"Whatever is bad goes back to the woman": The gendered blame game of sickle cell disease in Malawi and Uganda.

Mothers are commonly blamed for the ill-health of their children, and this is well documented in research. However, few studies have considered gendered patterns of blame for hereditary conditions caused by mutations from both parents through dual, shared genetic inheritance. This paper explores the 'gendering' of blame in the context of an inherited blood disorder known as sickle cell disease. The findings are drawn from 18 focus group discussions with 117 caregivers of children with sickle cell disease in Malawi and Uganda. Although one mutation from each parent is required for the disease to develop, low awareness about their status as healthy carriers of a sickle cell trait complicated the caregivers' recognition and acceptance of their genetic link to the child's condition. This study demonstrates how fathers and other members of the paternal side of the child's family would deflect blame from their own lineage by directing sole 'genetic responsibility' for the child's disease towards mothers. We discuss the implications of gendered blame on household dynamics and healthcare-seeking for children with sickle cell disease in this setting.

Impact of cash transfer programs on healthcare utilization and catastrophic health expenditures in rural Zambia: a cluster randomized controlled trial.

Background: Nearly 100 million people are pushed into poverty every year due to catastrophic health expenditures (CHE). We evaluated the impact of cash support programs on healthcare utilization and CHE among households participating in a cluster-randomized controlled trial focusing on adolescent childbearing in rural Zambia. Methods and findings: The trial recruited adolescent girls from 157 rural schools in 12 districts enrolled in grade 7 in 2016 and consisted of control, economic support, and economic support plus community dialogue arms. Economic support included 3 USD/month for the girls, 35 USD/year for their guardians, and up to 150 USD/year for school fees. Interviews were conducted with 3,870 guardians representing 4,110 girls, 1.5-2 years after the intervention period started. Utilization was defined as visits to formal health facilities, and CHE was health payments exceeding 10% of total household expenditures. The degree of inequality was measured using the Concentration Index. In the control arm, 26.1% of the households utilized inpatient care in the previous year compared to 26.7% in the economic arm (RR = 1.0; 95% CI: 0.9-1.2, p = 0.815) and 27.7% in the combined arm (RR = 1.1; 95% CI: 0.9-1.3, p = 0.586). Utilization of outpatient care in the previous 4 weeks was 40.7% in the control arm, 41.3% in the economic support (RR = 1.0; 95% CI: 0.8-1.3, p = 0.805), and 42.9% in the combined arm (RR = 1.1; 95% CI: 0.8-1.3, p = 0.378). About 10.4% of the households in the control arm experienced CHE compared to 11.6% in the economic (RR = 1.1; 95% CI: 0.8-1.5, p = 0.468) and 12.1% in the combined arm (RR = 1.1; 95% CI: 0.8-1.5, p = 0.468). Utilization of outpatient care and the risk of CHE was relatively higher among the least poor than the poorest households, however, the degree of inequality was relatively smaller in the intervention arms than in the control arm. Conclusions: Economic support alone and in combination with community dialogue aiming to reduce early childbearing did not appear to have a substantial impact on healthcare utilization and CHE in rural Zambia. However, although cash transfer did not significantly improve healthcare utilization, it reduced the degree of inequality in outpatient healthcare utilization and CHE across wealth groups. Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT02709967, ClinicalTrials.gov, identifier (NCT02709967).

Social contact patterns during the early COVID-19 pandemic in Norway: insights from a panel study, April to September 2020.

BACKGROUND: During the COVID-19 pandemic, many countries adopted social distance measures and lockdowns of varying strictness. Social contact patterns are essential in driving the spread of respiratory infections, and country-specific measurements are needed. This study aimed to gain insights into changes in social contacts and behaviour during the early pandemic phase in Norway. METHODS: We conducted an online panel study among a nationally representative sample of Norwegian adults by age and gender. The panel study included six data collections waves between April and September 2020, and 2017 survey data from a random sample of the Norwegian population (including children < 18 years old) were used as baseline. The market research company Ipsos was responsible for carrying out the 2020 surveys. We calculated mean daily contacts, and estimated age-stratified contact matrices during the study period employing imputation of child-to-child contacts. We used the next-generation method to assess the relative reduction of R0 and compared the results to reproduction numbers estimated for Norway during the 2020 study period. RESULTS: Over the six waves in 2020, 5 938 observations/responses were registered from 1 718 individuals who reported data on 22 074 contacts. The mean daily number of contacts among adults varied between 3.2 (95%CI 3.0-3.4) to 3.9 (95%CI 3.6-4.2) across the data collection waves, representing a 67-73% decline compared to pre-pandemic levels (baseline). Fewer contacts in the community setting largely drove the reduction; the drop was most prominent among younger adults. Despite gradual easing of social distance measures during the survey period, the estimated population contact matrices remained relatively stable and displayed more inter-age group mixing than at baseline. Contacts within households and the community outside schools and workplaces contributed most to social encounters. Using the next-generation method R0 was found to be roughly 25% of pre-pandemic levels during the study period, suggesting controlled transmission. CONCLUSION: Social contacts declined significantly in the months following the March 2020 lockdown, aligning with implementation of stringent social distancing measures. These findings contribute valuable empirical information into the social behaviour in Norway during the early pandemic, which can be used to enhance policy-relevant models for addressing future crises when mitigation measures might be implemented.

