The Allocation of the Economic Value of Second-Generation Antipsychotics Over the Product Life Cycle: The Case of Risperidone in Sweden and the United Kingdom.

OBJECTIVE: This article estimates the life-cycle value of risperidone as representative of second-generation antipsychotics (SGA) relative to haloperidol (first-generation antipsychotics). METHODS: We estimated the number of patients treated with risperidone in Sweden and the United Kingdom, from 1994 to 2017, using data of usage and volume sales. We collected data from the literature on the effectiveness (quality-adjusted life-years per patient per year), direct costs (health services), and indirect costs (productivity) of risperidone and haloperidol. We proxied the incremental value added by the new class (SGA) using a comparator from the inferior class. Next, we modeled the life-cycle uptake of risperidone to estimate the life-cycle incremental cost (ie, direct, indirect, and medicine costs), incremental quality-adjusted life-years, and net monetary benefit of risperidone. We also assessed the life-cycle distribution of the social surplus between the payer (consumer surplus) and the innovator (producer surplus). RESULTS: For the United Kingdom, consumer surplus represents around 72% of the total surplus before patent expiration and around 95% after patent expiration. For Sweden, the consumer surplus represents around 94% of the total surplus before patent expiration and around 99% after generic competition. CONCLUSION: These results suggest that the value added by SGAs to the system is higher than the expected value estimated using cost-effectiveness analysis at launch. Pricing and reimbursement decisions could recognize the full life cycle of value of innovative medicines. This not only presents a challenge of estimation but also of assessing the appropriate division of shares of social value.

Across-Country Variations of Real-World Data and Evidence for Drugs: A 5-European-Country Study.

OBJECTIVES: This study aimed to describe the role of real-world data (RWD) and real-world evidence (RWE) in health technology assessment (HTA) in 5 European countries and to identify the hurdles to the acceptance of RWE and suggest directions toward its more effective use. METHODS: Authors from France, Germany, Italy, and Sweden used a common template to extract evidence. For England, the Cancer Drugs Fund was described and analyzed as a particular model for the use of RWD to provide evidence for coverage decisions and managed entry agreements. RESULTS: In all countries except Germany, HTA bodies acknowledged the relevance of RWD/RWE to address postlaunch uncertainties. In Germany, evidence from randomized controlled trials remains the gold standard, and evidence based on RWD is generally rejected. Multiple sources of RWD exist, but the quality, the immediate relevance of existing sources, and their interoperability limit their adaptation to the specifics of a given drug. This leads to skepticism about the validity of the evidence. Timing is also a key issue: the production of evidence may not be synchronized with the HTA and pricing bodies' agendas. The Cancer Drugs Fund case emphasizes that a strong partnership among all stakeholders and a pragmatic use of existing data, alongside clinical evidence provided by companies, are key success factors. CONCLUSIONS: A continuous investment in national health information systems is a key issue for providing valid RWE. Processes and aids to guide the acceptability and usage of RWE derived from pairing between sources and questions are essential.

Comparing the results from a Swedish pregnancy cohort using data from three automated placental growth factor immunoassay platforms intended for first-trimester preeclampsia prediction.

