High prevalence of peripheral neuropathy in multiple myeloma patients and the impact of vitamin D levels, a cross-sectional study.

PURPOSE: Peripheral neuropathy (PN) is common in patients with multiple myeloma (MM). We hypothesized that the relationship between hypovitaminosis D and PN described in diabetes mellitus patients may also be present in MM patients. METHODS: To study this potential association, we assessed the incidence of hypovitaminosis D (vitamin D < 75 nmol/L [= 30 ng/mL]) in smouldering and active MM patients in two Dutch hospitals. Furthermore, a validated questionnaire was used to distinguish different PN grades. RESULTS: Of the 120 patients included between January 2017 and August 2018, 84% had an inadequate vitamin D level (median vitamin D level 49.5 nmol/L [IQR 34-65 nmol/L]; mean age: 68 years [SD ± 7.7]; males: 58%). PN was reported by 69% of patients (n = 83); however, of these 83 patients, PN was not documented in the medical records of 52%. An association was found between lower vitamin D levels and higher incidence of PN in the total population (P = 0.035), and in the active MM patients (P = 0.016). CONCLUSION: This multi-centre cohort study showed that PN and hypovitaminosis D are common in MM patients, and addressing low vitamin D levels in the treatment of MM patients might be beneficial in reducing the risk of PN. More attention for PN is warranted, as PN is underreported by clinicians. Further research is needed to fully understand the implications of vitamin D in the development of PN in patients with MM. CLINICAL TRIAL REGISTRATION: Netherland Trial Register NL5835, date of registration July 28, 2016.

The role of initial clinical presentation, comorbidity and treatment in multiple myeloma patients on survival: a detailed population-based cohort study.

PURPOSE: This prospective, observational population-based cohort study was performed to determine overall survival (OS) in multiple myeloma (MM) patients in Friesland, the Netherlands, in the era of novel agents and to analyse the influence of first-line treatment, MM-related end-organ damage and comorbidities at initial presentation on OS. METHODS: Detailed clinical information was obtained from the population-based registry 'HemoBase' during the period January 2005 to January 2013, with a follow-up to January 2014. RESULTS: Overall, the symptomatic MM patients (n = 225) had a median OS of 40 months. In the age categories <65, 65-75 and ≥75 years, 99, 94 and 87% of the patients received treatment, with a median OS of 92, 42 and 31 months, respectively. OS for patients with or without treatment was 43 and 3 months, respectively. In multivariable analysis, risk factors for worse OS were increasing age (<65: reference; 65-75: HRadj. = 2.2 (95% CI 1.3-3.7) and ≥75: HRadj. = 2.8 (95% CI 1.7-4.8); P < 0.001), not receiving initial treatment (HRadj. = 4.0 (95% CI 2.1-7.7); P < 0.001), hypercalcaemia (P < 0.001, HRadj. = 1.7 (95% CI 1.2-2.6), P = 0.006) and impaired renal function (HRadj. = 2.6 (95% CI 1.7-4.0); P < 0.001). CONCLUSIONS: Increasing age, not receiving initial treatment, hypercalcaemia and impaired renal function at initial presentation were independent risk factors for worse OS. Comorbidity according to Charlson comorbidity index score was not an independent variable predicting OS.

The perceived waning of biologics in severe asthma.

