CT or Invasive Coronary Angiography in Stable Chest Pain.

BACKGROUND: In the diagnosis of obstructive coronary artery disease (CAD), computed tomography (CT) is an accurate, noninvasive alternative to invasive coronary angiography (ICA). However, the comparative effectiveness of CT and ICA in the management of CAD to reduce the frequency of major adverse cardiovascular events is uncertain. METHODS: We conducted a pragmatic, randomized trial comparing CT with ICA as initial diagnostic imaging strategies for guiding the treatment of patients with stable chest pain who had an intermediate pretest probability of obstructive CAD and were referred for ICA at one of 26 European centers. The primary outcome was major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) over 3.5 years. Key secondary outcomes were procedure-related complications and angina pectoris. RESULTS: Among 3561 patients (56.2% of whom were women), follow-up was complete for 3523 (98.9%). Major adverse cardiovascular events occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 (3.0%) in the ICA group (hazard ratio, 0.70; 95% confidence interval [CI], 0.46 to 1.07; P = 0.10). Major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13 to 0.55). Angina during the final 4 weeks of follow-up was reported in 8.8% of the patients in the CT group and in 7.5% of those in the ICA group (odds ratio, 1.17; 95% CI, 0.92 to 1.48). CONCLUSIONS: Among patients referred for ICA because of stable chest pain and intermediate pretest probability of CAD, the risk of major adverse cardiovascular events was similar in the CT group and the ICA group. The frequency of major procedure-related complications was lower with an initial CT strategy. (Funded by the European Union Seventh Framework Program and others; DISCHARGE ClinicalTrials.gov number, NCT02400229.).

Effect of Body Mass Index on Effectiveness of CT versus Invasive Coronary Angiography in Stable Chest Pain: The DISCHARGE Trial.

Background Recent trials support the role of cardiac CT in the evaluation of symptomatic patients suspected of having coronary artery disease (CAD); however, body mass index (BMI) has been reported to negatively impact CT image quality. Purpose To compare initial use of CT versus invasive coronary angiography (ICA) on clinical outcomes in patients with stable chest pain stratified by BMI category. Materials and Methods This prospective study represents a prespecified BMI subgroup analysis of the multicenter Diagnostic Imaging Strategies for Patients with Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial conducted between October 2015 and April 2019. Adult patients with stable chest pain and a CAD pretest probability of 10%-60% were randomly assigned to undergo initial CT or ICA. The primary end point was major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, or stroke. The secondary end point was an expanded MACE composite, including transient ischemic attack, and major procedure-related complications. Competing risk analyses were performed using the Fine and Gray subdistribution Cox proportional hazard model to assess the impact of the relationship between BMI and initial management with CT or ICA on the study outcomes, whereas noncardiovascular death and unknown causes of death were considered competing risk events. Results Among the 3457 participants included, 831 (24.0%), 1358 (39.3%), and 1268 (36.7%) had a BMI of less than 25, between 25 and 30, and greater than 30 kg/m2, respectively. No interaction was found between CT or ICA and BMI for MACE (P = .29), the expanded MACE composite (P = .38), or major procedure-related complications (P = .49). Across all BMI subgroups, expanded MACE composite events (CT, 10 of 409 [2.4%] to 23 of 697 [3.3%]; ICA, 26 of 661 [3.9%] to 21 of 422 [5.1%]) and major procedure-related complications during initial management (CT, one of 638 [0.2%] to five of 697 [0.7%]; ICA, nine of 630 [1.4%] to 12 of 422 [2.9%]) were less frequent in the CT versus ICA group. Participants with a BMI exceeding 30 kg/m² exhibited a higher nondiagnostic CT rate (7.1%, P = .044) compared to participants with lower BMI. Conclusion There was no evidence of a difference in outcomes between CT and ICA across the three BMI subgroups. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article.

Coronary Artery Calcium Score Predicts Major Adverse Cardiovascular Events in Stable Chest Pain.

