Objective. To compare the clinical efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis (RA). Methods. In this multicentre, double‐blind trial, 999 subjects ...with active RA were randomized to leflunomide (n = 501; loading dose 100 mg/day for 3 days, maintenance dose 20 mg/day) or methotrexate (n = 498; 10–15 mg/week) for 52 weeks. After 1 yr the subjects could choose to stay for a second year of double‐blind treatment. The primary end‐points were tender and swollen joint counts and overall physician and patient assessments. Analyses were of the intent‐to‐treat group. Results. After 1 yr, the mean changes in the leflunomide and methotrexate groups, respectively, were −8.3 and −9.7 for tender joint count; −6.8 and −9.0 for swollen joint count; −0.9 and −1.2 for physician global assessment; −0.9 and −1.2 for patient global assessment; −14.4 and −28.2 for erythrocyte sedimentation rate. Improvements seen with methotrexate were significantly greater than those with leflunomide. No further improvement occurred after the second year of treatment and the distinction between the two treatments in terms of tender joint count and patient global assessment was lost. During the first year of treatment, a small and equivalent degree of radiographically assessed disease progression was seen with both drugs. After 2 yr, disease progression was significantly less with methotrexate. The most common treatment‐related adverse events in both groups were diarrhoea, nausea, alopecia, rash, headache, and elevated plasma liver enzyme levels. Over 2 yr, 21 subjects receiving methotrexate were withdrawn due to elevated plasma liver enzymes vs eight subjects taking leflunomide. Two drug‐related deaths from pulmonary causes were recorded with methotrexate vs no drug‐related deaths among the subjects receiving leflunomide. Conclusions. Both leflunomide and methotrexate are efficacious for prolonged treatment of RA. At the doses used, some clinical benefit of methotrexate over leflunomide was observed in the first year of treatment. This benefit must be weighed against the potential toxicity of this drug when used without folate supplementation.
Four kindreds segregating for Alport's syndrome (ASLN) compatible with a X-linked inheritance were studied for linkage with polymorphic markers of the human X chromosome. No recombinant was observed ...between the ASLN locus and the DXS101 and DXS94 loci, the maximum lod scores were z = 3.93 and 3.50 respectively. Linkage data between the ASLN locus and the other genetic markers used in the present study are in keeping with the assignment of the mutation to the proximal Xq arm.
Over the last two decades, increased interest of scientists to study bone marrow adiposity (BMA) in relation to bone and adipose tissue physiology has expanded the number of publications using ...different sources of bone marrow adipose tissue (BMAT). However, each source of BMAT has its limitations in the number of downstream analyses for which it can be used. Based on this increased scientific demand, the International Bone Marrow Adiposity Society (BMAS) established a Biobanking Working Group to identify the challenges of biobanking for human BMA-related samples and to develop guidelines to advance establishment of biobanks for BMA research. BMA is a young, growing field with increased interest among many diverse scientific communities. These bring new perspectives and important biological questions on how to improve and build an international community with biobank databases that can be used and shared all over the world. However, to create internationally accessible biobanks, several practical and legislative issues must be addressed to create a general ethical protocol used in all institutes, to allow for exchange of biological material internationally. In this position paper, the BMAS Biobanking Working Group describes similarities and differences of patient information (PIF) and consent forms from different institutes and addresses a possibility to create uniform documents for BMA biobanking purposes. Further, based on discussion among Working Group members, we report an overview of the current isolation protocols for human bone marrow adipocytes (BMAds) and bone marrow stromal cells (BMSCs, formerly mesenchymal), highlighting the specific points crucial for effective isolation. Although we remain far from a unified BMAd isolation protocol and PIF, we have summarized all of these important aspects, which are needed to build a BMA biobank. In conclusion, we believe that harmonizing isolation protocols and PIF globally will help to build international collaborations and improve the quality and interpretation of BMA research outcomes.
Please cite this paper as: von Dadelszen P, Dwinnell S, Magee LA, Carleton BC, Gruslin A, Lee B, Lim KI, Liston RM, Miller SP, Rurak D, Sherlock RL, Skoll MA, Wareing MM, Baker PN, for the Research ...into Advanced Fetal Diagnosis and Therapy (RAFT) Group. Sildenafil citrate therapy for severe early‐onset intrauterine growth restriction. BJOG 2011;118:624–628.
Currently, there is no effective therapy for severe early‐onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR‐complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early‐onset IUGR abdominal circumference (AC) < 5th percentile and either the gestational age was <25+0 weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil‐naive early‐onset IUGR controls. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early‐onset IUGR‐complicated pregnancies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective
To evaluate the subsequent rate of thrombosis among women with obstetric antiphospholipid syndrome (Ob‐APS) in a multicentre database of antiphospholipid antibody (aPL)‐positive patients, ...and the clinical utility of the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients.
Design
Retrospective study.
Setting
The Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository.
Population
Women with Ob‐APS.
Methods
Comparison of clinical and laboratory characteristics and measurement of aGAPSS in women with Ob‐APS, with or without thrombosis, after initial pregnancy morbidity (PM).
Main outcome measures
Risk factors for thrombosis and aGAPSS.
Results
Of 550 patients, 126 had Ob‐APS; 74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age at diagnosis of Ob‐APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had a higher aGAPSS compared with women with Ob‐APS alone median 11.5 (4–16) versus 9 (4–13); P = 0.0089.
Conclusion
Based on a retrospective analysis of our multicentre aPL database, 63% of women with Ob‐APS developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high‐risk aPL profile increased the risk. Women with subsequent thrombosis after Ob‐APS had a higher aGAPSS at entry to the registry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL‐positive women.
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More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.