BACKGROUND: Biologics are highly effective in severe asthma and used at fixed dosing intervals. However, in clinical practice, dosing intervals are sometimes shortened if patients perceive a decreased biologic effect before the next administration. The occurrence and clinical relevance of this perceived waning of biological effect is unknown. OBJECTIVE: To explore (1) the frequency, severity and conditions, (2) associated symptoms and (3) relationship with clinical characteristics of the patient-perceived waning effect of biologics before the next administration. METHODS: Severe asthma patients receiving biological treatment ≥4 months were included. Based on 17 semi-structured patient interviews, we developed a questionnaire focusing on the waning effect of biologics before the next administration, which was distributed among 129 patients. Clinical characteristics, including asthma control (ACQ) and quality of life (AQLQ) scores, were collected from patient files. RESULTS: 65/101 patients who completed the questionnaire reported a waning of biological effect, graded as severe (median (IQR) 6.5 (5-7.5) on a 0-10 BORG-scale). Waning manifested in a broad spectrum of symptoms. Patients reporting waning had higher ACQ and lower AQLQ scores versus those without (p < 0.05) and higher BORG-scores were associated with higher exacerbation rate (ρ = 0.309, p = 0.013). A third of all patients were in favor of extending or shortening their dosing interval. CONCLUSION: Two-thirds of severe asthma patients report waning of biologic effect at the end of the dosing interval, which is associated with poorer asthma control and quality of life. The diversity in observed waning of effect opens the way for research into more individualized dosing of biologics.

Doctors' beliefs and knowledge on corticosteroid-induced osteoporosis: identifying barriers to improve prevention.

WHAT IS KNOWN AND OBJECTIVE: Despite the availability of effective treatments for the management of corticosteroid-induced osteoporosis (CIOP), the condition is undertreated. Our objective was to assess prescribers' knowledge and likely prescribing patterns concerning the diagnosis and treatment of CIOP. Another goal was to identify key barriers to the use of preventive therapy in patients using long-term corticosteroids. METHODS: We used a postal survey of general practitioners (GPs) and specialists in the Netherlands. The survey comprised of questions on: demographic data, perceived barriers to the use of preventive therapy for CIOP, and knowledge of diagnosis and treatment of CIOP. Case scenarios were questioned to assess practice patterns. RESULTS: Responding prescribers correctly answered an average of 55% of knowledge questions and 69% of case scenarios. Multiple questions and cases showed that knowledge on the use of bone mineral density (BMD) determination was poor. BMD was determined in patients who, according to the national osteoporosis guideline, should be treated with bisphosphonates independent of BMD. Moreover, only 18% of doctors correctly answered that the BMD cutoff in CIOP patients is a T-score of ≤-1 or ≤-1·5. Key barriers identified were: (i) GPs, significantly more than specialists, consider prescription of preventive therapy the responsibility of another doctor; (ii) discontinuation of anti-resorptive medication due to adverse effects and (iii) the reluctance to prescribe preventive therapy in patients already prescribed multiple medications. WHAT IS NEW AND CONCLUSION: Doctors did not identify many barriers to the prescribing of anti-resorptive therapies. Lack of knowledge, especially concerning use of BMD-results, likely led to the under-treatment of the presented patients.

Postoperative urinary retention: risk factors, bladder filling rate and time to catheterization: an observational study as part of a randomized controlled trial.