INTRODUCTION: Risk evaluation for preeclampsia in early pregnancy allows identification of women at high risk. Prediction models for preeclampsia often include circulating concentrations of placental growth factor (PlGF); however, the models are usually limited to a specific PlGF method of analysis. The aim of this study was to compare three different PlGF methods of analysis in a Swedish cohort to assess their convergent validity and appropriateness for use in preeclampsia risk prediction models in the first trimester of pregnancy. MATERIAL AND METHODS: First-trimester blood samples were collected in gestational week 11+0 to 13+6 from 150 pregnant women at Uppsala University Hospital during November 2018 until November 2020. These samples were analyzed using the different PlGF methods from Perkin Elmer, Roche Diagnostics, and Thermo Fisher Scientific. RESULTS: There were strong correlations between the PlGF results obtained with the three methods, but the slopes of the correlations clearly differed from 1.0: PlGFPerkinElmer = 0.553 (95% confidence interval [CI] 0.518-0.588) * PlGFRoche -1.112 (95% CI -2.773 to 0.550); r = 0.966, mean difference -24.6 (95% CI -26.4 to -22.8). PlGFPerkinElmer = 0.673 (95% CI 0.618-0.729) * PlGFThermoFisher -0.199 (95% CI -2.292 to 1.894); r = 0.945, mean difference -13.8 (95% CI -15.1 to -12.6). PlGFRoche = 1.809 (95% CI 1.694-1.923) * PlGFPerkinElmer +2.010 (95% CI -0.877 to 4.897); r = 0.966, mean difference 24.6 (95% CI 22.8-26.4). PlGFRoche = 1.237 (95% CI 1.113-1.361) * PlGFThermoFisher +0.840 (95% CI -3.684 to 5.363); r = 0.937, mean difference 10.8 (95% CI 9.4-12.1). PlGFThermoFisher = 1.485 (95% CI 1.363-1.607) * PlGFPerkinElmer +0.296 (95% CI -2.784 to 3.375); r = 0.945, mean difference 13.8 (95% CI 12.6-15.1). PlGFThermoFisher = 0.808 (95% CI 0.726-0.891) * PlGFRoche -0.679 (95% CI -4.456 to 3.099); r = 0.937, mean difference -10.8 (95% CI -12.1 to -9.4). CONCLUSION: The three PlGF methods have different calibrations. This is most likely due to the lack of an internationally accepted reference material for PlGF. Despite different calibrations, the Deming regression analysis indicated good agreement between the three methods, which suggests that results from one method may be converted to the others and hence used in first-trimester prediction models for preeclampsia.

Reduced work absenteeism in patients with hepatitis C treated with second-generation direct-acting antivirals.

The cost-effectiveness of the second-generation direct-acting antivirals (DAA) has received considerable attention; however, their effect on wider societal costs has remained relatively unexplored. The aim of this study was to investigate the effect the new drugs have on sick leave compared to older treatment paradigms. This retrospective study utilized Swedish registry data to identify three cohorts: (a) patients treated with ribavirin and/or peginterferons (peg-IFN) during 2005-2011; (b) patients treated with the first generation of DAAs and ribavirin and/or peg-IFN 2011-2013; and (c) patients treated with the new generation of DAAs 2014-2018. Individual-level data on sick leave and early retirement were used to compare days away from work the year prior to the year following treatment initiation. A difference-in-difference model was estimated to test for differences between the cohorts adjusting for age and gender. Days away from work prior to treatment initiation was similar in the cohorts: 106, 85 and 94 days in cohorts 1 to 3. After treatment initiation, the number of days away from worked increased in cohort one and two to 150 and 140 days, while it remained similar in cohort three (88 days). The monetary value of the avoided sick leave was 7000-10 000 €. In conclusion, patients treated with second-generation DAAs without peg-IFN had fewer days of sick leave in the year following treatment initiation compared to older treatments. Some caution is advised when interpreting the absolute figures due to potential heterogeneity between cohorts as they were treated at different points in time.

Reference ranges of fetal superior vena cava blood flow velocities and pulsatility index in the second half of pregnancy: a longitudinal study.

BACKGROUND: Fetal superior vena cava (SVC) is essentially the single vessel returning blood from the upper body to the heart. With approximately 80-85% of SVC blood flow representing cerebral venous return, its interrogation may provide clinically relevant information about fetal brain circulation. However, normal reference values for fetal SVC Doppler velocities and pulsatility index are lacking. Our aim was to establish longitudinal reference intervals for blood flow velocities and pulsatility index of the SVC during the second half of pregnancy. METHODS: This was a prospective study of low-risk singleton pregnancies. Serial Doppler examinations were performed approximately every 4 weeks to obtain fetal SVC blood velocity waveforms during 20-41 weeks. Peak systolic (S) velocity, diastolic (D) velocity, time-averaged maximum velocity (TAMxV), time-averaged intensity-weighted mean velocity (TAMeanV), and end-diastolic velocity during atrial contraction (A-velocity) were measured. Pulsatility index for vein (PIV) was calculated. RESULTS: SVC blood flow velocities were successfully recorded in the 134 fetuses yielding 510 sets of observations. The velocities increased significantly with advancing gestation: mean S-velocity increased from 24.0 to 39.8 cm/s, D-velocity from 13.0 to 19.0 cm/s, and A-velocity from 4.8 to 7.1 cm/s. Mean TAMxV increased from 12.7 to 23.1 cm/s, and TAMeanV from 6.9 to 11.2 cm/s. The PIV remained stable at 1.5 throughout the second half of pregnancy. CONCLUSIONS: Longitudinal reference intervals of SVC blood flow velocities and PIV were established for the second half of pregnancy. The SVC velocities increased with advancing gestation, while the PIV remained stable from 20 weeks to term.

