Analyses of quality of life in cancer drug trials - a review of measurements and analytical choices in post-reimbursement studies.

OBJECTIVES: For drugs reimbursed with limited evidence of patient benefits, confirmatory evidence of overall survival (OS) and quality of life (QoL) benefits is important. For QoL data to serve as valuable input to patients and decision-makers, it must be measured and analyzed using appropriate methods. We aimed to assess the measurement and analyses of post-reimbursement QoL data for cancer drugs introduced in Swedish healthcare with limited evidence at the time of reimbursement. METHODS: We reviewed any published post-reimbursement trial data on QoL for cancer drugs reimbursed in Sweden between 2010 and 2020 with limited evidence of improvement in QoL and OS benefits at the time of reimbursement. We extracted information on the instruments used, frequency of measurement, extent of missing data, statistical approaches, and the use of pre-registration and study protocols. RESULTS: Out of 22 drugs satisfying our inclusion criteria, we identified published QoL data for 12 drugs in 22 studies covering multiple cancer types. The most frequently used QoL instruments were EORTC QLQ-C30 and EQ-5D-3/5L. We identified three areas needing improvement in QoL measurement and analysis: (i) motivation for the frequency of measurements, (ii) handling of the substantial missing data problem, and (iii) inclusion and adherence to QoL analyses in clinical trial pre-registration and study protocols. CONCLUSIONS: Our review shows that the measurements and analysis of QoL data in our sample of cancer trials covering drugs initially reimbursed without any confirmed QoL or OS evidence have significant room for improvement. The increasing use of QoL assessments must be accompanied by a stricter adherence to best-practice guidelines to provide valuable input to patients and decision-makers.

Effects of the COVID-19 pandemic on healthcare utilization among older adults with cardiovascular diseases and multimorbidity in Indonesia: an interrupted time-series analysis.

BACKGROUND: The COVID-19 pandemic has disrupted healthcare utilization globally, but little is known about the effects among patients with cardiovascular diseases (CVDs) and other multimorbidities. This study analyzed the impacts of COVID-19 on healthcare utilization for patients aged 30 years and older with cardiovascular diseases (CVDs) with or without other chronic disease comorbidities in Indonesia. METHODS: We designed a retrospective cohort study based on the Indonesian National Health Insurance (NHI) sample data from 2016-2020. We defined healthcare utilization as monthly outpatient and inpatient visits related to chronic diseases at the hospital and primary healthcare levels per 10,000 NHI members. We used interrupted time series analysis to evaluate how the healthcare utilization patterns had changed due to the COVID-19 pandemic. RESULTS: Overall, hospital outpatient visits decreased by 39% when the pandemic occurred (95% Confidence Interval (CI): 0.48,0.76), inpatient visits by 28% (95% CI: 0.62,0.83), and primary healthcare visits by 34% (95% CI:0.55, 0.81). For patients with CVDs and multimorbidity, hospital outpatient and inpatient visit rates were reduced by 36% and 38%, respectively and primary healthcare visits by 32%. Some insignificant differences in the reduction of out-and inpatient visits were observed across diagnosis groups and regions. CONCLUSION: Healthcare utilization among patients with chronic diseases decreased significantly during COVID-19 and consistently across different chronic diseases and regions. To cope with the unmet needs of healthcare utilization in the context of the pandemic, the healthcare system needs to be strengthened to cater to the needs of the population-at-risk, especially for patients with CVDs and multimorbidity.

