Glycated haemoglobin and the risk of postoperative complications in people without diabetes: a prospective population-based study in UK Biobank.

The aim of our study was to clarify the association between glycated haemoglobin (HbA1c ) and postoperative outcomes in people without an existing diagnosis of diabetes. Half a million adults were recruited into the UK Biobank prospective cohort study between March 2006 and October 2010. We divided participants into three groups: no diagnosis of diabetes and HbA1c < 42 mmol.mol-1 ; no diagnosis of diabetes and elevated HbA1c (≥ 42 mmol.mol-1 with no upper limit); and prevalent diabetes (regardless of HbA1c concentration) at recruitment. We followed up participants by linkage with routinely collected hospital data to determine any surgical procedures undertaken after recruitment and the associated postoperative outcomes. Our main outcome measure was a composite primary outcome of 30-day major postoperative complications and 90-day all-cause mortality. We used logistic regression to estimate the odds of the primary outcome by group. We limited analyses to those who underwent surgery within one year of recruitment (n = 26,653). In a combined effects logistic regression model, participants not known to have diabetes with HbA1c ≥ 42 mmol.mol-1 had increased odds of the primary outcome (OR [95% CI] 1.43 [1.02-2.02]; p = 0.04), when compared with those without diabetes and HbA1c < 42 mmol.mol-1 . This effect was attenuated and no longer statistically significant in a direct effects model with adjustment for hyperglycaemia-related comorbidity (OR [95% CI] 1.37 [0.97-1.93]; p = 0.07). Elevated pre-operative HbA1c in people without diabetes may be associated with an increased risk of complications, but the association is likely confounded by end-organ comorbidity. In contrast to previous evidence, our findings suggest that to prevent adverse postoperative outcomes, optimisation of pre-existing morbidity should take precedence over reducing HbA1c in people without diabetes.

Bi-directional interaction between hypoglycaemia and cognitive impairment in elderly patients treated with glucose-lowering agents: a systematic review and meta-analysis.

AIMS: To examine the bi-directional relationship, whereby hypoglycaemia is a risk factor for dementia, and where dementia increases risk of hypoglycaemia in older patients with diabetes mellitus treated with glucose-lowering agents. METHODS: We searched MEDLINE and EMBASE over a 10-year span from 2005 to 2015 (with automated PubMed updates to August 2015) for observational studies of the association between hypoglycaemia and cognitive impairment or dementia in participants aged >55 years. Assessment of study validity was based on ascertainment of hypoglycaemia, dementia and risk of confounding. We conducted random effects inverse variance meta-analyses, and assessed heterogeneity using the I(2) statistic. RESULTS: We screened 1177 citations, and selected 12 studies, of which nine were suitable for meta-analysis. There were a total of 1,439,818 participants, with a mean age of 75 years. Meta-analysis of five studies showed a significantly increased risk of dementia in patients who had hypoglycaemic episodes: pooled odds ratio 1.68 [95% confidence interval (CI) 1.45, 1.95]. We also found a significantly increased risk of hypoglycaemia in patients with dementia: pooled odds ratio from five studies 1.61 (95% CI 1.25, 2.06). Limitations of the study were heterogeneity in the meta-analysis, and uncertain ascertainment of dementia and hypoglycaemic outcomes and temporal relationships. Publication bias may have favoured the reporting of more significant findings. CONCLUSIONS: Our meta-analysis shows a bi-directional relationship between cognitive impairment and hypoglycaemia in older patients. Glucose-lowering therapy should be carefully tailored and monitored in older patients who are susceptible to cognitive decline.

Prognostic indices for early mortality in ischaemic stroke - meta-analysis.

