323,414 research outputs found
Glycoacetylenes in the synthesis and application of stable glycoamino acids and peptides
No full textContains fulltext :
72376.pdf (Publisher’s version ) (Open Access)Radboud Universiteit Nijmegen, 01 december 2008Promotor : Rutjes, F.P.J.T.122 p
Coordination-Mediated Bioconjugation Vinylboronic Acids as Bioorthogonal Reactants in the Tetrazine Ligation
No full textContains fulltext :
197532.pdf (Publisher’s version ) (Open Access)Radboud University, 20 november 2018Promotor : Rutjes, F.P.J.T. Co-promotor : Bonger, K.M.189 p
S-Adenosylmethionine for osteoarthritis of the knee or hip
No full textBACKGROUND: Osteoarthritis is the most common form of joint disease and the
leading cause of pain and disability in the elderly. S-Adenosylmethionine may be
a viable treatment option but the evidence about its effectiveness and safety is
equivocal.
OBJECTIVES: We set out to compare S-Adenosylmethionine (SAMe) with placebo or no
specific intervention in terms of effects on pain and function and safety
outcomes in patients with knee or hip osteoarthritis.
SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE, CINAHL and PEDro up to 5
August 2008, checked conference proceedings and reference lists, and contacted
authors.
SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that
compared SAMe at any dosage and in any formulation with placebo or no
intervention in patients with osteoarthritis of the knee or hip.
DATA COLLECTION AND ANALYSIS: Two independent authors extracted data using
standardised forms. We contacted investigators to obtain missing outcome
information. We calculated standardised mean differences (SMDs) for pain and
function, and relative risks for safety outcomes. We combined trials using
inverse-variance random-effects meta-analysis.
MAIN RESULTS: Four trials including 656 patients were included in the systematic
review, all compared SAMe with placebo. The methodological quality and the
quality of reporting were poor. For pain, the analysis indicated a small SMD of
-0.17 (95% CI -0.34 to 0.01), corresponding to a difference in pain scores
between SAMe and placebo of 0.4 cm on a 10 cm VAS, with no between trial
heterogeneity (I(2) = 0). For function, the analysis suggested a SMD of 0.02 (95%
CI -0.68 to 0.71) with a moderate degree of between-trial heterogeneity (I2 =
54%). The meta-analyses of the number of patients experiencing any adverse event,
and withdrawals or drop-outs due to adverse events, resulted in relative risks of
1.27 (95% CI 0.94 to 1.71) and 0.94 (95% CI 0.48 to 1.86), respectively, but
confidence intervals were wide and tests for overall effect were not significant.
No trial provided information concerning the occurrence of serious adverse
events.
AUTHORS' CONCLUSIONS: The current systematic review is inconclusive, hampered by
the inclusion of mainly small trials of questionable quality. The effects of SAMe
on both pain and function may be potentially clinically relevant and, although
effects are expected to be small, deserve further clinical evaluation in
adequately sized randomised, parallel-group trials in patients with knee or hip
osteoarthritis. Meanwhile, routine use of SAMe should not be advised
Doxycycline for osteoarthritis of the knee or hip
No full textBACKGROUND: Osteoarthritis is the most common form of joint disease and the
leading cause of pain and disability in the elderly. S-Adenosylmethionine may be
a viable treatment option but the evidence about its effectiveness and safety is
equivocal.
OBJECTIVES: We set out to compare S-Adenosylmethionine (SAMe) with placebo or no
specific intervention in terms of effects on pain and function and safety
outcomes in patients with knee or hip osteoarthritis.
SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE, CINAHL and PEDro up to 5
August 2008, checked conference proceedings and reference lists, and contacted
authors.
SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that
compared SAMe at any dosage and in any formulation with placebo or no
intervention in patients with osteoarthritis of the knee or hip.
DATA COLLECTION AND ANALYSIS: Two independent authors extracted data using
standardised forms. We contacted investigators to obtain missing outcome
information. We calculated standardised mean differences (SMDs) for pain and
function, and relative risks for safety outcomes. We combined trials using
inverse-variance random-effects meta-analysis.