Effect of second-trimester sonographic cervical length on the risk of spontaneous preterm delivery in different risk groups: A prospective observational multicenter study.

INTRODUCTION: The aim of the study is to compare the effect of cervical length measured with transvaginal ultrasound in the second trimester on the risk of spontaneous preterm delivery (PTD) between different risk groups of asymptomatic women with a singleton pregnancy. MATERIAL AND METHODS: This is a pre-planned exploratory analysis of the CERVIX study, a prospective blinded multicenter diagnostic accuracy study. Asymptomatic women with a singleton pregnancy were consecutively recruited at their second-trimester routine ultrasound examination at seven Swedish ultrasound centers. Cervical length was measured with transvaginal ultrasound at 18-20 weeks (Cx1; n = 11 072) and 21-23 weeks (Cx2, optional; n = 6288). The effect of cervical length on the risk of spontaneous PTD and its discriminative ability was compared between women with: (i) previous spontaneous PTD, late miscarriage or cervical conization (high-risk group; n = 1045); (ii) nulliparae without risk factors (n = 5173); (iii) parae without risk factors (n = 4740). Women with previous indicated PTD were excluded (n = 114). Main outcome measures were: effect of cervical length on the risk of spontaneous PTD expressed as odds ratio per 5-mm decrease in cervical length with interaction analysis using logistic regression to test whether the effect differed between groups, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, number needed to screen to detect one spontaneous PTD. RESULTS: The effect of cervical length at Cx2 on the risk of spontaneous PTD <33 weeks was similar in all groups (odds ratios 2.26-2.58, interaction p value 0.91). The discriminative ability at Cx2 was superior to that at Cx1 and was similar in all groups (AUC 0.69-0.76). Cervical length ≤25 mm at Cx2 identified 57% of spontaneous preterm deliveries <33 weeks in the high-risk group with number needed to screen 161. The number needed to screen for groups (ii) and (iii) were 1018 and 843. CONCLUSIONS: The effect of cervical length at 21-23 weeks on the risk of spontaneous PTD <33 weeks is similar in high- and low-risk pregnancies. The differences in number needed to screen should be considered before implementing a screening program.

Costs of diabetes complications: hospital-based care and absence from work for 392,200 people with type 2 diabetes and matched control participants in Sweden.

AIMS/HYPOTHESIS: The risk of complications and medical consequences of type 2 diabetes are well known. Hospital costs have been identified as a key driver of total costs in studies of the economic burden of type 2 diabetes. Less evidence has been generated on the impact of individual diabetic complications on the overall societal burden. The objective of this study was to analyse costs of hospital-based healthcare (inpatient and outpatient care) and work absence related to individual macrovascular and microvascular complications of type 2 diabetes in Sweden in 2016. METHODS: Data for 2016 were retrieved from a Swedish national retrospective observational database cross-linking individual-level data for 1997-2016. The database contained information from population-based health, social insurance and socioeconomic registers for 392,200 people with type 2 diabetes and matched control participants (5:1). Presence of type 2 diabetes and of diabetes complications were derived using all years, 1997-2016. Costs of hospital-based care and of absence from work due to diabetes complications were estimated for the year 2016. Regression analysis was used for comparison with control participants to attribute absence from work to individual complications, and to account for joint presence of complications. RESULTS: Use of hospital care for complications was higher in type 2 diabetes compared with control participants in 2016: 26% vs 12% had ≥1 hospital contact; there were 86,104 vs 24,608 outpatient visits per 100,000 people; and there were 9894 vs 2546 inpatient admissions per 100,000 people (all p < 0.001). The corresponding total costs of hospital-based care for complications were €919 vs €232 per person (p < 0.001), and 74.7% of costs were then directly attributed to diabetes (€687 per person). Regression analyses distributed the costs of days absent from work across diabetes complications per se, basic type 2 diabetes effect and unattributed causes. Diabetes complications amounted to €1317 per person in 2016, accounting for possible complex interactions (25% of total costs of days absent). Key drivers of costs were the macrovascular complications angina pectoris, heart failure and stroke; and the microvascular complications eye diseases, including retinopathy, kidney disease and neuropathy. Early mortality in working ages cost an additional €579 per person and medications used in risk-factor treatment amounted to €418 per person. CONCLUSIONS/INTERPRETATION: The economic burden of complications in type 2 diabetes is substantial. Costs of absence from work in this study were found to be greater than of hospital-based care, highlighting the need for considering treatment consequences in a societal perspective in research and policy. Graphical abstract.