OBJECTIVES: Several models have been developed to predict mortality in ischaemic stroke. We aimed to evaluate systematically the performance of published stroke prognostic scores. METHODS: We searched MEDLINE and EMBASE in February 2014 for prognostic models (published between 2003 and 2014) used in predicting early mortality (<6 months) after ischaemic stroke. We evaluated discriminant ability of the tools through meta-analysis of the area under the curve receiver operating characteristic curve (AUROC) or c-statistic. We evaluated the following components of study validity: collection of prognostic variables, neuroimaging, treatment pathways and missing data. RESULTS: We identified 18 articles (involving 163 240 patients) reporting on the performance of prognostic models for mortality in ischaemic stroke, with 15 articles providing AUC for meta-analysis. Most studies were either retrospective, or post hoc analyses of prospectively collected data; all but three reported validation data. The iSCORE had the largest number of validation cohorts (five) within our systematic review and showed good performance in four different countries, pooled AUC 0.84 (95% CI 0.82-0.87). We identified other potentially useful prognostic tools that have yet to be as extensively validated as iSCORE - these include SOAR (2 studies, pooled AUC 0.79, 95% CI 0.78-0.80), GWTG (2 studies, pooled AUC 0.72, 95% CI 0.72-0.72) and PLAN (1 study, pooled AUC 0.85, 95% CI 0.84-0.87). CONCLUSIONS: Our meta-analysis has identified and summarized the performance of several prognostic scores with modest to good predictive accuracy for early mortality in ischaemic stroke, with the iSCORE having the broadest evidence base.

Habitual chocolate consumption and the risk of incident heart failure among healthy men and women.

BACKGROUND: We aimed to examine the association between chocolate intake and the risk of incident heart failure in a UK general population. We conducted a systematic review and meta-analysis to quantify this association. METHODS AND RESULTS: We used data from a prospective population-based study, the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Chocolate intake was quantified based on a food frequency questionnaire obtained at baseline (1993-1997) and incident heart failure was ascertained up to March 2009. We supplemented the primary data with a systematic review and meta-analysis of studies which evaluated risk of incident heart failure with chocolate consumption. A total of 20,922 participants (53% women; mean age 58 ± 9 years) were included of whom 1101 developed heart failure during the follow up (mean 12.5 ± 2.7 years, total person years 262,291 years). After adjusting for lifestyle and dietary factors, we found 19% relative reduction in heart failure incidence in the top (up to 100 g/d) compared to the bottom quintile of chocolate consumption (HR 0.81 95%CI 0.66-0.98) but the results were no longer significant after controlling for comorbidities (HR 0.87 95%CI 0.71-1.06). Additional adjustment for potential mediators did not attenuate the results further. We identified five relevant studies including the current study (N = 75,408). The pooled results showed non-significant 19% relative risk reduction of heart failure incidence with higher chocolate consumption (HR 0.81 95%CI 0.66-1.01). CONCLUSIONS: Our results suggest that higher chocolate intake is not associated with subsequent incident heart failure.

Influenza, influenza-like symptoms and their association with cardiovascular risks: a systematic review and meta-analysis of observational studies.

AIMS: To synthesise the evidence relating influenza and influenza-like symptoms to the risks of myocardial infarction (MI), heart failure (HF) and stroke. METHODS: We conducted a systematic review and meta-analysis of the evidence relating influenza and influenza-like symptoms to the risks of MI, HF and stroke. We systematically searched all MEDLINE and EMBASE entries up to August 2014 for studies of influenza vs. the cardiovascular outcomes above. We conducted random effects meta-analysis using inverse variance method for pooled odds ratios (OR) and evaluated statistical heterogeneity using the I(2) statistic. RESULTS: We identified 12 studies with a total of 84,003 participants. The pooled OR for risk of MI vs. influenza (serologically confirmed) was 1.27 (95% CI, confidence interval 0.54-2.95), I(2)  = 47%, which was significant for the only study that adjusted for confounders (OR 5.50, 95% CI 1.31-23.13). The pooled OR for risk of MI vs. influenza-like symptoms was 2.17 (95% CI 1.68-2.80), I(2)  = 0%, which was significant for both unadjusted (OR 2.23, 95% CI 1.65-3.01, five studies) and adjusted studies (OR 2.01, 95% CI 1.24-3.27, two studies). We found one study that evaluated stroke risk, one study in patients with HF, and one that evaluated mortality from MI - all of these studies suggested increased risks of events with influenza-like symptoms. CONCLUSIONS: There is an association between influenza-like illness and cardiovascular events, but the relationship is less clear with serologically diagnosed influenza. We recommend renewed efforts to apply current clinical guidelines and maximise the uptake of annual influenza immunisation among patients with cardiovascular diseases, to decrease their risks of MI and stroke.