The impact of multimorbidity among adults with cardiovascular diseases on healthcare costs in Indonesia: a multilevel analysis.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death in Indonesia, accounting for 38% of the total mortality in 2019. Moreover, healthcare spending on CVDs has been at the top of the spending under the National Health Insurance (NHI) implementation. This study analyzed the association between the presence of CVDs with or without other chronic disease comorbidities and healthcare costs among adults (> 30 years old) and if the association differed between NHI members in the subsidized group (poorer) and non-subsidized households group (better-off) in Indonesia. METHODS: This retrospective cohort study analyzed the NHI database from 2016-2018 for individuals with chronic diseases (n = 271,065) ascertained based on ICD-10 codes. The outcome was measured as healthcare costs in USD value for 2018. We employed a three-level multilevel linear regression, with individuals at the first level, households at the second level, and districts at the third level. The outcome of healthcare costs was transformed with an inverse hyperbolic sine to account for observations with zero costs and skewed data. We conducted a cross-level interaction analysis to analyze if the association between individuals with different diagnosis groups and healthcare costs differed between those who lived in subsidized and non-subsidized households. RESULTS: The mean healthcare out- and inpatient costs were higher among patients diagnosed with CVDs and multimorbidity than patients with other diagnosis groups. The predicted mean outpatient costs for patients with CVDs and multimorbidity were more than double compared to those with CVDs but no comorbidity (USD 119.5 vs USD 49.1, respectively for non-subsidized households and USD 79.9 vs USD 36.7, respectively for subsidized households). The NHI household subsidy status modified relationship between group of diagnosis and healthcare costs which indicated a weaker effect in the subsidized household group (ß = -0.24, 95% CI -0.29, -0.19 for outpatient costs in patients with CVDs and multimorbidity). At the household level, higher out- and inpatient costs were associated with the number of household members with multimorbidity. At the district level, higher healthcare costs was associated with the availability of primary healthcare centres. CONCLUSIONS: CVDs and multimorbidity are associated with higher healthcare costs, and the association is stronger in non-subsidized NHI households. Households' subsidy status can be construed as indirect socioeconomic inequality that hampers access to healthcare facilities. Efforts to combat cardiovascular diseases (CVDs) and multimorbidity should consider their distinct impacts on subsidized households. The effort includes affirmative action on non-communicable disease (NCD) management programs that target subsidized households from the early stage of the disease.

Heterogeneous treatment effects of sodium-glucose cotransporter 2 inhibitors on risk of dementia in people with type 2 diabetes: A population-based cohort study.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors exhibit potential benefits in reducing dementia risk, yet the optimal beneficiary subgroups remain uncertain. METHODS: Individuals with type 2 diabetes (T2D) initiating either SGLT2 inhibitor or sulfonylurea were identified from OneFlorida+ Clinical Research Network (2016-2022). A doubly robust learning was deployed to estimate risk difference (RD) and 95% confidence interval (CI) of all-cause dementia. RESULTS: Among 35,458 individuals with T2D, 1.8% in the SGLT2 inhibitor group and 4.7% in the sulfonylurea group developed all-cause dementia over a 3.2-year follow-up, yielding a lower risk for SGLT2 inhibitors (RD, -2.5%; 95% CI, -3.0% to -2.1%). Hispanic ethnicity and chronic kidney disease were identified as the two important variables to define four subgroups in which RD ranged from -4.3% (-5.5 to -3.2) to -0.9% (-1.9 to 0.2). DISCUSSION: Compared to sulfonylureas, SGLT2 inhibitors were associated with a reduced risk of all-cause dementia, but the association varied among different subgroups. HIGHLIGHTS: New users of sodium-glucose cotransporter 2 (SGLT2) inhibitors were significantly associated with a lower risk of all-cause dementia as compared to those of sulfonylureas. The association varied among different subgroups defined by Hispanic ethnicity and chronic kidney disease. A significantly lower risk of Alzheimer's disease and vascular dementia was observed among new users of SGLT2 inhibitors compared to those of sulfonylureas.

Adverse events associated with microsurgial treatment for ruptured intracerebral aneurysms: a prospective nationwide study on subarachnoid haemorrhage in Sweden.

BACKGROUND: Adverse events (AEs) or complications may arise secondary to the treatment of aneurysmal subarachnoid haemorrhage (SAH). The aim of this study was to identify AEs associated with microsurgical occlusion of ruptured aneurysms, as well as to analyse their risk factors and impact on functional outcome. METHODS: Patients with aneurysmal SAH admitted to the neurosurgical centres in Sweden were prospectively registered during a 3.5-year period (2014-2018). AEs were categorised as intraoperative or postoperative. A range of variables from patient history and SAH characteristics were explored as potential risk factors for an AE. Functional outcome was assessed approximately 1 year after the bleeding using the extended Glasgow Outcome Scale. RESULTS: In total, 1037 patients were treated for ruptured aneurysms, of which, 322 patients were treated with microsurgery. There were 105 surgical AEs in 97 patients (30%); 94 were intraoperative AEs in 79 patients (25%). Aneurysm rerupture occurred in 43 patients (13%), temporary occlusion of the parent artery >5 min in 26 patients (8%) and adjacent vessel injury in 25 patients (8%). High Fisher grade and brain oedema on CT were related to increased risk of AEs. At follow-up, 38% of patients had unfavourable outcome. Patients suffering AEs were more likely to have unfavourable outcome (OR 2.3, 95% CI 1.10 to 4.69). CONCLUSION: Intraoperative AEs occurred in 25% of patients treated with microsurgery for ruptured intracerebral aneurysm in this nationwide survey. Although most operated patients had favourable outcome, AEs were associated with increased risk of unfavourable outcome.