Days absent from work as a result of complications associated with type 2 diabetes: Evidence from 20 years of linked national registry data in Sweden.

AIMS: To analyse days absent from work related to individual microvascular, macrovascular and other complications of type 2 diabetes (T2D) and to identify key drivers of absence. MATERIALS AND METHODS: National health and socio-economic individual-level data were analysed for the years 1997 to 2016 for people with T2D, and age-, sex- and residential region-matched controls (5:1) using linkage to Swedish national administrative registers, based on personal identity numbers. Regression analyses accounting for individual-level clustering and education were estimated to obtain days absent by individual complications. Alternative analyses, for example, workforce indicator and age subgroups, were explored for robustness and comparison purposes. RESULTS: A total of 413 000 people with T2D aged <66 years, comprising 4.9 million person-years, was included. The crude proportion with any absence was higher among those with T2D compared to controls (47% vs. 26%) in the index year, and the median (IQR) number of days was higher (223 [77;359] vs. 196 [59;352]) if any absence. Regression analyses showed that complications per se were a key driver of days absent: stroke (+102 days); end-stage renal disease (+70 days); severe vision loss (+56 days); and angina pectoris, heart failure, and osteoarthritis (+53 days each). The alternative analyses showed similar levels of days absent and age subgroups differed in expected directions. CONCLUSIONS: This study provides evidence of the persisting impact on productivity from complications that supports continued efforts to reduce risk factors in T2D. Future studies on burden of disease and economic evaluations of new therapies and disease management may use this new set of complication-specific estimates to improve understanding of the value of reducing complications.

Volume blood flow-based indices of fetal brain sparing in the second half of pregnancy: A longitudinal study.

INTRODUCTION: Cerebroplacental ratio (CPR) and umbilicocerebral ratio (UCR) are clinically used as a measure of fetal brain sparing. These are calculated as the ratios between the pulsatility indices (PIs) of middle cerebral (MCA) and umbilical (UA) arteries, and are an indirect representation of the balance between cerebral and placental perfusion. Volume blood flow (Q)-based ratios, ie Q-CPR or Q-UCR, would directly reflect the distribution of fetal cardiac output to the placenta and brain. Thus, we aimed to determine the development pattern of Q-CPR and Q-UCR during the second half of pregnancy, construct reference intervals, and evaluate their association with CPR and UCR. MATERIAL AND METHODS: In a longitudinal cohort study of low-risk pregnancies, the inner diameter of the fetal superior vena cava (SVC) and umbilical vein (UV) was measured and velocity waveforms were obtained from the MCA, UA, UV and SVC using ultrasound at approximately 4-weekly intervals from 20 to 41 weeks. The CPR was calculated as PIMCA /PIUA and the inverse ratio was the UCR. Cerebral and placental blood flows were estimated as the product of mean velocity and cross-sectional area of the SVC and UV, respectively. Q-CPR was calculated as QSVC /QUV and the inverse as the Q-UCR. Gestational age-specific reference intervals were calculated and associations between variables were tested using multilevel regression modeling. RESULTS: Longitudinal reference intervals of Q-CPR and Q-UCR were established based on 471 paired measurements of QSVC and QUV obtained serially from 134 singleton pregnancies. The mean Q-CPR increased from 0.4 to 0.8 during the second half of pregnancy and Q-UCR declined from 2.5 to 1.3, while the CPR and UCR had U-shaped curves but in opposite directions. No significant correlation was found between CPR and Q-CPR (R = 0.10; P = .051), or UCR and Q-UCR (R = 0.09; P = .11), and the agreement between PI-based and Q-based indices of fetal brain sparing was poor. CONCLUSIONS: Indices of fetal brain sparing based on placental and cerebral volume blood flow differ from those calculated from UA and MCA PIs. They correlated poorly with conventional CPR and UCR, indicating that they may provide additional/different physiological information. Reference values of Q-CPR and Q-UCR established here can be useful to investigate their clinical value further.

Second trimester cervical length measurements with transvaginal ultrasound: A prospective observational agreement and reliability study.