Age but not ABCD(2) score predicts any level of carotid stenosis in either symptomatic or asymptomatic side in transient ischaemic attack.

BACKGROUND: The ABCD(2) score is routinely used in assessment of transient ischaemic attack (TIA) to assess the risk of developing stroke. There remains uncertainty regarding whether the ABCD(2) score could be used to help predict extent of carotid artery stenosis (CAS). OBJECTIVES: We aimed to (i) collate and analyse all available published literature on this topic and (ii) compare the data from our local population to the existing evidence base. MATERIALS AND METHODS: We conducted a retrospective-observational study over a 6-month period using our East of England hospital-based TIA clinic data with a catchment population of ~750,000. We also searched the literature on studies reporting the association between ABCD(2) score and CAS. RESULTS: We included 341 patients in our observational study. The mean age in our cohort was 72.86 years (SD 10.91) with 52% male participants. ABCD(2) score was not significantly associated with CAS (p = 0.78). Only age > 60 years was significantly associated with ipsilateral (> 50%) and contralateral CAS (> 50% and > 70%) (p < 0.01) after controlling for other confounders. The systematic review identified four studies for inclusion and no significant association between ABCD(2) score and CAS was reported, confirming our findings. CONCLUSION: Our systematic review and observational study confirm that the ABCD(2) score does not predict CAS. However, our observational study has examined a larger number of possible predictors and demonstrates that age appears to be the single best predictor of CAS in patients presenting with a TIA. Selection of urgent carotid ultrasound scan thus should be based on individual patient's age and potential benefit of carotid intervention rather than ABCD(2) score.

Dexamethasone and haemorrhage risk in paediatric tonsillectomy: a systematic review and meta-analysis.

Summary In children undergoing tonsillectomy, dexamethasone is recommended to reduce the risk of postoperative nausea and vomiting while non-steroidal anti-inflammatory drugs (NSAIDs) are used for pain relief. We aimed to determine whether children who receive dexamethasone or dexamethasone with NSAID are more likely to experience haemorrhage post-tonsillectomy. Randomized and non-randomized studies in which children undergoing tonsillectomy received dexamethasone or dexamethasone and NSAID were sought within bibliographic databases and selected tertiary sources. The risk of bias assessment and evaluation of haemorrhage rate data collection and reporting were assessed using the Cochrane Risk of Bias Tool and McHarm tool. Synthesis methods comprised pooled estimate of the effect of dexamethasone on the risk of haemorrhage rate using the Peto odds ratio (OR) method. The pooled estimate for haemorrhage rate in children who received dexamethasone was 6.2%, OR 1.41 (95% confidence interval 0.89-2.25, P=0.15). There was risk of bias and inconsistent data collection and reporting rates of haemorrhage in many of the included studies. Clinical heterogeneity was observed between studies. The pooled analysis did not demonstrate a statistically significant increase in the risk of post-tonsillectomy haemorrhage with dexamethasone with/without NSAID use in children. However, the majority of the included studies were not designed to investigate this endpoint, and thus large studies which are specifically designed to collect data on haemorrhage rate are needed.

Chronic obstructive pulmonary disease and mortality from pneumonia: meta-analysis.

