Lars Hagberg

Background: The incidence and clinical relevance of asymptomatic cerebrospinal fluid escape (CSFE) during antiretroviral therapy (ART) is uncertain. We examined the impact and incidence of asymptomatic CSFE in a Swedish HIV cohort. Methods: Neuroasymptomatic people with HIV (PWH) who have been on ART for at least 6 months with suppressed plasma viral load were followed longitudinally. CSFE was defined as either increased CSF HIV-1 RNA with concurrent plasma suppression or CSF HIV-1 RNA exceeding that in plasma when both were quantifiable. Paired CSF and plasma were analyzed for HIV-1 RNA, neopterin, neurofilament light protein (NfL), white blood cell (WBC) count, and albumin ratio. Results: Asymptomatic CSFE (cutoff 50 copies/mL) was found in 4 of 173 PWH (2%) and 5 of 449 samples (1%). The corresponding proportions were 8% of PWH and 4% for samples using a 20 copies/mL cutoff for CSF HIV-1 RNA. CSFE samples (cutoff 20 copies/mL) had a 25% higher geometric mean of CSF neopterin (P = .01) and 8% higher albumin ratio (P = .04) compared to samples without CSFE. No differences were observed in CSF NfL levels (P = .8). The odds ratio for increased CSF WBC (≥ 3 cells/μL) in samples with CSFE was 3.9 (P = .004), compared to samples without elevated CSF viral load. Conclusions: Asymptomatic CSFE was identified in only 4 (2%) PWH, with no cases of continuous CSFE observed. Increased CSF HIV-1 RNA was associated with biomarkers of CNS immune activation and blood-brain barrier impairment, but not with biomarkers of neuronal injury.

Background and Objective Mapping algorithms can be used for estimating quality-adjusted life years (QALYs) when studies apply non-preference-based instruments. In this study, we estimate a regression-based algorithm for mapping between the World Health Organization Disability Assessment Schedule (WHODAS 2.0) and the preference-based instrument SF-6D to obtain preference estimates usable in health economic evaluations. This was done separately for the working and non-working populations, as WHODAS 2.0 discriminates between these groups when estimating scores. Methods Using a dataset including 2258 participants from the general Swedish population, we estimated the statistical relationship between SF-6D and WHODAS 2.0. We applied three regression methods, i.e., ordinary least squares (OLS), generalized linear models (GLM), and Tobit, in mapping onto SF-6D from WHODAS 2.0 at the overall-score and domain levels. Root mean squared error (RMSE) and mean absolute error (MAE) were used for validation of the models; R² was used to assess model fit. Results The best-performing models for both the working and non-working populations were GLM models with RMSE ranging from 0.084 to 0.088, MAE ranging from 0.068 to 0.071, and R² ranging from 0.503 to 0.608. When mapping from the WHODAS 2.0 overall score, the preferred model also included sex for both the working and non-working populations. When mapping from the WHODAS 2.0 domain level, the preferred model for the working population included the domains mobility, household activities, work/study activities, and sex. For the non-working population, the domain-level model included the domains mobility, household activities, participation, and education. Conclusions It is possible to apply the derived mapping algorithms for health economic evaluations in studies using WHODAS 2.0. As conceptual overlap is incomplete, we recommend using the domain-based algorithms over the overall score. Different algorithms must be applied depending on whether the population is working or non-working, due to the characteristics of WHODAS 2.0.

In Sweden, physical activity on prescription (PAP) is used to support patients in increasing their levels of physical activity (PA). The role of healthcare professionals in supporting PA behavior change requires optimization in terms of knowledge, quality and organization. This study aims to evaluate the cost-effectiveness of support from a physiotherapist (PT) compared to continued PAP at a healthcare center (HCC) for patients who remained insufficiently active after 6-month PAP treatment at the HCC. The PT strategy was constituted by a higher follow-up frequency as well as by aerobic physical fitness tests. The analysis was based on an RCT with a three-year time horizon, including 190 patients aged 27–77 with metabolic risk factors. The cost per QALY for the PT strategy compared to the HCC strategy was USD 16,771 with a societal perspective (including individual PA expenses, production loss and time cost for exercise, as well as healthcare resource use) and USD 33,450 with a healthcare perspective (including only costs related to healthcare resource use). Assuming a willingness-to-pay of USD 57,000 for a QALY, the probability of cost-effectiveness for the PT strategy was 0.5 for the societal perspective and 0.6 for the healthcare perspective. Subgroup analyses on cost-effectiveness based on individual characteristics regarding enjoyment, expectations and confidence indicated potential in identifying cost-effective strategies based on mediating factors. However, this needs to be further explored. In conclusion, both PT and HCC interventions are similar from a cost-effectiveness perspective, indicating that both strategies are equally valuable in healthcare’s range of treatments.

