Interpretation, translation and intercultural communication in refugee status determination procedures in the UK and France

This article explores the interplay between language and intercultural communication within refugee status determination procedures in the UK and France, using material taken from ethnographic research that involved a combination of participant observation, semi-structured interviews and documentary analysis in both countries over a two-year period (2007–2009). It is concerned, in particular, to examine the role played by interpreters in facilitating intercultural communication between asylum applicants and the different administrative and legal actors responsible for assessing or defending their claims. The first section provides an overview of refugee status determination procedures in the UK and France, introducing the main administrative and legal contexts of the asylum process within which interpreters operate in the two countries. The second section compares the organisation of interpreting services, codes of conduct for interpreters and institutional expectations about the nature of interpreters’ activity on the part of the relevant UK and French authorities. The third section then explores some of the practical dilemmas for interpreters and barriers to communication that exist in refugee status determination procedures in the two countries. The article concludes by emphasising the complex and active nature of the interpreter's role in UK and French refugee status determination procedures

Severe hemolysis during primaquine radical cure of Plasmodium vivax malaria: two systematic reviews and individual patient data descriptive analyses

Primaquine (PQ) kills Plasmodium vivax hypnozoites but can cause severe hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We conducted two systematic reviews. The first used data from clinical trials to determine the variety of definitions and frequency of hematological serious adverse events (SAEs) related to PQ treatment of vivax malaria. The second used data from prospective studies and case reports to describe the clinical presentation, management, and outcome of severe PQ-associated hemolysis necessitating hospitalization. In the first review, SAEs were reported in 70 of 249 clinical trials. There were 34 hematological SAEs among 9,824 patients with P. vivax malaria treated with PQ, nine of which necessitated hospitalization or blood transfusion. Criteria used to define SAEs were diverse. In the second review, 21 of 8,487 articles screened reported 163 patients hospitalized after PQ radical cure; 79.9% of whom (123 of 154) were prescribed PQ at ≥ 0.5 mg/kg/day. Overall, 101 patients were categorized as having probable or possible severe PQ-associated hemolysis, 96.8% of whom were G6PD deficient (< 30% activity). The first symptoms of hemolysis were reported primarily on day 2 or 3 (45.5%), and all patients were hospitalized within 7 days of PQ commencement. A total of 57.9% of patients (77 of 133) had blood transfusion. Seven patients (6.9%) with probable or possible hemolysis died. Even when G6PD testing is available, enhanced monitoring for hemolysis is warranted after PQ treatment. Clinical review within the first 5 days of treatment may facilitate early detection and management of hemolysis. More robust definitions of severe PQ-associated hemolysis are required

Response to comment on 'The clinical pharmacology of tafenoquine in the radical cure of Plasmodium vivax malaria: an individual patient data meta-analysis'

In our recent paper on the clinical pharmacology of tafenoquine (Watson et al., 2022), we used all available individual patient pharmacometric data from the tafenoquine pre-registration clinical efficacy trials to characterise the determinants of anti-relapse efficacy in tropical vivax malaria. We concluded that the currently recommended dose of tafenoquine (300 mg in adults, average dose of 5 mg/kg) is insufficient for cure in all adults, and a 50% increase to 450 mg (7.5 mg/kg) would halve the risk of vivax recurrence by four months. We recommended that clinical trials of higher doses should be carried out to assess their safety and tolerability. Sharma and colleagues at the pharmaceutical company GSK defend the currently recommended adult dose of 300 mg as the optimum balance between radical curative efficacy and haemolytic toxicity (Sharma et al., 2024). We contend that the relative haemolytic risks of the 300 mg and 450 mg doses have not been sufficiently well characterised to justify this opinion. In contrast, we provided evidence that the currently recommended 300 mg dose results in sub-maximal efficacy, and that prospective clinical trials of higher doses are warranted to assess their risks and benefits

The Impossibility of a Perfectly Competitive Labor Market

Using the institutional theory of transaction cost, I demonstrate that the assumptions of the competitive labor market model are internally contradictory and lead to the conclusion that on purely theoretical grounds a perfectly competitive labor market is a logical impossibility. By extension, the familiar diagram of wage determination by supply and demand is also a logical impossibility and the neoclassical labor demand curve is not a well-defined construct. The reason is that the perfectly competitive market model presumes zero transaction cost and with zero transaction cost all labor is hired as independent contractors, implying multi-person firms, the employment relationship, and labor market disappear. With positive transaction cost, on the other hand, employment contracts are incomplete and the labor supply curve to the firm is upward sloping, again causing the labor demand curve to be ill-defined. As a result, theory suggests that wage rates are always and everywhere an amalgam of an administered and bargained price. Working Paper 06-0

The social value of a QALY : raising the bar or barring the raise?