BACKGROUND: We aimed to determine whether patients with concomitant community-acquired pneumonia (CAP) and chronic obstructive pulmonary disease (COPD) are at greater risk of death when compared with those with CAP or acute COPD exacerbation alone. We also assessed the effect of inhaled corticosteroids (ICS) on pneumonia mortality in COPD. METHODS: We searched MEDLINE and EMBASE from inception to March 2012 for studies reporting on mortality in patients with COPD and CAP. We assessed ascertainment of disease, mortality, drug exposure and adjustment for confounders. Data were pooled using random effects meta-analysis, and heterogeneity was estimated using I². RESULTS: We identified 24 eligible articles overall. Evaluation of 13 studies revealed considerable heterogeneity and a non-significant mortality risk associated with concomitant COPD and CAP as compared with CAP in five studies that reported adjusted or severity-matched data, pooled RR 1.44 (95% CI 0.97-2.16, I² = 50%). There was also considerable inconsistency amongst the effect estimates from five studies that reported on the associated mortality with concomitant CAP and COPD as compared with acute COPD exacerbations alone. Evaluation of six datasets found that ICS use in COPD was not consistently associated with lower mortality in CAP. Reports of reduced mortality with prior ICS use stemmed from three studies that enrolled participants from the same healthcare database. CONCLUSIONS: Evidence on associated mortality risk with concomitant CAP and COPD (as opposed to CAP alone, or COPD exacerbation alone) is weak and heterogeneous. ICS use was not consistently associated with reduced mortality from pneumonia.

Systematic review evaluating cardiovascular events of the 5-alpha reductase inhibitor - Dutasteride.

WHAT IS KNOWN AND OBJECTIVES: A recently published large, long-term randomized controlled trial (RCT) brought into question the safety of dutasteride after a significantly increased risk of 'cardiac failure' was noted in the dutasteride arm of the trial compared with placebo. Our objective was to perform a meta-analysis to assess the risk of cardiovascular adverse events with the use of dutasteride for the prevention or treatment of prostatic disease. METHODS: We searched MEDLINE and EMBASE, unpublished articles identified through FDA/EMEA websites, study registers of pharmaceutical companies and reference lists of articles. Parallel-group, randomized controlled trials where men received dutasteride for the prevention of prostate cancer or treatment of prostatic hyperplasia against any comparator intervention were included. Heart failure was the primary outcome of interest but we also looked at myocardial infarction and stroke. Fixed-effect meta-analysis of pooled relative risk (RR) ratios of adverse effect outcomes was conducted. RESULTS AND DISCUSSION: In all, 12 RCTs were included in the meta-analysis after detailed screening of 564 citations. The total number of participants was 18,802, and study duration ranged from 6 to 208 weeks. Only two trials provided details on adequate allocation concealment, whereas all the trials stated they were double blind in nature. Dutasteride was not associated with a statistically significant increased risk of heart failure (RR 1·05; 95% confidence interval [CI], 0·71-1·57, I(2) = 20%), myocardial infarction (RR 1·00; 95% CI 0·77-1·30, I(2) = 0%) and stroke (RR, 1·20; 95% CI 0·88-1·64, I(2) = 0%) as compared to controls. WHAT IS NEW AND CONCLUSION: We did not find consistent evidence of a significant association between dutasteride therapy and the risk of cardiovascular adverse events.

Dabigatran and rivaroxaban for prevention of venous thromboembolism--systematic review and adjusted indirect comparison.

WHAT IS KNOWN AND OBJECTIVE: Dabigatran and rivaroxaban are new oral anticoagulants for thromboprophylaxis after elective orthopaedic surgery. We aimed to systematically compare their relative benefits and harms through meta-analysis, and adjusted indirect comparison. METHODS: We searched PubMed, EMBASE, trial registries and regulatory documents through May 2009 for randomized controlled trials (RCTs) of dabigatran (150 and 220 mg daily) and rivaroxaban (10 mg daily) compared with enoxaparin (40-60 mg daily) in elective orthopaedic surgery. We used random effects meta-analysis to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI) for the outcomes of total venous thromboembolism, VTE (deep venous thrombosis, non-fatal pulmonary embolism and all-cause mortality), and haemorrhagic adverse events (major and clinically relevant non-major bleeds). Adjusted indirect comparison was used for the pooled RRs of dabigatran and rivaroxaban with enoxaparin as the common control. RESULTS: Rivaroxaban was superior to enoxaparin for the prevention of venous thromoboembolism (RR 0.56, 95% CI 0.43-0.73, P<0.0001), with a trend for increased haemorrhage (RR 1.26, 95% CI 0.94-1.69, P=0.13). Dabigatran was not superior to enoxaparin for prevention of VTE (RR 1.12, 95% 0.97-1.29, P=0.12), and did not reduce haemorrhage risk (RR 1.10, 95% 0.90-1.35, P=0.32). Adjusted indirect comparison showed that rivaroxaban was superior to dabigatran in preventing VTE, RR 0.50 (95% CI 0.37-0.68), but with a slight trend towards increased haemorrhage RR 1.14 (95% CI 0.80-1.64). WHAT IS NEW AND CONCLUSION: Rivaroxaban may be more effective than dabigatran for prevention of VTE after elective orthopaedic surgery but might also slightly increase the risk of haemorrhage.

