The lived experience by patients and family members of extracorporeal membrane oxygenation: A qualitative study.

OBJECTIVE: To examine the lived experience of extracorporeal membrane oxygenation (ECMO) by patients and their families, and their relationship with intensive care clinicians. RESEARCH METHODOLOGY: Semi-structured interviews were conducted with six patients who had received ECMO and with four of their family members. The data were analysed narratively using a constant comparative method. SETTING: Patients were treated at a major acute care hospital in British Columbia between 2014 and 2021. ECMO was used either as a bridge to recovery or to organ transplant. Four had family members bedside throughout, while two had virtual visits due to COVID-19 infection control measures. FINDINGS: ECMO was experienced through a triad of relationships between the patient, key family members and key clinicians. The strength, directionality and focus of these relationships shifted during therapy and realigned once ECMO was removed. The largest shift involved family members. Post-ECMO, patients relied almost entirely on spouses, adult children and clinical team members to reconstruct their experience. The connection between families and clinical team members was limited and changed little. CONCLUSIONS: The lived experience of ECMO was complex in ways yet to be comprehensively reported in the literature. This technology had particular impact on family members when ECMO was used as a bridge to transplant and where run times extended to multiple weeks. COVID-19 infection control restrictions further complicated how this technology was experienced. Findings from this study highlight the importance of intensive care nurses recognising the critical role family members play as witnesses whose experiences later allow patients to make sense of their journey post-discharge.

A Cost-Utility Analysis of the Syncope: Pacing or Recording in The Later Years (SPRITELY) Trial.

Background: The Syncope: Pacing or Recording in the Later Years (SPRITELY) trial reported that a strategy of empiric permanent pacing in patients with syncope and bifascicular block reduces major adverse events more effectively than acting on the results of an implantable cardiac monitor (ICM). Our objective was to determine the cost-effectiveness of using the ICM, compared with a pacemaker (PM), in the management of older adults (age > 50 years) with bifascicular block and syncope enrolled in the SPRITELY trial. Methods: SPRITELY was a pragmatic, open-label randomized controlled trial with a median follow-up of 33 months. The primary outcome of this analysis is the cost per additional quality-adjusted life-year (QALY). Resource utilization and utility data were collected prospectively, and outcomes at 2 years were compared between the 2 arms. A decision analytic model simulated a 3-year time horizon. Results: The mean cost incurred by participants randomized to the PM arm was $9918, compared to $15,416 (both in Canadian dollars) for participants randomized to the ICM arm. The ICM strategy resulted in 0.167 QALYs fewer than the PM strategy. Cost and QALY outcomes are sensitive to the proportion of participants randomized to the ICM arm who subsequently required PM insertion. In 40,000 iterations of probabilistic sensitivity analysis, the PM strategy resulted in cost-savings in 99.7% of iterations, compared with the ICM strategy. Conclusions: The PM strategy was dominant-that is, less costly and estimated to result in a greater number of QALYs. For patients with unexplained syncope, bifascicular block, and age > 50 years, a PM is more likely to be cost-effective than an ICM.

Contexte: L'essai SPRITELY ( S yncope: P acing or R ecording i n t h e L ater Y ears) a été mené auprès de patients ayant subi une syncope et un bloc bifasciculaire. Elle a montré qu'une méthode de stimulation électrique permanente et empirique du cœur permet de réduire les événements indésirables majeurs plus efficacement qu'une méthode reposant sur les résultats d'un moniteur cardiaque implantable. Notre objectif était de déterminer le rapport coût-efficacité de l'utilisation du moniteur cardiaque implantable par rapport à un stimulateur cardiaque dans la prise en charge de personnes âgées de plus de 50 ans présentant un bloc bifasciculaire et une syncope, inscrits à l'essai SPRITELY. Méthodologie: SPRITELY était un essai contrôlé ouvert et pragmatique à répartition aléatoire, dont le suivi médian était de 33 mois. Le paramètre d'évaluation principal de cette analyse était le coût supplémentaire par année de vie ajustée en fonction de la qualité (AVAQ). Les données sur l'utilisation des ressources et l'utilité ont été recueillies de manière prospective, et les résultats à deux ans ont été comparés entre les deux groupes. Un modèle décisionnel analytique a été utilisé pour simuler un horizon temporel de trois ans. Résultats: Le coût moyen pour les participants répartis aléatoirement dans le groupe utilisant un stimulateur cardiaque était de 9 918 $ CAN comparativement à 15 416 $ CAN pour ceux utilisant un moniteur cardiaque implantable. La stratégie du moniteur cardiaque implantable s'est traduite par une réduction de 0,167 du nombre d'AVAQ par rapport à la stratégie reposant sur le stimulateur cardiaque. Les résultats relatifs aux coûts et aux AVAQ sont sensibles à la proportion de participants répartis aléatoirement dans le groupe du moniteur cardiaque implantable qui ont par la suite dû recevoir un stimulateur cardiaque. Sur 40 000 itérations de l'analyse de sensibilité probabiliste, la stratégie du stimulateur cardiaque a occasionné des économies dans 99,7 % des itérations comparativement à la stratégie du moniteur cardiaque implantable. Conclusions: La stratégie du stimulateur cardiaque était dominante, autrement dit moins coûteuse et, selon les estimations, entraînerait un plus grand nombre d'AVAQ. Pour les patients de plus de 50 ans présentant une syncope idiopathique et un bloc bifasciculaire, un stimulateur cardiaque est plus susceptible d'être moins coûteux qu'un moniteur cardiaque implantable.

