.ResultsThirty-five cancer survivors were included via medical specialists (4% of the initially invited group) and open invitations, and thereafter randomised to the intervention (n = 24) or control group (n = 11). Most participants were female (97%) with breast cancer (80%) and a permanent employment contract (94%). All predefined criteria for feasibility of a future definitive RCT were achieved, except that concerning the study’s reach (90 participants). After 6 months, 92% of the intervention group and 100% of the control group returned to work (RR: 0.92, 95% CI: 0.81–1.03); no difference were found with regard to secondary effect measures.ConclusionsWith the current design a future definitive RCT on the effectiveness of the MiLES intervention on successful RTW of cancer survivors is not feasible, since recruitment of survivors fell short of the predefined minimum for feasibility. There was selection bias towards survivors at low risk of adverse work outcomes, which reduced generalisability of the outcomes. An alternative study design is needed to study effectiveness of the MiLES intervention.Trial registrationThe study has been registered in the Dutch Trial Register (NL6758/NTR7627).

Critical review of oncology clinical trial design under non-proportional hazards

In trials of novel immuno-oncology drugs, the proportional hazards (PH) assumption often does not hold for the primary time-to-event (TTE) efficacy endpoint, likely due to the unique mechanism of action of these drugs. In practice, when it is anticipated that PH may not hold for the TTE endpoint with respect to treatment, the sample size is often still calculated under the PH assumption, and the hazard ratio (HR) from the Cox model is still reported as the primary measure of the treatment effect. Sensitivity analyses of the TTE data using methods that are suitable under non-proportional hazards (non-PH) are commonly pre-planned. In cases where a substantial deviation from the PH assumption is likely, we suggest designing the trial, calculating the sample size and analyzing the data, using a suitable method that accounts for non-PH, after gaining alignment with regulatory authorities. In this comprehensive review article, we describe methods to design a randomized oncology trial, calculate the sample size, analyze the trial data and obtain summary measures of the treatment effect in the presence of non-PH. For each method, we provide examples of its use from the recent oncology trials literature. We also summarize in the Appendix some methods to conduct sensitivity analyses for overall survival (OS) when patients in a randomized trial switch or cross-over to the other treatment arm after disease progression on the initial treatment arm, and obtain an adjusted or weighted HR for OS in the presence of cross-over. This is an example of the treatment itself changing at a specific point in time - this cross-over may lead to a non-PH pattern of diminishing treatment effect.

Aripiprazole vs Risperidone for the acute-phase treatment of first-episode psychosis: A 6-week randomized, flexible-dose, open-label clinical trial

Selecting the first antipsychotic agent for the acute phase of a first episode of psychosis (FEP) is a critical task that may impact on the long-term outcome. Despite that, there is a lack of research comparing head-to-head different second-generation antipsychotics at this stage. The aim of this study was to compare the effectiveness of aripiprazole and risperidone in the treatment of the acute phase after a FEP. For that purpose, from February 2011 to October 2018, a prospective, randomized, open-label study was undertaken. Two hundred-sixty-six first-episode, drug-naïve patients were randomly assigned to aripiprazole (n = 136), or risperidone (n = 130) and followed-up for 6-weeks. The primary effectiveness measure was all-cause treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted to assess clinical efficacy. The overall dropout rate at 6-week reached 19.5%. Effectiveness measures were similar between both treatment groups as treatment discontinuation rates (χ2 = 1.863; p = 0.172) and mean time until all-cause discontinuation (log rank = 1.421; p = 0.233) showed no statistically significant differences. In terms of clinical efficacy, risperidone proved a statistically significant better performance according to BPRS mean change between baseline and 6-week total score (t = 3.187; p = 0.002). Patients under risperidone treatment were significantly more likely to suffer sex-related adverse events. In conclusion, no differences regarding effectiveness were found between aripiprazole and risperidone for the acute-phase treatment of FEP. Despite the importance of efficacy during this phase of treatment, selecting the most effective treatment for the long-term outcome, requires addressing safety and patient´s preferences.

Using Re-Conviction Data to Measure Re-Offending: Incorporating Seriousness and Frequency into a Single Non-Binary Measure

Re-offending is usually operationalized as a binary variable, signaling whether the criminal justice system encountered a given offender within a specific time-period. An increase or decrease in the proportion of participants committing a certain type of offense is usually considered the primary measure of effectiveness of any intervention. Yet such a binary operationalization of re-offending does not provide a complete picture of re-offending and might provide distorted or even false results by failing to take into account the seriousness and frequency of the re-offending. This paper begins by outlining why re-offending should be measured in a non-binary way, discussing the aims of evaluated treatments, the black-and-white nature of dichotomization, results from studies on desistance, chronic offenders and the effectiveness of sanctions including incapacitation. I then discuss possible ways of measuring the seriousness and frequency of re-offending, with a specific focus on their measurement in the continental European context and on the measure of re-conviction (whereas re-arrest is usually used as the equivalent measure in common law countries). I discuss the possible use of sentencing ranges set by legislators or of starting points set within various forms of sentencing guidelines to measure seriousness, in a similar way as the Cambridge Crime Harm Index does. I pay particular attention to the operationalization of the re-conviction measure in studying the effect of sanctions.