Background Coronary artery calcium (CAC) has prognostic value for major adverse cardiovascular events (MACE) in asymptomatic individuals, whereas its role in symptomatic patients is less clear. Purpose To assess the prognostic value of CAC scoring for MACE in participants with stable chest pain initially referred for invasive coronary angiography (ICA). Materials and Methods This prespecified subgroup analysis from the Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial, conducted between October 2015 and April 2019 across 26 centers in 16 countries, focused on adult patients with stable chest pain referred for ICA. Participants were randomly assigned to undergo either ICA or coronary CT. CAC scores from noncontrast CT scans were categorized into low, intermediate, and high groups based on scores of 0, 1-399, and 400 or higher, respectively. The end point of the study was the occurrence of MACE (myocardial infarction, stroke, and cardiovascular death) over a median 3.5-year follow-up, analyzed using Cox proportional hazard regression tests. Results The study involved 1749 participants (mean age, 60 years ± 10 [SD]; 992 female). The prevalence of obstructive coronary artery disease (CAD) at CT angiography rose from 4.1% (95% CI: 2.8, 5.8) in the CAC score 0 group to 76.1% (95% CI: 70.3, 81.2) in the CAC score 400 or higher group. Revascularization rates increased from 1.7% to 46.2% across the same groups (P < .001). The CAC score 0 group had a lower MACE risk (0.5%; HR, 0.08 [95% CI: 0.02, 0.30]; P < .001), as did the 1-399 CAC score group (1.9%; HR, 0.27 [95% CI: 0.13, 0.59]; P = .001), compared with the 400 or higher CAC score group (6.8%). No significant difference in MACE between sexes was observed (P = .68). Conclusion In participants with stable chest pain initially referred for ICA, a CAC score of 0 showed very low risk of MACE, and higher CAC scores showed increasing risk of obstructive CAD, revascularization, and MACE at follow-up. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Hanneman and Gulsin in this issue.

The IGF-PAPP-A-Stanniocalcin Axis in Serum and Ascites Associates with Prognosis in Patients with Ovarian Cancer.

Pregnancy-associated plasma protein-A (PAPP-A) and PAPP-A2 modulate insulin-like growth factor (IGF) action and are inhibited by the stanniocalcins (STC1 and STC2). We previously demonstrated increased PAPP-A and IGF activity in ascites from women with ovarian carcinomas. In this prospective, longitudinal study of 107 women with ovarian cancer and ascites accumulation, we determined corresponding serum and ascites levels of IGF-1, IGF-2, PAPP-A, PAPP-A2, STC1, and STC2 and assessed their relationship with mortality. As compared to serum, we found highly increased ascites levels of PAPP-A (51-fold) and PAPP-A2 (4-fold). Elevated levels were also observed for IGF-1 (12%), STC1 (90%) and STC2 (68%). In contrast, IGF-2 was reduced by 29% in ascites. Patients were followed for a median of 38.4 months (range: 45 days to 8.9 years), during which 73 patients (68.2%) died. Overall survival was longer for patients with high serum IGF-1 (hazard ratio (HR) per doubling in protein concentration: 0.60, 95% CI: 0.40-0.90). However, patients with high ascites levels of IGF-1 showed a poorer prognosis (HR: 2.00 (1.26-3.27)). High serum and ascites IGF-2 levels were associated with increased risk of mortality (HR: 2.01 (1.22-3.30) and HR: 1.78 (1.24-2.54), respectively). Similarly, serum PAPP-A2 was associated with mortality (HR: 1.26 (1.08-1.48)). Our findings demonstrate the presence and activity of the IGF system in the local tumor ecosystem, which is likely a characteristic feature of malignant disease and plays a role in its peritoneal dissemination. The potential clinical implications are supported by our finding that serum levels of the proteins are associated with patient prognosis.

Impact of smoking in patients with suspected coronary artery disease in the randomised DISCHARGE trial.

