Economic evaluation of the prevention of falls resulting from missed care in polish hospitals.

Objectives: Falls are associated with increased morbidity, mortality, prolonged hospitalization and an increase in the cost of treatment in hospitals. They contribute to the deterioration of fitness and quality of life, especially among older patients, thus posing a serious social and economic problem. They increase the risk of premature death. Falls are adverse, costly, and potentially preventable. The aim of the study was to analyze the cost-effectiveness of avoiding one fall by nurse care provided by the nurses with higher education, from the perspective of the health service provider. Methods: The economic analysis included and compared only the cost of nurse intervention measured by the hours of care provided with higher education in non-surgical departments (40.5%) with higher time spend by nurses with higher education level an increase in the number of hours by 10% (50.5%) to avoid one fall. The time horizon for the study is 1 year (2021). Cost-effectiveness and Cost-benefit analysis were performed. All registered falls of all hospitalized patients were included in the study. Results: In the analyzed was based on the case control study where, 7,305 patients were hospitalized, which amounted to 41,762 patient care days. Care was provided by 100 nurses, including 40 nurses with bachelor's degrees and nurses with Master of Science in Nursing. Increasing the hours number of high-educated nurses care by 10% in non-surgical departments decreased the chance for falls by 9%; however, this dependence was statistically insignificant (OR = 1.09; 95% CI: 0.72-1.65; p = 0.65). After the intervention (a 10% increase in Bachelor's Degrees/Master of Science in Nursing hours), the number of additional Bachelor's Degrees/Master of Science hours was 6100.5, and the cost was USD 7630.4. The intervention eliminated four falls. The cost of preventing one fall is CER = USD 1697.1. Conclusion: The results of these studies broaden the understanding of the relationship among nursing education, falls, and the economic outcomes of hospital care. According to the authors, the proposed intervention has an economic justification.

Toddlers' Helping Behavior Is Affected by the Effortful Costs Associated With Helping Others.

Although the presence of early helping behavior has been firmly established, it is unclear to what extent children are willing to adopt costs to help others, as well as how this willingness changes as children get older. Canadian 21- to 36-month-olds (N = 48) participated in four helping tasks varying in the type and degree of effort required to help (lifting force, cognitive load, the number of steps in a task, and pushing force). When costs were lower, toddlers were not only more likely to help but also provided help more readily and helped in ways that prioritized others' needs. Importantly, we found that age and how costly helping was to individual children each uniquely predicted high-cost helping, but not low-cost helping. Overall, we demonstrate that toddlers' helping is sensitive to a variety of effortful costs, while simultaneously demonstrating that maturation and individual costs appear to uniquely influence high-cost helping.

Public health impact and return on investment of the pediatric national immunization program in Italy.

OBJECTIVES: We conducted a cost-benefit analysis of the pediatric National Immunization Program (NIP) in Italy. METHODS: An economic model evaluated the benefit-cost ratio (BCR) of the Italian pediatric NIP, including 10 pathogens for mandatory vaccines and 4 pathogens for recommended vaccines for children aged 0-10 years from the healthcare-sector and societal perspectives. Separate decision trees were used to model each vaccine-preventable disease (VPD). The 2020 birth cohort (n = 420,084) was followed over their lifetime; the model projected and compared discounted disease cases, life-years, quality-adjusted life-years (QALYs), and costs (2021 euros) with and without immunization (based on current and pre - vaccine era disease incidence estimates, respectively). RESULTS: The pediatric NIP was estimated to prevent 1.8 million cases of VPDs and 3,330 deaths, resulting in 45,900 fewer life-years lost and 57,000 fewer QALYs lost. Vaccination costs of €285 million were offset by disease cost savings of €1.6 billion, resulting in a BCR of 5.6 from a societal perspective (BCR = 1.7 from a healthcare-sector perspective). When QALYs gained were valued, the BCR increased to 15.6. CONCLUSIONS: The benefits of the Italian pediatric NIP, including averted disease-related morbidity, mortality, and associated costs, highlight the value of continued investment in pediatric immunization.

A comparative effectiveness study of usual care, simple Chuna manual therapy, and complex Chuna manual therapy for the treatment of pelvic biomechanical lesions in patients with non-acute low back pain: a protocol for multicenter, randomized controlled trial.

BACKGROUND: Chuna manual therapy (CMT), a Korean manual therapy technique predominantly used for treating low back pain (LBP) and related disorders, lacks well-conceived research focusing on its comparative effectiveness, safety, and economic evaluation, particularly with respect to complex CMT with established CMT diagnostic algorithms. This study aims to illustrate a protocol for a randomized clinical study for comparative effectiveness and cost-effectiveness of complex CMT with simple CMT and usual care. METHODS: This is a protocol for a three-armed, multicenter, assessor-blinded, pragmatic, randomized controlled trial study. A total of 81 patients suffering from non-acute LBP with pelvic biomechanical lesions (PBL), characterized by a pain duration of at least two weeks and a Numeric Rating Scale (NRS) score of 5 or higher, will be recruited from two Korean medicine hospitals. These participants will be randomly assigned to one of three groups: complex CMT plus usual care (UC; n = 27), simple CMT plus UC (n = 27), or UC groups (n = 27). They will undergo treatment for 4 weeks, and follow-up assessments will be performed 8 weeks after treatment completion. The primary outcome will be the NRS score of LBP, and secondary outcomes will include the Oswestry Disability Index, Patient Global Impression of Change, credibility and expectancy questionnaire, three-dimensional posture analysis indicators, quality of life assessment, economic evaluation, and safety assessments. DISCUSSION: This will be the first study to assess the comparative effectiveness, safety, and cost-effectiveness of complex CMT compared to UC and simple/complex CMT in patients with LBP and PBL. We will also analyze useful diagnostic methods to help in clinical practice for CMT diagnosis. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), KCT0009210. Registered on February 28, 2024.

Recommendations for Interchangeability in a Growing Biosimilar Market in Latin America.