Post-discharge malaria chemoprevention in children admitted with severe anaemia in malaria-endemic settings in Africa: a systematic review and individual patient data meta-analysis of randomised controlled trials.

BACKGROUND: Severe anaemia is associated with high in-hospital mortality among young children. In malaria-endemic areas, surviving children also have an increased risk of mortality or readmission after hospital discharge. We conducted a systematic review and individual patient data meta-analysis to determine the efficacy of monthly post-discharge malaria chemoprevention in children recovering from severe anaemia. METHODS: This analysis was conducted according to PRISMA-IPD guidelines. We searched multiple databases on Aug 28, 2023, without date or language restrictions, for randomised controlled trials comparing monthly post-discharge malaria chemoprevention with placebo or standard of care among children (aged <15 years) admitted with severe anaemia in malaria-endemic Africa. Trials using daily or weekly malaria prophylaxis were not eligible. The investigators from all eligible trials shared pseudonymised datasets, which were standardised and merged for analysis. The primary outcome was all-cause mortality during the intervention period. Analyses were performed in the modified intention-to-treat population, including all randomly assigned participants who contributed to the endpoint. Fixed-effects two-stage meta-analysis of risk ratios (RRs) was used to generate pooled effect estimates for mortality. Recurrent time-to-event data (readmissions or clinic visits) were analysed using one-stage mixed-effects Prentice-Williams-Peterson total-time models to obtain hazard ratios (HRs). This study is registered with PROSPERO, CRD42022308791. FINDINGS: Our search identified 91 articles, of which 78 were excluded by title and abstract, and a further ten did not meet eligibility criteria. Three double-blind, placebo-controlled trials, including 3663 children with severe anaemia, were included in the systematic review and meta-analysis; 3507 (95·7%) contributed to the modified intention-to-treat analysis. Participants received monthly sulfadoxine-pyrimethamine until the end of the malaria transmission season (mean 3·1 courses per child [range 1-6]; n=1085; The Gambia), monthly artemether-lumefantrine given at the end of weeks 4 and 8 post discharge (n=1373; Malawi), or monthly dihydroartemisinin-piperaquine given at the end of weeks 2, 6, and 10 post discharge (n=1049; Uganda and Kenya). During the intervention period, post-discharge malaria chemoprevention was associated with a 77% reduction in mortality (RR 0·23 [95% CI 0·08-0·70], p=0·0094, I2=0%) and a 55% reduction in all-cause readmissions (HR 0·45 [95% CI 0·36-0·56], p<0·0001) compared with placebo. The protective effect was restricted to the intervention period and was not sustained after the direct pharmacodynamic effect of the drugs had waned. The small number of trials limited our ability to assess heterogeneity, its sources, and publication bias. INTERPRETATION: In malaria-endemic Africa, post-discharge malaria chemoprevention reduces mortality and readmissions in recently discharged children recovering from severe anaemia. Post-discharge malaria chemoprevention could be a valuable strategy for the management of this group at high risk. Future research should focus on methods of delivery, options to prolong the protection duration, other hospitalised groups at high risk, and interventions targeting non-malarial causes of post-discharge morbidity. FUNDING: The Research-Council of Norway and the Bill-&-Melinda-Gates-Foundation through the Worldwide-Antimalarial-Research-Network.

Cost-Effectiveness of Hydroxyurea for Sickle Cell Anemia in a Low-Income African Setting: A Model-Based Evaluation of Two Dosing Regimens.

