Management of pain induced by exercise and mobilization during physical therapy programs: views of patients and care providers.

BACKGROUND: The expectations of patients for managing pain induced by exercise and mobilization (PIEM) have seldom been investigated. We identified the views of patients and care providers regarding pain management induced by exercise and mobilization during physical therapy programs. METHODS: We performed a qualitative study based on semi-structured interviews with a stratified sample of 12 patients (7 women) and 14 care providers (6 women): 4 general practitioners [GPs], 1 rheumatologist, 1 physical medicine physician, 1 geriatrician, 2 orthopedic surgeons, and 5 physical therapists. RESULTS: Patients and care providers have differing views on PIEM in the overall management of the state of disease. Patients' descriptions of PIEM were polymorphic, and they experienced it as decreased health-related quality of life. The impact of PIEM was complex, and patient views were sometimes ambivalent, ranging from denial of symptoms to discontinuation of therapy. Care providers agreed that PIEM is generally not integrated in management strategies. Care providers more often emphasized the positive and less often the negative dimensions of PIEM than did patients. However, the consequences of PIEM cited included worsened patient clinical condition, fears about physical therapy, rejection of the physical therapist and refusal of care. PIEM follow-up is not optimal and is characterized by poor transmission of information. Patients expected education on how better to prevent stress and anxiety generated by pain, education on mobilization, and adaptations of physical therapy programs according to pain intensity. CONCLUSION: PIEM management could be optimized by alerting care providers to the situation, improving communication among care providers, and providing education to patients and care providers.

Cost-effectiveness modelling of biological treatment sequences in moderate to severe rheumatoid arthritis in France.

OBJECTIVES: Modern treatment of RA includes the use of biologics. Their cost is high and comparison between different treatment strategies is needed. METHOD: Direct medical costs of RA in France were evaluated based on expert opinion. Then, simulation-decision analytical models were developed to assess four biologic treatment sequences over 2 years in patients failing to respond to at least one anti-TNF agent. Effectiveness was expressed in theoretical expected number of days (TEND) in remission or low disease activity [low disease activity score (LDAS)] based on DAS-28 scores. RESULTS: Direct medical costs of RA in France (excluding the cost of biologics) were estimated at euro 905 (s.d. 263) for 6 months and euro 696 (s.d. 240) for each subsequent 6 months (P < 0.001) for patients achieving LDAS and euro 1215 for 6 months (s.d. 405) for patients not achieving LDAS. Based on LDAS criteria, using abatacept after an inadequate response to the first anti-TNF agent (etanercept) appeared significantly (P < 0.01) more efficacious over a 2-year period (102 TEND) compared with using rituximab at a 6-month re-treatment interval (82 TEND). Mean cost-effectiveness ratios showed significantly lower costs (P < 0.01) per TEND with abatacept as second biologic agent (euro 278) compared with rituximab (euro 303). After an inadequate response to two anti-TNF agents, using abatacept also appeared significantly more efficacious than an anti-TNF agent (P < 0.01). All comparisons were confirmed when using remission criteria instead of LDAS. CONCLUSION: Advanced simulation models based on clinical evidence and medical practice appear to be a promising approach for comparing cost-effectiveness of biologic strategies in RA.

Pediatric intravenous paracetamol (propacetamol) pharmacokinetics: a population analysis.

BACKGROUND: The aim of this study was to describe propacetamol pharmacokinetics in children in order to predict concentrations after a standard dosing regimen of propacetamol 30 mg x kg(-1) (15 mg x kg(-1) paracetamol) 6 h. METHODS: A population pharmacokinetic analysis of paracetamol time-concentration profiles (846 observations) from 144 children [postconception age (PCA) 27 weeks-14 years] was undertaken using nonlinear mixed effects models (NONMEM). These data were taken from seven separate studies involving children given intravenous propacetamol. Time-concentration profiles (503 observations) from a further 86 children (PCA: 37 weeks-14 years) given paracetamol elixir orally were included in the analysis to assess relative bioavailability of intravenous propacetamol. RESULTS: A three-compartment (depot, central and peripheral) linear disposition model fitted data better than a two-compartment (depot and central) model. Population parameter estimates (between subject variability, %) were central volume (V2/F(oral)) 24 (55%) l x 70 kg(-1), peripheral volume of distribution (V3/F(oral)) 30 (32%) l x 70 kg(-1), clearance (CL/F(oral)) 16 (40%) l x h(-1) x 70 kg(-1) and intercompartment clearance (Q/F(oral)) 55 (116%) l x h(-1) x 70 kg(-1). Clearance increased from 27 weeks PCA (1.87 l x h(-1) 70 kg(-1)) to reach 84% of the mature value by 1 year of age (standardized to a 70 kg person using allometric '1/4 power' models). Peripheral volume of distribution decreased from 27 weeks PCA (45.0 l x 70 kg(-1)) to reach 110% of its mature value by 6 months of age. Central volume of distribution and intercompartment clearance did not change with age. Between occasions variability for the peripheral volume of distribution (V3/F(oral)) and clearance (CL/F(oral)) were 18.5 and 19.3%, respectively. A rate constant representing hydrolysis of propacetamol to paracetamol (K(a) 96 h(-1)) was size related, but not age related. The relative bioavailability of intravenous propacetamol compared with an oral elixir was 0.5. CONCLUSIONS: A mean paracetamol serum concentration of 10 mg x l(-1) is achieved in children 2-15 years given a standard dose of propacetamol 30 mg x kg(-1) 6 h. This concentration in the effect compartment is associated with a pain reduction of 2.6/10 after tonsillectomy and provides satisfactory analgesia for mild to moderate pain. Clearance is reduced in children less than 1 year of age and the target concentration of 10 mg x l(-1) may be achieved by scaling this standard dose regimen using predicted clearance in this younger age group.