OBJECTIVES: To investigate if the effect of cardiac computed tomography (CT) vs. invasive coronary angiography (ICA) on cardiovascular events differs based on smoking status. MATERIALS AND METHODS: This pre-specified subgroup analysis of the pragmatic, prospective, multicentre, randomised DISCHARGE trial (NCT02400229) involved 3561 patients with suspected coronary artery disease (CAD). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or stroke). Secondary endpoints included an expanded MACE composite (MACE, transient ischaemic attack, or major procedure-related complications). RESULTS: Of 3445 randomised patients with smoking data (mean age 59.1 years + / - 9.7, 1151 men), at 3.5-year follow-up, the effect of CT vs. ICA on MACE was consistent across smoking groups (p for interaction = 0.98). The percutaneous coronary intervention rate was significantly lower with a CT-first strategy in smokers and former smokers (p = 0.01 for both). A CT-first strategy reduced the hazard of major procedure-related complications (HR: 0.21, 95% CI: 0.03, 0.81; p = 0.045) across smoking groups. In current smokers, the expanded MACE composite was lower in the CT- compared to the ICA-first strategy (2.3% (8) vs 6.0% (18), HR: 0.38; 95% CI: 0.17, 0.88). The rate of non-obstructive CAD was significantly higher in all three smoking groups in the CT-first strategy. CONCLUSION: For patients with stable chest pain referred for ICA, the clinical outcomes of CT were consistent across smoking status. The CT-first approach led to a higher detection rate of non-obstructive CAD and fewer major procedure-related complications in smokers. CLINICAL RELEVANCE STATEMENT: This pre-specified sub-analysis of the DISCHARGE trial confirms that a CT-first strategy in patients with stable chest pain referred for invasive coronary angiography with an intermediate pre-test probability of coronary artery disease is as effective as and safer than invasive coronary angiography, irrespective of smoking status. TRIAL REGISTRATION: ClinicalTrials.gov NCT02400229. KEY POINTS: • No randomised studies have assessed smoking status on CT effectiveness in symptomatic patients referred for invasive coronary angiography. • A CT-first strategy results in comparable adverse events, fewer complications, and increased coronary artery disease detection, irrespective of smoking status. • A CT-first strategy is safe and effective for stable chest pain patients with intermediate pre-test probability for CAD, including never smokers.

Outbreak caused by the SARS-CoV-2 Omicron variant in Norway, November to December 2021.

In late November 2021, an outbreak of Omicron SARS-CoV-2 following a Christmas party with 117 attendees was detected in Oslo, Norway. We observed an attack rate of 74% and most cases developed symptoms. As at 13 December, none have been hospitalised. Most participants were 30-50 years old. Ninety-six percent of them were fully vaccinated. These findings corroborate reports that the Omicron variant may be more transmissible, and that vaccination may be less effective in preventing infection compared with Delta.

The absorption and multiplication of uncertainty in machine-learning-driven finance.

Uncertainty about market developments and their implications characterize financial markets. Increasingly, machine learning is deployed as a tool to absorb this uncertainty and transform it into manageable risk. This article analyses machine-learning-based uncertainty absorption in financial markets by drawing on 182 interviews in the finance industry, including 45 interviews with informants who were actively applying machine-learning techniques to investment management, trading, or risk management problems. We argue that while machine-learning models are deployed to absorb financial uncertainty, they also introduce a new and more profound type of uncertainty, which we call critical model uncertainty. Critical model uncertainty refers to the inability to explain how and why the machine-learning models (particularly neural networks) arrive at their predictions and decisions-their uncertainty-absorbing accomplishments. We suggest that the dialectical relation between machine-learning models' uncertainty absorption and multiplication calls for further research in the field of finance and beyond.

Using ex-ante economic evaluation to inform research priorities in pesticide self-poisoning prevention: the case of a shop-based gatekeeper training programme in rural Sri Lanka.

OBJECTIVES: Suicide by pesticide self-poisoning is a major public health challenge in low- and middle-income countries. While effectiveness studies are required to test alternative prevention approaches, economic evidence is lacking to inform decision-making in research priority setting. Therefore, this study aimed to estimate the costs of a shop-based gatekeeper training programme for pesticide vendors seeking to prevent pesticide self-poisoning in rural Sri Lanka and assess its potential for cost-effectiveness. METHODS: Ex-ante cost and cost-effectiveness threshold (CET) analyses were performed from a governmental perspective based on a three-year analytic horizon, using 'no programme' as a comparator. A programme model targeting all 535 pesticide shops in the North Central Province and border areas was applied. Total programme costs (TPC) were estimated in 2019 USD using an ingredients approach and 3% annual discounting. The Sri Lankan gross domestic product per capita and life years saved were used as CET and effectiveness measure, respectively. Sensitivity analyses were performed. RESULTS: TPC were estimated at 31 603.03 USD. TPC were sensitive to cost changes of training material and equipment and the programme lifetime. The programme needs to prevent an estimated 0.23 fatal pesticide self-poisoning cases over three years to be considered cost-effective. In the sensitivity analyses, the highest number of fatal cases needed to be prevented to obtain cost-effectiveness was 4.55 over three years. CONCLUSIONS: From an economic perspective, the programme has a very high potential to be cost-effective. Research assessing its effectiveness should therefore be completed, and research analysing its transferability to other settings prioritised.

