IR spectroscopy together with multivariate data analysis as a process analytical tool for in-line monitoring of crystallization process and solid-state analysis of crystalline product

Crystalline product should exist in optimal polymorphic form. Robust and reliable method for polymorph characterization is of great importance. In this work, infra red (IR) spectroscopy is applied for monitoring of crystallization process in situ. The results show that attenuated total reflection Fourier transform infra red (ATR-FTIR) spectroscopy provides valuable information on process, which can be utilized for more controlled crystallization processes. Diffuse reflectance Fourier transform infra red (DRIFT-IR) is applied for polymorphic characterization of crystalline product using X-ray powder diffraction (XRPD) as a reference technique. In order to fully utilize DRIFT, the application of multivariate techniques are needed, e.g., multivariate statistical process control (MSPC), principal component analysis (PCA) and partial least squares (PLS). The results demonstrate that multivariate techniques provide the powerful tool for rapid evaluation of spectral data and also enable more reliable quantification of polymorphic composition of samples being mixtures of two or more polymorphs. This opens new perspectives for understanding crystallization processes and increases the level of safety within the manufacture of pharmaceutics.     

2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis

This first update of the ASAS/EULAR recommendations on the management of ankylosing spondylitis (AS) is based on the original paper, a systematic review of existing recommendations and the literature since 2005 and the discussion and agreement among 21 international experts, 2 patients and 2 physiotherapists in a meeting in February 2010. Each original bullet point was discussed in detail and reworded if necessary. Decisions on new recommendations were made - if necessary after voting. The strength of the recommendations (SOR) was scored on an 11-point numerical rating scale after the meeting by email. These recommendations apply to patients of all ages that fulfill the modified NY criteria for AS, independent of extra-articular manifestations, and they take into account all drug and non-drug interventions related to AS. Four overarching principles were introduced, implying that one bullet has been moved to this section. There are now 11 bullet points including 2 new ones, one related to extra-articular manifestations and one to changes in the disease course. With a mean score of 9.1 (range 8-10) the SOR was generally very good.     

Reactive arthritis or post-infectious arthritis?

The term 'reactive arthritis' was first used in 1969 to describe the development of sterile inflammatory arthritis as a sequel to remote infection, often in the gastrointestinal or urogenital tract. The demonstration of antigenic material (e.g. Salmonella and Yersinia lipopolysaccharide), DNA and RNA, and, in occasional cases, evidence of metabolically active Chlamydia spp. in the joints has blurred the boundary between reactive and post-infectious forms of arthritis. No validated and generally agreed diagnostic criteria exist, but the diagnosis of reactive arthritis is mainly clinical based on acute oligoarticular arthritis of larger joints that develops within 2-4 weeks of the preceding infection. In about 25% of patients, the infection can be asymptomatic. Diagnosis of the triggering infection is very helpful for the diagnosis of reactive arthritis. This is mainly achieved by isolating the triggering infection (stools, urogenital tract) by cultures (stool cultures for enteric microbes) or ligase reaction (Chlamydia trachomatis). However, after the onset of arthritis, this is less likely to be possible. Therefore, the diagnosis must rely on various serological tests to demonstrate evidence of previous infection, but, these serological tests are unfortunately not standardized. Treatment with antibiotics to cure Chlamydia infection is important, but the use of either short or prolonged courses of antibiotics in established arthritis has not been found to be effective for the cure of arthritis. The long-term outcome of reactive arthritis is usually good; however, about 25-50% of patients, depending on the triggering infections and possible new infections, subsequently develop acute arthritis. About 25% of patients proceed to chronic spondyloarthritis of varying activity.     

Infectious causes of death in patients with rheumatoid arthritis: an autopsy study

OBJECTIVE: To study mortality from infections and accuracy of pre-mortem diagnoses in patients with rheumatoid arthritis (RA) autopsied during a 40-year period. METHODS: We investigated infectious causes of death, findings at autopsy, and clinicians' estimation of cause of death in 369 consecutively autopsied RA and 371 autopsied non-RA patients with same sex, age at death, and year of autopsy. We also compiled clinical features of RA patients from medical records available and examined the association between these and infectious causes of death. RESULTS: Deaths from any infection were more frequent in RA (36%) than in non-RA (26%) patients. In both groups, respiratory and urinary tract infections were the most common infectious causes of death. More RA patients died from urinary tract infections than non-RA patients. In approximately half of the patients in both groups, infection as a cause of death was unrecognized before death, with no major change occurring over the 40-year study period. CONCLUSIONS: Infections, especially respiratory and urinary tract infections, are frequent causes of death in RA patients. The high proportion of undiscovered infections as a cause of death highlights the diagnostic difficulty. With a decreasing number of autopsies being performed at present, greater numbers of infections may be under-reported.     