Background: Since the inception of the National Institute for Health and Clinical Excellence (NICE) in England, there have been questions about the empirical basis for the cost-per-QALY threshold used by NICE and whether QALYs gained by different beneficiaries of health care should be weighted equally. The Social Value of a QALY (SVQ) project, reported in this paper, was commissioned to address these two questions. The results of SVQ were released during a time of considerable debate about the NICE threshold, and authors with differing perspectives have drawn on the SVQ results to support their cases. As these discussions continue, and given the selective use of results by those involved, it is important, therefore, not only to present a summary overview of SVQ, but also for those who conducted the research to contribute to the debate as to its implications for NICE. Discussion: The issue of the threshold was addressed in two ways: first, by combining, via a set of models, the current UK Value of a Prevented Fatality (used in transport policy) with data on fatality age, life expectancy and age-related quality of life; and, second, via a survey designed to test the feasibility of combining respondents’ answers to willingness to pay and health state utility questions to arrive at values of a QALY. Modelling resulted in values of £10,000-£70,000 per QALY. Via survey research, most methods of aggregating the data resulted in values of a QALY of £18,000-£40,000, although others resulted in implausibly high values. An additional survey, addressing the issue of weighting QALYs, used two methods, one indicating that QALYs should not be weighted and the other that greater weight could be given to QALYs gained by some groups. Summary: Although we conducted only a feasibility study and a modelling exercise, neither present compelling evidence for moving the NICE threshold up or down. Some preliminary evidence would indicate it could be moved up for some types of QALY and down for others. While many members of the public appear to be open to the possibility of using somewhat different QALY weights for different groups of beneficiaries, we do not yet have any secure evidence base for introducing such a system

A randomised controlled trial to compare the efficacy, safety, and tolerability of low dose, short course primaquine in adults with uncomplicated P. vivax malaria in two hospitals in India

Background: Plasmodium vivax remains a major challenge for malaria control and elimination due to its ability to cause relapsing illness. To prevent relapses the Indian National Center for Vector Borne Diseases Control (NCVBDC) recommends treatment with primaquine at a dose of 0.25 mg/kg/day provided over 14 days. Shorter treatment courses may improve adherence and treatment effectiveness. Methods: This is a hospital-based, randomised, controlled, open-label trial in two centres in India. Patients above the age of 16 years, with uncomplicated vivax malaria, G6PD activity of ≥ 30% of the adjusted male median (AMM) and haemoglobin levels ≥ 8 g/dL will be recruited into the study and randomised in a 1:1 ratio to receive standard schizonticidal treatment plus 7-day primaquine at 0.50 mg/kg/day or standard care with schizonticidal treatment plus 14-day primaquine at 0.25 mg/kg/day. Patients will be followed up for 6 months. The primary endpoint is the incidence risk of any P. vivax parasitaemia at 6 months. Safety outcomes include the incidence risk of severe anaemia (haemoglobin 25% fall in haemoglobin and an acute drop in haemoglobin of > 5 g/dL during primaquine treatment. Discussion: This study will evaluate the efficacy and safety of a 7-day primaquine regimen compared to the standard 14-day regimen in India. Results from this trial are likely to directly inform national treatment guidelines. Trial registration: Trial is registered on CTRI portal, Registration No: CTRI/2022/12/048283

Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: a systematic review and individual patient data meta-analysis