BACKGROUND: Biosimilars offer significant advantages for improving access to biologic treatments in Latin America. However, their uptake has been slow due to misconceptions, regulatory uncertainties, and inadequate pharmacovigilance. OBJECTIVE: To address these issues, Americas Health Foundation convened a multidisciplinary panel of regional experts in biosimilar use and interchangeability from Latin America. The panel assessed the current landscape and recommended steps to enhance access. RESULTS: Key recommendations include strengthening biosimilar regulations, ensuring transparent enforcement, implementing robust pharmacovigilance, and promoting collaboration among stakeholders to educate about the safety, efficacy, and economic advantages of biosimilars and their interchangeability. CONCLUSIONS: By embracing biosimilars and interchangeability, Latin American countries can expand patient access, foster competition, diversify treatment sources, and enhance the sustainability of their healthcare systems. However, achieving these goals requires addressing knowledge gaps and biases among healthcare providers, patients, regulators, and government agencies. This can be accomplished through clear communication and the use of real-world evidence.

Biosimilars offer an opportunity to expand access to crucial biologic treatments in Latin America by providing lower-cost alternatives when patents expire. However, adopting biosimilars has been slow due to misconceptions and regulatory uncertainties. To address this, experts recommend considering approved biosimilars as interchangeable with reference products, allowing for switching without compromising safety or efficacy, with the limitation of switching only once per year. To improve access, well-defined regulations, enforcement, and transparency from regulatory agencies are necessary, along with education for healthcare providers, patients, and other stakeholders to address knowledge gaps and negative perceptions. Improved pharmacovigilance systems and collaboration between stakeholders can help communicate the benefits of biosimilars and interchangeability. By embracing biosimilars, Latin American countries can expand patient access, foster market competition, diversify treatment options, and improve the sustainability of healthcare systems.

Implementing a Streamlined Hypoglossal Nerve Stimulator Pathway: Cost, Time to Surgery, and Outcomes.

Objective: To evaluate the costs, time to surgery, and clinical outcomes associated with implementing a streamlined hypoglossal nerve stimulator (HGNS) implantation pathway. Study Design: Retrospective cohort study. Setting: Single tertiary care center in the United States from 2016 to 2023. Methods: Patients with a lack of complete concentric collapse of the velum during volitional snore on in-office laryngoscopy qualified for the streamlined HGNS pathway. This pathway consisted of confirmatory drug-induced sleep endoscopy (DISE) followed immediately by HGNS implantation during the same surgical encounter. Outcomes were compared to patients in the traditional pathway (standalone DISE followed by HGNS implantation on a later date). Results: A total of 68 patients (13 streamlined, 55 traditional) with obstructive sleep apnea who underwent HGNS implantation were included. Patients were predominately male (70.6%) and White (95.6%) and had a mean (SD) age of 63.5 (10.0) years. The streamlined pathway was associated with a significant reduction in both hospital costs (mean difference $9258, 95% confidence interval [CI]: 3690-14,825; P = .002) and time to surgery (mean decrease of 3.82 months, 95% CI: 0.83-6.80 months; P = .013) compared to the traditional pathway. Patients in both groups had reduction in apnea-hypopnea index and Epworth Sleepiness Scale score, with no significant differences in comparisons between groups. Conclusion: In select patients, the streamlined HGNS pathway may expedite time to surgery and reduce hospital costs with comparable clinical outcomes to a traditional 2-stage pathway. Further research is warranted to validate patient selection and better understand longitudinal outcomes.

The effect of two speech and language approaches on speech problems in people with Parkinson's disease: the PD COMM RCT.

Background: Speech impairments are common with Parkinson's disease (reported prevalence 68%), increasing conversational demands, reliance on family and social withdrawal. Objective(s): The PD COMM trial compared the clinical and cost-effectiveness of two speech and language therapy approaches: Lee Silverman Voice Treatment LOUD and National Health Service speech and language therapy for the treatment of speech or voice problems in people with Parkinson's disease to no speech and language therapy (control) and against each other. Design: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Participants were randomised in a 1 : 1 : 1 ratio to control, National Health Service speech and language therapy or Lee Silverman Voice Treatment LOUD via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Mixed-methods process and health economic evaluations were conducted. Setting: United Kingdom outpatient and home settings. Participants: People with idiopathic Parkinson's disease, with self-reported or carer-reported speech or voice problems. We excluded people with dementia, laryngeal pathology and those within 24 months of previous speech and language therapy. Interventions: The Lee Silverman Voice Treatment LOUD intervention included maximum effort drills and high-effort speech production tasks delivered over four 50-minute therapist-led personalised sessions per week, for 4 weeks with prescribed daily home practice. National Health Service speech and language therapy content and dosage reflected local non-Lee Silverman Voice Treatment speech and language therapy practices, usually 1 hour, once weekly, for 6 weeks. Trained, experienced speech and language therapists or assistants provided interventions. The control was no speech and language therapy until the trial was completed. Main outcome measures: Primary outcome: Voice Handicap Index total score at 3 months. Secondary outcomes: Voice Handicap Index subscales, Parkinson's Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5L; ICEpop Capabilities Measure for Older Adults; Parkinson's Disease Questionnaire - Carers; resource utilisation; and adverse events. Assessments were completed pre-randomisation and at 3, 6 and 12 months post randomisation. Results: Three hundred and eighty-eight participants were randomised to Lee Silverman Voice Treatment LOUD (n = 130), National Health Service speech and language therapy (n = 129) and control (n = 129). The impact of voice problems at 3 months after randomisation was lower for Lee Silverman Voice Treatment LOUD participants than control [-8.0 (99% confidence interval: -13.3, -2.6); p = 0.001]. There was no evidence of improvement for those with access to National Health Service speech and language therapy when compared to control [1.7 (99% confidence interval: -3.8, 7.1); p = 0.4]. Participants randomised to Lee Silverman Voice Treatment LOUD reported a lower impact of their voice problems than participants randomised to National Health Service speech and language therapy [99% confidence interval: -9.6 (-14.9, -4.4); p < 0.0001]. There were no reports of serious adverse events. Staff were confident with the trial interventions; a range of patient and therapist enablers of implementing Lee Silverman Voice Treatment LOUD were identified. The economic evaluation results suggested Lee Silverman Voice Treatment LOUD was more expensive and more effective than control or National Health Service speech and language therapy but was not cost-effective with incremental cost-effectiveness ratios of £197,772 per quality-adjusted life-year gained and £77,017 per quality-adjusted life-year gained, respectively. Limitations: The number of participants recruited to the trial did not meet the pre-specified power. Conclusions: People that had access to Lee Silverman Voice Treatment LOUD described a significantly greater reduction in the impact of their Parkinson's disease-related speech problems 3 months after randomisation compared to people that had no speech and language therapy. There was no evidence of a difference between National Health Service speech and language therapy and those that received no speech and language therapy. Lee Silverman Voice Treatment LOUD resulted in a significantly lower impact of voice problems compared to National Health Service speech and language therapy 3 months after randomisation which was still present after 12 months; however, Lee Silverman Voice Treatment LOUD was not found to be cost-effective. Future work: Implementing Lee Silverman Voice Treatment LOUD in the National Health Service and identifying alternatives to Lee Silverman Voice Treatment LOUD for those who cannot tolerate it. Investigation of less costly alternative options for Lee Silverman Voice Treatment delivery require investigation, with economic evaluation using a preference-based outcome measure that captures improvement in communication. Study registration: This study is registered as ISRCTN12421382. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 10/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 58. See the NIHR Funding and Awards website for further award information.