BACKGROUND AND OBJECTIVE: The disease burden of sickle cell anemia (SCA) in sub-Saharan African (SSA) countries is substantial, with many children dying without an established diagnosis or proper treatment. The global burden of SCA is increasing each year, making therapeutic intervention a high priority. Hydroxyurea is the only disease-modifying therapy with proven feasibility and efficacy suitable for SSA; however, no one has quantified the health economic implications of its use. Therefore, from the perspective of the health care provider, we estimated the incremental cost-effectiveness of hydroxyurea as a fixed-dose regimen or maximum tolerated dose (MTD) regimen, versus SCA care without hydroxyurea. METHODS: We estimated the cost of providing outpatient treatment at a pediatric sickle cell clinic in Kampala, Uganda. These estimates were used in a discrete-event simulation model to project mean costs (2021 US$), disability-adjusted life years (DALYs), and consumption of blood products per patient (450 mL units), for patients between 9 months and 18 years of age. We calculated cost-effectiveness as the ratio of incremental costs over incremental DALYs averted, discounted at 3% annually. To test the robustness of our findings, and the impact of uncertainty, we conducted probabilistic and one-way sensitivity analyses, scenario analysis, and price threshold analyses. RESULTS: Hydroxyurea treatment averted an expected 1.37 DALYs and saved US$ 191 per patient if administered at the MTD, compared with SCA care without hydroxyurea. In comparison, hydroxyurea at a fixed dose averted 0.80 DALYs per patient at an incremental cost of US$ 2. The MTD strategy saved 11.2 (95% CI 11.1-11.4) units of blood per patient, compared with 9.1 (95% CI 9.0-9.2) units of blood per patient at the fixed-dose alternative. CONCLUSIONS: Hydroxyurea at MTD is likely to improve quality of life and reduce the consumption of blood products for children with SCA living in Uganda. Compared with a fixed dose regimen, treatment dosing at MTD is likely to be a cost-effective treatment for SCA, using realistic ranges of hydroxyurea costs that are relevant across SSA. Compared with no use of the drug, hydroxyurea could lead to substantial net savings per patient, while reducing the disease morbidity and mortality and increasing quality of life.

Dihydroartemisinin-piperaquine or sulphadoxine-pyrimethamine for the chemoprevention of malaria in children with sickle cell anaemia in eastern and southern Africa (CHEMCHA): a protocol for a multi-centre, two-arm, double-blind, randomised, placebo-controlled superiority trial.

BACKGROUND: An estimated 300,000 babies are born with sickle cell anaemia (SCA) annually. Affected children have chronic ill health and suffer premature death. Febrile illnesses such as malaria commonly precipitate acute crises in children with SCA. Thus, chemoprophylaxis for malaria is an important preventive strategy, but current regimes are either sub-optimally effective (e.g. monthly sulphadoxine-pyrimethamine, SP) or difficult to adhere to (e.g. daily proguanil). We propose dihydroartemisinin-piperaquine (DP) as the agent with the most potential to be used across Africa. METHODS: This will be a randomised, double-blind, parallel-group superiority trial of weekly single-day courses of DP compared to monthly single-day courses of SP in children with SCA. The study will be conducted in eastern (Uganda) and southern (Malawi) Africa using randomisation stratified by body weight and study centre. Participants will be randomised using an allocation of 1:1 to DP or SP. We will investigate the efficacy, safety, acceptability and uptake and cost-effectiveness of malaria chemoprevention with weekly courses of DP vs monthly SP in 548 to 824 children with SCA followed up for 12-18 months. We will also assess toxicity from cumulative DP dosing and the development of resistance. Participant recruitment commenced on 30 April 2021; follow-up is ongoing. DISCUSSION: At the end of this study, findings will be used to inform regional health policy. This manuscript is prepared from protocol version 2.1 dated 1 January 2022. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov, NCT04844099 . Registered on 08 April 2021.

Predicting adherence to postdischarge malaria chemoprevention in Malawian pre-school children: A prognostic multivariable analysis.

Chemoprevention with antimalarials is a key strategy for malaria control in sub-Saharan Africa. Three months of postdischarge malaria chemoprevention (PDMC) reduces malaria-related mortality and morbidity in pre-school children recently discharged from hospital following recovery from severe anemia. Research on adherence to preventive antimalarials in children is scarce. We aimed to investigate the predictors for caregivers' adherence to three courses of monthly PDMC in Malawi. We used data from a cluster randomized implementation trial of PDMC in Malawi (n = 357). Modified Poisson regression for clustered data was used to obtain relative risks of predictors for full adherence to PDMC. We did not find a conclusive set of predictors for PDMC adherence. The distribution of households across a socio-economic index and caregivers' education showed mixed associations with poor adherence. Caregivers of children with four or more malaria infections in the past year were associated with reduced adherence. With these results, we cannot confirm the associations established in the literature for caregiver adherence to artemisinin-based combination therapies (ACTs). PDMC combines multiple factors that complicate adherence. Our results may indicate that prevention interventions introduce a distinct complexity to ACT adherence behavior. Until we better understand this relationship, PDMC programs should ensure high program fidelity to sustain adherence by caregivers during implementation.

Projected health impact of post-discharge malaria chemoprevention among children with severe malarial anaemia in Africa.