BACKGROUND: Knowledge of risk factors for postoperative urinary retention may guide appropriate and timely urinary catheterization. We aimed to determine independent risk factors for postoperative urinary catheterization in general surgical patients. In addition, we calculated bladder filling rate and assessed the time to spontaneous voiding or catheterization. We used the patients previously determined individual maximum bladder capacity as threshold for urinary catheterization. METHODS: Risk factors for urinary catheterization were prospectively determined in 936 general surgical patients. Patients were at least 18 years of age and operated under general or spinal anesthesia without the need for an indwelling urinary catheter. Patients measured their maximum bladder capacity preoperatively at home, by voiding in a calibrated bowl after a strong urge that could no longer be ignored. Postoperatively, bladder volumes were assessed hourly with ultrasound. When patients reached their maximum bladder capacity and were unable to void, they were catheterized by the nursing staff. Bladder filling rate and time to catheterization were determined. RESULTS: Spinal anesthesia was the main independent modifiable risk factor for urinary catheterization (hyperbaric bupivacaine, relative risk 8.1, articaine RR 3.1). Unmodifiable risk factors were a maximum bladder capacity < 500 mL (RR 6.7), duration of surgery ≥ 60 min (RR 5.5), first scanned bladder volume at the Post Anesthesia Care Unit ≥250mL (RR 2.1), and age ≥ 60 years (RR 2.0). Urine production varied from 100 to 200 mL/h. Catheterization or spontaneous voiding took place approximately 4 h postoperatively. CONCLUSION: Spinal anesthesia, longer surgery time, and older age are the main risk factors for urinary retention catheterization. Awareness of these risk factors, regularly bladder volume scanning (at least every 3 h) and using the individual maximum bladder capacity as volume threshold for urinary catheterization may avoid unnecessary urinary catheterization and will prevent bladder overdistention with the attendant risk of lower urinary tract injury. TRIAL REGISTRATION: Dutch Central Committee for Human Studies registered trial database: NL 21058.099.07. Current Controlled Trials database: Preventing Bladder Catheterization after an Operation under General or Spinal Anesthesia by Using the Patient's Own Maximum Bladder Capacity as a Limit for Maximum Bladder Volume. ISRCTN97786497 . Registered 18 July 2011 -Retrospectively registered. The original study started 19 May 2008, and ended 30 April 2009, when the last patient was included.

Fifteen years' experience with methylphenidate for attention-deficit disorder during pregnancy: Effects on birth weight, Apgar score and congenital malformation rates.

BACKGROUND: Methylphenidate (MPD) is increasingly prescribed to fertile women with Attention-Deficit Disorder (AD(H)D), with or without hyperactivity, despite advice for discontinuation during pregnancy. Few studies report on results concerning safety after methylphenidate exposure during pregnancy for the offspring. AIM: Safety for the offspring of exposure to MPD during pregnancy. METHODS: This is an observational retrospective cohort study in a population of pregnant women and their offspring, treated with MPD for ADHD in the Psychiatry-Gynaecology-Pediatrics outpatient clinic between 1 January 2005 and 1 June 2020 at Isala hospital. The primary endpoints were birth weight and Apgar score in offspring exposed to MPD during pregnancy, compared to offspring unexposed to MPD. Birth weight was analysed using linear mixed model analysis. Apgar score and (secondary endpoint) neonatal malformations, at 20 week ultrasound, were analysed using basic univariate statistical analysis. RESULTS: MPD continuation, compared to discontinuation, was associated with higher neonatal birth weight (p = 0.049), but lost statistical significance after incorporating covariates (p = 0.079). There were no significant differences in Apgar scores and congenital malformations between neonates exposed and unexposed to MPD. CONCLUSIONS: MPD does not seem to affect birth weight, Apgar score and the frequency of neonatal malformations at the 20 week ultrasound.

Methotrexate bioavailability.

The clinical relevance of the concept of bioavailability rests on two main principles. First, that measurement of the active component at the site of action is generally not possible and, secondly, that a relationship exists between on the one hand efficacy and/or safety and on the other hand concentration of the active compound or its active metabolite(s) in the systemic circulation. Applying these principles to the current knowledge on methotrexate (MTX), it is clear that bioavailability of MTX is an important parameter for optimal dosing. In this manuscript the current knowledge on MTX bioavailability is reviewed. This review reveals that bioavailability of MTX in higher oral doses is decreased, most probably by limitation of absorption from the gastro-intestinal tract. It is suggested that higher doses can be given either by splitting the oral dose or by parenteral administration. Both will result in improved bioavailability as compared with one higher oral dose. However, larger, prospective studies directly comparing the efficacy and safety of the splitted oral dose strategy and the switch to parenteral MTX are needed.

Prediction of response to biological treatment with monoclonal antibodies in severe asthma.