Most people with Parkinson's disease develop difficulties with their speech and voice. Communicating becomes difficult. This affects their relationships, work, social life and how they feel about themselves. Our PD COMM trial compared two types of speech and language therapy to find out if they helped the speech and voice problems people with Parkinson's have. We measured changes in the way their voice and speech problems affected their lives and how much therapy cost the National Health Service and families. Everyone taking part had speech or voice problems because of their Parkinson's disease. People could not take part if they had dementia, evidence of laryngeal pathology or previous laryngeal surgery or received speech and therapy for Parkinson's disease in the last 2 years. People who agreed to take part joined one of three groups, which were alike except for the therapy they received. A computer decided which group they joined by chance. National Health Service speech and language therapy Lee Silverman Voice Treatment LOUD No speech and language therapy for 12 months The 388 people who took part came from 41 outpatient clinics in Scotland, England and Wales. Most were older men. The people that received Lee Silverman Voice Treatment LOUD felt better about their speech and voice after 3 months compared to people in the other groups. A year later, they still felt better about it. People that received National Health Service therapy had no benefit compared to people with no access to therapy. Analysis of cost-effectiveness indicated that Lee Silverman Voice Treatment LOUD did not offer value for money and the intervention cost more because more speech and language therapy time was needed to deliver it. Our next question is to ask how we can provide Lee Silverman Voice Treatment LOUD in a way that costs less, for example, using therapy assistants and computer packages or at home. Clear speech and language therapy approaches for people with Parkinson's disease and speech or voice problems should be tested in trials that measure changes in people's lives.

Transperineal biopsy devices in people with suspected prostate cancer - a systematic review and economic evaluation.

Background: People with suspected prostate cancer are usually offered either a local anaesthetic transrectal ultrasound-guided prostate biopsy or a general anaesthetic transperineal prostate biopsy. Transperineal prostate biopsy is often carried out under general anaesthetic due to pain caused by the procedure. However, recent studies suggest that performing local anaesthetic transperineal prostate biopsy may better identify cancer in particular regions of the prostate and reduce infection rates, while being carried out in an outpatient setting. Devices to assist with freehand methods of local anaesthetic transperineal prostate may also help practitioners performing prostate biopsies. Objectives: To evaluate the clinical effectiveness and cost-effectiveness of local anaesthetic transperineal prostate compared to local anaesthetic transrectal ultrasound-guided prostate and general anaesthetic transperineal prostate biopsy for people with suspected prostate cancer, and local anaesthetic transperineal prostate with specific freehand devices in comparison with local anaesthetic transrectal ultrasound-guided prostate and transperineal prostate biopsy conducted with a grid and stepping device conducted under local or general anaesthetic. Data sources and methods: We conducted a systematic review of studies comparing the diagnostic yield and clinical effectiveness of different methods for performing prostate biopsies. We used pairwise and network meta-analyses to pool evidence on cancer detection rates and structured narrative synthesis for other outcomes. For the economic evaluation, we reviewed published and submitted evidence and developed a model to assess the cost-effectiveness of the different biopsy methods. Results: We included 19 comparative studies (6 randomised controlled trials and 13 observational comparative studies) and 4 single-arm studies of freehand devices. There were no statistically significant differences in cancer detection rates for local anaesthetic transperineal prostate (any method) compared to local anaesthetic transrectal ultrasound-guided prostate (relative risk 1.00, 95% confidence interval 0.85 to 1.18) (n = 5 randomised controlled trials), as was the case for local anaesthetic transperineal prostate with a freehand device compared to local anaesthetic transrectal ultrasound-guided prostate (relative risk 1.40, 95% confidence interval 0.96 to 2.04) (n = 1 randomised controlled trial). Results of meta-analyses of observational studies were similar. The economic analysis indicated that local anaesthetic transperineal prostate is likely to be cost-effective compared with local anaesthetic transrectal ultrasound-guided prostate (incremental cost below £20,000 per quality-adjusted life-year gained) and less costly and no less effective than general anaesthetic transperineal prostate. local anaesthetic transperineal prostate with a freehand device is likely to be the most cost-effective strategy: incremental cost versus local anaesthetic transrectal ultrasound-guided prostate of £743 per quality-adjusted life-year for people with magnetic resonance imaging Likert score of 3 or more at first biopsy. Limitations: There is limited evidence for efficacy in detecting clinically significant prostate cancer. There is comparative evidence for the PrecisionPoint™ Transperineal Access System (BXTAccelyon Ltd, Burnham, UK) but limited or no evidence for the other freehand devices. Evidence for other outcomes is sparse. The cost-effectiveness results are sensitive to uncertainty over cancer detection rates, complication rates and the numbers of core samples taken with the different biopsy methods and the costs of processing them. Conclusions: Transperineal prostate biopsy under local anaesthetic is equally efficient at detecting prostate cancer as transrectal ultrasound-guided prostate biopsy under local anaesthetic but it may be better with a freehand device. local anaesthetic transperineal prostate is associated with urinary retention type complications, whereas local anaesthetic transrectal ultrasound-guided prostate has a higher infection rate. local anaesthetic transperineal prostate biopsy with a freehand device appears to meet conventional levels of costeffectiveness compared with local anaesthetic transrectal ultrasound-guided prostate. Study registration: This study is registered as PROSPERO CRD42021266443. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR134220) and is published in full in Health Technology Assessment Vol. 28, No. 60. See the NIHR Funding and Awards website for further award information.