Children recovering from severe malarial anaemia (SMA) remain at high risk of readmission and death after discharge from hospital. However, a recent trial found that post-discharge malaria chemoprevention (PDMC) with dihydroartemisinin-piperaquine reduces this risk. We developed a mathematical model describing the daily incidence of uncomplicated and severe malaria requiring readmission among 0-5-year old children after hospitalised SMA. We fitted the model to a multicentre clinical PDMC trial using Bayesian methods and modelled the potential impact of PDMC across malaria-endemic African countries. In the 20 highest-burden countries, we estimate that only 2-5 children need to be given PDMC to prevent one hospitalised malaria episode, and less than 100 to prevent one death. If all hospitalised SMA cases access PDMC in moderate-to-high transmission areas, 38,600 (range 16,900-88,400) malaria-associated readmissions could be prevented annually, depending on access to hospital care. We estimate that recurrent SMA post-discharge constitutes 19% of all SMA episodes in moderate-to-high transmission settings.

Economic evaluation of postdischarge malaria chemoprevention in preschool children treated for severe anaemia in Malawi, Kenya, and Uganda: A cost-effectiveness analysis.

Background: Children hospitalised with severe anaemia in malaria-endemic areas are at a high risk of dying or being readmitted within six months of discharge. A trial in Kenya and Uganda showed that three months of postdischarge malaria chemoprevention (PDMC) with monthly dihydroartemisinin-piperaquine (DP) substantially reduced this risk. The World Health Organization recently included PDMC in its malaria chemoprevention guidelines. We conducted a cost-effectiveness analysis of community-based PDMC delivery (supplying all three PDMC-DP courses to caregivers at discharge to administer at home), facility-based PDMC delivery (monthly dispensing of PDMC-DP at the hospital), and the standard of care (no PDMC). Methods: We combined data from two recently completed trials; one placebo-controlled trial in Kenya and Uganda collecting efficacy data (May 6, 2016 until November 15, 2018; n=1049), and one delivery mechanism trial from Malawi collecting adherence data (March 24, 2016 until October 3, 2018; n=375). Cost data were collected alongside both trials. Three Markov decision models, one each for Malawi, Kenya, and Uganda, were used to compute incremental cost-effectiveness ratios expressed as costs per quality-adjusted life-year (QALY) gained. Deterministic and probabilistic sensitivity analyses were performed to account for uncertainty. Findings: Both PDMC strategies were cost-saving in each country, meaning less costly and more effective in increasing health-adjusted life expectancy than the standard of care. The estimated incremental cost savings for community-based PDMC compared to the standard of care were US$ 22·10 (Malawi), 38·52 (Kenya), and 26·23 (Uganda) per child treated. The incremental effectiveness gain using either PDMC strategy varied between 0·3 and 0·4 QALYs. Community-based PDMC was less costly and more effective than facility-based PDMC. These results remained robust in sensitivity analyses. Interpretation: PDMC under implementation conditions is cost-saving. Caregivers receiving PDMC at discharge is a cost-effective delivery strategy for implementation in malaria-endemic southeastern African settings. Funding: Research Council of Norway.

Cost-Effectiveness of Mobile Stroke Unit Care in Norway.

BACKGROUND: Acute ischemic stroke treatment in mobile stroke units (MSUs) reduces time-to-treatment and increases thrombolytic rates, but implementation requires substantial investments. We wanted to explore the cost-effectiveness of MSU care incorporating novel efficacy data from the Norwegian MSU study, Treat-NASPP (the Norwegian Acute Stroke Prehospital Project). METHODS: We developed a Markov model linking improvements in time-to-treatment and thrombolytic rates delivered by treatment in an MSU to functional outcomes for the patients in a lifetime perspective. We estimated incremental costs, health benefits, and cost-effectiveness of MSU care as compared with conventional care. In addition, we estimated a minimal MSU utilization level for the intervention to be cost-effective in the publicly funded health care system in Norway. RESULTS: MSU care was associated with an expected quality-adjusted life-year-gain of 0.065 per patient, compared with standard care. Our analysis suggests that about 260 patients with ischemic stroke need to be treated with MSU annually to result in an incremental cost-effectiveness ratio of about NOK385 000 (US$43 780) per quality-adjusted life-year for MSU compared with standard care. The incremental cost-effectiveness ratio varies between some NOK1 000 000 (US$113 700) per quality-adjusted life-year if an MSU treats 100 patients per year and to about NOK340 000 (US$38 660) per quality-adjusted life-year if 300 patients with acute ischemic stroke are treated. CONCLUSIONS: MSU care in Norwegian settings is potentially cost-effective compared with conventional care, but this depends on a relatively high annual number of treated patients with acute ischemic stroke per vehicle. These results provide important information for MSU implementation in government-funded health care systems.

Appraising Drugs Based on Cost-effectiveness and Severity of Disease in Norwegian Drug Coverage Decisions.

