Background Having to pay out-of-pocket for health care can be prohibitive and even cause financial catastrophe for patients, especially those with low and irregular incomes. Health services at Government-owned hospitals in Malawi are provided free of charge but patients do incur costs when they access facilities and some of them forego income. This research paper presents findings on the direct and indirect expenditure incurred by patients who underwent hernia surgery at district and central hospitals in Malawi. It reports the main cost drivers, how costs relate to patients’ household incomes, the financial burden of undergoing surgery and the extent to which hernia patients had recovered and restored their capacity to work and earn an income. Materials and methods Using a cross-sectional study design, surveys were held with patients who had undergone hernia surgery in four district and two central hospitals in Malawi. Interviews were conducted by surgically trained clinical officers, trained in survey administration, and included, inter alia, questions about patients’ hospital stay, the direct and indirect cost they incurred in accessing surgery, and how they financed the expenditure. Follow-up interviews by telephone were held 8–10 weeks after discharge. Results The sample included 137 patients from district and 86 patients from central hospitals. The main direct cost drivers were transport and food & groceries. More than three quarters of patients who had their surgery at a district hospital incurred indirect costs, because of income lost due to hospital admission, compared with just over a third among central hospital patients. Median reported income losses were US$ 90 and US$ 71, respectively. Catastrophic expenditure for surgery occurred in 94% of district and 87% of central hospital patients. When indirect costs are added to the out-of-pocket expenditure, it constituted more than 10% of the monthly per capita income for 97% and 90% of the district and central hospital patients, respectively. Conclusion Out-of-pocket household expenditure associated with essential surgery in Malawi is high and in many instances catastrophic, putting households, especially those who are already poor, at risk of further impoverishment. The much needed scaling-up of surgical services in rural areas of Malawi needs to be accompanied by financial risk protection measures.

Background To date, survival data on risk factors for COVID-19 mortality in western Europe is limited, and none of the published survival studies have used a competing risk approach. This study aims to identify risk factors for in-hospital mortality in COVID-19 patients in the Netherlands, considering recovery as a competing risk. Methods In this observational multicenter cohort study we included adults with PCR-confirmed SARS-CoV-2 infection that were admitted to one of five hospitals in the Netherlands (March to May 2020). We performed a competing risk survival analysis, presenting cause-specific hazard ratios (HRCS) for the effect of preselected factors on the absolute risk of death and recovery. Results 1,006 patients were included (63.9% male; median age 69 years, IQR: 58–77). Patients were hospitalized for a median duration of 6 days (IQR: 3–13); 243 (24.6%) of them died, 689 (69.9%) recovered, and 74 (7.4%) were censored. Patients with higher age (HRCS 1.10, 95% CI 1.08–1.12), immunocompromised state (HRCS 1.46, 95% CI 1.08–1.98), who used anticoagulants or antiplatelet medication (HRCS 1.38, 95% CI 1.01–1.88), with higher modified early warning score (MEWS) (HRCS 1.09, 95% CI 1.01–1.18), and higher blood LDH at time of admission (HRCS 6.68, 95% CI 1.95–22.8) had increased risk of death, whereas fever (HRCS 0.70, 95% CI 0.52–0.95) decreased risk of death. We found no increased mortality risk in male patients, high BMI or diabetes. Conclusion Our competing risk survival analysis confirms specific risk factors for COVID-19 mortality in a the Netherlands, which can be used for prediction research, more intense in-hospital monitoring or prioritizing particular patients for new treatments or vaccination.