A prostate biopsy can help determine if a person has prostate cancer. The main ways of performing a prostate biopsy involve taking small samples of the prostate out through the rectum (back passage) or through the perineum ­ the skin area between the anus and the scrotum (testicles). Both methods use ultrasound images from a probe inserted into the rectum to help the clinician see what they are doing. Taking samples through the rectum is usually carried out under local anaesthetic, whereas taking samples through the perineum is usually carried out under general anaesthetic. We wanted to find out if taking samples through the perineum under local anaesthetic (instead of general anaesthetic) would be equally effective at detecting prostate cancer as the other biopsy methods and whether there was any improvement or change in the sorts of side effects people may have. We also wanted to know if people found the biopsy painful or not. We carried out searches of computer research databases to find relevant clinical and cost-effectiveness studies and compared the effectiveness of the different biopsy methods they used. We read and summarised the results of the studies we found in our search. Our findings showed that taking biopsy samples through the perineum under local anaesthetic had rates of detecting prostate cancer similar to those of the other biopsy methods. But if the clinician also used a freehand device that helps guide the biopsy needle as part of the procedure, then this may be a better method for detecting cancer. The studies we found agreed that performing this prostate biopsy under local anaesthetic was not too painful for most people. Our economic estimates suggest that using a freehand device for local anaesthetic perineal (through the skin of the perineum) biopsy may be a cost-effective use of National Health Service resources.

Clinical and economic impact of pharmacist interventions to identify drug-related problems in multidisciplinary cancer care: a prospective trial.

BACKGROUND: The prescription of antitumor drugs has often been associated with drug-related problems. Pretherapeutic multidisciplinary risk assessment programs including pharmaceutical care have been established to secure the initiation of injectable and oral antitumor therapies. This prospective cross-sectional double-center study evaluated the clinical and economic impact of the pharmacist in detecting drug-related problems in patients initiating antitumor therapies. MATERIALS AND METHODS: Following pharmaceutical consultations, pharmaceutical interventions were validated by a multidisciplinary team. A committee of independent clinical experts assessed the potential clinical impact of drug-drug interactions. The association of clinical variables with pharmaceutical interventions was tested using a multivariate logistic regression model. Pharmacist cost of the program was assessed by valuing pharmacists' time at their salaries and compared with potentially avoided costs. RESULTS: Four hundred thirty-eight patients with solid tumors were included: 62% males, mean age of 65 ±â€…13 years, and average of 6 medications. Half of the patients required at least one pharmaceutical intervention and independent factors associated with pharmaceutical interventions were the number of medications (5-9 vs <5: OR = 2.91 [95% CI 1.82-4.65], P < .001) and the type of antitumor treatment (immunotherapy vs intravenous chemotherapy: OR = 0.35 [95% CI 0.18-0.68], P = .002). One hundred seventy-four out of 266 pharmaceutical interventions (130 patients) involved clinically significant drug-drug interactions. Pharmacist costs were estimated to range between €4899 and €6125. Average costs were estimated at €11.4-14.3 per patient. Avoided hospitalization costs were estimated to be €180 633. CONCLUSION: Clinical pharmacists contribute to the cost-effective reduction of drug-related problems in pre-therapeutic assessment programs for patients with cancer.

Environmental and socio-economic evaluation of a groundwater bioremediation technology using social Cost-Benefit Analysis: Application to an in-situ metal(loid) precipitation case study.

Bioremediation can be an alternative or complementary approach to conventional soil and water treatment technologies. Determining the environmental and socio-economic impacts of bioremediation is important but rarely addressed. This work presents a comprehensive sustainability assessment for a specific groundwater bioremediation case study based on In-situ Metal(loid) Precipitation (ISMP) by conducting a social Cost-Benefit Analysis (CBA) using two different approaches: environmental Life Cycle Costing (eLCC) and Impact Pathway Approach (IPA). Externalities are calculated in two ways: i) using Environmental Prices (EP) to monetize Life Cycle Assessment (LCA) results and metal(loid)s removed at field scale, and ii) following the IPA steps to determine the social costs avoided by removing arsenic contamination at full scale. The results show that, in the baseline scenario, the project is not socio-economically viable in both cases as the Net Present Value (NPV) is -129,512.61 € and - 415,185,140 € respectively. Sensitivity and scenario analyses are performed to identify the key parameters and actions needed to reach a positive NPV. For instance, increasing the amount of water treated per year to 90 m3 and assuming a 20 % increase in operation costs and a 60 % increase in construction costs can make the project socio-economically viable at the field scale, while a reduction in the social discount rate from a 4 % to a 2 % can lead to a positive NPV at the full scale. The approaches proposed in this work may be useful for practitioners and policymakers when evaluating the environmental and socio-economic impacts of bioremediation technologies at different scales and regions, as well as human health impacts caused by contaminants at the current legal limits.

Cost-Benefit Analysis of a Pediatric ICU Sedation Weaning Protocol.

OBJECTIVE: A risk stratified sedation weaning protocol improved patient outcomes in a pediatric intensive care unit (PICU). We sought to determine the protocol effect on medication costs. METHODS: This was a retrospective observational cohort study in an academic tertiary care children's hospital PICU (2018-2020) comparing the cost when weaning benzodiazepine, alpha agonist, and/or opioid infusions in intubated children <18 years of age. RESULTS: There were 84 total sedation weaning instances (pre-protocol n = 41 and post-protocol n = 41); 2 patients had 2 encounters, 1 in each phase. The total cost (in 2022 United States Dollars) of sedation weaning was $400,328.87 ($15,994.44/kg) pre-protocol compared with $170,458.85 ($11,227.52/kg) post-protocol. The median cost of sedation wean per patient for pre-protocol patients was $3197.42 (IQR: $322.66-$12,643.29) and post-protocol patients was $1851.44 (IQR: $425.05-$5355.85; p = 0.275). A linear regression model estimated the expected cost of sedation wean for post-protocol patients to be $5173.20 lower than for pre-protocol patients of the same weight and overall drug risk (p = 0.036). The proportion of withdrawal symptoms in the pre-protocol patients (16%) was not significantly different from the proportion in the post-protocol patients (14%; p = 0.435). CONCLUSIONS: Implementation of a PICU sedation weaning protocol in a single-center conferred cost benefit without negatively impacting patient outcomes. A larger multicenter study would provide insight to the applicability to PICUs in varied settings with differing patient populations.