INTRODUCTION: Universal screening for preterm delivery by adding transvaginal ultrasound measurement of cervical length to routine second trimester ultrasound has been proposed. The aim is to estimate inter- and intraobserver agreement and reliability of second trimester transvaginal ultrasound measurements of cervical length performed by specially trained midwife sonographers. MATERIAL AND METHODS: This is a prospective reliability and agreement study performed in seven Swedish ultrasound centers. In total, 18 midwife sonographers specially trained to perform ultrasound measurements of cervical length and 286 women in the second trimester were included. In each center, two midwife sonographers measured cervical length a few minutes apart in the same woman, the number of women examined per examiner pair varying between 24 and 30 (LIVE study). Sixteen midwife sonographers measured cervical length twice ≥2 months apart on 93 video clips (CLIPS study). The main outcome measures were mean difference, limits of agreement, intraclass correlation coefficient, intra-individual standard deviation, repeatability, Cohen's kappa and Fleiss kappa. RESULTS: The limits of agreement and intraclass correlation coefficient of the best examiner pair in the LIVE study were -4.06 to 4.72 mm and 0.91, and those of the poorest were -11.11 to 11.39 mm and 0.31. In the CLIPS study, median (range) intra-individual standard deviation was 2.14 mm (1.40-3.46), repeatability 5.93 mm (3.88-9.58), intraclass correlation coefficient 0.84 (0.66-0.94). Median (range) interobserver agreement for cervical length ≤25 mm in the CLIPS study was 94.6% (84.9%-98.9%) and Cohen's kappa 0.56 (0.12-0.92), median (range) intraobserver agreement was 95.2% (87.1%-98.9%) and Cohen's kappa 0.68 (0.27-0.93). CONCLUSIONS: Agreement and reliability of cervical length measurements differed substantially between examiner pairs and examiners. If cervical length measurements are used to guide management there is potential for both over- and under-treatment. Uniform training and rigorous supervision and quality control are advised.

Fetal cardiac function at intrauterine transfusion assessed by automated analysis of color tissue Doppler recordings.

BACKGROUND: Fetal anemia is associated with a hyperdynamic circulation and cardiac remodeling. Rapid intrauterine transfusion (IUT) of blood with high hematocrit and viscosity into the umbilical vein used to treat this condition can temporarily further affect fetal heart function. The aim of this study was to evaluate the short-term changes in fetal myocardial function caused by IUT using automated analysis of cine-loops of the fetal heart obtained by color tissue Doppler imaging (cTDI). METHODS: Fetal echocardiography was performed before and after IUT. cTDI recordings were obtained in a four-chamber view and regions of interest were placed at the atrioventricular plane in the left ventricular (LV), right ventricular (RV) and septal walls. Myocardial velocities were analyzed by an automated analysis software to obtain peak myocardial velocities during atrial contraction (Am), ventricular ejection (Sm), rapid ventricular filling (Em) and Em/Am ratio was calculated. Myocardial velocities were converted to z-scores using published reference ranges. Delta z-scores (after minus before IUT) were calculated. Correlations were assessed between variables and hemoglobin before IUT. RESULTS: Thirty-two fetuses underwent 70 IUTs. Fourteen were first time transfusions. In the LV and septal walls, all myocardial velocities were significantly increased compared to normal values, whereas in the RV only Sm was increased before IUT (z-scores 0.26-0.52). In first time IUTs, there was a negative correlation between LV Em (rho = - 0.61, p = 0.036) and LV Em/Am (rho = - 0.82, p = 0.001) z-scores and hemoglobin before IUT. The peak myocardial velocities that were increased before IUT decreased, whereas LV Em/Am increased significantly after IUT. CONCLUSIONS: This study showed that peak myocardial velocities assessed by cTDI are increased in fetuses before IUT reflecting the physiology of hyperdynamic circulation. In these fetuses, the fetal heart is able to adapt and efficiently handle the volume load caused by IUT by altering its myocardial function.

A Swedish primary healthcare prevention programme focusing on promotion of physical activity and a healthy lifestyle reduced cardiovascular events and mortality: 22-year follow-up of 5761 study participants and a reference group.