In recent years, major developments have occurred in severe asthma management. Different asthma phenotypes and subgroups have been identified and new treatment options have become available. A total of five monoclonal antibodies are currently approved in severe asthma treatment: omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab. These drugs have been shown to reduce exacerbations and to have an oral corticosteroid-sparing effect in many severe asthma patients. However, biological treatment is not successful in all patients and should be discontinued in non-responsive patients. Treating the right patient with the right biologic, and therefore biologic response prediction, has become a major point of interest in severe asthma management. A variety of response outcomes is utilized in the different clinical trials, as well as a huge range of potential predicting factors. Also, regarding the timing of the response evaluation, there are considerable differences between studies. This review summarizes the results from studies on predicting responses and responders to biological treatment in severe asthma, taking into account clinical, functional and inflammatory parameters assessed prior to the start of treatment as well as following a few months of therapy. In addition, future perspectives are discussed, highlighting the need for more research to improve patient identification and treatment responses in the field of biological treatment in severe asthma.

Urea for hyponatraemia due to the syndrome of inappropriate antidiuretic hormone secretion.

BACKGROUND: Hyponatraemia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) can pose a therapeutic challenge. After fluid restriction, urea is recommended as a second-line treatment by Dutch and European treatment guidelines. Data on this practice are still scarce. We introduced urea for the treatment of SIADH in our hospital and prospectively collected data on its effectiveness and tolerability. METHODS: In hospitalised patients with a serum sodium level ≤ 129 mmol/l due to SIADH, urea in a dosage of 0.25-0.50 g/kg/day was indicated if prescribed fluid restriction had no effect or could not be applied. Measurement of serum sodium was performed at baseline, after the first and second day of urea therapy and at the end of the first inpatient treatment episode (EIT). The primary outcomes were normonatraemia (serum sodium level 135-145 mmol/l) at EIT and discontinuation of urea due to side effects. RESULTS: Thirteen patients were treated with urea over a median of 5 days (range 2-10 days). The median serum sodium level at baseline was 124 mmol/l (IQR 122-128), which increased to 128 mmol/l (IQR 123-130) (p = 0.003) after the first dose of urea and to 130 mmol/l (IQR 127-133) (p = 0.002) after the second dose of urea. Normonatraemia at EIT was observed in 8 (62%) patients. Seven (54%) patients reported distaste. In one of these patients, urea was discontinued because of nausea. Overcorrection was not observed. CONCLUSION: Our data show that urea is an effective treatment for hospitalised patients with SIADH. Distaste was a frequent side effect, but usually did not lead to early treatment discontinuation.

Efficacy and tolerability of urate-lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol.

OBJECTIVES: To investigate the efficacy and tolerability of allopurinol as the first-choice antihyperuricaemic treatment for gout, and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment. METHODS: Prospective, multicentre, open-label, two-stage randomised controlled trial in gout patients with normal renal function. Enrolled patients were given 300 mg allopurinol for 2 months (stage 1). Those patients who could not tolerate allopurinol or who did not attain the target serum urate concentration (sUr) < or=0.30 mmol/l (5.0 mg/dl), which was defined as successful, were randomised to benzbromarone 200 mg/day or probenecid 2 g/day for another 2 months (stage 2). RESULTS: 96 patients were enrolled in stage 1. 82 patients (85%) were eligible for the analysis at the end of stage 1: there was a mean (SD) decrease in sUr concentration of 35 (11)% from baseline; 20 patients (24%) attained target sUr < or=0.30 mmol/l; and 9 patients (11%) stopped allopurinol because of adverse drug reactions. 62 patients were enrolled in stage 2. 27 patients received benzbromarone (3 patients not eligible for analysis) and 35 received probenecid (4 patients not eligible for analysis). Treatment with benzbromarone was successful in 22/24 patients (92%) and with probenecid in 20/31 patients (65%) (p = 0.03 compared with benzbromarone). Compared with baseline values, there was a mean (SD) decrease of sUr concentration of 64 (9)% with benzbromarone and 50 (7)% with probenecid (p<0.001). CONCLUSION: This study showed that allopurinol 300 mg/day has a poor efficacy and tolerability profile when used to attain a biochemical predefined target level of sUr < or =0.30 mmol/l, following 2 months of treatment. In stage 2, benzbromarone 200 mg/day was more effective and better tolerated than probenecid 2 g/day.