Enhancing Patient Comprehension in Skull-Base Meningioma Surgery through 3D Volumetric Reconstructions: A Cost-Effective Approach.

BACKGROUND: Understanding complex neurosurgical procedures and diseases, such as skull-base meningiomas, is challenging for patients due to the intricate anatomy and the involvement of critical neurovascular structures. Enhanced patient comprehension is crucial for satisfaction and improved clinical outcomes. Patient-specific 3D models have demonstrated benefits in patient education, though they are costly and time-intensive to produce. This study investigates whether the use of 3D volumetric reconstructions with anatomical segmentation, widely available via neuronavigation software, can improve patients' understanding of skull-base meningiomas, surgical procedures, and potential complications. MATERIALS AND METHODS: This study included twenty patients with skull-base meningiomas. Three-dimensional volume reconstructions and anatomical segmentations were created using preoperative MRI sequences with neuronavigation software. These reconstructions were used during patient consultations where a surgeon explained key aspects of the disease, the surgical intervention, and potential complications. A questionnaire assessed the patients' perceptions of the utility of these 3D reconstructions. RESULTS: The majority of patients (75%) found the 3D volumetric reconstructions and anatomical segmentations to be more beneficial than MRI images for understanding their disease. Similarly, 75% reported improved comprehension of the surgical approach, and 85% felt that the reconstructions enhanced their understanding of potential surgical complications. Overall, 65% of patients considered the 3D reconstructions valuable in medical consultations. CONCLUSIONS: Our study indicates that using accessible, cost-effective, and non-time-consuming 3D volumetric reconstructions with anatomical segmentation enhances patient understanding of skull-base meningiomas. Further research is necessary to confirm these findings, compare these reconstructions with physical 3D models and virtual reality models, and evaluate their impact on patient anxiety regarding the surgical procedure.

Why animals construct helical burrows: Construction vs. post-construction benefits.

The extended phenotype of helical burrowing behavior in animals has evolved independently many times since the Cambrian explosion (~540 million years ago [MYA]). A number of hypotheses have been proposed to explain the evolution of helical burrowing in certain taxa, but no study has searched for a general explanation encompassing all taxa. We reviewed helical burrowing in both extant and extinct animals and from the trace fossil record and compiled 10 hypotheses for why animals construct helical burrows, including our own ideas. Of these, six are post-construction hypotheses-benefits to the creator or offspring, realized after burrow construction-and four are construction hypotheses reflecting direct benefits to the creator during construction. We examine the fit of these hypotheses to a total of 21 extant taxa and ichnotaxa representing 59-184 possible species. Only two hypotheses, antipredator and biomechanical advantage, cannot be rejected for any species (possible in 100% of taxa), but six of the hypotheses cannot be rejected for most species (possible in 86%-100% of taxa): microclimate buffer, reduced falling sediment (soil), anticrowding, and vertical patch. Four of these six are construction hypotheses, raising the possibility that helical burrowing may have evolved without providing post-construction benefits. Our analysis shows that increased drainage, deposit feeding, microbial farming, and offspring escape cannot explain helical burrowing behavior in the majority of taxa (5%-48%). Overall, the evidence does not support a general explanation for the evolution of helical burrowing in animals. The function and evolution of the helix as an extended phenotype seems to provide different advantages for different taxa in different environments under different physicochemical controls (some traces/tracemakers are discussed in more detail due to their association with body fossils and well-constrained physicochemical parameters). Although direct tests of many of the hypotheses would be difficult, we nevertheless offer ways to test some of the hypotheses for selected taxa.

Silicone adhesive multilayer foam dressings to prevent hospital-acquired sacrum pressure ulcers: An economic evaluation based on a publicly funded pragmatic randomized controlled trial linked with real-world data.

OBJECTIVES: To estimate the cost-effectiveness of sacrum multilayer silicone foam dressings as an adjuvant prophylactic therapy compared to standard pressure ulcer prevention in a hospital population at high risk for pressure ulcer development. METHODS: An economic evaluation is performed from a healthcare payer's perspective. This evaluation is based on a Belgian publicly funded pragmatic randomized controlled trial (RCT), linked with real-world data from administrative claims database and a Belgian cost analysis. A cost-consequences analysis with a one-year time horizon is performed. RESULTS: The RCT has shown that the risk of developing a new pressure ulcer on the sacrum was statistically significantly reduced by 41 % in the treatment group (RR = 0.59, 95 % CI 0.35-0.98, p = 0.04). The absolute risk reduction of 2.0 % (95 % CI -0.1-4.1 %) coincides with a number needed to treat of 50.0 to prevent one new pressure ulcer of category II or worse. The evolution of quality of life is on average negative for patients who developed a pressure ulcer before day 3, while it is positive for patients without pressure ulcers. In a scenario with conservative assumptions, i.e. without inclusion of price discounts for the multilayer silicone foam dressings and only including costs during the hospitalization, pressure ulcer prevention with dressings on the sacrum was already cost-neutral. CONCLUSIONS: The preventive use of silicone adhesive multilayer foam dressings on the sacrum for a population similar to the pragmatic trial population can be supported both from a clinical and economic point of view.

Is it worth screening quarry workers for TB infection in high-incidence areas? A cost-benefit analysis.