Health-related quality of life in patients with common rheumatic diseases referred to a university clinic

The aim of the present study was to assess the health-related quality of life (HRQoL) in patients with common rheumatic diseases referred to a rheumatology clinic and to compare it to the HRQoL of the general population. All patients with a new referral to the Department of Rheumatology of the Helsinki University Central Hospital were asked to participate in the study during the period from May 2002 to April 2003. A total of 295 patients with various rheumatic diseases were included in the analysis: 99 patients with rheumatoid arthritis (RA), 47 with arthralgia and fibromyalgia, 43 with other chronic arthritis (spondyloarthritis, psoriatic arthritis, enteropathic arthritis), 44 with osteoarthritis (OA), 22 with active reactive arthritis (ReA), 17 with systemic rheumatic diseases, 9 adults with juvenile idiopathic arthritis (JIA) and 14 with other diagnoses. HRQoL was measured by a disease specific instrument, the Stanford health assessment questionnaire (HAQ) and by a generic instrument, 15D. The mean baseline 15D score of the 295 included patients (0.822, SD 0.114) was significantly lower than of the general population (0.903, SD 0.098). Patients with OA and chronic arthritis reported the poorest HRQoL scores (both 0.810 on a 0-1 scale). In patients with RA and ReA the 15D score improved in a statistically significant and clinically important manner during the 8-month follow-up. Discomfort and symptoms caused by the disease were alleviated in a statistically significant manner in patients with RA as well as in those with arthralgia and fibromyalgia, chronic arthritis, ReA and systemic rheumatic diseases. HAQ score improved significantly in patients with RA, arthralgia and fibromyalgia, and ReA. The HRQoL of patients with common rheumatic diseases at referral to rheumatology clinic is significantly lower than the HRQoL of age-standardized general population. The most affected patients are those with OA, chronic arthritis and RA. A significant improvement in HRQoL with conventional interventions was achieved in patients with RA and ReA.     

School health nurses and substance use among adolescents - towards individual identification and early intervention

Adolescents' health is today threatened by the use of alcohol and other psychoactive substances. It is therefore important to develop interventions related to substance use in school health care. The aim of this study was to examine the empowering or risk background factors related to substance use among adolescents, and the ability of school nurses (PHN) to identify these factors and to provide needed individual early intervention. The data were collected by semistructured questionnaires completed by 14- to 18-year-old adolescents (n = 326, response rate 79) and PHNs (n = 10) in 2004. The adolescent questionnaire consisted of items related to the respondents' background and Adolescents' Substance Use Measurement (ADSUME). Following individual consent, adolescents' ADSUME responses were sent to the PHNs for intervention. The PHNs assessed the adolescents' empowering background factors and intervention using the questionnaire, and 70% (n = 228) of their answers matched the adolescents' answers. The data were analysed with the SPSS software using the chi-squared test, Fisher's exact test, kappa coefficient and agreement percentages. Substance use among adolescents was associated with parental support, mother's education and smoking, the adolescents' knowledge about substances, peer support and hobbies. The PHNs' assessments regarding supportive background were not in agreement with the assessments of adolescents who were using hazardous substances. One-fifth of the adolescents received the brief intervention, although many of them might have needed extra support and follow-up on the basis of their ADSUME results. The research findings can be generalized only for alcohol use, because only 3% of the study informants used substances other than alcohol. Further research is warranted concerning PHNs' ability to identify hazardous substance use and to ensure preventive early intervention and requisite support among substance-using adolescents in order to improve evidence-based health promotion.     

SuPAR and PAI-1 in critically ill, mechanically ventilated patients

Purpose

SuPAR (soluble urokinase plasminogen activator receptor) and PAI-1 (plasminogen activator inhibitor 1) are active in the coagulation-fibrinolysis pathway. Both have been suggested as biomarkers for disease severity. We evaluated them in prediction of mortality, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), sepsis and renal replacement therapy (RRT) in operative and non-operative ventilated patients.

Methods

We conducted a prospective, multicenter, observational study. Blood samples and data of intensive care were collected. Mechanically ventilated patients with baseline suPAR and PAI-1 measurements were included in the analysis, and healthy volunteers were analysed for comparison. Receiver operating characteristics (ROC), logistic regression, likelihood ratios and Kaplan–Meier analysis were performed.

Results

Baseline suPAR was 11.6 ng/ml (quartiles Q1–Q3, 9.6–14.0), compared to healthy volunteers with suPAR of 0.6 ng/ml (0.5–11.0). PAI-1 concentrations were 2.67 ng/ml (1.53–4.69) and 0.3 ng/ml (0.3–0.4), respectively. ROC analysis for suPAR 90-day mortality areas under receiver operating characteristic curves (AUC) 0.61 (95 % confidence interval (CI): 0.55–0.67), sepsis 0.68 (0.61–0.76), ALI/ARDS 0.64 (0.56–0.73) and RRT 0.65 (0.56–0.73). Patients with the highest quartile of suPAR concentrations had an odds ratio of 2.52 (1.37–4.64, p = 0.003) for 90-day mortality and 3.16 (1.19–8.41, p = 0.02) for ALI/ARDS. In non-operative patients, the AUC’s for suPAR were 90-day mortality 0.61 (0.54–0.68), RRT 0.73 (0.64–0.83), sepsis 0.70 (0.60–0.80), ALI/ARDS 0.61 (0.51–0.71). Predictive value of PAI-1 was negligible.

Conclusions

In non-operative patients, low concentrations of suPAR were predictive for survival and high concentrations for RRT and mortality. SuPAR may be used for screening for patients with potentially good survival. The association with RRT may supply an early warning sign for acute renal failure.