Background The optimal dosing of primaquine to prevent relapsing Plasmodium vivax malaria in South Asia remains unclear. We investigated the efficacy and safety of different primaquine regimens to prevent P. vivax relapse. Methods A systematic review identified P. vivax efficacy studies from South Asia published between 1 January 2000 and 23 August 2021. In a one-stage meta-analysis of available individual patient data, the cumulative risks of P. vivax recurrence at day 42 and 180 were assessed by primaquine total mg/kg dose and duration. The risk of recurrence by day 180 was also determined in a two-stage meta-analysis. Patients with a >25% drop in haemoglobin to 50 g/L between days 1 and 14 were categorised by daily mg/kg primaquine dose. Results In 791 patients from 7 studies in the one-stage meta-analysis, the day 180 cumulative risk of recurrence was 61.1% (95% CI 42.2% to 80.4%; 201 patients; 25 recurrences) after treatment without primaquine, 28.8% (95% CI 8.2% to 74.1%; 398 patients; 4 recurrences) following low total (2 to 25% drop in haemoglobin to <70 g/L. Conclusions Primaquine treatment led to a marked decrease in P. vivax recurrences following low (~3.5 mg/kg) and high (~7 mg/kg) total doses, with no reported severe haemolytic events. PROSPERO registration number CRD42022313730

Primaquine dose and the risk of haemolysis in patients with uncomplicated Plasmodium vivax malaria: a systematic review and individual patient data meta-analysis

Background: Primaquine radical cure is used to treat dormant liver-stage parasites and prevent relapsing Plasmodium vivax malaria but is limited by concerns of haemolysis. We undertook a systematic review and individual patient data meta-analysis to investigate the haematological safety of different primaquine regimens for P vivax radical cure. Methods: For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, if they included a treatment group with daily primaquine given over multiple days where primaquine was commenced within 3 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether–lumefantrine, artesunate–mefloquine, artesunate–amodiaquine, or dihydroartemisinin–piperaquine), and if they recorded haemoglobin or haematocrit concentrations on day 0. We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. The main outcome was haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL by day 14. Haemoglobin concentration changes between day 0 and days 2–3 and between day 0 and days 5–7 were assessed by mixed-effects linear regression for patients with glucose-6-phosphate dehydrogenase (G6PD) activity of (1) 30% or higher and (2) between 30% and less than 70%. The study was registered with PROSPERO, CRD42019154470 and CRD42022303680. Findings: Of 226 identified studies, 18 studies with patient-level data from 5462 patients from 15 countries were included in the analysis. A haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL occurred in one (0·1%) of 1208 patients treated without primaquine, none of 893 patients treated with a low daily dose of primaquine (<0·375 mg/kg per day), five (0·3%) of 1464 patients treated with an intermediate daily dose (0·375 mg/kg per day to <0·75 mg/kg per day), and six (0·5%) of 1269 patients treated with a high daily dose (≥0·75 mg/kg per day). The covariate-adjusted mean estimated haemoglobin changes at days 2–3 were –0·6 g/dL (95% CI –0·7 to –0·5), –0·7 g/dL (–0·8 to –0·5), –0·6 g/dL (–0·7 to –0·4), and –0·5 g/dL (–0·7 to –0·4), respectively. In 51 patients with G6PD activity between 30% and less than 70%, the adjusted mean haemoglobin concentration on days 2–3 decreased as G6PD activity decreased; two patients in this group who were treated with a high daily dose of primaquine had a reduction of more than 25% to a concentration of less than 7 g/dL. 17 of 18 included studies had a low or unclear risk of bias. Interpretation: Treatment of patients with G6PD activity of 30% or higher with 0·25–0·5 mg/kg per day primaquine regimens and patients with G6PD activity of 70% or higher with 0·25–1 mg/kg per day regimens were associated with similar risks of haemolysis to those in patients treated without primaquine, supporting the safe use of primaquine radical cure at these doses. Funding: Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture

Effect of primaquine dose on the risk of recurrence in patients with uncomplicated Plasmodium vivax: a systematic review and individual patient data meta-analysis