A randomised controlled trial on the efficacy and tolerability with dose escalation of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day in patients with gout.

OBJECTIVES: To compare the efficacy and tolerability of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day used to attain a target serum urate concentration (sUr) < or =0.30 mmol/l (5 mg/dl). METHODS: A randomised, controlled, open-label, multicentre trial in gout patients with renal function defined as a calculated creatinine clearance > or =50 ml/min. Patients were treated with 300 mg allopurinol or 100 mg benzbromarone once a day (stage 1). If sUr < or =0.30 mmol/l was not attained after 2 months, the dose was doubled to allopurinol 300 mg twice a day or benzbromarone 200 mg once a day (stage 2). The primary end point was treatment success in either of the two stages, defined as clinical tolerability and attainment of biochemical target sUr. RESULTS: Sixty-five patients were enrolled in stage 1; 36 received allopurinol and 29 received benzbromarone. Fifty-five patients (85%) were analysed at stage 1: the success rates were 8/31 (26%) and 13/25 (52%), respectively, and the difference was -0.26 (95% CI from -0.486 to -0.005), p = 0.049. At stage 2, the success rates were 21/27 (78%) and 18/23 (78%), respectively, and the difference was -0.005 (95% CI from -0.223 to 0.220), p = 1.00. Two patients stopped receiving allopurinol and three stopped receiving benzbromarone because of adverse drug reactions. CONCLUSIONS: Increasing the allopurinol dose from 300 to 600 mg/day and the benzbromarone dose from 100 to 200 mg/day according to the target sUr produced significantly higher success rates (both 78% successful in attaining sUr < or =0.30 mmol/l). No significant differences in treatment success between benzbromarone and allopurinol were found after dose escalation. TRIAL REGISTRATION NUMBER: ISRCTN49563848).

[Effects of a structured medication review by geriatrician and clinical pharmacologist on appropriateness of pharmacotherapy in frail elderly inpatients]. / Interventies na een gestructureerde medicatie-analyse door klinisch geriater en ziekenhuisapotheker bij klinisch opgenomen kwetsbare oudere patiënten.

OBJECTIVE: To study the results of a structured medication review of geriatric inpatients by both geriatrician and hospital pharmacist/clinical pharmacologist. METHODS: Patients who were present at the geriatric ward were eligible for a review of their medication and medical problems using a screening form. Recommendations and questions following these forms were subsequently discussed in the gerontopharmacologic meeting ('GFO') held every two weeks. RESULTS: In a 30 month-period 44 GFO's were held during which 184 patients were discussed. A total of 206 recommendations were made and 115 questions were asked. Of the recommended interventions,134 (65%) were accepted by the geriatrician. To stop a medication (64/206), to change the dosage of a medication (60/206) and to switch to another medication (44/206) were the types of interventions most accounted for. CONCLUSION: Structured medication review led to a substantial number of medication changes in geriatric inpatients. Nearly two-thirds of the recommended interventions were accepted by the geriatricians. Seventy-two recommendations (35%) were not implemented due to logistic or patient-related reasons.

Interventies na een gestructureerde medicatie-analyse door klinisch geriater en ziekenhuisapotheker bij klinisch opgenomen kwetsbare oudere patiënten.