Disease Specific Health Related Quality of Life in Patients With Chronic Limb Threatening Ischaemia Undergoing Revascularisation of Femoropopliteal Lesions.

OBJECTIVE: Patients with chronic limb threatening ischaemia (CLTI) suffer from pain and non-healing ulcers, which impact negatively on both their physical and mental health. While maintaining and improving quality of life is a principal aim with all treatments, little is known about the health related quality of life (HRQoL) of CLTI patients and how revascularisation procedures impact on HRQoL endpoints. The aim of this study was to investigate disease specific HRQoL before and after revascularisation in patients with CLTI undergoing femoropopliteal revascularisation. METHODS: HRQoL was prospectively analysed in 190 CLTI patients with main atherosclerotic target lesions in the femoropopliteal segment, who were planned for endovascular or open revascularisation. The choice of revascularisation method was made by the vascular team, represented by both open and endovascular expertise. The Vascular Quality of Life (VascuQoL) questionnaire was used to assess disease specific HRQoL before revascularisation and one month, one year, and two years after the procedure. Main endpoints were mean VascuQoL score changes, effect sizes of observed changes and the proportion reaching a minimally important difference (half a standard deviation change from baseline) during two years after revascularisation. RESULTS: Patient reported VascuQoL scores were low at baseline (mean 2.68, 95% CI 1.18 - 4.17). After revascularisation, the mean VascuQoL score improved statistically significantly over time, with the largest improvement observed after one year (difference from baseline 2.02, 95% CI 1.75 - 2.29; p < .001). No differences in HRQoL change over time were observed between patients treated with endovascular approaches compared with bypass surgery. Approximately half the patients reached the minimally important threshold at one year (53%), which was largely maintained also at two years (41%). CONCLUSION: While CLTI profoundly affected HRQoL, a large and clinically meaningful HRQoL increase was observed after revascularisation. This confirms the value of CLTI revascularisation on HRQoL and underlines the importance of including patient reported outcomes when evaluating revascularisation procedures in CLTI patients.

Quasi-experimental evaluation of municipal ice cleat distribution programmes for older adults in Sweden.

INTRODUCTION: Fall injuries caused by icy road conditions are a prevalent public health problem during winters in Sweden, especially in older populations. To combat this problem, many Swedish municipalities have distributed ice cleats to older adults. While previous research has shown promising results, there is a lack of comprehensive empirical data on the effectiveness of ice cleat distribution. We address this gap by investigating the impact of these distribution programmes on ice-related fall injuries among older adults. METHODS: We combined survey data on ice cleat distribution in Swedish municipalities with injury data from the Swedish National Patient Register (NPR). The survey was used to identify municipalities that have distributed ice cleats to older adults at some point between 2001 and 2019. Data from NPR were used to identify municipality-level data on patients who have been treated for injuries related to snow and ice. We used a triple differences design-a generalisation of difference in differences-that compared ice-related fall injury rates before and after intervention in 73 treatment and 200 control municipalities, with unexposed age groups serving as within-municipality controls. RESULTS: We estimate that the average ice cleat distribution programmes reduced ice-related fall injury rates by -0.24 (95% CI -0.49 to 0.02) per 1000 person-winters. The impact estimate was larger in municipalities that distributed more ice cleats (-0.38 (95% CI -0.76 to -0.09)). No similar patterns were found for fall injuries unrelated to snow and ice. CONCLUSION: Our results suggest that ice cleat distribution can decrease the incidence of ice-related injuries among older adults.

Lifetime healthcare expenditures across socioeconomic groups in Sweden.