Risk of myocardial infarction and cardiovascular death associated with inhaled corticosteroids in COPD.

The effect of long-term inhaled corticosteroid (ICS) use on myocardial infarction (MI) and cardiovascular (CV) death in chronic obstructive pulmonary disease (COPD) remains uncertain. We conducted a systematic search of MEDLINE, EMBASE, ISI, regulatory documents and manufacturers' trial registries for long-term (>24 weeks duration) randomised controlled trials (RCTs) or controlled observational studies reporting on CV outcomes or death with ICS use in COPD. A fixed effects model was used to calculate the relative risks (RRs) and 95% CIs. 23 RCTs with 24-160 weeks of follow-up were included. In the RCTs, ICS were not associated with a significantly reduced risk of MI (RR 0.95, 95% CI 0.73-1.23; p = 0.68, I(2) = 0%), CV death (RR 1.02; 95% CI 0.81-1.27; p = 0.89, I(2) = 0%), or mortality (RR 0.96, 95% CI 0.86-1.07; p = 0.43, I(2) = 0%). In the observational studies, ICS use was associated with a significant reduction in CV death (two studies: RR 0.79, 95% CI 0.72-0, 86; p <0.0001, I(2) = 44%) and mortality (11 studies: RR 0.78, 95% CI 0.75-0.80; p<0.001, I(2) = 33%). Publication bias via funnel plot asymmetry was noted for mortality in the observational studies (Egger test, p = 0.05). We conclude that while observational studies suggest that ICS may potentially confer CV or mortality benefit, RCTs failed to show any significant effect of ICS therapy on MI or CV death. These conflicting findings need to be clarified through further research.

Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT-ROC feasibility study.

BACKGROUND: Statins inhibit proliferative signalling in oesophageal adenocarcinoma (OAC) and their use is associated with better survival in observational studies. The present study was undertaken to examine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III RCT. METHODS: For this multicentre, double-blind, parallel-group, randomized, placebo-controlled feasibility trial, adults with OAC (including Siewert I-II lesions) who had undergone oesophagectomy were centrally allocated (1 : 1) to simvastatin 40 mg or matching placebo by block randomization, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Patients received treatment for up to 1 year. Feasibility outcomes were recruitment, retention, drug absorption, adherence, safety, quality of life, generalizability and survival. RESULTS: A total of 120 patients were assessed for eligibility at four centres, of whom 32 (26·7 per cent) were randomized, 16 in each group. Seven patients withdrew. Participants allocated to simvastatin had lower low-density lipoprotein cholesterol levels by 3 months (adjusted mean difference -0·83 (95 per cent c.i. -1·4 to -0·22) mmol/l; P = 0·009). Median adherence to medication was greater than 90 per cent between 3 and 12 months' follow-up. Adverse events were similar between the groups. Quality-of-life data were complete for 98·3 per cent of questionnaire items. Cardiovascular disease, diabetes and aspirin use were more prevalent in the non-randomized group, whereas tumour site, stage and grade were similar between groups. Survival estimates were imprecise. CONCLUSION: This RCT supports the conduct and informs the design considerations for a future phase III trial of adjuvant statin therapy in patients with OAC. Registration number: ISRCTN98060456 (www.isrctn/com).