BACKGROUND: Tuberculosis (TB) infection screening of high-risk groups is an important strategy for achieving End TB targets. A TB infection screening program was implemented for quarry workers from a Portuguese high-incidence area in 2018-2022. We aimed to calculate the cost-benefit of the screening program from the societal perspective. METHODS: We calculated medical and non-medical direct and indirect screening costs and compared them with the cost savings from averted cases of TB disease. We estimated the number of potentially averted TB disease cases based on the risk of progression of TB infection to TB disease found in the literature. RESULTS: During the screening program, 997 workers were screened. TB infection was diagnosed in 215 workers, 150 of those initiated preventive treatment. Screening program total costs were €136,295. Twenty-nine TB cases were potentially prevented, what would have costed €152,386. Savings of €16,091 were obtained (€4516, €40898, and -€29322 from the workers, employers, and NHS, respectively). CONCLUSIONS: The monetary benefit of a TB infection screening program directed to quarry workers in a high-incidence area was greater than its cost. Companies and workers saved substantially more money. TB infection tests that are better predictors of progression to TB disease could reduce NHS costs.

Temporary treatment cessation compared with continuation of tyrosine kinase inhibitors for adults with renal cancer: the STAR non-inferiority RCT.

Background: There is interest in using treatment breaks in oncology, to reduce toxicity without compromising efficacy. Trial design: A Phase II/III multicentre, open-label, parallel-group, randomised controlled non-inferiority trial assessing treatment breaks in patients with renal cell carcinoma. Methods: Patients with locally advanced or metastatic renal cell carcinoma, starting tyrosine kinase inhibitor as first-line treatment at United Kingdom National Health Service hospitals. Interventions: At trial entry, patients were randomised (1 : 1) to a drug-free interval strategy or a conventional continuation strategy. After 24 weeks of treatment with sunitinib/pazopanib, drug-free interval strategy patients took up a treatment break until disease progression with additional breaks dependent on disease response and patient choice. Conventional continuation strategy patients continued on treatment. Both trial strategies continued until treatment intolerance, disease progression on treatment, withdrawal or death. Objective: To determine if a drug-free interval strategy is non-inferior to a conventional continuation strategy in terms of the co-primary outcomes of overall survival and quality-adjusted life-years. Co-primary outcomes: For non-inferiority to be concluded, a margin of ≤ 7.5% in overall survival and ≤ 10% in quality-adjusted life-years was required in both intention-to-treat and per-protocol analyses. This equated to the 95% confidence interval of the estimates being above 0.812 and -0.156, respectively. Quality-adjusted life-years were calculated using the utility index of the EuroQol-5 Dimensions questionnaire. Results: Nine hundred and twenty patients were randomised (461 conventional continuation strategy vs. 459 drug-free interval strategy) from 13 January 2012 to 12 September 2017. Trial treatment and follow-up stopped on 31 December 2020. Four hundred and eighty-eight (53.0%) patients [240 (52.1%) vs. 248 (54.0%)] continued on trial post week 24. The median treatment-break length was 87 days. Nine hundred and nineteen patients were included in the intention-to-treat analysis (461 vs. 458) and 871 patients in the per-protocol analysis (453 vs. 418). For overall survival, non-inferiority was concluded in the intention-to-treat analysis but not in the per-protocol analysis [hazard ratio (95% confidence interval) intention to treat 0.97 (0.83 to 1.12); per-protocol 0.94 (0.80 to 1.09) non-inferiority margin: 95% confidence interval ≥ 0.812, intention to treat: 0.83 > 0.812 non-inferior, per-protocol: 0.80 < 0.812 not non-inferior]. Therefore, a drug-free interval strategy was not concluded to be non-inferior to a conventional continuation strategy in terms of overall survival. For quality-adjusted life-years, non-inferiority was concluded in both the intention-to-treat and per-protocol analyses [marginal effect (95% confidence interval) intention to treat -0.05 (-0.15 to 0.05); per-protocol 0.04 (-0.14 to 0.21) non-inferiority margin: 95% confidence interval ≥ -0.156]. Therefore, a drug-free interval strategy was concluded to be non-inferior to a conventional continuation strategy in terms of quality-adjusted life-years. Limitations: The main limitation of the study is the fewer than expected overall survival events, resulting in lower power for the non-inferiority comparison. Future work: Future studies should investigate treatment breaks with more contemporary treatments for renal cell carcinoma. Conclusions: Non-inferiority was shown for the quality-adjusted life-year end point but not for overall survival as pre-defined. Nevertheless, despite not meeting the primary end point of non-inferiority as per protocol, the study suggested that a treatment-break strategy may not meaningfully reduce life expectancy, does not reduce quality of life and has economic benefits. Although the treating clinicians' perspectives were not formally collected, the fact that clinicians recruited a large number of patients over a long period suggests support for the study and provides clear evidence that a treatment-break strategy for patients with renal cell carcinoma receiving tyrosine kinase inhibitor therapy is feasible. Trial registration: This trial is registered as ISRCTN06473203. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Programme (NIHR award ref: 09/91/21) and is published in full in Health Technology Assessment; Vol. 28, No. 45. See the NIHR Funding and Awards website for further award information.

Treatment breaks in cancer are of significant interest to patients and health professionals. Renal cell carcinoma is the most common type of kidney cancer. Sunitinib and pazopanib are both targeted treatments. They were commonly used to treat advanced kidney cancer but often cause side effects, sometimes requiring use of a reduced dose or even stopping treatment. The STAR trial was designed to see whether planned treatment breaks made patients with advanced kidney cancer being treated with sunitinib and pazopanib feel better, without substantially affecting how well the treatment worked. After 24 weeks of treatment, patients took sunitinib and pazopanib either as they normally would or in the alternative way with planned treatment breaks. Treating patients in this way was continued until drug-related side effects stopped treatment, patients' disease worsened while taking treatment or the patient died. The trial compared how well the different treatment strategies worked in terms of how long patients lived and their quality of life over that time. This trial is the largest United Kingdom trial in advanced renal cell carcinoma. Patients took part from 60 United Kingdom centres between 2012 and 2017. It was funded by the National Institute for Health and Care Research Health Technology Assessment Programme and run by the Leeds Clinical Trials Research Unit. In total, 920 patients took part. Four hundred and sixty-one patients were allocated to continue treatment and 459 were allocated to start at least one treatment break. Treatment breaks lasted on average 87 days. The length of time patients lived in both arms of the trial appeared similar, but this cannot be concluded due to insufficient information. Being allocated to have treatment breaks rather than continuing treatment did not negatively impact a patient's quality of life. Additionally, allocating patients to have treatment breaks was shown to have significant cost savings compared to just continuing treatment. Importantly planned treatment breaks were shown to be feasible.