BACKGROUND: Individuals of lower socioeconomic status generally have higher healthcare expenditures than individuals of higher socioeconomic status. However, little is known about how expenditures are distributed across socioeconomic groups over a lifetime, once accounting for differences in life expectancy. This study describes how lifetime healthcare expenditures are distributed across age, sex and socioeconomic groups in Sweden while adjusting for differences in life expectancy. METHODS: Healthcare utilization from 2016 were linked to demographic and socioeconomic data for a random sample of individuals aged 20 and above in the four largest Swedish regions (n = 440 659). Mortality data were used to estimate income- and sex-specific survival rates. Expected lifetime healthcare expenditures were estimated by combining survival rates with mean healthcare expenditures over age, by sex, and income quintile. RESULTS: We find that expected lifetime healthcare expenditures are highest among the first (lowest) income quintile despite their evident lower life expectancy. Expected lifetime expenditures were 17.9% (16.8%) higher in the first income quintile compared to the fifth (highest) quintile for women (men). Individuals in the first income quintile had higher expected lifetime expenditures for all care categories except for primary care. CONCLUSION: We conclude that despite a lower life expectancy, the quintile of the lowest socioeconomic status still had higher lifetime healthcare expenditures.

Long-term effects on healthcare utilisation among spouses of persons with stroke.

BACKGROUND: Stroke is a common and costly disease affecting the person with stroke and their relatives. If the negative effect on the health of informal caregivers to a person with stroke translates into an increased healthcare consumption has not yet been studied. Further, the importance of including costs and health consequences of informal caregiving in health economic evaluation supporting decision-making is an ongoing discussion. Therefore, this study aims to estimate the long-term effect on healthcare utilisation among spouses of persons with a first-ever stroke. METHOD: The study population consists of spouses of persons with first-ever stroke events in 2010-2011 and a reference population matched on age, sex and municipality of residence. We have access to information on healthcare utilisation five years before and five years after the stroke event for the whole study population. Using a difference-in-difference approach, the main analysis estimates the effects on primary and specialist outpatient care visits and days with inpatient care per year. Further, we analyse the healthcare utilisation among spouses depending on the modified Rankin Scale (mRS) of the person with stroke. RESULTS: Our main analysis indicates that spouses have slightly more days with inpatient care five years after the stroke event than the reference population (p = 0.03). In contrast, spouses have fewer primary and specialist outpatient care visits than the reference population following the stroke event. In the analysis where spouses' healthcare utilisation is analysed according to the mRS status of the person with stroke, we identify the most notable change in the number of visits to specialist outpatient and days with inpatient care among spouses of persons with mRS 3 (dependency in daily activities). CONCLUSION: Our study suggests that being the spouse of a person with stroke has minor effects on healthcare utilisation. Further, healthcare utilisation is most affected among the spouses of persons with stroke and dependency in daily activities (mRS 3). According to our results, it does not seem vital to include spouses of persons with stroke healthcare utilisation in health economic evaluations.

The impact of previous health on the mortality after aneurysmal subarachnoid hemorrhage: analysis of a prospective Swedish multicenter study.

PURPOSE: There is an an increasing awareness of the importance of health and lifestyle for stroke diseases like spontaneous subarachnoid hemorrhage (SAH). However, the importance of pre-existing medical conditions for clinical course and mortality after SAH has not been studied. The aim of the present study was to identify pre-existing conditions contributing to mortality after SAH. METHODS: Data were extracted from a Swedish national prospective study on patients with SAH. Variables were defined for age, sex, body mass index (BMI), clinical condition at admission, and for 10 pre-existing medical conditions. Models predicting mortality in three time intervals with all possible subsets of these variables were generated, compared and selected using Akaike's information criterion. RESULTS: 1155 patients with ruptured aneurysms were included. The mortality within 1 week was 7.6%, 1 month 14.3%, and 1 year 18.7%. The most common pre-existing medical conditions were smoking (57.6%) and hypertension (38.7%). The model's best predicting mortality within 1 week and from 1 week to 1 month included only the level of consciousness at admission and age, and these two variables were present in all the models among the top 200 in Akaike score for each time period. The most predictive model for mortality between 1 month and 1 year added previous stroke, diabetes, psychiatric disease, and BMI as predictors. CONCLUSION: Mortality within the first month was best predicted simply by initial level of consciousness and age, while mortality within from 1 month to 1 year was significantly influenced by pre-existing medical conditions.