OBJECTIVE: To evaluate long-term risk of first cardiovascular (CV) events, CV deaths and all-cause deaths in community-dwelling participants of a cardiovascular disease (CVD) prevention programme delivered in a primary care setting. METHODS: Individuals who visited a primary healthcare service in Sollentuna (Sweden) and agreed to participate in the programme between 1988 and 1993 were followed. They had at least one CV risk factor but no prior myocardial infarction and received support to increase physical activity using the programme Physical Activity on Prescription and to adopt health-promoting behaviours including cooking classes, weight reduction, smoking cessation and stress management. Participants (n=5761) were compared with a randomly selected, propensity score-matched reference group from the general population in Stockholm County (n=34 556). All individuals were followed in Swedish registers until December 2011. RESULTS: In the intervention group and the reference group there were 698 (12.1%) and 4647 (13.4%) first CV events, 308 (5.3%) and 2261 (6.5%) CV deaths, and 919 (16.5%) and 6405 (18.5%) all-cause deaths, respectively, during a mean follow-up of 22 years. The HR (95% CI) in the intervention group compared with the reference group was 0.88 (0.81 to 0.95) for first CV events, 0.79 (0.70 to 0.89) for CV deaths and 0.83 (0.78 to 0.89) for all-cause deaths. CONCLUSIONS: Participation in a CVD prevention programme in primary healthcare focusing on promotion of physical activity and healthy lifestyle was associated with lower risk of CV events (12%), CV deaths (21%) and all-cause deaths (17%) after two decades. Promoting physical activity and healthy living in the primary healthcare setting may prevent CVD.

Healthcare pathways and resource use: mapping consequences of ambulance assessment for direct care with alternative healthcare providers.

BACKGROUND: A decision system in the ambulance allowing alternative pathways to alternate healthcare providers has been developed for older patients in Stockholm, Sweden. However, subsequent healthcare resource use resulting from these pathways has not yet been addressed. The aim of this study was therefore to describe patient pathways, healthcare utilisation and costs following ambulance transportation to alternative healthcare providers. METHODS: The design of this study was descriptive and observational. Data from a previous RCT, where a decision system in the ambulance enabled alternative healthcare pathways to alternate healthcare providers were linked to register data. The receiving providers were: primary acute care centre or secondary geriatric ward, both located at the same community hospital, or the conventional pathway to the emergency department at an acute hospital. Resource use over 10 days, subsequent to assessment with the decision system, was mapped in terms of healthcare pathways, utilisation and costs for the 98 included cases. RESULTS: Almost 90% were transported to the acute care centre or geriatric ward. The vast majority arriving to the geriatric ward stayed there until the end of follow-up or until discharged, whereas patients conveyed to the acute care centre to a large extent were admitted to hospital. The median patient had 6 hospital days, 2 outpatient visits and costed roughly 4000 euros over the 10-day period. Arrival destination geriatric ward indicated the longest hospital stay and the emergency department the shortest. However, the cost for the 10-day period was lower for cases arriving to the geriatric ward than for those arriving to the emergency department. CONCLUSIONS: The findings support the appropriateness of admittance directly to secondary geriatric care for older adults. However, patients conveyed to the acute care centre ought to be studied in more detail with regards to appropriate level of care.

Postmortem magnetic resonance imaging vs autopsy of second trimester fetuses terminated due to anomalies.

INTRODUCTION: Our aim was to investigate the accuracy of postmortem fetal magnetic resonance imaging (MRI) compared with fetal autopsy in second trimester pregnancies terminated due to fetal anomalies. A secondary aim was to compare the MRI evaluations of two senior radiologists. MATERIAL AND METHODS: This was a prospective study including 34 fetuses from pregnancies terminated in the second trimester due to fetal anomalies. All women accepted a postmortem MRI and an autopsy of the fetus. Two senior radiologists performed independent evaluations of the MRI images. A senior pathologist performed the fetal autopsies. The degree of concordance between the MRI evaluations and the autopsy reports was estimated as well as the consensus between the radiologists. RESULTS: Thirty-four fetuses were evaluated. Sixteen cases were associated with the central nervous system (CNS), five were musculoskeletal, one cardiovascular, one was associated with the urinary tract, and 11 cases had miscellaneous anomalies such as chromosomal aberrations, infections and syndromes. In the 16 cases related to the CNS, both radiologists reported all or some, including the most clinically significant anomalies in 15 (94%; CI 70%-100%) cases. In the 18 non-CNS cases, both radiologists reported all or some, including the most clinically significant anomalies in six (33%; CI 5%-85%) cases. In 21 cases (62%; CI 44%-78%), both radiologists held opinions that were consistent with the autopsy reports. The degree of agreement between the radiologists was high, with a Cohen's Kappa of 0.87. CONCLUSIONS: Postmortem fetal MRI can replace autopsy for second trimester fetuses with CNS anomalies. For non-CNS anomalies, the concordance is lower but postmortem MRI can still be of value when autopsy is not an option.