OBJECTIFS: Le suicide par auto-intoxication par les pesticides est un défi majeur de santé publique dans les pays à revenu faible ou intermédiaire. Bien que des études d'efficacité soient nécessaires pour tester d'autres approches de prévention, les données économiques manquent pour informer la prise de décision dans les priorités de recherche. Par conséquent, cette étude visait à estimer les coûts d'un programme de formation des vendeurs dans les magasins de pesticides visant à prévenir l'auto-intoxication par les pesticides dans les régions rurales du Sri Lanka et à évaluer son potentiel de rentabilité. MÉTHODES: Les analyses ex-ante des coûts et des seuils de rentabilité (SR) ont été réalisées dans une perspective gouvernementale sur la base d'un horizon analytique de trois ans, en utilisant «l'absence de programme¼ comme comparateur. Un modèle de programme ciblant les 535 magasins de pesticides de la province du Centre-Nord et des zones frontalières a été appliqué. Les coûts totaux du programme (CTP) ont été estimés en USD 2019 en utilisant une approche d'ingrédients et une remise annuelle de 3%. Le produit intérieur brut sri-lankais par habitant et les années de vie sauvées ont été utilisés comme SR et mesure d'efficacité, respectivement. Des analyses de sensibilité ont été effectuées. RÉSULTATS: le CTP a été estimé à 31.603,03 USD. Le CTP était sensible aux changements de coût du matériel et de l'équipement de formation et de la durée de vie du programme. Le programme devrait prévenir environ 0,23 cas d'auto-intoxication mortelle par des pesticide sur trois ans pour être considéré comme rentable. Dans les analyses de sensibilité, le plus grand nombre de cas mortels à prévenir pour obtenir une rentabilité était de 4,55 sur trois ans. CONCLUSIONS: D'un point de vue économique, le programme a un potentiel très élevé pour être rentable. La recherche évaluant son efficacité doit donc être complétée et la recherche analysant sa transférabilité à d'autres contextes doit être priorisée.

Generalist predator contributions to the control of Tetranychus urticae in strawberry crops documented by PCR-based gut content analysis.

The contribution of generalist insect predators to the control of the two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), an herbivorous pest of many crops, is poorly understood. One of the common insect predators in strawberries is the generalist predatory bug Anthocoris nemorum L. (Hemiptera: Anthocoridae), which has the potential to contribute to the control of pest populations. The feeding of adult A. nemorum on T. urticae was assessed by sampling individuals from an organic strawberry field in Denmark, and using PCR gut content analysis to detect remains of T. urticae within their gut. In the lab, we assessed that the DNA half-life detectability was 21.5 h. Significant numbers of field-collected A. nemorum tested positive for T. urticae prey DNA, with very high numbers in June (62.8%) and August (38.8%). This study presents conclusive evidence that the generalist predator A. nemorum can contribute to the decrease of T. urticae densities in strawberry fields, although the actual contribution in the present study is probably limited because predator populations were relatively low compared to T. urticae. The abundance of T. urticae did not increase significantly during the period of sampling, suggesting that a complex of natural enemies can achieve biological control of T. urticae in protected strawberries.

Microdialysis as a tool to determine the local tissue concentration of dicloxacillin in man.

AIMS: The most common pathogen to cause postoperative infections in Denmark is Staphylococcus aureus. Despite using prophylactic antibiotics, infections are still seen. Whether the tissue concentration is above the minimal inhibitory concentration (MIC) for the pathogen is unknown. Thus, the concentration of dicloxacillin in muscle and adipose tissue was measured after intravenous administration, in healthy men. METHODS: MIC for dicloxacillin against S. aureus was determined using the broth macrodilution method. A microdialysis (MD) catheter was placed in the subcutaneous tissue of the abdomen and in the lateral vastus muscle of the thigh of six healthy male volunteers. They were given 2 g dicloxacillin intravenously. Samples from blood and MD fluid were collected. The unbound dicloxacillin was isolated from plasma. Samples were analysed with high performance liquid chromatography (HPLC). RESULTS: The maximum concentration was reached in muscle tissue after 0.5 h and in adipose tissue after 0.8 h. AUC0-6h for the dicloxacillin concentration in adipose tissue was significantly lower when compared to the unbound dicloxacillin concentration in plasma. The dicloxacillin concentration was above the MIC for sensitive S. aureus for a minimum of 2.3 h and a median of 4.1 h in muscle tissue and a minimum of 1.8 h and a median of 3.2 h in adipose tissue. CONCLUSIONS: The unbound dicloxacillin concentration in adipose and muscle tissue remained above the MIC for sensitive S. aureus, for a period sufficient for many orthopaedic procedures. Whether this is true in patients with compromised circulation remains to be investigated.