Time Course and Clinical Significance of Hematoma Expansion in Moderate-to-Severe Traumatic Brain Injury: An Observational Cohort Study.

BACKGROUND: Preventing intracranial hematoma expansion has been advertised as a possible treatment opportunity in traumatic brain injury (TBI). However, the time course of hematoma expansion, and whether the expansion affects outcome, remains poorly understood. In light of this, the aim of this study was to use 3D volume rendering to determine how traumatic intracranial hematomas expand over time and evaluate its impact on outcome. METHODS: Single-center, population-based, observational cohort study of adults with moderate-to-severe TBI. Hematoma expansion was defined as the change in hematoma volume from the baseline computed tomography scan until the lesion had stopped progressing. Volumes were calculated by using semiautomated volumetric segmentation. Functional outcome was measured by using the 12 month Glasgow outcome scale (GOS). RESULTS: In total, 643 patients were included. The mean baseline hematoma volume was 4.2 ml, and the subsequent mean hematoma expansion was 3.8 ml. Overall, 33% of hematomas had stopped progressing within 3 h, and 94% of hematomas had stopped progressing within 24 h of injury. Contusions expanded significantly more, and for a longer period of time, than extra-axial hematomas. There was a significant dose-response relationship between hematoma expansion and 12 month GOS, even after adjusting for known outcome predictors, with every 1-ml increase in hematoma volume associated with a 6% increased risk of 1-point GOS deduction. CONCLUSIONS: Hematoma expansion is a driver of unfavorable outcome in TBI, with small changes in hematoma volume also impacting functional outcome. This study also proposes a wider window of opportunity to prevent lesion progression than what has previously been suggested.

Cost-effectiveness analysis of left atrial appendage occlusion in patients with atrial fibrillation and contraindication to oral anticoagulation.

AIMS: This study aims to estimate the cost-effectiveness of percutaneous left atrial appendage occlusion (LAAO) compared to standard stroke prevention care for patients with atrial fibrillation (AF) and contraindication to oral anticoagulation (OAC) in a Swedish healthcare and public sector perspective. METHODS AND RESULTS: We used a combined decision tree and cohort Markov model to estimate costs and quality-adjusted life-years (QALYs) over a lifetime horizon with LAAO compared to standard of care where the treatment effect is based on a recent meta-analysis. According to our analysis, LAAO gives more QALYs than standard of care (7.11 vs. 6.12). Furthermore, LAAO treatment is related to the first-year cost of 14 984 Euro (EUR) and higher average healthcare costs over the lifetime by about 4010 EUR, which gives an incremental cost-effectiveness ratio of LAAO vs. standard of care at 4047 EUR per gained QALY. From a public sector perspective, LAAO reduces average costs due to substantial reductions in long-term care and, thus, implies that LAAO is dominant from a public sector perspective (lower average costs and better health outcomes). CONCLUSION: From both Swedish healthcare and public sector perspectives, LAAO can be considered cost-effective compared to standard of care for individuals with AF and contraindication to OAC. However, these results must be confirmed in health economic evaluations alongside the ongoing randomized clinical trials. KEY QUESTION: Is left atrial appendage occlusion (LAAO) cost-effective for patients with atrial fibrillation (AF) and contraindication to oral anticoagulation (OAC) compared to the standard of care from a Swedish healthcare and public sector perspective? KEY FINDING: LAAO is associated with lower cost than the standard of care from a public sector perspective and an incremental cost of 4010 Euro from a healthcare perspective. Furthermore, LAAO is related to better health outcomes than the standard of care. TAKE HOME MESSAGE: Treatment with LAAO among individuals with AF and contraindication to OAC can be considered as cost-effective compared to the standard of care from a Swedish healthcare and public sector perspective.

Spinal Cord Injury Induces Permanent Reprogramming of Microglia into a Disease-Associated State Which Contributes to Functional Recovery.