Trends in Canadian prescription drug purchasing: 2001-2020.

BACKGROUND: In 2019, more than $34.5 billion was spent on prescription drugs in Canada. However, little is known about the distribution of this spending across medications and settings (outpatient and inpatient) over time. The objective of this paper is to describe the largest expenditures by medication class over time in inpatient and outpatient settings. This information can help to guide policies to control prescription medication expenditures. METHODS: IQVIA's Canadian Drugstore and Hospital Purchases Audit data from January 1, 2001, to December 31, 2020, were used. In this dataset, purchasing was stratified by outpatient drugstore and inpatient hospital. Spending trajectories in both settings were compared to total expenditure over time. Total expenditure of the 25 medications with the largest expenditure were compared over time, stratified by setting. Nominal costs were used for all analysis. RESULTS: In 2001, spending in the outpatient and inpatient settings was greatest on atorvastatin ($467.0 million) and erythropoietin alpha ($91.2 million), respectively. In 2020, spending was greatest on infliximab at $1.2 billion (outpatient) and pembrolizumab at $361.6 million (inpatient). Annual outpatient spending, although increasing, has been growing at a slower rate (5.3%) than inpatient spending (7.0%). In both settings, spending for the top 25 medications has become increasingly concentrated on biologic agents, with a reduction in the diversity of therapeutic classes of agents over time. DISCUSSION: Identification of the concentration on spending on biologic agents is a key step in managing costs of prescription medications in Canada. Given the increases in spending on biologic agents over the last 20 years, current cost-control mechanisms may be insufficient. Future research efforts should focus on examining the effectiveness of current cost-control mechanisms and identifying new approaches to cost control for biologic agents.

Increasing the impact of budget impact analysis: incorporating uncertainty for decision-makers in small markets.

For decision-makers considering new medicines for reimbursement and public use, both value for money and affordability are important considerations. Whereas a cost-effectiveness model provides information about value for money, a budget impact assessment (BIA) is customized to a specific context and estimates the total investment needed; one part of affordability. Both analytic approaches have parameter uncertainty within them, yet comparatively little attention is given to parameter uncertainty in BIA. Currently, within BIA, uncertainty exploration is limited to point estimates for plausible scenarios, prompting the question: can a decision-maker be confident in point estimates? Within this paper, our intent is to revitalize the discussion of uncertainty in BIA. In the context of health technology assessments submitted to support reimbursement decision-making, we propose reliance on probabilistic sensitivity analysis conducted in the cost-effectiveness model. If assumptions made in a cost-effectiveness model are valid, probabilistic cost estimates from the model, with the same perspective adopted as the BIA, should also inform BIA. Mean and variance of population outcomes, given parameter uncertainty in model inputs, are estimable from model outputs. As sufficiently large random samples are drawn from a population, the distribution of sample means will follow an approximately normal distribution. Therefore, when drawing samples from the model to inform estimates of budget impact, the assumption of an approximately normal distribution for costs is reasonable. We propose that the variance in mean costs from the cost-effectiveness model also reflects the variance in budget impact estimates and should be used to estimate budget impact confidence intervals.

The effect of interventions targeting gut microbiota on depressive symptoms: a systematic review and meta-analysis.