Does multidisciplinary rehabilitation of tortured refugees represent 'value-for-money'? A follow-up of a Danish case-study.

BACKGROUND: The recent surge of asylum seekers in the European Union (EU) is raising questions about the EU's ability to integrate newcomers into the economy and into society; particularly those who need specialized services for the treatment of severe trauma. This study investigated whether rehabilitating traumatised refugees represents 'value-for-money' (VfM) in terms of intervention cost per health gain and in a long-term and societal perspective. METHODS: The economic evaluation comprised a cost-utility analysis (CUA) and a partial cost-benefit analysis (CBA). The CUA incorporated data on Quality Adjusted Life Years (QALY) for 45 patients who were treated at the Rehabilitation and Research Centre for Torture Victims, Copenhagen, Denmark, in 2001-2004 and followed for up to 2 years, to determine the incremental cost effectiveness ratio (ICER). For the CBA, data was collected for 44 patients who completed treatment between 2001 and 2004 and 44 matched controls on the waiting list, for the patients' primary health care utilisation, and personal and family labour income from 2001 to 2014. This was analysed to evaluate the Net Social Benefit (NSB) of the programme. RESULTS: The average cost of treatment was found to be about 32,000 USD per patient (2016 prices) with an average gain in QALY of 0.82. The treatment was cost effective according to the ICER threshold suggested by the National Institute of Health and Care Excellence (UK). At the individual level, the NSB remained negative throughout the study period. However, at the family income level the intervention proved to have been beneficial after 3 years. CONCLUSION: The implication of the study is, that providing rehabilitation to severely traumatised refugee families can be an economically viable strategy, considering the economic effects observed at the family level.

Correction to: does multidisciplinary rehabilitation of tortured refugees represent 'value-for-money'? A follow-up of a Danish case-study.

Following publication of the original article [1], the authors reported a correction in the name of one of the authors.

Caregivers' compliance with referral advice: evidence from two studies introducing mRDTs into community case management of malaria in Uganda.

BACKGROUND: Several malaria endemic countries have implemented community health worker (CHW) programmes to increase access to populations underserved by health care. There is considerable evidence on CHW adherence to case management guidelines, however, there is limited evidence on the compliance to referral advice and the outcomes of children under-5 referred by CHWs. This analysis examined whether caregivers complied with CHWs referral advice. METHODS: Data from two cluster (village) randomised trials, one in a moderate-to-high malaria transmission setting, another in a low-transmission setting conducted between January 2010-July 2011 were analysed. CHW were trained to recognise signs and symptoms that required referral to a health centre. CHW in the intervention arm also had training on; malaria rapid diagnostic tests (mRDT) and administering artemisinin based combination therapy (ACT); CHW in the control arm were trained to treat malaria with ACTs based on fever symptoms. Caregivers' referral forms were linked with CHW treatment forms to determine whether caregivers complied with the referral advice. Factors associated with compliance were examined with logistic regression. RESULTS: CHW saw 18,497 child visits in the moderate-to-high transmission setting and referred 15.2% (2815/18,497) of all visits; in the low-transmission setting, 35.0% (1135/3223) of all visits were referred. Compliance to referral was low, in both settings < 10% of caregivers complied with referral advice. In the moderate-to-high transmission setting compliance was higher if children were tested with mRDT compared to children who were not tested with mRDT. In both settings, nearly all children treated with pre-referral rectal artesunate failed to comply with referral and compliance was independently associated with factors such as health centre distance and day of referral by a CHW. In the moderate-to-high transmission setting, time of presentation, severity of referral were also associated with compliance, whilst in the low-transmission setting, compliance was low if an ACT was prescribed. CONCLUSIONS: This analysis suggests there are several barriers to comply with CHWs referral advice by caregivers. This is concerning for children who received rectal artesunate. As CHW programmes continue scale-up, barriers to referral compliance need to be addressed to ensure a continuum of care from the community to the health centre. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov. Identifier NCT01048801 , 13th January 2010.

Referral of children seeking care at private health facilities in Uganda.