Validating costly protected area restoration after (increasing) disasters.

Protected areas such as national parks constitute an increasing land mass globally, but these areas are under increasing threat from climate change events such as drought, flooding, and bushfires. The recent Yosemite National Park fires in California provide an example of this issue. After any such disaster, authorities will need to restore those protected areas to their former state at significant costs within any public funding cycle. To corroborate that request, clear economic assessments of total costs and benefits will be required. However, in previous studies of these issues a complete set of government cost and/or benefit data may not be provided, skewing assessment results accordingly. Using South Australia's Kangaroo Island protected areas-which were significantly destroyed by bushfire in 2019-20-as a case study with a unique set of State government cost data we calculate a set of analyses via economic methods. Despite significant restoration costs the study found the discounted net present value of returning tourists to the Island is 3.15 over ten years for park tourism and regional economic impacts, providing an internal rate of return of 22%. The rebuild work is also expected to support around 430 full time equivalent (FTE) jobs during construction, with a return to full tourism supporting another 744 FTEs across relevant sectors (e.g. accommodation, retail) of the Kangaroo Island economy. This robust assessment makes it far easier for protected area managers to argue their funding case.

The "Other E" in ELSI: The Use of Economic Evaluation to Inform the Expansion of Newborn Screening.

The utilization and application of genomic information generated from precision medicine continues to increase with the goal of improving health outcomes. Increasingly researchers, health care professionals, and public health teams include an examination of the ethical, legal, and social issues (ELSI) in their consideration of the use of precision medicine for newborn and pediatric health. In addition to ELSI considerations, stakeholders could benefit from an understanding of economics, the other "E" in ELSI. The use of an economic evaluation could aid decision-making on whether to screen newborns who may be at risk for disease, to diagnose newborns and children who present with symptoms, to inform the treatment and management of diagnosed individuals. In this manuscript we review the core concepts of economic evaluation, the framework of decision-analysis, and key parameters for consideration in assessing the economics of NBS program(s). We describe the common language used in the economic evaluation and provide a practical overview of health economic evaluations including 1) their purpose, 2) different types and components, 3) evaluation of the different types and components of economic evaluations (i.e., cost-effectiveness vs. cost-benefit analysis), 4) impact of societal or healthcare perspectives on the analysis, 5) health outcomes, 6) time horizon for the analysis, 7) identification of appropriate comparators, and 8) resources for economic data. We conclude with a use case to demonstrate the application and understanding of economic considerations for in the advancement and expansion of NBS.

Clinical and cost-effectiveness of spironolactone in treating persistent facial acne in women: SAFA double-blinded RCT.

Background: Acne is common, can cause significant impact on quality of life and is a frequent reason for long-term antibiotic use. Spironolactone has been prescribed for acne in women for many years, but robust evidence is lacking. Objective: To evaluate whether spironolactone is clinically effective and cost-effective in treating acne in women. Design: Pragmatic, parallel, double-blind, randomised superiority trial. Setting: Primary and secondary healthcare and community settings (community and social media advertising). Participants: Women aged 18 years and older with facial acne persisting for at least 6 months, judged to potentially warrant oral antibiotic treatment. Interventions: Participants were randomised 1 : 1, using an independent web-based procedure, to either 50 mg/day spironolactone or matched placebo until week 6, increasing to 100 mg/day spironolactone or matched placebo until week 24. Participants continued usual topical treatment. Main outcome measures: Primary outcome was the adjusted mean difference in Acne-Specific Quality of Life symptom subscale score at 12 weeks. Secondary outcomes included Acne-Specific Quality of Life total and subscales; participant self-assessed improvement; Investigator's Global Assessment; Participant's Global Assessment; satisfaction; adverse effects and cost-effectiveness. Results: Of 1267 women assessed for eligibility, 410 were randomised (201 intervention, 209 control), 342 in the primary analysis (176 intervention, 166 control). Mean age was 29.2 years (standard deviation 7.2) and 7.9% (28/356) were from non-white backgrounds. At baseline, Investigator's Global Assessment classified acne as mild in 46%, moderate in 40% and severe in 13%. At baseline, 82.9% were using topical treatments. Over 95% of participants in both groups tolerated the treatment and increased their dose. Mean baseline Acne-Specific Quality of Life symptom subscale was 13.0 (standard deviation 4.7) across both groups. Mean scores at week 12 were 19.2 (standard deviation 6.1) for spironolactone and 17.8 (standard deviation 5.6) for placebo [difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46) adjusting for baseline variables]. Mean scores at week 24 were 21.2 (standard deviation 5.9) in spironolactone group and 17.4 (standard deviation 5.8) in placebo group [adjusted difference 3.77 (95% confidence interval 2.50 to 5.03) adjusted]. Secondary outcomes also favoured spironolactone at 12 weeks with greater differences at 24 weeks. Participants taking spironolactone were more likely than those taking placebo to report overall acne improvement at 12 weeks {72.2% vs. 67.9% [adjusted odds ratio 1.16 (95% confidence interval 0.70 to 1.91)]} and at 24 weeks {81.9% vs. 63.3% [adjusted odds ratio 2.72 (95% confidence interval 1.50 to 4.93)]}. Investigator's Global Assessment was judged successful at week 12 for 31/201 (18.5%) taking spironolactone and 9/209 (5.6%) taking placebo [adjusted odds ratio 5.18 (95% confidence interval 2.18 to 12.28)]. Satisfaction with treatment improved in 70.6% of participants taking spironolactone compared with 43.1% taking placebo [adjusted odds ratio 3.12 (95% confidence interval 1.80 to 5.41)]. Adverse reactions were similar between groups, but headaches were reported more commonly on spironolactone (20.4% vs. 12.0%). No serious adverse reactions were reported. Taking account for missing data through multiple imputation gave an incremental cost per quality-adjusted life-year of £27,879 (adjusted) compared to placebo or £2683 per quality-adjusted life-year compared to oral antibiotics. Conclusions: Spironolactone resulted in better participant-reported and investigator-reported outcomes than placebo, with greater differences at week 24 than week 12. Trial registration: This trial is registered as ISRCTN12892056 and EudraCT (2018-003630-33). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/13/02) and is published in full in Health Technology Assessment; Vol. 28, No. 56. See the NIHR Funding and Awards website for further award information.

