Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 12417866

[Randomised controlled trials: a reading guide].

A Perrier
View original source ↗Export metadata ↓

Abstract

This paper, first of a series devoted to evidence-based medicine, describes how to critically read an article on a randomised controlled intervention trial. This guide is applied to the common clinical question, whether or not to prescribe systemic glucocorticoids for patients with exacerbation of chronic obstructive pulmonary disease, through the analysis of two recently published series. It comprises a three-step evaluation: the assessment of the study methods to ensure that the results are valid, the analysis of the results of the larger of the two studies, and the evaluation of whether the results can be applied to a patient whose clinical case illustrates this article. Finally, a few limitations of randomised controlled trials are discussed.

Explore related subjects

Anti-Inflammatory AgentsBiasCost-Benefit AnalysisEvidence-Based MedicineHumansMaleMiddle AgedPatient SelectionPractice Patterns, Physicians'Pulmonary Disease, Chronic ObstructiveRandomized Controlled Trials as TopicReproducibility of ResultsResearch DesignReview Literature as TopicSteroidsSurvival AnalysisTreatment OutcomeCase ReportsJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

A Perrier. 2002. [Randomised controlled trials: a reading guide].. https://pubmed.ncbi.nlm.nih.gov/12417866/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2003

General patterns in the photochemistry of pregna-1,4-dien-3,20-diones.

The photochemistry of six pregna-1,4-dien-3,20-diones has been compared and found to involve both the cyclohexadienone moiety in ring A and the isolated ketone at C-20. The two reactions take place proportionally to the fraction of light absorbed by each chromophore. The cross-conjugated ketone absorbs predominantly or exclusively at both 254 and 366 nm and undergoes the "lumi" rearrangement to bicyclo[3.1.0]hex-3-en-2-one. The quantum yield of the reaction diminished somewhat with increasing lambda(exc), e.g., for prednisolone Phi(254) (nm) = 0.42, Phi(366) (nm) = 0.3. A much stronger lowering is caused by halogen substitution in position 9 (by a factor of 3 for F, >50 for Cl), apparently due to a shortened triplet lifetime caused by heavy atom effect. At 310 nm, both chromophores absorb to a comparable degree and both may react. The reaction at C(20) ketone involves either quite efficient alpha-cleavage (C(17)-C(20)) for compounds bearing an acetal or hydroxyl function at C(17) or less effective (by a factor of ca. 10) hydrogen abstraction from the 18-methyl group in the other cases (finally resulting in Norrish II fragmentation or Yang cyclization). The results allow generalizing how the substitution pattern surrounding each chromophore affects the photoreactivity at that site and the competition between the two modes, allowing predicting the photochemistry of this family of antiinflammatory drugs.

Anti-Inflammatory Agents↗
PubMed2003

A convergent solution-phase synthesis of the macrocycle Ac-Phe-[Orn-Pro-D-Cha-Trp-Arg], a potent new antiinflammatory drug.

Relatively few cyclic peptides have reached the pharmaceutical marketplace during the past decade, most produced through fermentation rather than made synthetically. Generally, this class of compounds is synthesized for research purposes on milligram scales by solid-phase methods, but if the potential of macrocyclic peptidomimetics is to be realized, low-cost larger scale solution-phase syntheses need to be devised and optimized to provide sufficient quantities for preclinical, clinical, and commercial uses. Here, we describe a cheap, medium-scale, solution-phase synthesis of the first reported highly potent, selective, and orally active antagonist of the human C5a receptor. This compound, Ac-Phe[Orn-Pro-d-Cha-Trp-Arg], known as 3D53, is a macrocyclic peptidomimetic of the human plasma protein C5a and displays excellent antiinflammatory activity in numerous animal models of human disease. In a convergent approach, two tripeptide fragments Ac-Phe-Orn(Boc)-Pro-OH and H-d-Cha-Trp(For)-Arg-OEt were first prepared by high-yielding solution-phase couplings using a mixed anhydride method before coupling them to give a linear hexapeptide which, after deprotection, was obtained in 38% overall yield from the commercially available amino acids. Cyclization in solution using BOP reagent gave the antagonist in 33% yield (13% overall) after HPLC purification. Significant features of the synthesis were that the Arg side chain was left unprotected throughout, the component Boc-d-Cha-OH was obtained very efficiently via hydrogenation of d-Phe with PtO(2) in TFA/water, the tripeptides were coupled at the Pro-Cha junction to minimize racemization via the oxazolone pathway, and the entire synthesis was carried out without purification of any intermediates. The target cyclic product was purified (>97%) by reversed-phase HPLC. This convergent synthesis with minimal use of protecting groups allowed batches of 50-100 g to be prepared efficiently in high yield using standard laboratory equipment. This type of procedure should be useful for making even larger quantities of this and other macrocyclic peptidomimetic drugs.

Anti-Inflammatory Agents↗
PubMed2003

Pamidronate in a girl with chronic renal insufficiency dependent on parenteral nutrition.

A 10-year-old 40-kg African-American female with megacystis microcolon hypoperistalsis syndrome maintained on total parenteral nutrition (TPN), with a history of metabolic bone disease and renal insufficiency, was admitted with a Candida parapsilosis central venous line infection. During her 280-day hospital stay, she had multiple episodes of bacteremia and recurrent candidemia. Furthermore, she developed pathological fractures and hip displacement with osteomyelitis due to Enterobacter. Hypercalcemia and a history of nephrocalcinosis had prevented appropriate dosing of calcium prior to and during the first months of her hospital stay. Pamidronate and chlorothiazide were added to her regimen. The urinary calcium to creatinine ratio and ionized calcium decreased. The pamidronate dose was increased to 60 mg once a week and was well tolerated. Daily calcium was added to her TPN solution and was increased to 10 mEq/day by the time of discharge. We conclude that relatively large doses of pamidronate may be required in certain cases of refractory hypercalcemia and are well tolerated in children.

Anti-Inflammatory Agents↗