ANTECEDENTES: Las estatinas inhiben las señalizaciones proliferativas en el adenocarcinoma de esófago (oesophageal adenocarcinoma, OAC) y su uso se asocia con mejor supervivencia en estudios observacionales. El presente estudio se llevó a cabo para examinar la viabilidad de evaluar el tratamiento adyuvante con estatinas en pacientes con OAC operable en un ensayo aleatorizado y controlado de fase III. MÉTODOS: En este ensayo de viabilidad controlado por placebo, aleatorizado, de grupos paralelos, doble ciego y multicéntrico, los pacientes adultos con OAC (incluyendo lesiones Siewert I/II) que fueron sometidos a esofaguectomía se asignaron de forma centralizada (1:1) a tratamiento con simvastatina 40 mg o placebo equivalente mediante aleatorización en bloques, estratificados por centro. Los participantes, los clínicos y los investigadores desconocían la asignación del tratamiento. Los pacientes recibieron el tratamiento hasta un año. Los resultados de viabilidad fueron reclutamiento, retención, absorción del fármaco, adherencia, seguridad, calidad de vida, generalización, y supervivencia. RESULTADOS: Un total de 120 pacientes fueron evaluados para elegibilidad en 4 centros, de los cuales 32 (26,7%) fueron aleatorizados, 16 en cada grupo. Siete pacientes abandonaron el ensayo. Los pacientes asignados a tratamiento con simvastatina tenían niveles de colesterol LDL más bajos a los 3 meses (diferencia media ajustada, −0,83 mmol/L, i.c. del 95% −1,4 a −0,22, P = 0,009). La mediana de la adherencia a la medicación fue mayor del 90% entre los 3-12 meses de seguimiento. Los eventos adversos fueron similares entre los grupos. Los datos de calidad de vida estaban completos en el 98,3% de las preguntas del cuestionario. Enfermedad cardiovascular, diabetes y uso de aspirina eran más prevalentes en el grupo no aleatorizado, mientras que la localización del tumor, el estadio y el grado fueron similares entre los grupos. Las estimaciones de supervivencia fueron imprecisas. CONCLUSIÓN: Este RCT apoya la realización e informa de las consideraciones de diseño para un futuro ensayo de fase III de tratamiento adyuvante con estatinas en pacientes con OAC.

Homocysteine and peripheral arterial disease: systematic review and meta-analysis.

OBJECTIVE: To evaluate homocysteine (Hcy) levels in patients with peripheral arterial disease (PAD) as compared to unaffected controls, and to review the clinical effects of therapy aimed at lowering homocysteine in PAD patients. METHODS: MEDLINE, EMBASE and Cochrane databases were searched from 1950 to December 2007. We selected observational studies and trials that evaluated Hcy levels in patients with PAD compared to unaffected controls. We also included trials on the effect of Hcy-lowering therapy (folate supplementation) in PAD patients. Continuous outcomes were pooled in a random effects meta-analysis of the weighted mean difference between comparator groups. RESULTS: We retrieved 33 potentially suitable articles from our search. Meta-analysis of 14 relevant studies showed that Hcy was significantly elevated (pooled mean difference +4.31micromoll; 95% C.I. 1.71, 6.31, p<0.0001 with significant heterogeneity) in patients with PAD compared to controls. As all 14 studies consistently demonstrated raised plasma Hcy levels in PAD patients, the significant heterogeneity in this meta-analysis probably arises from differences in the degree of Hcy elevation. The effect of folate supplementation on PAD was tested in eight clinical trials but clinically important end points were inconsistently reported. CONCLUSION: Patients with PAD have significantly higher Hcy levels than unaffected controls. However, we did not find any robust evidence on clinically beneficial effects of folate supplementation in PAD.

Detection of asymptomatic drug-induced hypoglycemia using continuous glucose monitoring in older people - Systematic review.