BACKGROUND: In Uganda, referral of sick children seeking care at public health facilities is poor and widely reported. However, studies focusing on the private health sector are scanty. The main objective of this study was to assess referral practices for sick children seeking care at private health facilities in order to explore ways of improving treatment and referral of sick children in this sector. METHODS: A survey was conducted from August to October 2014 in Mukono district, central Uganda. Data was collected using a structured questionnaire supplemented by Focus Group Discussions and Key Informant interviews with private providers and community members. RESULTS: A total of 241 private health facilities were surveyed; 170 (70.5%) were registered drug shops, 59 (24.5%) private clinics and 12 (5.0%) pharmacies. Overall, 104/241 (43.2%) of the private health facilities reported that they had referred sick children to higher levels of care in the two weeks prior to the survey. The main constraints to follow referral advice as perceived by caretakers were: not appreciating the importance of referral, gender-related decision-making and negotiations at household level, poor quality of care at referral facilities, inadequate finances at household level; while the perception that referral leads to loss of prestige and profit was a major constraint to private providers. CONCLUSION: In conclusion, the results show that referral of sick children at private health facilities faces many challenges at provider, caretaker, household and community levels. Thus, interventions to address constraints to referral of sick children are urgently needed.

Comparison of the capacity between public and private health facilities to manage under-five children with febrile illnesses in Uganda.

BACKGROUND: Public health facilities are usually the first to receive interventions compared to private facilities, yet majority of health seeking care is first done with the latter. This study compared the capacity to manage acute febrile illnesses in children below 5 years in private vs public health facilities in order to design interventions to improve quality of care. METHODS: A survey was conducted within 57 geographical areas (parishes), from August to October 2014 in Mukono district, central Uganda. The survey comprised both facility and health worker assessment. Data were collected on drug stocks, availability of treatment guidelines, diagnostic equipment, and knowledge in management of malaria, pneumonia and diarrhoea, using a structured questionnaire. RESULTS: A total of 53 public and 241 private health facilities participated in the study. While similar proportions of private and public health facilities stocked Coartem, the first-line anti-malarial drug, (98 vs 95%, p = 0.22), significantly more private than public health facilities stocked quinine (85 vs 53%, p < 0.01). Stocks of obsolete anti-malarial drugs, such as chloroquine, were reported in few public and private facilities (3.7 vs 12.5%, p = 0.06). Stocks of antibiotics-amoxycillin and gentamycin were similar in both sectors (≥90% for amoxicillin; ≥50 for gentamycin). Training in malaria was reported by 65% of public health facilities vs 56% in the private sector, p = 0.25), while, only 21% in the public facility and 12% in the private facilities, p = 0.11, reported receiving training in pneumonia. Only 55% of public facilities had microscopes. Malaria treatment guidelines were significantly lacking in the private sector, p = 0.01. Knowledge about first-line management of uncomplicated malaria, pneumonia and diarrhoea was significantly better in the public facilities compared to the private ones, though still sub-optimal. CONCLUSION: Deficiencies of equipment, supplies and training exist even in public health facilities. In order to significantly improve the capacity to handle acute febrile illness among children under five, training in proper case management, availability of supplies and diagnostics need to be addressed in both sectors.

Cost-effectiveness analysis of the national implementation of integrated community case management and community-based health planning and services in Ghana for the treatment of malaria, diarrhoea and pneumonia.

BACKGROUND: Ghana has developed two main community-based strategies that aim to increase access to quality treatment for malaria, diarrhoea and suspected pneumonia: the integrated community case management (iCCM) and the community-based health planning and services (CHPS). The aim of the study was to assess the cost-effectiveness of these strategies under programme conditions. METHODS: A cost-effectiveness analysis was conducted. Appropriate diagnosis and treatment given was the effectiveness measure used. Appropriate diagnosis and treatment data was obtained from a household survey conducted 2 and 8 years after implementation of iCCM in the Volta and Northern Regions of Ghana, respectively. The study population was carers of children under-5 years who had fever, diarrhoea and/or cough in the last 2 weeks prior to the interview. Costs data was obtained mainly from the National Malaria Control Programme (NMCP), the Ministry of Health, CHPS compounds and from a household survey. RESULTS: Appropriate diagnosis and treatment of malaria, diarrhoea and suspected pneumonia was more cost-effective under the iCCM than under CHPS in the Volta Region, even after adjusting for different discount rates, facility costs and iCCM and CHPS utilization, but not when iCCM appropriate treatment was reduced by 50%. Due to low numbers of carers visiting a CBA in the Northern Region it was not possible to conduct a cost-effectiveness analysis in this region. However, the cost analysis showed that iCCM in the Northern Region had higher cost per malaria, diarrhoea and suspected pneumonia case diagnosed and treated when compared to the Volta Region and to the CHPS strategy in the Northern Region. CONCLUSIONS: Integrated community case management was more cost-effective than CHPS for the treatment of malaria, diarrhoea and suspected pneumonia when utilized by carers of children under-5 years in the Volta Region. A revision of the iCCM strategy in the Northern Region is needed to improve its cost-effectiveness. Long-term financing strategies should be explored including potential inclusion in the National Health Insurance Scheme (NHIS) benefit package. An acceptability study of including iCCM in the NHIS should be conducted.