Background Functional abdominal pain disorders (FAPDs) affect children worldwide, being more prevalent among girls. The individual and societal burdens of the disease are substantial, and evidence-based interventions are needed. Non-pharmacological treatments have generally produced promising results, with dance and yoga specifically having potential as an effective treatment option. Beside efficacy, the cost-effectiveness of interventions is important when prioritizing and allocating public resources. Objective This study evaluated the cost-effectiveness of an 8-month dance and yoga intervention for girls with functional abdominal pain or irritable bowel syndrome, based on a randomized control trial called ‘Just in TIME’. Methods The intervention, performed in Sweden, was studied using a decision analysis tool, i.e., a decision tree within the trial followed by a Markov model with a time horizon of 10 years. The base case considered healthcare costs as well as productivity losses, measuring the effects in gained quality-adjusted life-years (QALYs) and presenting an incremental cost-effectiveness ratio (ICER). Results The base case results show that the intervention, compared with current practice, was the dominant strategy from both the 12-month and long-term perspectives. The sensitivity analyses indicated that the long-term, but not the short-term, findings were robust for different assumptions and changes in parameter estimates, resulting in ICERs similar to those of the base case scenario. Conclusions Offering dance and yoga to young girls with FAPDs generates small QALY gains and monetary savings compared with standard healthcare and is likely cost-effective. These findings make a valuable contribution to an area where evidence-based and cost-effective treatment interventions are needed. Clinical Trials Registration Number ClinicalTrials.gov identifier: NCT02920268; Name: Just in TIME—Intervention With Dance and Yoga for Girls With Recurrent Abdominal Pain

Background: In health care interventions aimed at increased physical activity, the individual’s time spent on exercise is a substantial input. Time costs should therefore be considered in cost-effectiveness analyses. The aim of this study was to estimate the cost of time spent on exercise among 333 primary health care patients with metabolic risk factors receiving physical activity on prescription.Methods: Based on a theoretical framework, a yardstick was constructed with experience of work (representing claim of salary as compensation) as the lower anchor-point, and experience of leisure activity forgone due to extended exercise time (no claim) as the higher anchor-point. Using this yardstick experience of exercise can be valued. Another yardstick was constructed with experience of cleaning at home in combination with willingness to pay for cleaning as the lowest anchor-point.Results: The estimated costs of exercise time were between 14 and 37% of net wages, with physical activity level being the most important factor in determining the cost. Among sedentary individuals, the time cost was 21–51% of net wages while among individuals performing regular exercise it was 2–10%. When estimating the cost of time spent on exercise in a cost-effectiveness analysis, experience of exercise, work, leisure activity forgone, and cleaning at home (or other household work that may be relevant to purchase) should be measured. The individual’s willingness to pay for cleaning at home and their net salary should also be measured.Conclusions: When using a single valuation of cost of time spent on exercise in health care interventions, for employed participants 15–30% of net salary should be used. Among unemployed individuals, lower cost estimation should be applied. Better precision in cost estimations can be achieved if participants are stratified by physical activity levels.Trial registrationThe study was conducted as a survey of existing clinical physical activity on prescription work, and was approved by the Regional Ethical Review Board in Gothenburg, Sweden (ref: 678-14)

There is robust evidence that regular physical activity (PA) has positive health effects. However, the best PA methods and the most important correlates for promoting PA remain unclear. Physical activity on prescription (PAP) aims to increase the patient’s motivation for and level of PA. This study investigated possible predictive baseline correlates associated with changes in the PA level over a 6-month period of PAP treatment in order to identify the primary care patients most likely to benefit from a PAP intervention. The study included 444 patients with metabolic risk factors who were aged 27 to 85 years and physically inactive. The patients received PAP treatment that included individual counseling plus an individually-tailored PA recommendation with a written prescription and individualised structured follow-up for 6 months. Eight baseline correlates of PA were analysed against the PA level at the 6-month follow-up in a predictor analysis. Five baseline correlates predicted the PA level at the 6-month follow-up: self-efficacy expectations for changing PA; the patient’s preparedness and confidence regarding readiness to change PA; a BMI < 30; and a positive valued physical health. The proportion of patients increasing the PA level and achieving a PA level that was in accordance with public health recommendations was higher with a positive valued baseline correlate. The odds of achieving the recommended PA level increased substantially when 2 to 4 predictive correlates were present. PA levels increased to a greater extent among patients with low PA at baseline than patients with high PA at baseline, especially in combination with 2 to 4 positively-valued correlates (87–95% vs. 62–75%). This study identified potential predictive correlates of an increased PA level after a 6-month PAP intervention. This contributes to our understanding of PAP and could help individualise PAP support. The proportion of patients with the lowest PA level at baseline increased their PA level in a higher extent (84%) and thus may benefit the most from PAP. These results have clinical implications for behavioural change in those patients having the greatest health gains by increasing their PA level. ClinicalTrials.gov ; NCT03586011 . Retrospectively registered on July 17, 2018.