EFFECTS OF A STRUCTURED MEDICATION REVIEW BY GERIATRICIAN AND CLINICAL PHARMACOLOGIST ON APPROPRIATENESS OF PHARMACOTHERAPY OF FRAIL ELDERLY INPATIENTS: Objective To study the results of a structured medication review of geriatric inpatients by both geriatrician and hospital pharmacist/clinical pharmacologist. Methods Patients who were present at the geriatric ward were eligible for a review of their medication and medical problems using a screening form. Recommendations and questions following these forms were subsequently discussed in the gerontopharmacologic meeting ('GFO') held every two weeks. Results In a 30 month-period 44 GFO's were held during which 184 patients were discussed. A total of 206 recommendations were made and 115 questions were asked. Of the recommended interventions,134 (65%) were accepted by the geriatrician. To stop a medication (64/206), to change the dosage of a medication (60/206) and to switch to another medication (44/206) were the types of interventions most accounted for. Conclusion Structured medication review led to a substantial number of medication changes in geriatric inpatients. Nearly two-thirds of the recommended interventions were accepted by the geriatricians. Seventy-two recommendations (35%) were not implemented due to logistic or patient-related reasons.

Systematic review of trends in prophylaxis of corticosteroid-induced osteoporosis: the need for standard audit guidelines.

UNLABELLED: Corticosteroid-induced osteoporosis (CIOP) is currently undertreated. Systematic review of the literature revealed that the percentage of patients treated adequately is dependent on study quality. Therefore, it remains unknown whether adherence to the guidelines is really so poor. Five major quality criteria provide the standard for future studies on this scope. INTRODUCTION: It has recently been stated that the degree of prophylaxis of corticosteroid-induced osteoporosis (CIOP) is low and effort should be put into determining reasons for non-prescribing of preventive agents. The aim of this study was to identify: how many studies adequately audit the prevalent guideline; the longitudinal trends in prevention of CIOP; which patient groups appear to be most undertreated; and which intervention strategies are effective. METHODS: We performed a comprehensive search of MEDLINE and systematically recorded the outcomes and quality of published studies, using five major criteria. RESULTS: Twenty-four studies were included in the analysis. The quality of the included studies was poor (31%) or moderate (37%). There was a longitudinal increase in quality of the studies and percentage of prevention. Multivariable linear regression showed that the quality of the study was the only independent predictor of the prevention rate reported in the study. CONCLUSIONS: The results show undertreatment of CIOP might be due to insufficient quality of the studies rather than poor practice or failure to recognise the right patients. Future interventions should comply with five major quality criteria, and a multifaceted approach is required in order to make an impact on the underprescribing of CIOP prophylaxis.

Treatment of pregnant and non-pregnant rheumatic patients: a survey among Dutch rheumatologists.

BACKGROUND: The aim of this study was to explore, among Dutch rheumatologists, aspects such as attitude towards guidelines, pharmacotherapy and information needs in the treatment of pregnant as well as non-pregnant rheumatoid arthritis (RA) patients. METHODS: Fifteen rheumatologists from nine different hospitals were interviewed by means of a semi-structured interview. Questions addressing attitude towards guidelines, pharmacotherapy preferences and information needs with respect to the pregnant and non-pregnant patient were asked. The analysis will be based on descriptive statistics. RESULTS: Guidelines are used by almost half of the hospitals with respect to pregnant RA patients and by all hospitals for RA patients in general. With respect to pregnant women, nine respondents preferred stopping the medication as soon pregnancy is known. When treating RA patients, in general sulfasalazine and methotrexate would be drugs of first choice. Information is found in international and national books and guidelines. CONCLUSION: Dutch rheumatologists are of the view that there is sufficient information on the treatment of RA in pregnant women or women wishing to become pregnant, except for safe use of medication during pregnancy. In the future, pregnancy risk categorization should be updated and discussed regularly. This should be based on more recent literature and experience. A good monitoring system for following all young patients with a rheumatic disease should be set up as a first step to collect more information on the safe use of medication during pregnancy.

Bridging the gap between the randomised clinical trial world and the real world by combination of population-based registry and electronic health record data: A case study in haemato-oncology.