BACKGROUND: Despite their popularity, the efficacy of interventions targeting gut microbiota to improve depressive symptoms is unknown. Our objective is to summarize the effect of microbiome-targeting interventions on depressive symptoms. METHODS: We conducted a systematic review and meta-analysis. We searched MEDLINE, Embase, PsycINFO, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews and the Cochrane Controlled Register of Trials from inception to Mar. 5, 2021. We included studies that evaluated probiotic, prebiotic, synbiotic, paraprobiotic or fecal microbiota transplant interventions in an adult population (age ≥ 18 yr) with an inactive or placebo comparator (defined by the absence of active intervention). Studies must have measured depressive symptoms with a validated scale, and used a randomized controlled trial study design. We conducted a random effects meta-analysis of change scores, using standardized mean difference as the measure of effect. RESULTS: Sixty-two studies formed the final data set, with 50 included in the meta-analysis. Probiotic, prebiotic, and synbiotic interventions on depressive symptoms showed statistically significant benefits. In the single studies evaluating each of fecal microbiota transplant and paraprobiotic interventions, neither showed a statistically significant benefit. INTERPRETATION: Despite promising findings of benefit of probiotic, prebiotic and synbiotic interventions for depressive symptoms in study populations, there is not yet strong enough evidence to favour inclusion of these interventions in treatment guidelines for depression. Critical questions about species administered, dosage and timing relative to other antidepressant medications remain to be answered. STUDY REGISTRATION: PROSPERO no. 143178.

Cost-effectiveness Analysis of the Elder-Friendly Approaches to the Surgical Environment (EASE) Intervention for Emergency Abdominal Surgical Care of Adults Aged 65 Years and Older.

Importance: The Elder-Friendly Approaches to the Surgical Environment (EASE) initiative is a novel approach to acute surgical care for elderly patients. Objective: To determine the cost-effectiveness of EASE. Design, Setting, and Participants: An economic evaluation from the perspective of the health care system was conducted as part of the controlled before-and-after EASE study at 2 tertiary care centers, the University of Alberta Hospital and Foothills Medical Centre. Participants included elderly adults (aged ≥65 years) admitted for emergency abdominal surgery between 2014 and 2017. Data were analyzed from April 2018 to February 2019. Main Outcomes and Measures: Data were captured at both control and intervention sites before and after implementation of the EASE intervention. Resource use was captured over 6 months of follow-up and was converted to costs. Utility was measured with the EuroQol Five-Dimensions Three-Levels instrument at 6 weeks and 6 months of follow-up. The differences-in-differences method was used to estimate the association of the intervention with cost and quality-adjusted life-years. For a subset of participants, self-reported out-of-pocket health care costs were collected using the Resource Use Inventory at 6 months. Results: A total of 675 participants were included (mean [SD] age, 75.3 [7.9] years; 333 women [49.3%]), 289 in the intervention group and 386 in the control group. The mean (SD) cost per control participant was $36 995 ($44 169) before EASE and $35 032 ($43 611) after EASE (all costs are shown in 2018 Canadian dollars). The mean (SD) cost per intervention participant was $56 143 ($74 039) before EASE and $39 001 ($59 854) after EASE. Controlling for age, sex, and Clinical Frailty Score, the EASE intervention was associated with a mean (SE) cost reduction of 23.5% (12.5%) (P = .02). The change in quality-adjusted life-years observed associated with the intervention was not statistically significant (mean [SE], 0.00001 [0.0001] quality-adjusted life-year; P = .72). The Resource Use Inventory was collected for 331 participants. The mean (SE) odds ratio for having 0 out-of-pocket expenses because of the intervention, compared with having expenses greater than 0, was 15.77 (3.37) (P = .02). Among participants with Resource Use Inventory costs greater than 0, EASE was not associated with a change in spending (mean [SE] reduction associated with EASE, 19.1% [45.2%]; P = .57). Conclusions and Relevance: This study suggests that the EASE intervention was associated with a reduction in costs and no change in quality-adjusted life-years. In locations that lack capacity to implement this intervention, costs to increase capacity should be weighed against the estimated costs avoided.

A Systematic Review and Jurisdictional Scan of the Evidence Characterizing and Evaluating Assisted Peritoneal Dialysis Models.