Pregnancy has been identified as a contributor to obesity. We have shown that a diet intervention postpartum produced a 2-y weight loss of 8%. Here, we present the impact of the diet intervention on cost-effectiveness and explore changes in quality of life (QOL). A total of 110 postpartum women with overweight/obesity were randomly assigned to diet (D-group) or control (C-group). D-group received a 12-wk diet intervention within primary health care followed by monthly emails up to the 1-y follow-up. C-group received a brochure. Changes in QOL were measured using the 36-item Short Form Health Survey and EQ-5D. The analysis of cost-effectiveness was a cost-utility analysis with a health care perspective and included costs of intervention for stakeholder, quality-adjusted life-years (QALYs) gained and savings in health care. The likelihood of cost-effectiveness was examined using the net monetary benefit method. The D-group increased their QOL more than the C-group at 12 wk. and 1 y, with pronounced differences for the dimensions general health and mental health, and the mental component summary score (all p < 0.05). Cost per gained QALY was 1704–7889 USD. The likelihood for cost-effectiveness, based on a willingness to pay 50,000 USD per QALY, was 0.77–1.00. A diet intervention that produced clinically relevant postpartum weight loss also resulted in increased QOL and was cost-effective. Clinical trials, NCT01949558 , 2013-09-24

The proportion of pregnant women delivered by cesarean section has increased steadily during the past three decades. The risk of infection is 10-fold augmented after elective cesarean section compared to vaginal delivery. Antibiotic prophylaxis may reduce endometritis by 62% and superficial wound infection by 38% after elective cesarean section. International guidelines recommend antibiotic prophylaxis in elective cesarean section, but this procedure is not routinely followed in Sweden. Studies of costs of antibiotic prophylaxis in cesarean section show conflicting results and are based on substantially different incidence of postoperative infections. No study of costs of antibiotic prophylaxis in elective cesarean section in a Swedish or Nordic context has been pursued. The aim of this study was to investigate if antibiotic prophylaxis is cost-reducing in elective cesarean section in Örebro County, Sweden. All women undergoing elective cesarean in the Region Örebro County health care system during 2011–2012 were eligible for inclusion. Postoperative infections and risk factors for infections were registered. A hypothetical situation in which all participants had received antibiotic prophylaxis was compared to the actual situation, in which none of them had received antibiotic prophylaxis. The reduction in the risk of postoperative infections resulting from antibiotic prophylaxis was based on a meta-analysis. Costs for in-patient care of postoperative infections were extracted from the accounting system, and costs for out-patient care were calculated according to standard costs. Costs for antibiotic prophylaxis were calculated and compared with the cost reduction that would be implied by the introduction of such prophylaxis. The incidences of deep and superficial surgical site infection were 3.5% and 1.3% respectively. Introduction of antibiotic prophylaxis would reduce health care costs by 31 Euro per cesarean section performed (95% credible interval 4–58 Euro). The probability of cost-saving was 99%. Antibiotic prophylaxis in elective cesarean section is cost-reducing in this health care setting. Our results indicate that the introduction of antibiotic prophylaxis in elective cesarean section can also be cost-saving in low infection rate settings. Trial registration Ethical approval was given by the Regional Ethical Review Board in Uppsala (registration number 2013/484).

The extensive vaccination programme against swine flu resulted in an increased incidence of narcolepsy among children and adolescents. There is a need to explore if these young persons’ experiences have affected their trust in healthcare, their willingness to participate in future prevention programmes, and their contacts with the healthcare system. The overall aim is to identify factors important for the life-situation of children and adolescents with narcolepsy and their families, and factors that correlate with trust in healthcare. Data will be collected via questionnaires from all available children with narcolepsy following the vaccination and their families, as well as a control group of children with diabetes and their families. Longitudinal descriptive interviews will also be conducted with a selection of 20–25 children and their families. Techniques from media research will be used for Internet-based data collection and analysis of information relating to narcolepsy from social media. This project will use the situation of young persons with narcolepsy after the swine flu vaccination as a case to build a model that can be used in situations where trust in healthcare is essential. This model will be based on findings from the included studies on how trust is influenced by support, quality of life, burden of disease, impact on family, and use of social media. The model developed in this project will be beneficial in future situations where trust in healthcare is essential, such as new pandemic outbreaks but also for “everyday” adherence to health advice.