Microglia are resident myeloid cells of the CNS. Recently, single-cell RNA sequencing (scRNAseq) has enabled description of a disease-associated microglia (DAM) with a role in neurodegeneration and demyelination. In this study, we use scRNAseq to investigate the temporal dynamics of immune cells harvested from the epicenter of traumatic spinal cord injury (SCI) induced in female mice. We find that as a consequence of SCI, baseline microglia undergo permanent transcriptional reprogramming into a previously uncharacterized subtype of microglia with striking similarities to previously reported DAM as well as a distinct microglial state found during development. Using a microglia depletion model we showed that DAM in SCI are derived from baseline microglia and strongly enhance recovery of hindlimb locomotor function following injury.SIGNIFICANCE STATEMENT Although disease-associated microglia (DAM) have been the subject of strong research interest during recent years (Keren-Shaul, 2017; Jordão, 2019), their cellular origin and their role in "normal" acute injury processes is not well understood. Our work directly addresses the origin and the role of DAM in traumatic injury response. Further, we use a microglia depletion model to prove that DAM in spinal cord injury (SCI) are indeed derived from homeostatic microglia, and that they strongly enhance recovery. Thus, in this work we significantly expand the knowledge of immune response to traumatic injury, demonstrate the applicability to human injury via our unique access to injured human spinal cord tissue, and provide the community with a comprehensive dataset for further exploration.

Clinical Significance of Vascular Occlusive Events following Moderate-to-Severe Traumatic Brain Injury: An Observational Cohort Study.

Preventing hemorrhage progression is a potential therapeutic opportunity in traumatic brain injury (TBI) management, but its use has been limited by fear of provoking vascular occlusive events (VOEs). However, it is currently unclear whether VOE actually affects outcome in these patients. The aim of this study was to determine incidence, risk factors, and clinical significance of VOE in patients with moderate-to-severe TBI. A retrospective observational cohort study of adults (≥15 years) with moderate-to-severe TBI was performed. The presence of a VOE during hospitalization was noted from hospital charts and radiological reports. Functional outcome, using the Glasgow Outcome Scale (GOS), was assessed at 12 months posttrauma. Univariate and multivariate logistic regressions were used for endpoint assessment. In total, 848 patients were included, with a median admission Glasgow Coma Scale of 7. A VOE was detected in 54 (6.4%) patients, of which cerebral venous thrombosis was the most common (3.2%), followed by pulmonary embolism (1.7%) and deep vein thrombosis (1.3%). Length of ICU stay (p < 0.001), body weight (p = 0.002), and skull fracture (p = 0.004) were independent predictors of VOE. VOE development did not significantly impact 12-month GOS, even after adjusting for potential confounders using propensity score matching. In conclusion, VOE in moderate-to-severe TBI patients was relatively uncommon, and did not affect 12-month GOS. This suggests that the potential benefit of treating bleeding progression might outweigh the risks of VOE.

Induction of labour at 41 weeks of gestation versus expectant management and induction of labour at 42 weeks of gestation: A cost-effectiveness analysis.

OBJECTIVE: To assess the cost-effectiveness of induction of labour (IOL) at 41 weeks of gestation compared with expectant management until 42 weeks of gestation. DESIGN: A cost-effectiveness analysis alongside the Swedish Post-term Induction Study (SWEPIS), a multicentre, randomised controlled superiority trial. SETTING: Fourteen Swedish hospitals during 2016-2018. POPULATION: Women with an uncomplicated singleton pregnancy with a fetus in cephalic position were randomised at 41 weeks of gestation to IOL or to expectant management and induction at 42 weeks of gestation. METHODS: Health benefits were measured in life years and quality-adjusted life years (QALYs) for mother and child. Total cost per birth was calculated, including healthcare costs from randomisation to discharge after delivery, for mother and child. Incremental cost-effectiveness ratios (ICERs) were calculated by dividing the difference in mean cost between the trial arms by the difference in life years and QALYs, respectively. Sampling uncertainty was evaluated using non-parametric bootstrapping. MAIN OUTCOME MEASURES: The cost per gained life year and per gained QALY. RESULTS: The differences in life years and QALYs gained were driven by the difference in perinatal mortality alone. The absolute risk reduction in mortality was 0.004 (from 6/1373 to 0/1373). Based on Swedish life tables, this gives a mean gain in discounted life years and QALYs of 0.14 and 0.12 per birth, respectively. The mean cost per birth was €4108 in the IOL group (n = 1373) and €4037 in the expectant management group (n = 1373), with a mean difference of €71 (95% CI -€232 to €379). The ICER for IOL compared with expectant management was €545 per life year gained and €623 per QALY gained. Confidence intervals were relatively wide and included the possibility that IOL had both lower costs and better health outcomes. CONCLUSIONS: Induction of labour at 41 weeks of gestation results in a better health outcome and no significant difference in costs. IOL is cost-effective compared with expectant management until 42 weeks of gestation using standard threshold values for acceptable cost per life year/QALY. TWEETABLE ABSTRACT: Induction of labour at 41 weeks of gestation is cost-effective compared with expectant management until 42 weeks of gestation.

