Meta-analysis weaknesses

Cross-reactions with aspirin and NSAIDs are of practical importance. Typically, AIA patients are sensitive to all NSAIDs that preferentially inhibit COX-1 (table 2). Acetaminophen (paracetamol), a weak inhibitor of COX-1, is regarded as a relatively safe therapeutic alternative for almost all patients with AIA. High doses of the drug (>1,000 mg) have been reported to provoke mild, easily reversed bronchos-pasm in some AIA patients [13]. Some rare, well-documented cases of coexistence of aspirin and paracetamol sensitivity have been described. However, according to a recent meta-analysis, less that 2% of asthmatics are sensitive to both aspirin and paracetamol [14]. 

Uses of meta-analysis and their strengths and weaknesses... 

There are two major types of weaknesses associated with meta-analysis. Bias and heterogeneity. When planning a clinical trial every effort is made to minimise the impact of bias on the results. For example, clinicians and patients are kept unaware of the treatment being used for each individual patient, so-called double-blind studies and patients are randomly allocated to a treatment. However, in meta-analysis there... 

In a meta-analysis of megatrials with simvastatin, the overall incidence of myopathy was 0.025% (32). The authors suggested that potent inhibitors of CYP3A4 greatly increase the risk, but that weak inhibitors do not. Episodes of gout occurred in three of nine patients with chronic renal insufficiency who took simvastatin (33). 

A recent meta-analysis examined the association between smoking and the risk of systemic lupus erythematosus in seven case-control and two cohort studies (Costenbader et al., 2004) (Table 12). The combined estimate showed a weak association with current smoking (OR = 1.5), but no association with past smoking (OR = 0.98). 

A practical challenge of Bayesian meta-analysis for rare AE data is that noninformative priors may lead to convergence failure due to very sparse data. Weakly informative priors may be used to solve this issue. In the example of the previous Bayesian meta-analysis with piecewise exponential survival models, the following priors for log hazard ratio (HR) (see Table 14.1) were considered. Prior 1 assumes a nonzero treatment effect with a mean log(HR) of 0.7 and a standard deviation of 2. This roughly translates to that the 95% confidence interval (Cl) of HR is between 0.04 and 110, with an estimate of HR to be 2.0. Prior 2 assumes a 0 treatment effect, with a mean log(HR) of 0 and a standard deviation of 2. This roughly translates to the assumption that we are 95% sure that the HR for treatment effect is between 0.02 and 55, with an estimate of the mean hazard of 1.0. Prior 3 assumes a nonzero treatment effect that is more informative than that of Prior 1, with a mean log(HR) of 0.7 and a standard deviation of 0.7. This roughly translates to the assumption that we are 95% sure that the HR... 

Three Weakly Informative Prior Sp>ecifications for Bayesian Meta-Analysis... 

A meta-analysis of 32 pubhcations of nerve-conduction studies and occupational lead exposure foimd BLL to be a weak predictor of peripheral nerve impairment (Davis and Svendsgaard 1990). Nerve-conduction testing includes analysis of latent period (time it takes for stimulatory impulse to initiate an evoked potential), conduction velocity, and amplitude. Reduced nerve-conduction velocities in lead-exposed subjects revealed that the median motor nerve was most sensitive. 

Meta-Analysis. Meta-analysis is a widely used method that employs statistical analysis to synthesize the findings of a number of independent studies. Meta-analyses assume that random variation accounts for differences in results from one study to another. These analyses require both statistical expertise and extensive clinical knowledge of the topic. Weaknesses of meta-analyses are implicit in the process. The included studies may have measured slightly different outcomes, they may have used different research designs, and there may have been selection bias in the criteria used to include a study. 

Death In a Bayesian meta-analysis of studies that had previously been included in meta-analyses of the relation between dose of vitamin E and all-cause mortality there was no evidence of an increases risk in those taking vitamin E [48 ]. The weaknesses of the Bayesian approach have been discussed [49 ], as have problems with other types of meta-analysis [50 ]. 

Greenland S. Weaknesses of Bayesian model averaging for meta-analysis in the study of vitamin E and mortality. Clin Trials 2009 6(1) 42-6. 

Boron trioxide is not particularly soluble in water but it slowly dissolves to form both dioxo(HB02)(meta) and trioxo(H3B03) (ortho) boric acids. It is a dimorphous oxide and exists as either a glassy or a crystalline solid. Boron trioxide is an acidic oxide and combines with metal oxides and hydroxides to form borates, some of which have characteristic colours—a fact utilised in analysis as the "borax bead test , cf alumina p. 150. Boric acid. H3BO3. properly called trioxoboric acid, may be prepared by adding excess hydrochloric or sulphuric acid to a hot saturated solution of borax, sodium heptaoxotetraborate, Na2B407, when the only moderately soluble boric acid separates as white flaky crystals on cooling. Boric acid is a very weak monobasic acid it is, in fact, a Lewis acid since its acidity is due to an initial acceptance of a lone pair of electrons from water rather than direct proton donation as in the case of Lowry-Bronsted acids, i.e. 

The competition of ortho and meta photocycloaddition is much more expressed when the mesomeric effects of the substituents are weak [30,31]. A more precise analysis of the products revealed that ortho and even para side products are formed in minor amounts in cases were normally the meta cycloaddition should be observed as dominant reaction [32]. Bichro-mophroric substrates carrying electron donor substituents on the benzene ring and any electron active groups on the alkene moiety range in this category [15,31,33]. 

Interactions leading to para cycloaddition (S -i- ethylene LUMO) are only weakly stabUized. Para cycloadditions are also disfavored by the distance-determined (2.79 A) poor overlrq> between interacting orbitals of the arene with those of the alkene. From this analysis it is predicted that an ortho mode of cycloaddition will be favored for an arene AS"" transition while ortho but preferentially meta cycloaddition will be stabilized in the SA " transition. In addition to symmetry considerations, the effectiveness of the... 

In order to define the association between dietary protein restriction and CKD progression, two meta-analyses (comprised of several smaller studies) evaluated the effect of dietary protein restriction in diabetic and nondiabetic kidney diseases. The larger study, comprising over 1000 patients (who were predominantly nondiabetic) from 13 randomized controlled trials, found a weak association between dietary protein restriction and reduction in the rate of kidney disease progression. An analysis of the diabetic group from this... 

Using the silver polyphosphates obtained by the above procedures, one can determine the chemical composition of the polyphosphates and thereby estimate the structure of a given sodium meta-arsenate-phosphate. Several methods can be used for this purpose (a) paper chromatographic analysis of the polyphosphates, (b) determination of Ag/P ratios of the silver polyphosphates, (c) titrimetric determination of weak acid hydrogen of the polyphosphates, (d) measurement of depression of transition points of sodium sulfate decahydrate by the addition of the polyphosphates, and (e) fractional precipitation of the polyphosphates with silver nitrate... 

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