Appropriate targeting of artemisinin-based combination therapy by community health workers using malaria rapid diagnostic tests: findings from randomized trials in two contrasting areas of high and low malaria transmission in south-western Uganda.

OBJECTIVE: To compare the impact of malaria rapid diagnostic tests (mRDTs), used by community health workers (CHWs), on the proportion of children <5 years of age receiving appropriately targeted treatment with artemisinin-based combination therapy (ACT), vs. presumptive treatment. METHODS: Cluster-randomized trials were conducted in two contrasting areas of moderate-to-high and low malaria transmission in rural Uganda. Each trial examined the effectiveness of mRDTs in the management of malaria and targeting of ACTs by CHWs comparing two diagnostic approaches: (i) presumptive clinical diagnosis of malaria [control arm] and (ii) confirmatory diagnosis with mRDTs followed by ACT treatment for positive patients [intervention arm], with village as the unit of randomisation. Treatment decisions by CHWs were validated by microscopy on a reference blood slide collected at the time of consultation, to compare the proportion of children <5 years receiving appropriately targeted ACT treatment, defined as patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving artemether-lumefantrine or rectal artesunate, and patients with no malaria parasites not given ACT. RESULTS: In the moderate-to-high transmission area, ACT treatment was appropriately targeted in 79.3% (520/656) of children seen by CHWs using mRDTs to diagnose malaria, vs. 30.8% (215/699) of children seen by CHWs using presumptive diagnosis (P < 0.001). In the low transmission area, 90.1% (363/403) children seen by CHWs using mRDTs received appropriately targeted ACT treatment vs. 7.8% (64/817) seen by CHWs using presumptive diagnosis (P < 0.001). Low mRDT sensitivity in children with low-density parasitaemia (<200 parasites/µl) was identified as a potential concern. CONCLUSION: When equipped with mRDTs, ACT treatments delivered by CHWs are more accurately targeted to children with malaria parasites. mRDT use could play an important role in reducing overdiagnosis of malaria and improving fever case management within iCCM, in both moderate-to-high and low transmission areas. Nonetheless, missed treatments due to the low sensitivity of current mRDTs in patients with low parasite density are a concern. For community-based treatment in areas of low transmission and/or non-immune populations, presumptive treatment of all fevers as malaria may be advisable, until more sensitive diagnostic assays, suitable for routine use by CHWs in remote settings, become available.

Optimal price subsidies for appropriate malaria testing and treatment behaviour.

BACKGROUND: Malaria continues to be a serious public health problem particularly in Africa. Many people infected with malaria do not access effective treatment due to high price. At the same time many individuals receiving malaria drugs do not suffer from malaria because of the common practice of presumptive diagnosis. A global subsidy on artemisinin-based combination therapy (ACT) has recently been suggested to increase access to the most effective malaria treatment. METHODS: Following the recommendation by World Health Organization that parasitological testing should be performed before treatment and ACT prescribed to confirmed cases only, it is investigated in this paper if a subsidy on malaria rapid diagnostic tests (RDTs) should be incorporated. A model is developed consisting of a representative individual with fever suspected to be malaria, seeking care at a specialized drug shop where RDTs, ACT medicines, and cheap, less effective anti-malarials are sold. Assuming that the individual has certain beliefs of the accuracy of the RDT and the probability that the fever is malaria, the model predicts the diagnosis-treatment behaviour of the individual. Subsidies on RDTs and ACT are introduced to incentivize appropriate behaviour: choose an RDT before treatment and purchase ACT only if the test is positive. RESULTS: Solving the model numerically suggests that a combined subsidy on both RDT and ACT is cost minimizing and improves diagnosis-treatment behaviour of individuals. For certain beliefs, such as low trust in RDT accuracy and strong belief that a fever is malaria, subsidization is not sufficient to incentivize appropriate behaviour. CONCLUSIONS: A combined subsidy on both RDT and ACT rather than a single subsidy is likely required to improve diagnosis-treatment behaviour among individuals seeking care for malaria in the private sector.