BACKGROUND AND OBJECTIVES: Compared with hemodialysis, home peritoneal dialysis alleviates the burden of travel, facilitates independence, and is less costly. Physical, cognitive, or psychosocial factors may preclude peritoneal dialysis in otherwise eligible patients. Assisted peritoneal dialysis, where trained personnel assist with home peritoneal dialysis, may be an option, but the optimal model is unknown. The objective of this work is to characterize existing assisted peritoneal dialysis models and synthesize clinical outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A systematic review of MEDLINE, Cochrane Central Register of Controlled Trails, Cochrane Database of Systematic Reviews, Embase, PsycINFO, and CINAHL was conducted (search dates: January 1995-September 2018). A focused gray literature search was also completed, limited to developed nations. Included studies focused on home-based assisted peritoneal dialysis; studies with the assist provided exclusively by unpaid family caregivers were excluded. All outcomes were narratively synthesized; quantitative outcomes were graphically depicted. RESULTS: We included 34 studies, totaling 46,597 patients, with assisted peritoneal dialysis programs identified in 20 jurisdictions. Two categories emerged for models of assisted peritoneal dialysis on the basis of type of assistance: health care and non-health care professional assistance. Reported outcomes were heterogeneous, ranging from patient-level outcomes of survival, to resource use and transfer to hemodialysis; however, the comparative effect of assisted peritoneal dialysis was unclear. In two qualitative studies examining the patient experience, the maintenance of independence was identified as an important theme. CONCLUSIONS: Reported outcomes and quality were heterogeneous, and relative efficacy of assisted peritoneal dialysis could not be determined from included studies. Although the patient voice was under-represented, suggestions to improve assisted peritoneal dialysis included using a person-centered model of care, ensuring continuity of nurses providing the peritoneal dialysis assist, and measures to support patient independence. Although attractive elements of assisted peritoneal dialysis are identified, further evidence is needed to connect assisted peritoneal dialysis outcomes with programmatic features and their associated funding models.

Effectiveness of Neurostimulation Technologies for the Management of Chronic Pain: A Systematic Review.

OBJECTIVES: To describe the state of the literature for clinical effectiveness of neurostimulation used for the management of chronic pain. METHODS: A systematic review of spinal cord stimulation (SCS), peripheral nerve stimulation (PNS), peripheral nerve field stimulation (PNFS), and supraorbital transcutaneous electrical nerve stimulation in patients with cancer and noncancer chronic pain was conducted. MEDLINE, Embase, CINAHL, and the Cochrane CENTRAL Register of Controlled Trials were searched, using terms like "electrical stimulation therapy" and "pain management." Direction of effect, consistency across studies, and strength of evidence for effects of neurostimulation on chronic pain were narratively synthesized. RESULTS: A total of 15 randomized controlled trials (RCTs) examining SCS, 7 RCTs examining PNS/PNFS, and 1 nonrandomized trial examining supraorbital transcutaneous electrical nerve stimulation (TENS) were included. In nine SCS studies, neurostimulation had positive effects on pain. In three studies, neurostimulation did not significantly reduce pain. For PNS/PNFS, five studies found improvements in pain offered by neurostimulation; pain outcomes were not reported in two studies. In the TENS study, neurostimulation reduced headaches per month and medication consumption. Overall, 21 studies were of low or unclear risk of bias, 4 were high risk of bias, and the TENS study was not appropriate for assessment using the Cochrane Risk of Bias tool. CONCLUSIONS: A robust body of evidence examining SCS and PNS was identified. Only one study for PNFS and TENS was identified; both reported pain reductions. Generally, neurostimulation improved pain control. Future studies should examine the effectiveness of neurostimulation offered early in the trajectory of chronic pain.

Ultrasound- versus fluoroscopy-guided injections in the lower back for the management of pain: a systematic review.