BackgroundAfter adalimumab treatment failure, tumour necrosis factor inhibition (TNFi) and non-TNFi biological disease-modifying anti-rheumatic drugs (bDMARDs) are equally viable options on a group level as subsequent treatment in rheumatoid arthritis (RA) based on the current best evidence synthesis. However, preliminary data suggest that anti-adalimumab antibodies (anti-drug antibodies, ADA) and adalimumab serum levels (ADL) during treatment predict response to a TNFi as subsequent treatment.ObjectiveTo validate the association of presence of ADA and/or low ADL with response to a subsequent TNFi bDMARD or non-TNFi bDMARD. Sub-analyses were performed for primary and secondary non-responders.MethodsA diagnostic test accuracy retrospective cohort study was done in consenting RA patients who discontinued adalimumab after >3 months of treatment due to inefficacy and started another bDMARD. Inclusion criteria included the availability of (random timed) serum samples between ≥8 weeks after start and ≤2 weeks after discontinuation of adalimumab, and clinical outcome measurements Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) between 3 to 6 months after treatment switch. Test characteristics for EULAR (European League Against Rheumatism) good response (DAS28-CRP based) after treatment with the next (non-)TNFi bDMARD were assessed using area under the receiver operating characteristic and sensitivity/specificity.Results137 patients were included. ADA presence was not predictive for response in switchers to a TNFi (sensitivity/specificity 18%/75%) or a non-TNFi (sensitivity/specificity 33%/70%). The same was true for ADL levels in patients that switched to a TNFi (sensitivity/specificity 50%/52%) and patients that switched to a non-TNFi (sensitivity/specificity 32%/69%). Predictive value of ADA and ADL were similar for both primary and secondary non-responders to adalimumab.ConclusionsIn contrast to earlier research, we could not find predictive value for response to a second TNFi or non-TNFi for either ADA or random timed ADL.

Biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) have improved the treatment outcomes of inflammatory rheumatic diseases including Rheumatoid Arthritis and spondyloarthropathies. Inter-individual variation exists in (maintenance of) response to bDMARDs. Therapeutic Drug Monitoring (TDM) of bDMARDs could potentially help in optimizing treatment for the individual patient. Areas covered: Evidence of clinical utility of TDM in bDMARD treatment is reviewed. Different clinical scenarios will be discussed, including: prediction of response after start of treatment, prediction of response to a next bDMARD in case of treatment failure of the first, prediction of successful dose reduction or discontinuation in case of low disease activity, prediction of response to dose-escalation in case of active disease and prediction of response to bDMARD in case of flare in disease activity. Expert opinion: The limited available evidence does often not report important outcomes for diagnostic studies, such as sensitivity and specificity. In most clinical relevant scenarios, predictive value of serum (anti-) drug levels is absent, therefore the use of TDM of bDMARDs cannot be advocated. Well-designed prospective studies should be done to further investigate the promising scenarios to determine the place of TDM in clinical practice.

Objectives The REDO trial showed that ultra-low dose rituximab (500 mg or 200 mg) was similarly effective in the majority of rheumatoid arthritis (RA) patients. This pre-planned secondary analysis investigates 1) associations between rituximab dosage, drug levels, anti-drug antibodies (ADA) and B cell counts and 2) the predictive value of pharmacokinetic and -dynamic parameters, patient, disease and treatment characteristics in relation to response to ultra-low dose rituximab. Methods For 140 RA patients from the REDO trial, differences in drug levels, ADA and B cell counts were examined at baseline, three and six months after dosing. Treatment response was defined as absence of flare and no extra rituximab or > 1 glucocorticoid injection received during follow-up. The association between potential predictors and response was investigated using logistic regression analyses. Results Lower doses of rituximab resulted in lower drug levels but did not significantly affect ADA levels and B cell counts. 3 (10.7%), 12 (20.7%) and 7 (13.0%) patients failed to meet response-criteria in respectively the 1000 mg, 500 mg and 200 mg group. Drug levels, ADA and B cell counts as well as patient, disease and treatment characteristics were not predictive for response to ultra-low dose rituximab. Conclusion Results of this study further support that continued treatment with 500 or 200 mg rituximab is similarly effective as 1000 mg in RA patients doing well on rituximab. These results, combined with absence of clinical dose response relation in the original REDO study, suggest that 200 mg rituximab is not yet the lowest effective rituximab retreatment dose in RA.