Regional variation in prescription drug spending: Evidence from regional migrants in Sweden.

There is substantial variation in drug spending across regions in Sweden, which can be justified if caused by differences in health need, but an indication of inefficiencies if primarily caused by differences in place-specific supply-side factors. This paper aims to estimate the relative effect of individual demand-side factors and place-specific supply-side factors as drivers of geographical variation in drug spending in Sweden. We use individual-level register data on purchases of prescription drugs matched with demographic and socioeconomic data of a random sample of about 900,000 individuals over 2007-2016. The primary empirical approach is a two-way fixed effect model and an event study where we identify demand- and supply-side effects based on how regional and local migrants change drug spending when moving across regional and municipal borders. As an alternative approach in robustness checks, we also use a decomposition analysis. The results show that the place-specific supply-side effect accounts for only about 5%-10% of variation in drug spending and remaining variation is due to individual demand-side effects. These results imply that health policies to reduce regional variation in drug spending would have limited impact if targeted at place-specific characteristics.

Model-based economic evaluation of ice cleat distribution programmes for the prevention of outdoor falls among adults from a Swedish societal perspective.

BACKGROUND: Slipping on snow or ice poses a significant health risk among older adults in Sweden. To combat this problem, about 80 Swedish municipalities have distributed ice cleats to older citizens (65+ years old) over the last decade. This paper details a cost-benefit analysis of such programmes. MATERIALS AND METHODS: We developed a decision-analytical model to estimate the costs and benefits of ice cleat programmes in Swedish municipalities compared with a business-as-usual scenario. The modelled benefits of the programme were based on effect estimates from previous research, data from population and healthcare registers and a survey of attitudes to and actual ice cleat use. The modelled costs of the programme were based on resource use data collected from 34 municipalities with existing ice cleat programmes. We assessed heterogeneity in the potential impact and benefit-to-cost ratios across all Swedish municipalities as a function of the average number of days with snow cover per year. Uncertainty in the cost-benefit results was assessed using deterministic and probabilistic sensitivity analyses. RESULTS: The average benefit-to-cost ratio was 87, ranging from about 40 in low-risk municipalities to 140 in high-risk municipalities, implying that the potential benefits of ice cleat programmes greatly outweigh their costs. Probabilistic and deterministic sensitivity analyses support the robustness of this conclusion to parameter uncertainty and large changes in assumptions about the magnitude of the impact on ice cleat use and injuries. CONCLUSION: The benefits of distributing ice cleats to older adults appear to outweigh the costs from a Swedish societal perspective.

Ice cleat distribution programmes and ice cleat use among older adults: repeated cross-sectional evidence from 63 municipal interventions in Sweden.

INTRODUCTION: Ice cleats may help prevent ice-related falls in places with icy roads, but there is limited evidence about the association between ice cleat distribution and ice cleat use. Our study examined the association between Swedish municipal distribution programmes and ice cleat use among older adults (65+ years). METHODS: We combined data on municipal ice cleat distribution programmes (n=63) with repeated cross-sectional self-reports of ice cleat use in Sweden from 2007, 2010, 2014 and 2018. Respondents (n=63 234) were classified as exposed if they lived in a municipality with a programme, belonged to an eligible age group and responded after distribution (n=2507). Dose-response was assessed using distributed ice cleat pairs per capita (mean: 0.38). Linear probability models were used to estimate probability differences in ice cleat use between exposed and unexposed respondents, adjusting for age, sex, country of birth, education, survey wave and municipality. Ineligible age groups living in programme municipalities, who should be unaffected by ice cleat distribution, were used for bias assessment. RESULTS: Exposure to ice cleat distribution programmes was associated with 7.5 percentage points (95% CI 4.2 to 10.9) higher self-reported ice cleat use after confounding adjustment. The association was larger in municipalities that distributed one pair of ice cleats per capita (17.3 percentage points (95% CI 11.2 to 23.4)). No association was found among the ineligible age groups (-2.3 (95% CI -5.5 to 1.0)). CONCLUSION: Distributing ice cleats to older adults may help increase their use of ice cleats in settings with icy road conditions.

