Book Reviews

Principles of Cardiac Arrhythmias. 3rd ed. By Edward K. Chung. Pp. xiii 809. Illustrated. Baltimore: Williams &Wilkins. 1983.Ethical Issues in Reproductive Medicine. Ed. by M. Reidy. Pp. 176. Illustrated. RI9,60. Dublin: Gill & Macmillan. 1982.From Parasitic Infection to Parasitic Disease (Contribution to Microbiology and Immunology, vol. 7). Ed. by P. L. Gigase and E. A. C. van Marck. Pp. ix + 269. Illustrated. DM 216,-. Basle: S. Karger. 1983.Prolonged Arrest of Cancer (New Horizons in Oncology, vol. I). Ed. by B. A. Stoll. Pp. xiv + 454. Illustrated. £25,75. London: John Wiley. 1982.Pediatric Angiography. Ed. by P. Stanley. Pp. xv + 425. Illustrated. Baltimore: Williams & Wilkins. 1982.Thin-needle Aspiration Biopsy (Major Problems in Pathology, vol. 14). By W. J. Frable. Pp. X\'iii + 358. Illustrated. £42,25. Philadelphia: \'(t B. Saunders. 1983.Essentials of Pulmonary Medicine. By M. H. Williams. Pp. xi + 190. Illustrated. Philadelphia: W. B. Saunders. 1982.Noninvasive Assessment of the Cardiovascular System: Diagnostic Principles and Techniques. Ed. by E. B. Diethrich. Pp. xxiii + 319. Illustrated. £25,75. London: Wright PSG. 1982.Periodic Abstinence for Family Planning. Ed. by R. L. Kleinman. Pp. 60. Illustrated. £1,75 (in K only). London: IPPF Medical Publications. 1983

Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.  Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.  Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.  Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months

A Multicenter, Randomized, Placebo-Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis

OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. METHODS: A randomized, double‐blind, placebo‐controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P 50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. RESULTS: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient‐years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low‐density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C‐reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI −14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. CONCLUSION: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta‐analysis of statin effects in other populations

Socioeconomic deprivation is associated with reduced response and lower treatment persistence with TNF inhibitors in rheumatoid arthritis

Objective To investigate the association between socioeconomic deprivation and outcomes following TNF inhibitor (TNFi) treatment. Methods Individuals commencing their first TNFi in the British Society for Rheumatology Biologics Register for RA (BSRBR-RA) and Biologics in RA Genetics and Genomics Study Syndicate (BRAGGSS) cohort were included. Socioeconomic deprivation was proxied using the Index of Multiple Deprivation and categorized as 20% most deprived, middle 40% or 40% least deprived. DAS28-derived outcomes at 6 months (BSRBR-RA) and 3 months (BRAGGSS) were compared using regression models with the least deprived as referent. Risks of all-cause and cause-specific drug discontinuation were compared using Cox models in the BSRBR-RA. Additional analyses adjusted for lifestyle factors (e.g. smoking, BMI) as potential mediators. Results 16 085 individuals in the BSRBR-RA were included (mean age 56 years, 76% female), of whom 18%, 41% and 41% were in the most, middle and least deprived groups, respectively. Of 3459 included in BRAGGSS (mean age 57, 77% female), proportions were 22%, 36% and 41%, respectively. The most deprived group had 0.3-unit higher 6-month DAS28 (95% CI 0.22, 0.37) and were less likely to achieve low disease activity (odds ratio [OR] 0.76; 95% CI 0.68, 0.84) in unadjusted models. Results were similar for 3-month DAS28 (β = 0.23; 95% CI 0.11, 0.36) and low disease activity (OR 0.77; 95% CI 0.63, 0.94). The most deprived were more likely to discontinue treatment (hazard ratio 1.18; 95% CI 1.12, 1.25), driven by ineffectiveness rather than adverse events. Adjusted estimates were generally attenuated. Conclusion Socioeconomic deprivation is associated with reduced response to TNFi. Improvements in determinants of health other than lifestyle factors are needed to address socioeconomic inequities

A Multicenter, Randomized, Placebo‐Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis

Objective: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. Methods: A randomized, double‐blind, placebo‐controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P 50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. Results: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient‐years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low‐density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C‐reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI −14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. Conclusion: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta‐analysis of statin effects in other populations

Global Boundary Stratotype Section and Point (GSSP) for the Anthropocene Series: Where and how to look for potential candidates

International audienc

Viscosity of simple liquids including measurement and prediction at elevated pressure

A falling body viscometer with self-centring sinkers has been developed and used to measure the viscosities of benzene, carbon tetrachloride and eight halogenated hydrocarbons at pressures up to 500 MN m⁻² in the temperature range 25˚C to 100˚C. Two isotherms of water have also been measured at pressures up to 1000 MN m⁻² . Details of the viscometer and its pressurising equipment are given together with an analysis of the performance of the system. The results are estimated to be accurate to within ±2 per cent, and show good agreement with other measured data where available. The change of viscosity with pressure for the halogenated hydrocarbons is generally similar to that of other simple liquids. The results show that liquids having molecules of similar shape also have a similar change in relative viscosity with pressure.Theories of liquid viscosity are reviewed and constants required by Eyring's significant structure theory are obtained for more than sixty liquids using literature data. Methods are derived for calculating these constants from correlations with readily available critical properties or chemical structure. The correlations are tested using the new measurements and literature data. These tests show that the methods derived work well if one or two values of viscosity at atmospheric pressure can be used but are less reliable if only structural information is available. Since at least one measured viscosity isavailable for most liquids it is concluded that the method will be useful for predicting viscosities at other temperatures and pressures.A falling body viscometer with self-centring sinkers has been developed and used to measure the viscosities of benzene, carbon tetrachloride and eight halogenated hydrocarbons at pressures up to 500 MN m⁻² in the temperature range 25˚C to 100˚C. Two isotherms of water have also been measured at pressures up to 1000 MN m⁻² . Details of the viscometer and its pressurising equipment are given together with an analysis of the performance of the system. The results are estimated to be accurate to within ±2 per cent, and show good agreement with other measured data where available. The change of viscosity with pressure for the halogenated hydrocarbons is generally similar to that of other simple liquids. The results show that liquids having molecules of similar shape also have a similar change in relative viscosity with pressure.Theories of liquid viscosity are reviewed and constants required by Eyring's significant structure theory are obtained for more than sixty liquids using literature data. Methods are derived for calculating these constants from correlations with readily available critical properties or chemical structure. The correlations are tested using the new measurements and literature data. These tests show that the methods derived work well if one or two values of viscosity at atmospheric pressure can be used but are less reliable if only structural information is available. Since at least one measured viscosity isavailable for most liquids it is concluded that the method will be useful for predicting viscosities at other temperatures and pressures