Health Economic Modelling of Treatment Sequences for Rheumatoid Arthritis: A Systematic Review

The objective of the work reported in this paper was to critically assess how sequential disease-modifying anti-rheumatic drugs (DMARDs) have been modelled in the context of economic evaluation of the use of DMARDs for treatment of rheumatoid arthritis (RA). A secondary purpose was to identify the methodological challenges of modelling sequential therapies. Systematic searches of 10 databases were undertaken in February 2013. Studies were included if they were in the English language and a full comparative economic evaluation was reported. They were appraised by use of the Drummond checklist (Appendix to this paper). Data extracted included economic evaluation data, data relating to sequential treatment, and data on the modelling methods used. Fifty-seven studies were identified, with 25 (44 %) modelling a sequence of treatments. Forty-three (75 %) were cost–utility analyses. Eleven (19 %) were UK studies and 11 (19 %) were US. The remainder were mainly European (26 (46 %)). A distinction was made between studies of recent-onset RA (14 (25 %)) and those of established RA (42 (74 %)). One study (1 %) was unclear. Individual-level models were more likely to meet the Drummond criteria and evaluate sequences. No study identified an optimum sequence of multiple treatments given a set of treatment options. The level of reporting of the methods and evidence used to assess the effect of downstream treatments in the sequence was generally poor. When lifelong models and downstream treatment sequences were considered, evidence gaps were identified. The review discovered that methods have not been consistently applied, leading to varied estimates of cost-effectiveness. Treatment sequences have not been fully considered and modelled, potentially resulting in inaccurate estimates of cost-effectiveness.     

Aberrant SOX2 expression in colorectal cancers does not correlate with mucinous differentiation and gastric mucin MUC5AC expression

Colorectal cancer (CRC) can be divided into non-mucinous and mucinous subtypes, of which the latter portends to have a worse clinical prognosis. A previous study suggested a putative link between SOX2 expression observed selectively in mucinous CRC and the induction of the gastric mucin MUC5AC. In this study, we re-evaluated the expression behavior of SOX2, MUC5AC, and CDX2 in both types of CRC. We performed immunohistochemical analysis on 90 cases of non-mucinous CRCs, 57 cases of mucinous CRCs, and 15 case-matched normal intestinal mucosa. In contrast to the previously suggested link between SOX2 and mucinous CRC, we observe aberrant expression of SOX2 at equal levels in both subtypes. Fluorescence in situ hybridization (FISH) analysis shows that expression is not attributed to genomic amplification. While SOX2 and CDX2 are normally expressed in a reciprocal manner, SOX2-positive tumor cells co-express CDX2. Furthermore, we show that MUC5AC is expressed independently of SOX2. In conclusion, we show that aberrant SOX2 expression is specifically linked neither to mucinous CRCs nor to the induction of MUC5AC, in contrast to previous suggestions.     

Circulating peroxiredoxin 4 and type 2 diabetes risk: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

Aims/hypothesis

Oxidative stress plays a key role in the development of type 2 diabetes mellitus. We previously showed that the circulating antioxidant peroxiredoxin 4 (Prx4) is associated with cardiometabolic risk factors. We aimed to evaluate the association of Prx4 with type 2 diabetes risk in the general population.

Methods

We analysed data on 7,972 individuals from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study (49% men, aged 28–75 years) with no diabetes at baseline. Logistic regression models adjusted for age, sex, smoking, waist circumference, hypertension and family history of diabetes were used to estimate the ORs for type 2 diabetes.

Results

During a median follow up of 7.7 years, 496 individuals (288 men; 58%) developed type 2 diabetes. The median (Q1–Q3) Prx4 level was 0.84 (0.53–1.40) U/l in individuals who developed type 2 diabetes and 0.68 (0.43–1.08) U/l in individuals who did not develop type 2 diabetes. For every doubling of Prx4 levels, the adjusted OR (95% CI) for type 2 diabetes was 1.16 (1.05–1.29) in the whole population; by sex, it was 1.31 (1.14–1.50) for men and 1.03 (0.87–1.21) for women. Further adjustment for other clinical measures did not materially change the results. The addition of Prx4 to a validated diabetes risk score significantly improved the prediction of type 2 diabetes in men (p?=?0.002 for reclassification improvement).

Conclusions/interpretation

Our findings suggest that elevated serum Prx4 levels are associated with a higher risk of incident type 2 diabetes. For men, taking Prx4 into consideration can improve type 2 diabetes prediction over a validated diabetes risk score; in contrast, there is no improvement in risk prediction for women.     

Risk of Future Offense Among Probationers with Co-occurring Substance Use and Mental Health Disorders

The criminal justice system is the primary service delivery system for many adults with drug and alcohol dependence, mental health, and other health service needs. The purpose of this study was to examine the relationship between risk of future offense, mental health status and co-occurring disorders in a large substance abuse diversion probationer population. A purposive sample of 2,077 probationers completed an assessment to screen for mental health disorders, substance use disorders, risk of future crime and violence, and several demographic characteristics. Probationers who screened positive for co-occurring substance use and mental health disorders were significantly more likely to be at higher risk of future crime and violence compared to probationers who screened positive for only substance use, only a mental health disorder, or no substance use or mental health disorder. Implications for substance use and mental health service delivery are discussed, and recommendations are made for further research.