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More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background. Many studies have found high levels of compulsory admission to psychiatric hospital in the UK among African-Caribbean and Black African patients with a psychotic illness. Aims. To ...establish whether African-Caribbean and Black African ethnicity is associated with compulsory admission in an epidemiological sample of patients with a first episode of psychosis drawn from two UK centres. Method. All patients with a first episode of psychosis who made contact with psychiatric services over a 2-year period and were living in defined areas were included in the (AESOP) study. For this analysis we included all White British, other White, African-Caribbean and Black African patients from the AESOP sampling frame. Clinical, socio-demographic and pathways to care data were collected from patients, relatives and case notes. Results. African-Caribbean patients were significantly more likely to be compulsorily admitted than White British patients, as were Black African patients. African-Caribbean men were the most likely to be compulsorily admitted. Conclusions. These findings suggest that factors are operating at or prior to first presentation to increase the risk of compulsory admission among African-Caribbean and Black African patients. Declaration of interest. None. (Original abstract)
The standard of care for gastroesophageal cancer patients with hepatic or pulmonary metastases is best supportive care or palliative chemotherapy. Occasionally, patients can be selected for curative ...treatment instead. This study aimed to evaluate patients who underwent a resection of hepatic or pulmonary metastasis with curative intent. The Dutch national registry for histo- and cytopathology was used to identify these patients. Data were retrieved from the individual patient files. Kaplan-Meier survival analysis was performed. Between 1991 and 2016, 32,057 patients received a gastrectomy or esophagectomy for gastroesophageal cancer in the Netherlands. Of these patients, 34 selected patients received a resection of hepatic metastasis (n = 19) or pulmonary metastasis (n = 15) in 21 different hospitals. Only 4 patients received neoadjuvant therapy before metastasectomy. The majority of patients had solitary, metachronous metastases. After metastasectomy, grade 3 (Clavien-Dindo) complications occurred in 7 patients and mortality in 1 patient. After resection of hepatic metastases, the median potential follow-up time was 54 months. Median overall survival (OS) was 28 months and the 1-, 3-, and 5- year OS was 84%, 41%, and 31%, respectively. After pulmonary metastases resection, the median potential follow-up time was 80 months. The median OS was not reached and the 1-, 3-, and 5- year OS was 67%, 53%, and 53%, respectively. In selected patients with gastroesophageal cancer with hepatic or pulmonary metastases, metastasectomy was performed with limited morbidity and mortality and offered a 5-year OS of 31-53%. Further prospective studies are required.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Overweight and obesity are rapidly increasing in countries like India. This study was aimed at determining the prevalence of generalized, abdominal and combined obesity in urban and rural India.
...Phase I of the ICMR-INDIAB study was conducted in a representative population of three States Tamil Nadu (TN), Maharashtra (MH) and Jharkhand (JH) and one Union Territory (UT)Chandigarh (CH) of India. A stratified multi-stage sampling design was adopted and individuals ≥ 20 yr of age were included. WHO Asia Pacific guidelines were used to define overweight body mass index (BMI) ≥ 23 kg/m 2 but < 25 kg/m 2, generalized obesity (GO, BMI ≥ 25 kg/m 2, abdominal obesity (AO, waist circumference ≥ 90 cm for men and ≥ 80 cm for women) and combined obesity (CO, GO plus AO). Of the 14,277 participants, 13,800 subjects (response rate, 96.7%) were included for the analysis (urban: n = 4,063; rural: n = 9737).
The prevalence of GO was 24.6, 16.6, 11.8 and 31.3 per cent among residents of TN, MH, JH and CH, while the prevalence of AO was 26.6, 18.7, 16.9 and 36.1 per cent, respectively. CO was present in 19.3, 13.0, 9.8 and 26.6 per cent of the TN, MH, JH and CH population. The prevalence of GO, AO and CO were significantly higher among urban residents compared to rural residents in all the four regions studied. The prevalence of overweight was 15.2, 11.3, 7.8 and 15.9 per cent among residents of TN, MH, JH and CH, respectively. Multiple logistic regression analysis showed that female gender, hypertension, diabetes, higher socio-economic status, physical inactivity and urban residence were significantly associated with GO, AO and CO in all the four regions studied. Age was significantly associated with AO and CO, but not with GO.
Prevalence of AO as well as of GO were high in India. Extrapolated to the whole country, 135, 153 and 107 million individuals will have GO, AO and CO, respectively. However, these figures have been estimated from three States and one UT of India and the results may be viewed in this light.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND Increased microvascular permeability inducing leakage of plasma from the intravascular to the extravascular space after trauma is a pathophysiologic event of great clinical significance. A ...substance reducing an increased microvascular permeability, and especially an increased protein permeability, therefore could be of value to maintain normovolemia and to reduce the need for plasma substitution. Prostacyclin is suggested to have permeability-reducing properties as shown for fluid permeability, but its effects on protein permeability, which may be controlled by partly different mechanisms, are unclear. The present study evaluates whether prostacyclin at a low, clinically relevant, nonvasodilating dose can reestablish an increased protein permeability after trauma.
METHODS The study was randomized, blinded, and performed on surgically traumatized, autoperfused, and denervated cat calf muscle. Relative changes in the osmotic reflection coefficient for albumin after 1.5 hours of prostacyclin (1 ng/min/kg) (n = 7) or vehicle (n = 7) treatment were used as a measure of altered protein permeability from a state of increased permeability after trauma.
RESULTS We found that the osmotic reflection coefficient for albumin was increased by about 35% in the prostacyclin group compared with the vehicle-treated group (p < 0.001).
CONCLUSION If applicable to humans, prostacyclin is a potential therapy for reducing plasma leakage in the critically ill trauma patient by restoring permeability from an increased level.
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