AIM: We conducted a systematic review of the use of continuous glucose monitoring (CGM) in older patients, in order to consolidate the growing evidence base in this area. METHODS: Our protocol was registered on PROSPERO (CRD42017068523). We searched SCI Web of Science, Ovid SP MEDLINE and EMBASE from January 2010 to June 2017 for observational studies and randomized controlled trial of CGM in older patients (mean age 65 or older) with diabetes. We excluded studies that involved only hospitalized patients. Two reviewers independently extracted data blood sugar values (in particular, hypoglycemic episodes) captured with the use of CGM. We also assessed adverse events and acceptability of CGM. RESULTS: After screening 901 abstracts, we included nine studies with a total of 989 older patients with diabetes. The CGM studies reveal that hypoglycemic episodes were occurring in a sizeable proportion (28-65%) of participants. Most (80-100%) of these episodes were asymptomatic, with some patients spending nearly 2 h per day in the hypoglycemic range. Older people with diabetes found CGM acceptable and experienced improved health-related well-being. CONCLUSION: CGM frequently picks up asymptomatic hypoglycemic episodes in older patients with diabetes. Users of CGM report improved well-being, and reduction of diabetes-related stress.

Incomplete evidence: the inadequacy of databases in tracing published adverse drug reactions in clinical trials.

BACKGROUND: We would expect information on adverse drug reactions in randomised clinical trials to be easily retrievable from specific searches of electronic databases. However, complete retrieval of such information may not be straightforward, for two reasons. First, not all clinical drug trials provide data on the frequency of adverse effects. Secondly, not all electronic records of trials include terms in the abstract or indexing fields that enable us to select those with adverse effects data. We have determined how often automated search methods, using indexing terms and/or textwords in the title or abstract, would fail to retrieve trials with adverse effects data. METHODS: We used a sample set of 107 trials known to report frequencies of adverse drug effects, and measured the proportion that (i) were not assigned the appropriate adverse effects indexing terms in the electronic databases, and (ii) did not contain identifiable adverse effects textwords in the title or abstract. RESULTS: Of the 81 trials with records on both MEDLINE and EMBASE, 25 were not indexed for adverse effects in either database. Twenty-six trials were indexed in one database but not the other. Only 66 of the 107 trials reporting adverse effects data mentioned this in the abstract or title of the paper. Simultaneous use of textword and indexing terms retrieved only 82/107 (77%) papers. CONCLUSIONS: Specific search strategies based on adverse effects textwords and indexing terms will fail to identify nearly a quarter of trials that report on the rate of drug adverse effects.

Single dose piroxicam for acute postoperative pain.

BACKGROUND: Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties, and is used mainly for treating rheumatic disorders. Some drugs have been directly compared against each other within a trial setting to determine their relative efficacies, whereas other have not. It is possible, however, to compare analgesics indirectly by examining the effectiveness of each drug against placebo when used in similar clinical situations. OBJECTIVES: To determine the analgesic efficacy and adverse effects of single-dose piroxicam compared with placebo in moderate to severe postoperative pain. To compare the effects of piroxicam with other analgesics. SEARCH STRATEGY: Published reports were identified from systematic searching of Medline, Biological Abstracts, Embase, The Cochrane Library and the Oxford Pain Relief Database. Additional studies were identified from the reference lists of retrieved reports. SELECTION CRITERIA: The following inclusion criteria were used: full journal publication, randomised placebo controlled trial, double-blind design, adult patients, postoperative pain of moderate to severe intensity at the baseline assessment, postoperative administration of oral or intramuscular piroxicam. DATA COLLECTION AND ANALYSIS: Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients obtaining at least 50% pain relief. This was used to calculate estimates of relative benefit and number-needed-to-treat for one patient to obtain at least 50% pain relief. Information was collected on adverse effects and estimates of relative risk and number-needed-to-harm were calculated. MAIN RESULTS: Three trials (141 patients) compared oral piroxicam 20 mg with placebo and one (15 patients) compared oral piroxicam 40 mg with placebo. For single doses of piroxicam 20 mg and 40 mg the respective numbers-needed-to-treat for at least 50% pain relief were 2.7 (2.1 to 3.8) [95% confidence interval] and 1.9 (1.2 to 4.3) [95% confidence interval] compared with placebo over 4-6 hours in moderate to severe postoperative pain. The reported incidence of adverse effects was no higher with piroxicam (20 mg or 40 mg) than with placebo. REVIEWER'S CONCLUSIONS: Piroxicam appears to be of similar efficacy to other non-steroidal anti-inflammatory drugs (NSAIDs) and intramuscular morphine 10 mg when used as a single oral dose in the treatment of moderate to severe postoperative pain.