MAIN RESULTS: Four trials including 656 patients were included in the systematic
review, all compared SAMe with placebo. The methodological quality and the
quality of reporting were poor. For pain, the analysis indicated a small SMD of
-0.17 (95% CI -0.34 to 0.01), corresponding to a difference in pain scores
between SAMe and placebo of 0.4 cm on a 10 cm VAS, with no between trial
heterogeneity (I(2) = 0). For function, the analysis suggested a SMD of 0.02 (95%
CI -0.68 to 0.71) with a moderate degree of between-trial heterogeneity (I2 =
54%). The meta-analyses of the number of patients experiencing any adverse event,
and withdrawals or drop-outs due to adverse events, resulted in relative risks of
1.27 (95% CI 0.94 to 1.71) and 0.94 (95% CI 0.48 to 1.86), respectively, but
confidence intervals were wide and tests for overall effect were not significant.
No trial provided information concerning the occurrence of serious adverse
events.
AUTHORS' CONCLUSIONS: The current systematic review is inconclusive, hampered by
the inclusion of mainly small trials of questionable quality. The effects of SAMe
on both pain and function may be potentially clinically relevant and, although
effects are expected to be small, deserve further clinical evaluation in
adequately sized randomised, parallel-group trials in patients with knee or hip
osteoarthritis. Meanwhile, routine use of SAMe should not be advised
Cyclic adenosine monophoshate phosphodiesterase: a possible marker of thyroid pathology? [letter]
No full textThe aim of this study was to evaluate whether or not the expression of cAMP-phosphodiesterases (cAMP-PDE) varies in different thyroid pathologies and to elucidate the relationship between the expression of cAMP-PDE and clinic-pathologic factors. Forty thyroid biopsy samples, excised to perform the biopsy, were microscopically examined and classified. Then cAMP-PDE expression was assessed using high performance liquid chromatography. The expression of cAMP-PDE showed different patterns according to the histological features of the samples (p less than 0.001). A strong expression of cAMP-PDE was observed more frequently in papillar and follicular carcinoma than in controls and benign pathologies. We did not detect any level of endogenous cAMP. cAMP could be used as additional diagnostic or prognostic biomarker in patients suspected of thyroid disease, however further studies are needed to confirm these results.
Key words: thyroid, cAMP-Phosphodiesterase, cAMP, carcinom
Low-molecular-weight heparin for the treatment of acute venous thromboembolism in patients with active cancer.
No full textThe effects of excluding patients from the analysis in randomised controlled trials: meta-epidemiological study.
No full textOBJECTIVE: To examine whether excluding patients from the analysis of randomised trials are associated with biased estimates of treatment effects and higher heterogeneity between trials. DESIGN: Meta-epidemiological study based on a collection of meta-analyses of randomised trials. DATA SOURCES: 14 meta-analyses including 167 trials that compared therapeutic interventions with placebo or non-intervention control in patients with osteoarthritis of the hip or knee and used patient reported pain as an outcome. METHODS: Effect sizes were calculated from differences in means of pain intensity between groups at the end of follow-up, divided by the pooled standard deviation. Trials were combined by using random effects meta-analysis. Estimates of treatment effects were compared between trials with and trials without exclusions from the analysis, and the impact of restricting meta-analyses to trials without exclusions was assessed. RESULTS: 39 trials (23%) had included all patients in the analysis. In 128 trials (77%) some patients were excluded from the analysis. Effect sizes from trials with exclusions tended to be more beneficial than those from trials without exclusions (difference -0.13, 95% confidence interval -0.29 to 0.04). However, estimates of bias between individual meta-analyses varied considerably (tau(2)=0.07). Tests of interaction between exclusions from the analysis and estimates of treatment effects were positive in five meta-analyses. Stratified analyses indicated that differences in effect sizes between trials with and trials without exclusions were more pronounced in meta-analyses with high between trial heterogeneity, in meta-analyses with large estimated treatment benefits, and in meta-analyses of complementary medicine. Restriction of meta-analyses to trials without exclusions resulted in smaller estimated treatment benefits, larger P values, and considerable decreases in between trial heterogeneity. CONCLUSION: Excluding patients from the analysis in randomised trials often results in biased estimates of treatment effects, but the extent and direction of bias is unpredictable. Results from intention to treat analyses should always be described in reports of randomised trials. In systematic reviews, the influence of exclusions from the analysis on estimated treatment effects should routinely be assessed
Joint lavage for osteoarthritis of the knee
No full textBACKGROUND: Osteoarthritis is the most common form of joint disorder and a
leading cause of pain and physical disability. Observational studies suggested a
benefit for joint lavage, but recent, sham-controlled trials yielded conflicting
results, suggesting joint lavage not to be effective.