Importance: Rising health care costs are a major health policy challenge globally. Norway has implemented a priority-setting system intended to balance cost-effectiveness and concerns for fair distribution, but little is known about this strategy and whether it works in practice. Objective: To present and evaluate a systematic drug appraisal method that uses the severity of disease to account for a fair distribution of health in cost-effectiveness analysis, forming the basis for price negotiations and coverage decisions. Design, Setting, and Participants: This cross-sectional study uses confidential drug price information and publicly available data from health technology assessments and logistic and linear regression analyses to evaluate drug coverage decisions for the Norwegian specialized health care sector from 2014 to 2019. Main Outcomes and Measures: Drug coverage decisions by Norwegian authorities and incremental cost-effectiveness and severity of disease measured as absolute shortfall of quality adjusted life years. Results: Between 2014 and 2019, a total of 188 drugs were appraised, of which 113 were cancer drugs. The overall coverage rate was 73% (138 of 188). The number of annual appraisals increased during the observation period. Based on 83 chosen decisions, regression analysis showed that incremental cost-effectiveness ratios (ICER) based on negotiated drug prices, adjusted for severity-differentiated cost-effectiveness thresholds, was the variable that best projected drug approvals (OR, 0.60; 95% CI, 0.42-0.86). An increase in the ICER by $10 000 was associated with a reduction in the odds for approval of 40% for drugs assessed from 2018 to 2019. Conclusions and Relevance: This cross-sectional study demonstrated how concerns for efficiency and fair distribution of health can be implemented systematically into drug appraisals and reimbursement decisions. New, expensive drugs are expected to escalate health care costs in the years to come, and it may be feasible to control costs by negotiating the prices of new drugs while appraising both their cost-effectiveness and how their health benefits are distributed.

Post-discharge morbidity and mortality in children admitted with severe anaemia and other health conditions in malaria-endemic settings in Africa: a systematic review and meta-analysis.

BACKGROUND: Severe anaemia is associated with high in-hospital mortality among young children. In malaria-endemic areas, surviving children also remain at increased risk of mortality for several months after hospital discharge. We aimed to compare the risks of morbidity and mortality among children discharged from hospital after recovery from severe anaemia versus other health conditions in malaria-endemic settings in Africa. METHODS: Following PRISMA guidelines, we searched PubMed, Scopus, Web of Science, and Cochrane Central from inception to Nov 30, 2021, without language restrictions, for prospective or retrospective cohort studies and randomised controlled trials that followed up children younger than 15 years for defined periods after hospital discharge in malaria-endemic countries in Africa. We excluded the intervention groups in trials and studies or subgroups involving children with sickle cell anaemia, malignancies, or surgery or trauma, or those reporting follow-up data that were combined with the in-hospital period. Two independent reviewers extracted the data and assessed the quality and risk of bias using the Newcastle Ottawa Scale or the Cochrane Collaboration's tool. The coprimary outcomes were all-cause death and all-cause readmissions 6 months after discharge. This study is registered with PROSPERO, CRD42017079282. FINDINGS: Of 2930 articles identified in our search, 27 studies were included. For children who were recently discharged following hospital admission with severe anaemia, all-cause mortality by 6 months was higher than during the in-hospital period (n=5 studies; Mantel-Haenszel odds ratio 1·72, 95% CI 1·22-2·44; p=0·0020; I2=51·5%) and more than two times higher than children previously admitted without severe anaemia (n=4 studies; relative risk [RR] 2·69, 95% CI 1·59-4·53; p<0·0001; I2=69·2%). Readmissions within 6 months of discharge were also more common in children admitted with severe anaemia than in children admitted with other conditions (n=1 study; RR 3·05, 1·12-8·35; p<0·0001). Children admitted with severe acute malnutrition (regardless of severe anaemia) also had a higher 6-month mortality after discharge than those admitted for other reasons (n=2 studies; RR=3·12, 2·02-4·68; p<0·0001; I2=54·7%). Other predictors of mortality after discharge included discharge against medical advice, HIV, bacteraemia, and hypoxia. INTERPRETATION: In malaria-endemic settings in Africa, children admitted to hospital with severe anaemia and severe acute malnutrition are at increased risk of mortality in the first 6 months after discharge compared with children admitted with other health conditions. Improved strategies are needed for the management of these high-risk groups during the period after discharge. FUNDING: Research Council of Norway and US Centers for Disease Control and Prevention.

Is amalgam removal in patients with medically unexplained physical symptoms cost-effective? A prospective cohort and decision modelling study in Norway.