Background: Primaquine is used to eliminate Plasmodium vivax hypnozoites, but its optimal dosing regimen remains unclear. We undertook a systematic review and individual patient data meta-analysis to investigate the efficacy and tolerability of different primaquine dosing regimens to prevent P vivax recurrence. Methods: For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, and if they included a treatment group with daily primaquine given over multiple days, where primaquine was commenced within 7 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether–lumefantrine, artesunate–mefloquine, artesunate–amodiaquine, or dihydroartemisinin–piperaquine). We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. We assessed the effects of total dose and duration of primaquine regimens on the rate of first P vivax recurrence between day 7 and day 180 by Cox's proportional hazards regression (efficacy analysis). The effect of primaquine daily dose on gastrointestinal symptoms on days 5–7 was assessed by modified Poisson regression (tolerability analysis). The study was registered with PROSPERO, CRD42019154470. Findings: Of 226 identified studies, 23 studies with patient-level data from 6879 patients from 16 countries were included in the efficacy analysis. At day 180, the risk of recurrence was 51·0% (95% CI 48·2–53·9) in 1470 patients treated without primaquine, 19·3% (16·9–21·9) in 2569 patients treated with a low total dose of primaquine (approximately 3·5 mg/kg), and 8·1% (7·0–9·4) in 2811 patients treated with a high total dose of primaquine (approximately 7 mg/kg), regardless of primaquine treatment duration. Compared with treatment without primaquine, the rate of P vivax recurrence was lower after treatment with low-dose primaquine (adjusted hazard ratio 0·21, 95% CI 0·17–0·27; p<0·0001) and high-dose primaquine (0·10, 0·08–0·12; p<0·0001). High-dose primaquine had greater efficacy than low-dose primaquine in regions with high and low relapse periodicity (ie, the time from initial infection to vivax relapse). 16 studies with patient-level data from 5609 patients from ten countries were included in the tolerability analysis. Gastrointestinal symptoms on days 5–7 were reported by 4·0% (95% CI 0·0–8·7) of 893 patients treated without primaquine, 6·2% (0·5–12·0) of 737 patients treated with a low daily dose of primaquine (approximately 0·25 mg/kg per day), 5·9% (1·8–10·1) of 1123 patients treated with an intermediate daily dose (approximately 0·5 mg/kg per day) and 10·9% (5·7–16·1) of 1178 patients treated with a high daily dose (approximately 1 mg/kg per day). 20 of 23 studies included in the efficacy analysis and 15 of 16 in the tolerability analysis had a low or unclear risk of bias. Interpretation: Increasing the total dose of primaquine from 3·5 mg/kg to 7 mg/kg can reduce P vivax recurrences by more than 50% in most endemic regions, with a small associated increase in gastrointestinal symptoms. Funding: Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture

Effect of adherence to primaquine on the risk of Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis

Background: Imperfect adherence is a major barrier to effective primaquine radical cure of Plasmodium vivax. This study investigated the effect of reduced adherence on the risk of P. vivax recurrence. Methods: Efficacy studies of patients with uncomplicated P. vivax malaria, including a treatment arm with daily primaquine, published between January 1999 and March 2020 were identified. Individual patient data from eligible studies were pooled using standardized methodology. Adherence to primaquine was inferred from i) the percentage of supervised doses and ii) the total mg/kg dose received compared to the target total mg/kg dose per protocol. The effect of adherence to primaquine on the incidence of P. vivax recurrence between days 7 and 90 was investigated by Cox regression analysis. Results: Of 82 eligible studies, 32 were available including 6917 patients from 18 countries. For adherence assessed by percentage of supervised primaquine, 2790 patients (40.3%) had poor adherence (≤ 50%) and 4127 (59.7%) had complete adherence. The risk of recurrence by day 90 was 14.0% [95% confidence interval: 12.1–16.1] in patients with poor adherence compared to 5.8% [5.0–6.7] following full adherence; p = 0.014. After controlling for age, sex, baseline parasitaemia, and total primaquine dose per protocol, the rate of the first recurrence was higher following poor adherence compared to patients with full adherence (adjusted hazard ratio (AHR) = 2.3 [1.8–2.9]). When adherence was quantified by total mg/kg dose received among 3706 patients, 347 (9.4%) had poor adherence, 88 (2.4%) had moderate adherence, and 3271 (88.2%) had complete adherence to treatment. The risks of recurrence by day 90 were 8.2% [4.3–15.2] in patients with poor adherence and 4.9% [4.1–5.8] in patients with full adherence; p < 0.001. Conclusion: Reduced adherence, including less supervision, increases the risk of vivax recurrence