Acne (or spots) is common and often persists into adulthood. Many people take long courses of antibiotic tablets, but concerns about antibiotic resistance mean alternatives are needed. Spironolactone is a medicine that is sometimes used for acne in women. However, we do not know whether it works. This trial aimed to answer this question. We invited women aged over 18 who had acne on their face for at least 6 months to take part via their general practitioner surgery, hospital or advertising. Women were randomly assigned to two groups: one group was given spironolactone and the other group was given identical-looking placebo ('dummy pill') daily for 24 weeks. Women in both groups could continue using acne treatments applied to the skin (gels/creams/lotions). We asked participants to rate their acne using a questionnaire called Acne-Specific Quality of Life, asked whether they felt their skin had improved and asked skin specialists to assess their skin. Four hundred and ten women took part, many of whom had had acne for a long time. Acne-Specific Quality of Life scores improved in both groups by 12 weeks but improved more in the spironolactone group at 12 and 24 weeks. When asked directly whether their skin had improved, 71% of participants in the spironolactone group said it had, compared with 43% on placebo. Skin specialists were also more likely to report that the acne had improved in the spironolactone group. Side effects were mild and similar in both groups but there were slightly more headaches on spironolactone (20% compared with 12%). Spironolactone is likely to represent value for money for the National Health Service, though this depends on a number of factors including what it is compared to. This trial suggests that spironolactone is a useful additional treatment for women with persistent acne.

Preventing recurrence of endometriosis-related pain by means of long-acting progestogen therapy: the PRE-EMPT RCT.

Background: Endometriosis affects 1 in 10 women, many of whom have surgery for persistent pain. Recurrence of symptoms following an operation is common. Although hormonal treatment can reduce this risk, there is uncertainty about the best option. Objectives: To evaluate the clinical and cost-effectiveness of long-acting progestogen therapy compared with the combined oral contraceptive pill in preventing recurrence of endometriosis-related pain and quality of life. Design: A multicentre, open, randomised trial with parallel economic evaluation. The final design was informed by a pilot study, qualitative exploration of women's lived experience of endometriosis and a pretrial economic model. Setting: Thirty-four United Kingdom hospitals. Participants: Women of reproductive age undergoing conservative surgery for endometriosis. Interventions: Long-acting progestogen reversible contraceptive (either 150 mg depot medroxyprogesterone acetate or 52 mg levonorgestrel-releasing intrauterine system) or combined oral contraceptive pill (30 µg ethinylestradiol, 150 µg levonorgestrel). Main outcome measures: The primary outcome was the pain domain of the Endometriosis Health Profile-30 questionnaire at 36 months post randomisation. The economic evaluation estimated the cost per quality-adjusted life-years gained. Results: Four hundred and five women were randomised to receive either long-acting reversible contraceptive (N = 205) or combined oral contraceptive pill (N = 200). Pain scores improved in both groups (24 and 23 points on average) compared with preoperative values but there was no difference between the two (adjusted mean difference: -0.8, 95% confidence interval -5.7 to 4.2; p = 0.76). The long-acting reversible contraceptive group underwent fewer surgical procedures or second-line treatments compared with the combined oral contraceptive group (73 vs. 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00). The mean adjusted quality-adjusted life-year difference between two arms was 0.043 (95% confidence interval -0.069 to 0.152) in favour of the combined oral contraceptive pill, although this cost an additional £533 (95% confidence interval 52 to 983) per woman. Limitations: Limitations include the absence of a no-treatment group and the fact that many women changed treatments over the 3 years of follow-up. Use of telephone follow-up to collect primary outcome data in those who failed to return questionnaires resulted in missing data for secondary outcomes. The COVID pandemic may have affected rates of further surgical treatment. Conclusions: At 36 months, women allocated to either intervention had comparable levels of pain, with both groups showing around a 40% improvement from presurgical levels. Although the combined oral contraceptive was cost-effective at a threshold of £20,000 per quality-adjusted life-year, the difference between the two was marginal and lower rates of repeat surgery might make long-acting reversible contraceptives preferable to some women. Future work: Future research needs to focus on evaluating newer hormonal preparations, a more holistic approach to symptom suppression and identification of biomarkers to diagnose endometriosis and its recurrence. Trial registration: This trial is registered as ISRCTN97865475. https://doi.org/10.1186/ISRCTN97865475. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/114/01) and is published in full in Health Technology Assessment; Vol. 28, No. 55. See the NIHR Funding and Awards website for further award information. The NIHR recognises that people have diverse gender identities, and in this report, the word 'woman' is used to describe patients or individuals whose sex assigned at birth was female, whether they identify as female, male or non-binary.

Endometriosis is a condition where cells similar to ones that line the womb are found elsewhere in the body. Endometriosis affects 1 in 10 women, many of whom have surgery for persistent pain. Unfortunately, symptoms often return and some women will need repeat operations. Hormonal contraceptives can prevent the return of endometriosis-related pain: either long-acting reversible contraceptives (injections or a coil, fitted inside the womb) or the combined oral contraceptive pill (often called 'the pill'). We do not know which is the best option. The aim of this trial was to find out which of these two hormone treatments was more effective in terms of symptom relief, avoidance of further surgery and costs. Four hundred and five women with endometriosis, who were not intending to get pregnant, participated in a clinical trial. Half of the participants took long-acting reversible contraceptives, and the other half took the pill for 3 years following endometriosis surgery. The choice of treatment was made at random by a computer to ensure a fair comparison, although those allocated to the long-acting contraceptive could choose between injections or the coil. Participants completed questionnaires about their symptoms and life quality at intervals up to 3 years. Both treatments were equally good at reducing pain but more women using the pill had repeat operations. The pill was a little more costly overall but associated with a slightly higher quality of life. Both treatments are equally effective in reducing pain up to 3 years after surgery for endometriosis. The differences in costs are small and the choice of treatment should be based on personal preference.