Randomised clinical trials (RCTs) are considered the basis of evidence-based medicine. It is recognised more and more that application of RCT results in daily practice of clinical decision-making is limited because the RCT world does not correspond with the clinical real world. Recent strategies aiming at substitution of RCT databases by improved population-based registries (PBRs) or by improved electronic health record (EHR) systems to provide significant data for clinical science are discussed. A novel approach exemplified by the HemoBase haemato-oncology project is presented. In this approach, a PBR is combined with an advanced EHR, providing high-quality data for observational studies and support of best practice development. This PBR + EHR approach opens a perspective on randomised registry trials.

Safety of citrate based hemofiltration in critically ill patients at high risk for bleeding: a comparison with nadroparin.

PURPOSE: To study the incidence and severity of bleeding in high risk critically ill patients during high volume, citrate based continuous veno-venous hemofiltration (CVVH). DESIGN: A prospective 1-year observational cohort study comparing citrate based CVVH with nadroparin based CVVH. PROCEDURES: Critically ill patients with multiple organ dysfunction and in need of CVVH were observed for bleeding complications during their CVVH sessions. Pre-defined criteria determined that patients were treated with citrate based CVVH in case of active bleeding or increased risk for bleeding. Otherwise nadroparin was used as anticoagulant. Statistical and outcome methods: The incidence of bleeding complications, the number of transfused blood cell concentrates and the filter-run-time were recorded. Analyses were made by non-parametric tests. MAIN FINDINGS: Fifty-five patients received 272 CVVH sessions. In the citrate group 14.8% experienced a bleeding complication compared to 25% in the nadroparin group (p=0.04). The number of transfused red blood cell concentrates was not different between groups. The nadroparin group had a longer filter run time (median 31.5 hours versus 22.5 hours, p=0.0001). CONCLUSIONS: In high risk critically ill patients citrate based anticoagulation for CVVH is safe in terms of bleeding complications and transfusion requirements.

A rapid and simple determination of A77 1726 in human serum by high-performance liquid chromatography and its application for optimization of leflunomide therapy.

Leflunomide is a disease-modifying antirheumatic drug, which is bioactivated by formation of A77 1726. In this study a rapid and simple quantitative assay using a reversed phase HPLC-UV method is validated for detection of A77 1726 in human serum. The HPLC-UV method uses a mobile phase consisting of methanol and a KH2PO4-buffer (45 mM, pH = 3) (50:50,v/v), at a flow rate of 1 mL/min. A77 1726 is detected by UV-absorption at 295 nm with a retention time of 8.9 min. Demoxepam is used as internal standard. Validation showed lower and upper limits of quantitation of 0.5 and 100 mg/L, respectively. The assay was linear over the concentration range of 0.5-100 mg/L (r2 > 0.999). Intra- and inter-day precision showed coefficients of variation within 15% over the complete concentration range; accuracy was within 8%. Commonly prescribed drugs to treat rheumatoid arthritis like disease-modifying antirheumatic drugs, analgesics and corticosteroids, and their main metabolites, are separated from A77 1726 with a resolution >2. Serum levels of A77 1726 in 37 patients on leflunomide therapy were determined using this HPLC-UV method. Measured serum A77 1726 serum concentrations in patient samples showed large variability with a range of 3-176 mg/L.

Four cases of a secondary Cushingoid state following local triamcinolone acetonide (Kenacort) injection.

Intra-articular, paratendinous or other soft tissue corticosteroid injections are well-recognised treatment modalities for rheumatic conditions in which a debilitating inflammatory component persists. A corticosteroid injection that is locally administered only sporadically evokes adverse effects. We report four cases of secondary Cushingoid state, twice due to single, and twice due to repetitive triamcinolone acetonide (TCA: Kenacort) injection. A consulted general practitioner, internist and gynaecologist were not aware of the possibility that such a local injection may evoke a Cushingoid state with moon face, buffalo hump and/or disturbance of the menstrual cycle. Therefore we describe here the four cases we recently encountered.