Inter-hospital variations in health outcomes in childbirth care in Sweden: a register-based study.

OBJECTIVE: The objective of this study was to estimate case mix adjusted variations in central indicators of health outcomes in childbirth care and to assess whether hospitals who perform well on one indicator also perform well on others. DESIGN: Register-based study using regional administrative data, linked to clinical data and population data. SETTING: Twenty-one hospitals in seven Swedish regions covering 67% of deliveries in Sweden. PARTICIPANTS: The study included 139 756 women who gave birth in 2011 and 2012. INTERVENTION(S): N/A. MAIN OUTCOME MEASURE(S): Four indicators of health outcomes were studied: obstetric anal sphincter injuries (OASIS), haemorrhage >1000 ml, postpartum infection and Apgar <4 at 5 min. Variations between hospitals were estimated using fixed effects logistic regression, adjusted for numerous sociodemographic and clinical characteristics. RESULTS: Significant variations after case mix adjustment were observed for all four indicators. If all hospitals had performed as the average of the top five hospitals for each indicator, a total of 890 OASIS, 2700 haemorrhages, 1500 postpartum infections and 180 instances of low Apgar would have been avoided. A certain degree of correlation was observed between different indicators of outcomes. However, no hospital had a statistically significant higher or lower rate across all four indicators of health outcomes. CONCLUSIONS: The significant variations in all four indicators demonstrate a potential for improvement in performance at all studied hospitals. Hospital performance was not consistent across different indicators of outcomes and all hospitals have potential for improvement in certain aspects of labour management.

Exploring staff experience of economic efficiency requirements in health care: A mixed method study.

BACKGROUND: Economic resources are limited in health care, and governance strategies are used to push provider organizations to use resources efficiently. Although studies show that hybrid managers are successful in reconciling economic efficiency requirements with professional values to meet patient needs, surprisingly few studies focus on staff. The aim of this study is to explore staff members' experience of economic efficiency requirements. METHODS: A mixed method design was applied, targeting multi-professional staff in the Department of Rehabilitation Medicine in a Swedish university hospital. Survey data was collected (n = 93), followed by focus-group interviews to support the understanding of the quantitative findings. FINDINGS: The findings show that health care staff is knowledgeable and intrinsically motivated to consider efficiency requirements, albeit it should not dominate clinical decisions. However, staff experiences little influence over resource allocation and identifies limitations in the system's abilities to meet patient needs. Staff experience incorporates a local unit and a system perspective. CONCLUSION: Staff members are aware of economic efficiency requirements and will behave accordingly if patients are not at risk. However, their engagement seems to rely on how economic efficiency requirements are handled at multiple system levels and their trust in the system to fairly support patient needs.

Association between sociodemographic determinants and health outcomes in individuals with type 2 diabetes in Sweden.

BACKGROUND: Concurrent multifactorial treatment is needed to reduce consequent risks of diabetes, yet most studies investigating the relationship between sociodemographic factors and health outcomes have focused on only one risk factor at a time. Swedish health care is mainly tax-funded, thus providing an environment that should facilitate equal health outcomes in patients, independent of background, socioeconomic status, or health profile. This study aimed at investigating the association between several sociodemographic factors and diabetes-related health outcomes represented by HbA1c , systolic blood pressure, low-density lipoprotein cholesterol, predicted 5-year risk of cardiovascular disease, and statin use. METHODS: This large retrospective registry study was based on patient-level data from individuals diagnosed with type 2 diabetes during 2010 to 2011 (n = 416,228) in any of 7 Swedish regions (~65% of the Swedish population). Health equity in diabetes care analysed through multivariate regression analyses on intermediary outcomes (HbA1c , systolic blood pressure, and low-density lipoprotein), predicted 5-year risk of cardiovascular disease and process (i.e., statin use) after 1-year follow-up, adjusting for several sociodemographic factors. RESULTS: We observed differences in intermediary risk measures, predicted 5-year risk of cardiovascular disease, and process dependent on place of birth, sex, age, education, and social setting, despite Sweden's articulated vision of equal health care. CONCLUSIONS: Diabetes patients' health was associated with sociodemographic prerequisites. Furthermore, in addition to demographics (age and sex) and disease history, educational level, marital status, and region of birth are important factors to consider when benchmarking health outcomes, e.g., average HbA1c level, and evaluating the level of health equity between organizational units or between different administrative regions.