There are many patients in general practice with health complaints that cannot be medically explained. Some of these patients attribute their health complaints to dental amalgam restorations. This study examined the cost-effectiveness of the removal of amalgam restorations in patients with medically unexplained physical symptoms (MUPS) attributed to amalgam fillings compared to usual care, based on a prospective cohort study in Norway. Costs were determined using a micro-costing approach at the individual level. Health outcomes were documented at baseline and approximately two years later for both the intervention and the usual care using EQ-5D-5L. Quality adjusted life year (QALY) was used as a main outcome measure. A decision analytical model was developed to estimate the incremental cost-effectiveness of the intervention. Both probabilistic and one-way sensitivity analyses were conducted to assess the impact of uncertainty in costs and effectiveness. In patients who attribute health complaints to dental amalgam restorations and fulfil the inclusion and exclusion criteria, amalgam removal is associated with modest increase in costs at societal level as well as improved health outcomes. In the base-case analysis, the mean incremental cost per patient in the amalgam group was NOK 19 416 compared to the MUPS group, while mean incremental QALY was 0.119 with a time horizon of two years. Thus, the incremental costs per QALY of the intervention was NOK 162 680, which is usually considered cost effective in Norway. The estimated incremental cost per QALY decreased with increasing time horizon, and amalgam removal was found to be cost saving over both 5 and 10 years. This study provides insight into the costs and health outcomes associated with the removal of amalgam restorations in patients who attribute health complaints to dental amalgam fillings, which are appropriate instruments to inform health care priorities.

Public participation: healthcare rationing in the newspaper media.

BACKGROUND: It is impossible to meet all healthcare demands, but an open and fair rationing process may improve the public acceptability of priority setting in healthcare. Decision-making is subject to scrutiny by newspaper media, an important public institution and information source for discussions about rationing. In Norway, healthcare rationing has been subject to public debate both before and after the establishment of "The National System for Managed Introduction of New Health Technologies within the Specialist Health Service" (New Methods) in 2013. AIM: To describe and assess the development of the public debate on Norwegian healthcare rationing through three cases in print media. METHODS: We purposively sampled Norwegian newspaper articles between 2012 and 2018 concerning three reimbursement decisions in the Norwegian system. The reimbursement decisions were ipilimumab (Yervoy, n = 45) against metastatic melanoma, nivolumab (Opdivo, n = 23) against non-small cell lung cancer, and nusinersen (Spinraza, n = 68) against spinal muscular atrophy. Cases were analysed separately using the qualitative method of systematic text condensation. RESULTS: Our analysis highlighted four common themes-money, rationales, patient stories, and process-and a unique theme for each case. Ipilimumab was uniquely themed by rationing rejection, nivolumab by healthcare two-tiering, and Spinraza by patients' rights. We found wide media deliberation among a multitude of stakeholders in all cases. Perceptions of rationing were found to be chiefly aligned with previous empirical research. We found that the media reported more frequently on opposition to rationing compared to findings from previous studies on Norwegian healthcare decision-making attitudes. We think this was influenced by our selection of cases receiving extraordinary media attention, and from media sources being subject to political communication from special interest groups. CONCLUSION: We observed that the introduction of New Methods institutionalised Norwegian healthcare rationing and isolated the public debate into conversations between stakeholders and decision makers outside the political sphere. The findings from these three extraordinary debates are not generalisable and should be seen as a stakeholder learning opportunity regarding media coverage and engagement with expensive specialist healthcare decision-making in Norway.

Validity and responsiveness of GHC-index in patients with amalgam-attributed health complaints.

OBJECTIVE: Many patients have medically unexplained physical symptoms (MUPS); some of them attribute their health complaints to dental amalgam fillings. The aim of this study was to assess the validity and responsiveness of General Health Complaints index (GHC-index) for measuring the symptom load in MUPS patients compared to the widely used symptom outcome measure, Giessen Subjective Complaints List (GBB-24). METHODS: Three outcome measures - GHC-index, GBB-24, and Munich Amalgam Scale (MAS) - were administered at baseline and 12 months after removal of all dental amalgam restorations. The validity and responsiveness of these symptom measures were tested against external anchors: bodily distress syndrome (BDS), SF-36 vitality, and visual analogue scale (VAS). We tested both convergent and known group validities. We also examined the predictive validity and responsiveness to changes for each instrument. RESULTS: All the main outcome measures showed evidence of convergent and known group validities. The GHC-index, GBB-24 and MAS were all able to detect the anticipated differences in BDS and Energy. But the GBB-24 was more efficient in discriminating the BDS compared with the GHC-index (relative efficiency: RE = 0.69; 95% CI: 0.41-0.96) and MAS (RE = 0.59; 95% CI: 0.32-0.86). Each main outcome variable revealed good predictive validity for vitality (standardized coefficient: b ≈ 0.71 and R2 ≈ 0.50). Moderate to high sensitivity to change over time was demonstrated, with GHC-index performing better. CONCLUSION: The GHC-index is a valid and responsive instrument for assessing symptom load in MUPS patients attributing their health complaints to amalgam fillings and undergoing amalgam removal.

Visiting crowded places during the COVID-19 pandemic. A panel study among adult Norwegians.