Economic costs of fever to households in the middle belt of Ghana.

BACKGROUND: Malaria is one of the main health problems in the sub-Saharan Africa accounting for approximately 198 million morbidity and close to 600,000 mortality cases. Households incur out-of-pocket expenditure for treatment and lose income as a result of not being able to work or care for family members. The main objective of this survey was to assess the economic cost of treating malaria and/or fever with the new ACT to households in the Kintampo districts of Ghana where a health and demographic surveillance systems (KHDSS) are set up to document population dynamics. METHODS: The study was a cross-sectional survey conducted from October 2009 to July 2011 using community members' accessed using KHDSS population in the Kintampo area. An estimated sample size of 4226 was randomly selected from the active members of the KHDSS. A structured questionnaire was administered to the selected populates who reported of fever within the last 2 weeks prior to the visit. Data was collected on treatment-seeking behaviour, direct and indirect costs of malaria from the patient perspective. RESULTS: Of the 4226 households selected, 947 households with 1222 household members had fever out of which 92 % sought treatment outside home; 55 % of these were females. 31.6 % of these patients sought care from chemical shops. A mean amount of GHS 4.2 (US$2.76) and GHS 18.0 (US$11.84) were incurred by households as direct and indirect cost respectively. On average a household incurred a total cost of GHS 22.2 (US$14.61) per patient per episode. Total economic cost was lowest for those in the highest quintile and highest for those in the middle quintile. CONCLUSION: The total cost of treating fever/malaria episode is relatively high in the study area considering the poverty levels in Ghana. The NHIS has positively influenced health-seeking behaviours and reduced the financial burden of seeking care for those that are insured.

Community health workers adherence to referral guidelines: evidence from studies introducing RDTs in two malaria transmission settings in Uganda.

BACKGROUND: Many malaria-endemic countries have implemented national community health worker (CHW) programmes to serve remote populations that have poor access to malaria diagnosis and treatment. Despite mounting evidence of CHWs' ability to adhere to malaria rapid diagnostic tests (RDTs) and treatment guidelines, there is limited evidence whether CHWs adhere to the referral guidelines and refer severely ill children for further management. In southwest Uganda, this study examined whether CHWs referred children according to training guidelines and described factors associated with adherence to the referral guideline. METHODS: A secondary analysis was undertaken of data collected during two cluster-randomized trials conducted between January 2010 and July 2011, one in a moderate-to-high malaria transmission setting and the other in a low malaria transmission setting. All CHWs were trained to prescribe artemisinin-based combination therapy (ACT) and recognize symptoms in children that required immediate referral to the nearest health centre. Intervention arm CHWs had additional training on how to conduct an RDT; CHWs in the control arm used a presumptive diagnosis for malaria using clinical signs and symptoms. CHW treatment registers were reviewed to identify children eligible for referral according to training guidelines (temperature of ≥38.5 °C), to assess whether CHWs adhered to the guidelines and referred them. Factors associated with adherence were examined with logistic regression models. RESULTS: CHWs failed to refer 58.8% of children eligible in the moderate-to-high transmission and 31.2% of children in the low transmission setting. CHWs using RDTs adhered to the referral guidelines more frequently than CHWs not using RDTs (moderate-to-high transmission: 50.1 vs 18.0%, p = 0.003; low transmission: 88.5 vs 44.1%, p < 0.001). In both settings, fewer than 20% of eligible children received pre-referral treatment with rectal artesunate. Children who were prescribed ACT were very unlikely to be referred in both settings (97.7 and 73.3% were not referred in the moderate-to-high and low transmission settings, respectively). In the moderate-to-high transmission setting, day and season of visit were also associated with the likelihood of adherence to the referral guidelines, but not in the low transmission setting. CONCLUSIONS: CHW adherence to referral guidelines was poor in both transmission settings. However, training CHWs to use RDT improved correct referral of children with a high fever compared to a presumptive diagnosis using sign and symptoms. As many countries scale up CHW programmes, routine monitoring of reported data should be examined carefully to assess whether CHWs adhere to referral guidelines and take remedial actions where required.