Psychometric analysis of the pediatric quality of life inventory 3.0 neuromuscular module administered to patients with duchenne muscular dystrophy: A rasch analysis.

INTRODUCTION: Our objective in this study was to assess the psychometric properties of the English (UK and USA) version of the Pediatric Quality of Life Inventory 3.0 Neuromuscular Module (PedsQL NMM) administered to patients with Duchenne muscular dystrophy (DMD). METHODS: Patients with DMD from the UK and the US completed the PedsQL NMM online. The psychometric properties of the instrument were examined using Rasch analysis. RESULTS: A total of 278 patients completed the PedsQL NMM. Model misfit was identified for 6 of 25 items (item fit residual: mean 0.162, standard deviation [SD] 2.333), 22 of 25 items displayed disordered thresholds, and item dependency was high. The mean person fit residual was estimated at -0.183 (SD 1.475). The Person Separation Index and Cronbach's α were estimated at 0.904 and 0.915, respectively. DISCUSSION: The English version of the PedsQL NMM may not be a valid measure of health-related quality of life in patients with DMD. Muscle Nerve 58: 367-373, 2018.

Excess costs of non-infectious comorbidities among people living with HIV - estimates from Denmark and Sweden.

People living with HIV have an increased risk of comorbidities with non-communicable diseases such as cardiovascular disease, chronic kidney disease and osteoporotic fractures, compared to the general population. The burden of these comorbidities is expected to rise as the HIV-infected population ages. This development may require additional health care resources and it is relevant to ascertain the costs associated with these comorbidities. The population attributed risk approach was applied to estimate excess costs associated with the higher rates of comorbidities among HIV patients in Denmark and Sweden compared to their respective general populations. Excess direct and indirect costs for one year were calculated for myocardial infarction, stroke, osteoporotic fractures and chronic kidney disease. Cost estimates were presented in age and sex subgroups. In the course of one year the excess costs for myocardial infarction, stroke, osteoporotic fractures and chronic kidney disease attributable to HIV was estimated to €3.4 million for Denmark and €2.6 million for Sweden. Chronic kidney disease accounted for the majority of the total excess costs, followed by osteoporotic fractures, myocardial infarction and stroke. The high prevalence of comorbidities in the HIV-infected population is associated with substantial excess costs. Focus on primary and secondary prophylactic interventions is warranted. Additional studies, preferably large-scale case-control studies, may give further insights on the extent and the predictors of these excess costs.

The development and validation of a scale to explore staff experience of governance of economic efficiency and quality (GOV-EQ) of health care.

BACKGROUND: In publicly funded health care systems, governance models are developed to push public service providers to use tax payers' money more efficiently and maintain a high quality of service. Although this implies change in staff behaviors, evaluation studies commonly focus on organizational outputs. Unintended consequences for staff have been observed in case studies, but theoretical and methodological development is necessary to enable studies of staff experience in larger populations across various settings. The aim of the study is to develop a self-assessment scale of staff experience of the governance of economic efficiency and quality of health care and to assess its psychometric properties. METHODS: Factors relevant to staff members' experience of economic efficiency and quality requirements of health care were identified in the literature and through interviews with practitioners, and then compared to a theoretical model of behavior change. Relevant experiences were developed into sub-factors and items. The scale was tested in collaboration with the Department of Rehabilitation Medicine at a university hospital. 93 staff members participated. The scale's psychometric properties were assessed using exploratory factor analysis, analysis of internal consistency and criterion-related validity. RESULTS: The analysis revealed an eight factor structure (including sub-factors knowledge and awareness, opportunity to influence, motivation, impact on professional autonomy and organizational alignment), and items showed strong factor loadings and high internal consistency within sub-factors. Sub-factors were interrelated and contributed to the prediction of impact on clinical behavior (criterion). CONCLUSIONS: The scale clearly distinguishes between various experiences regarding economic efficiency and quality requirements among health care staff, and shows satisfactory psychometric quality. The scale has broad applications for research and practice, as it serves as a tool for capturing staff members' perspectives when evaluating and improving health care governance. The scale could also be useful for understanding the underlying processes of changes in provider performance and for adapting management strategies to engage staff in driving change that contributes to increased economic efficiency and quality, for the benefit of health care systems, patients and staff.