Non-pharmaceutical interventions, including promotion of social distancing, have been applied extensively in managing the COVID-19 pandemic. Understanding cognitive and psychological factors regulating precautionary behavior is important for future management. The present study examines the importance of selected factors as predictors of having visited or intended to visit crowded places. Six online questionnaire-based waves of data collection were conducted in April-October 2020 in a Norwegian panel (≥18 years). Sample size at Wave 1 was 1,400. In the present study, "Visited or intended to visit crowded places" for different types of locations were the dependent variables. Predictors included the following categories of items: Perceived response effectiveness, Self-efficacy, Vulnerability, Facilitating factors and Barriers. Data were analyzed with frequency and percentage distributions, descriptives, correlations, principal components analysis, negative binomial-, binary logistic-, and multiple linear regression, and cross-lagged panel models. Analyses of dimensionality revealed that a distinction had to be made between Grocery stores, a location visited by most, and locations visited by few (e.g., "Pub," "Restaurants," "Sports event"). We merged the latter set of variables into a countscore denoted as "Crowded places." On the predictor side, 25 items were reduced to eight meanscores. Analyses of data from Wave 1 revealed a rather strong prediction of "Crowded places" and weaker associations with "Supermarket or other store for food." Across waves, in multiple negative binomial regression models, three meanscore predictors turned out to be consistently associated with "Crowded places." These include "Response effectiveness of individual action," "Self-efficacy with regard to avoiding people," and "Barriers." In a prospective cross-lagged model, a combined Response effectiveness and Self-efficacy score (Cognition) predicted behavior ("Visited or intended to visit crowded places") prospectively and vice versa. The results of this study suggest some potential to reduce people's visits to crowded locations during the pandemic through health education and behavior change approaches that focus on strengthening individuals' perceived response effectiveness and self-efficacy.

Implementing standard antenatal care interventions: health system cost at primary health facilities in Tanzania.

BACKGROUND: Since 2002, Tanzania has been implementing the focused Antenatal Care (ANC) model that recommended four antenatal care visits. In 2016, the World Health Organization (WHO) reintroduced the standard ANC model with more interventions including a minimum of eight contacts. However, cost-implications of these changes to the health system are unknown, particularly in countries like Tanzania, that failed to optimally implement the simpler focused ANC model. We compared the health system cost of providing ANC under the focused and the standard models at primary health facilities in Tanzania. METHODS: We used a micro-costing approach to identify and quantify resources used to implement the focused ANC model at six primary health facilities in Tanzania from July 2018 to June 2019. We also used the standard ANC implementation manual to identify and quantify additional resources required. We used basic salary and allowances to value personnel time while the Medical Store Department price catalogue and local market prices were used for other resources. Costs were collected in Tanzanian shillings and converted to 2018 US$. RESULTS: The health system cost of providing ANC services at six facilities (2 health centres and 4 dispensaries) was US$185,282 under the focused model. We estimated that the cost would increase by about 90% at health centres and 97% at dispensaries to US$358,290 by introducing the standard model. Personnel cost accounted for more than one third of the total cost, and more than two additional nurses are required per facility for the standard model. The costs per pregnancy increased from about US$33 to US$63 at health centres and from about US$37 to US$72 at dispensaries. CONCLUSION: Introduction of a standard ANC model at primary health facilities in Tanzania may double resources requirement compared to current practice. Resources availability has been one of the challenges to effective implementation of the current focused ANC model. More research is required, to consider whether the additional costs are reasonable compared to the additional value for maternal and child health.

Protocol for a multicentre, parallel-group, open-label randomised controlled trial comparing ferric carboxymaltose with the standard of care in anaemic Malawian pregnant women: the REVAMP trial.

INTRODUCTION: Anaemia in pregnancy remains a critical global health problem, affecting 46% of pregnant women in Africa and 49% in Asia. Oral iron therapy requires extended adherence to achieve correction of anaemia and replenishment of iron stores. Ferric carboxymaltose (FCM) is a recently established intravenous iron formulation associated with substantial advantages in safety, speed of delivery and total dose deliverable in a single infusion. We aim to determine whether FCM given once during the second trimester of pregnancy compared with standard oral iron distributed through routine antenatal services is effective and safe for treatment of moderate to severe maternal anaemia in sub-Saharan Africa. METHODS AND ANALYSIS: The randomized controlled trial of the effect of intravenous iron on anaemia in Malawian pregnant women (REVAMP) is a two-arm confirmatory individually randomised trial set in Blantyre and Zomba districts in Malawi. The trial will randomise 862 women in the second trimester of pregnancy with a capillary haemoglobin concentration below 100.0 g/L. The study comprises two arms: (a) intravenous FCM (20 mg/kg up to 1000 mg) given once at randomisation, and (b) standard of care oral iron (65 mg elemental iron two times per day) for 90 days (or the duration of pregnancy, whichever is shorter) provided according to local healthcare practices. Both arms receive sulfadoxine-pyrimethamine as intermittent preventive treatment in pregnancy. The primary outcome is the prevalence of anaemia (Hb <110.0 g/L) at 36 weeks' gestation. Secondary outcomes include birth weight, gestation duration and safety outcomes, including clinical malaria, serious perinatal events and postpartum haematologic and health-related outcomes in the mother and child. ETHICS AND DISSEMINATION: Ethical approval was granted by the Research Ethics Committee (COMREC P.02/18/2357) in Malawi and the Human Research Ethics Committee (WEHI: 18/02), Melbourne, Australia. The protocol is registered with the Australian and New Zealand Clinical Trials Registry. The results will be shared with the local community that enabled the research, and also to the international fora. TRIAL REGISTRATION NUMBER: ACTRN12618001268235; Pre-results.