Production loss and sick leave caused by antibiotic resistance: a register-based cohort study.

BACKGROUND: Adverse economic consequences of antibiotic resistance, both in health care systems and in society at large, have been estimated to emerge and significantly affect the global economy. To date, most studies of the societal costs of antibiotic resistance have had a macroeconomic perspective, using the number of attributable deaths as a quantifier for production loss. In contrast, there have been few studies of the consequences of antibiotic resistance in terms of the length of sick leave and hence the impact of morbidity on production loss. The aim of our study was to estimate the production loss from ill health caused by antibiotic resistance. METHOD: To estimate additional production loss due to antibiotic resistance, we used Swedish register-based cohort data to determine days of long-term sick leave (LTSL) for episodes of infection caused by resistant and susceptible bacteria respectively. We collected patient data for four common infection types (bloodstream infection, urinary tract infection, skin and soft tissue infection, and pneumonia), as well as, antibiotic susceptibility test data, and total days of LTSL. We used a two-part model to estimate the number of LTSL days attributable to resistance, and controlled for comorbidities and demographic variables such as age and gender. RESULTS: The results show that antibiotic resistance adds an additional 8.19 days of LTSL compared with a similar infection caused by susceptible bacteria, independent of infection type and resistance type. Furthermore, the results suggest that production loss due to temporary sick leave caused by antibiotic resistance in a working-age population amounts to about 7% of total health care costs attributable to antibiotic resistance in Sweden. CONCLUSION: Estimating the effect of antibiotic resistance in terms of temporary production loss is important to gain a better understanding of the economic consequences of antibiotic resistance in society and, by extension, enable more effective resource allocation to combat further emergence of resistance. Society's economic costs of antibiotic resistance are, however, probably much greater than those of sick leave due to disease alone.

Physiotherapist or physician as primary assessor for patients with suspected knee osteoarthritis in primary care - a cost-effectiveness analysis of a pragmatic trial.

BACKGROUND: Over the next decade, the number of osteoarthritis consultations in health care is expected to increase. Physiotherapists may be considered equally qualified as primary assessors as physicians for patients with knee osteoarthritis. However, economic evaluations of this model of care have not yet been described. To determine whether physiotherapists as primary assessors for patients with suspected knee osteoarthritis in primary care are a cost-effective alternative compared with traditional physician-led care, we conducted a cost-effectiveness analysis alongside a randomized controlled pragmatic trial. METHODS: Patients were randomized to be assessed and treated by either a physiotherapist or physician first in primary care. A cost-effectiveness analysis compared costs and effects in quality adjusted life years (QALY) for the different care models. Analyses were applied with intention to treat, using complete case dataset, and missing data approaches included last observation carried forward and multiple imputation. Non-parametric bootstrapping was conducted to assess sampling uncertainty, presented with a cost-effectiveness plane and cost-effectiveness acceptability curve. RESULTS: 69 patients were randomized to a physiotherapist (n = 35) or physician first (n = 34). There were significantly higher costs for physician visits and radiography in the physician group (p < 0.001 and p = 0.01). Both groups improved their health-related quality of life 1 year after assessment compared with baseline. There were no statistically significant differences in QALYs or total costs between groups. The incremental cost-effectiveness ratio for physiotherapist versus physician was savings of 24,266 €/lost QALY (societal perspective) and 15,533 €/lost QALY (health care perspective). There is a 72-80% probability that physiotherapist first for patients with suspected knee osteoarthritis is less costly and differs less than ±0.1 in QALY compared to traditional physician-led care. CONCLUSION: These findings suggest that physiotherapist-led care model might reduce health care costs and lead to marginally less QALYs, but confidence intervals were wide and overlapped no difference at all. Health consequences depending on the profession of the first assessor for knee osteoarthritis seem to be comparable for physiotherapists and physicians. Direct access to physiotherapist in primary care seems to lead to fewer physician consultations and radiography. However, larger clinical trials and qualitative studies to evaluate patients' perception of this model of care are needed. CLINICAL TRIAL REGISTRATION: The study was retrospectively registered in clinicaltrial.gov, ID: NCT03822533.