PURPOSE: Ultrasound-guided spinal injections are less common than fluoroscopy-guided injections. Although unable to penetrate bones, ultrasound guidance has a number of advantages including convenience and reduced exposure to ionizing radiation. However, it is not known how ultrasound-guided injections compare to fluoroscopy-guided injections in the management of lower back pain. Our objective is to systematically review the literature comparing ultrasound-guided injections to fluoroscopy-guided injections for the management of lower back pain. METHODS: Medline, Cochrane CENTRAL Register of Controlled Trials, Embase, and NHSEED were searched from 2007 to September 26, 2017. Inclusion criteria included (1) randomized controlled trial design, (2) compared ultrasound-guided and fluoroscopy-guided injections for lower back pain, (3) dose and volume of medications injected were identical between trial arms, and (4) reported original data. RESULTS: One hundred one unique records were identified, and 21 studies were considered for full-text inclusion. Nine studies formed the final data set. Studies comparing ultrasound- and fluoroscopy-guided injections for lower back pain management reported no difference in pain relief, procedure time, number of needle passes, changes in disability indices, complications or adverse events, post-procedure opioid consumption, or patient satisfaction. CONCLUSION: Fluoroscopic guidance of injections for the management of lower back pain is similar in efficacy to ultrasound guidance. The exact role of ultrasound guidance needs to be further studied, especially for nerve root injections, where safety is the major concern. KEY POINTS: • There were no differences in pain relief, procedure time, number of needle passes, changes in disability indices, complications or adverse events, post-procedure opioid consumption, or patient satisfaction between ultrasound- and fluoroscopy-guided injections for the management of lower back pain. • Given the lack of evidence to demonstrate superior efficacy and the added harms with fluoroscopic guidance, ultrasound guidance may be the preferred method of guidance for injections to manage lower back pain in appropriate patients. Further study is required to understand the exact role of ultrasound in image-guided injections.

The Effect of Biologic and Targeted Synthetic Drugs on Work- and Productivity-related Outcomes for Patients with Psoriatic Arthritis: A Systematic Review.

OBJECTIVE: To systematically review the effects of biologic therapies for psoriatic arthritis [secukinumab, ustekinumab, adalimumab, etanercept, certolizumab pegol (CZP), apremilast, golimumab (GOL), or infliximab (IFX)] on work productivity. METHODS: A systematic review of Medline, EMBASE, CENTRAL, and ClinicalTrials.gov was conducted to identify randomized controlled trials reporting on work productivity outcomes at the end of the placebo-controlled double-blind period. RESULTS: There were 7959 records identified. Full text of 377 records was further assessed for eligibility, of which 5 trials were included. All included trials were assessed with the Cochrane Risk of Bias Tool, and 4 out of 5 were judged to be of low risk of bias in most domains. Improvements in self-assessed work productivity were observed in 5 trials (IFX, GOL, CZP, ustekinumab, and apremilast), ranging from a mean difference of -0.9 to -1.8 on a 1-10 scale of self-assessed work productivity (negative change represents improvement), although statistical significance of the results was not reported for CZP and apremilast. Treatment with CZP resulted in a statistically significant reduction in absenteeism (200 mg) and presenteeism (200 and 400 mg). IFX and GOL reported a nonsignificant reduction of absenteeism. The Work Productivity Survey, the Work Limitations Questionnaire, and visual analog scales were used to measure work productivity. CONCLUSION: Treatment with IFX, GOL, CZP, ustekinumab, and apremilast resulted in improvements in self-reported work productivity. A pooled analysis was not possible because of the clinical heterogeneity of the trials and variability in outcome reporting.

Palliative care in the home: a scoping review of study quality, primary outcomes, and thematic component analysis.

BACKGROUND: The aim of palliative care is to improve the quality of life of patients and families through the prevention and relief of suffering. Frequently, patients may choose to receive palliative care in the home. The objective of this paper is to summarize the quality and primary outcomes measured within the palliative care in the home literature. This will synthesize the current state of the literature and inform future work. METHODS: A scoping review was completed using PRISMA guidelines. PubMed, Embase, CINAHL, Web of Science, Cochrane Library, EconLit, PsycINFO, Centre for Reviews and Dissemination, Database of Abstracts of Reviews of Effects, and National Health Service Economic Evaluation Database were searched from inception to August 2016. Inclusion criteria included: 1) care was provided in the "home of the patient" as defined by the study, 2) outcomes were reported, and 3) reported original data. Thematic component analysis was completed to categorize interventions. RESULTS: Fifty-three studies formed the final data set. The literature varied extensively. Five themes were identified: accessibility of healthcare, caregiver support, individualized patient centered care, multidisciplinary care provision, and quality improvement. Primary outcomes were resource use, symptom burden, quality of life, satisfaction, caregiver distress, place of death, cost analysis, or described experiences. The majority of studies were of moderate or unclear quality. CONCLUSIONS: There is robust literature of varying quality, assessing different components of palliative care in the home interventions, and measuring different outcomes. To be meaningful to patients, these interventions need to be consistently evaluated with outcomes that matter to patients. Future research could focus on reaching a consensus for outcomes to evaluate palliative care in the home interventions.