Cost-effectiveness of household contact investigation for detection of tuberculosis in Pakistan.

OBJECTIVES: Despite WHO guidelines recommending household contact investigation, and studies showing the impact of active screening, most tuberculosis (TB) programmes in resource-limited settings only carry out passive contact investigation. The cost of such strategies is often cited as barriers to their implementation. However, little data are available for the additional costs required to implement this strategy. We aimed to estimate the cost and cost-effectiveness of active contact investigation as compared with passive contact investigation in urban Pakistan. METHODS: We estimated the cost-effectiveness of 'enhanced' (passive with follow-up) and 'active' (household visit) contact investigations compared with standard 'passive' contact investigation from providers and the programme's perspective using a simple decision tree. Costs were collected in Pakistan from a TB clinic performing passive contact investigation and from studies of active contact tracing interventions conducted. The effectiveness was based on the number of patients with TB identified among household contacts screened. RESULTS: The addition of enhanced contact investigation to the existing passive mode detected 3.8 times more cases of TB per index patient compared with passive contact investigation alone. The incremental cost was US$30 per index patient, which yielded an incremental cost of US$120 per incremental patient identified with TB. The active contact investigation was 1.5 times more effective than enhanced contact investigation with an incremental cost of US$238 per incremental patient with TB identified. CONCLUSION: Our results show that enhanced and active approaches to contact investigation effectively identify additional patients with TB among household contacts at a relatively modest cost. These strategies can be added to the passive contact investigation in a high burden setting to find the people with TB who are missed and meet the End TB strategy goals.

Adherence to community versus facility-based delivery of monthly malaria chemoprevention with dihydroartemisinin-piperaquine for the post-discharge management of severe anemia in Malawian children: A cluster randomized trial.

BACKGROUND: The provision of post-discharge malaria chemoprevention (PMC) in children recently admitted with severe anemia reduces the risk of death and re-admissions in malaria endemic countries. The main objective of this trial was to identify the most effective method of delivering dihydroartemesinin-piperaquine to children recovering from severe anemia. METHODS: This was a 5-arm, cluster-randomized trial among under-5 children hospitalized with severe anemia at Zomba Central Hospital in Southern Malawi. Children were randomized to receive three day treatment doses of dihydroartemesinin-piperaquine monthly either; 1) in the community without a short text reminder; 2) in the community with a short message reminder; 3) in the community with a community health worker reminder; 4) at the facility without a short text reminder; or 5) at the facility with a short message reminder. The primary outcome measure was adherence to all treatment doses of dihydroartemesinin-piperaquine and this was assessed by pill-counts done by field workers during home visits. Poisson regression was utilized for analysis. RESULTS: Between March 2016 and October 2018, 1460 clusters were randomized. A total of 667 children were screened and 375 from 329 clusters were eligible and enrolled from the hospital. Adherence was higher in all three community-based compared to the two facility-based delivery (156/221 [70·6%] vs. 78/150 [52·0%], IRR = 1·24,95%CI 1·06-1·44, p = 0·006). This was observed in both the SMS group (IRR = 1·41,1·21-1·64, p<0·001) and in the non-SMS group (IRR = 1·37,1·18-1·61, p<0·001). Although adherence was higher among SMS recipients (98/148 66·2%] vs. non-SMS 82/144 (56·9%), there was no statistical evidence that SMS reminders resulted in greater adherence ([IRR = 1·03,0·88-1·21, p = 0·68). When compared to the facility-based non-SMS arm (control arm), community-based delivery utilizing CHWs resulted in higher adherence [39/76 (51·3%) vs. 54/79 (68·4%), IRR = 1·32, 1·14-1·54, p<0·001]. INTERPRETATION: Community-based delivery of dihydroartemesinin-piperaquine for post-discharge malaria chemoprevention in children recovering from severe anemia resulted in higher adherence compared to facility-based methods. TRIAL REGISTRATION: NCT02721420; ClinicalTrials.gov.