OBJECTIVES: To compare joint lavage with sham intervention, placebo or
non-intervention control in terms of effects on pain, function and safety
outcomes in patients with knee osteoarthritis.
SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE, and CINAHL up to 3 August
2009, checked conference proceedings, reference lists, and contacted authors.
SELECTION CRITERIA: We included studies if they were randomised or
quasi-randomised trials that compared arthroscopic and non-arthroscopic joint
lavage with a control intervention in patients with osteoarthritis of the knee.
We did not apply any language restrictions.
DATA COLLECTION AND ANALYSIS: Two independent review authors extracted data using
standardised forms. We contacted investigators to obtain missing outcome
information. We calculated standardised mean differences (SMDs) for pain and
function, and risk ratios for safety outcomes. We combined trials using
inverse-variance random-effects meta-analysis.
MAIN RESULTS: We included seven trials with 567 patients. Three trials examined
arthroscopic joint lavage, two non-arthroscopic joint lavage and two tidal
irrigation. The methodological quality and the quality of reporting was poor and
we identified a moderate to large degree of heterogeneity among the trials (I(2)
= 65%). We found little evidence for a benefit of joint lavage in terms of pain
relief at three months (SMD -0.11, 95% CI -0.42 to 0.21), corresponding to a
difference in pain scores between joint lavage and control of 0.3 cm on a 10-cm
visual analogue scale (VAS). Results for improvement in function at three months
were similar (SMD -0.10, 95% CI -0.30 to 0.11), corresponding to a difference in
function scores between joint lavage and control of 0.2 cm on a WOMAC disability
sub-scale from 0 to 10. For pain, estimates of effect sizes varied to some degree
depending on the type of lavage, but this variation was likely to be explained by
differences in the credibility of control interventions: trials using sham
interventions to closely mimic the process of joint lavage showed a null-effect.
Reporting on adverse events and drop out rates was unsatisfactory, and we were
unable to draw conclusions for these secondary outcomes.
AUTHORS' CONCLUSIONS: Joint lavage does not result in a relevant benefit for
patients with knee osteoarthritis in terms of pain relief or improvement of
function
Age- versus clinical pretest probability-adjusted D-dimer to rule out lower-extremity deep vein thrombosis in ambulatory patients with active cancer.
No full textBACKGROUND
In patients with suspected deep vein thrombosis (DVT), D-dimer thresholds adjusted to age or clinical pretest probability (CPTP) increase the proportion of patients in whom DVT can be safely excluded compared to a standard approach using a fixed D-dimer threshold. Performance of these diagnostic strategies among cancer patients is uncertain.
AIM
To compare the performance of age- and CPTP-adjusted D-dimer approaches among cancer outpatients with clinically suspected DVT, and derive a cancer-specific CPTP rule.
PATIENTS AND METHODS
Consecutive ambulatory patients with active cancer and clinically suspected DVT of the lower extremity underwent CPTP assessment using the Wells rule, D-dimer testing, and whole-leg compression ultrasonography. Patients with normal ultrasonography were followed-up for 3 months for the occurrence of symptomatic venous thromboembolism.
RESULTS
Upon referral, DVT was diagnosed in 48 of 239 (20.1 %) patients. The age-adjusted approach showed higher specificity and efficiency than the standard approach. Compared to the standard and age-adjusted strategies, the CPTP-adjusted approach had 35 % and 21 % higher specificity, and 34 % and 21 % higher efficiency, respectively. Failure rate, sensitivity, and predictive values were similar across strategies. A simplified CPTP score derived from the Wells rule reduced unnecessary imaging with similar accuracy and efficiency, but higher failure rate.
CONCLUSIONS
In this prospective cohort of ambulatory cancer patients with clinically suspected DVT, the CPTP-adjusted D-dimer approach held the highest specificity and efficiency, potentially safely reducing unnecessary ultrasonography examinations compared to other approaches. Additional studies are warranted to evaluate the use of a simplified clinical prediction rule in this setting
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