RESUMEN
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.
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Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Adulto , Bancos de Muestras Biológicas , Diabetes Mellitus/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Hemoglobina Glucada/análisis , Humanos , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Idiopathic pulmonary fibrosis is a progressive disease and antifibrotic therapies do not reverse existing fibrosis. There has been emerging evidence of potential role for statins in idiopathic pulmonary fibrosis. The aim of this review is to synthesise the evidence on the efficacy of statins in idiopathic pulmonary fibrosis, focusing on associations with all-cause mortality, disease-specific mortality and change in pulmonary function. METHODS: Medline and Embase were reviewed to identify relevant publications. Studies were selected if they examined disease-related outcomes including mortality, pulmonary function and adverse events in people with idiopathic pulmonary fibrosis receiving statin therapy. RESULTS: Five studies with a total of 3407 people with IPF were selected and analysed. The overall risk of bias of five included studies was moderate to serious. In the fixed effect meta-analysis, statin use was associated with a reduction in mortality (RR 0.8; 95% CI 0.72-0.99). However, in the random effects model, there was no longer any significant association between statin use and all-cause mortality (RR 0.87; 95% CI 0.68-1.12). There was no statistically significant association between statin use and decline in FVC % predicted. CONCLUSION: There is currently insufficient evidence to conclude the effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis. Considering the limitations of available literature, we would recommend a prospective cohort study with capture of dosage and preparation of statin, statin adherence and use of concurrent antifibrotic treatment. PROSPERO REGISTRATION NUMBER: CRD42019122745.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Fibrosis Pulmonar Idiopática , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Estudios ProspectivosRESUMEN
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.
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Adenocarcinoma/tratamiento farmacológico , LDL-Colesterol/efectos de los fármacos , Neoplasias Esofágicas/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Simvastatina/administración & dosificación , Adenocarcinoma/mortalidad , Anciano , Quimioterapia Adyuvante , LDL-Colesterol/sangre , Terapia Combinada , Método Doble Ciego , Neoplasias Esofágicas/mortalidad , Esofagectomía , Estudios de Factibilidad , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Masculino , Cumplimiento de la Medicación/estadística & datos numéricos , Persona de Mediana Edad , Calidad de Vida , Simvastatina/efectos adversos , Resultado del Tratamiento , Reino UnidoRESUMEN
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 2â¯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.
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Glucemia/análisis , Diabetes Mellitus/sangre , Hipoglucemia/inducido químicamente , Hipoglucemia/diagnóstico , Hipoglucemiantes/efectos adversos , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedades Asintomáticas , Automonitorización de la Glucosa Sanguínea/instrumentación , Automonitorización de la Glucosa Sanguínea/métodos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Humanos , Hipoglucemia/sangre , Hipoglucemiantes/uso terapéutico , Estudios Observacionales como Asunto/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricosRESUMEN
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.
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Dulces , Chocolate , Conducta Alimentaria , Insuficiencia Cardíaca/epidemiología , Anciano , Dulces/efectos adversos , Chocolate/efectos adversos , Inglaterra/epidemiología , Femenino , Voluntarios Sanos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/prevención & control , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
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.
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Envejecimiento , Trastornos del Conocimiento/etiología , Costo de Enfermedad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Medicina Basada en la Evidencia , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Anciano , Anciano de 80 o más Años , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/prevención & control , Envejecimiento Cognitivo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/psicología , Monitoreo de Drogas , Humanos , Hiperglucemia/prevención & control , Hipoglucemia/epidemiología , Hipoglucemia/fisiopatología , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Estudios Observacionales como Asunto , Reproducibilidad de los Resultados , Factores de RiesgoRESUMEN
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.
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Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidad , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Anciano de 80 o más Años , Área Bajo la Curva , Femenino , Humanos , Masculino , Modelos Teóricos , Mortalidad/tendencias , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Curva ROC , Estudios RetrospectivosRESUMEN
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.
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Insuficiencia Cardíaca/etiología , Gripe Humana/complicaciones , Infarto del Miocardio/etiología , Accidente Cerebrovascular/etiología , Humanos , Estudios Observacionales como Asunto , Oportunidad Relativa , Factores de RiesgoRESUMEN
In vitro fertilization (IVF) and its subset intracytoplasmic sperm injection (ICSI), are widely used medical treatments for conception. There has been controversy over whether IVF is associated with adverse short- and long-term health outcomes of offspring. As with other prenatal factors, epigenetic change is thought to be a molecular mediator of any in utero programming effects. Most studies focused on DNA methylation at gene-specific and genomic level, with only a few on associations between DNA methylation and IVF. Using buccal epithelium from 208 twin pairs from the Peri/Postnatal Epigenetic Twin Study (PETS), we investigated associations between IVF and DNA methylation on a global level, using the proxies of Alu and LINE-1 interspersed repeats in addition to two locus-specific regulatory regions within IGF2/H19, controlling for 13 potentially confounding factors. Using multiple correction testing, we found strong evidence that IVF-conceived twins have lower DNA methylation in Alu, and weak evidence of lower methylation in one of the two IGF2/H19 regulatory regions and LINE-1, compared with naturally conceived twins. Weak evidence of a relationship between ICSI and DNA methylation within IGF2/H19 regulatory region was found, suggesting that one or more of the processes associated with IVF/ICSI may contribute to these methylation differences. Lower within- and between-pair DNA methylation variation was also found in IVF-conceived twins for LINE-1, Alu and one IGF2/H19 regulatory region. Although larger sample sizes are needed, our results provide additional insight to the possible influence of IVF and ICSI on DNA methylation. To our knowledge, this is the largest study to date investigating the association of IVF and DNA methylation.
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Metilación de ADN , Fertilización In Vitro/efectos adversos , Factor II del Crecimiento Similar a la Insulina/genética , ARN Largo no Codificante/genética , Gemelos , Adulto , Epigénesis Genética , Femenino , Humanos , Recién Nacido , Masculino , EmbarazoRESUMEN
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.
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Estenosis Carotídea/diagnóstico , Ataque Isquémico Transitorio/diagnóstico , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/diagnóstico , Factores de Edad , Anciano , Presión Sanguínea/fisiología , Estenosis Carotídea/fisiopatología , Femenino , Humanos , Ataque Isquémico Transitorio/fisiopatología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Literatura de Revisión como Asunto , Factores de Riesgo , Accidente Cerebrovascular/fisiopatologíaRESUMEN
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.
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Antiinflamatorios no Esteroideos/efectos adversos , Dexametasona/efectos adversos , Hemorragia Posoperatoria/inducido químicamente , Tonsilectomía/efectos adversos , Antiinflamatorios no Esteroideos/uso terapéutico , Niño , Dexametasona/uso terapéutico , Humanos , Hemorragia Posoperatoria/etiología , Náusea y Vómito Posoperatorios/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Medición de Riesgo/métodosRESUMEN
BACKGROUND: Most data on outcomes in Idiopathic Pulmonary Fibrosis (IPF) pre-dates current guidelines. Data on rates of infection is sparse; the effect of low-dose corticosteroids and disease severity is unknown. METHODS: We identified randomised-controlled trials of IPF and analysed rates of mortality, lower respiratory tract infections (LRTIs), IPF progression and acute exacerbations from the placebo arms. We standardised event rates and compared differences using incidence rate ratios (IRRs) between subgroups according to disease severity or use of low-dose immunosuppression. RESULTS: Mortality was lower in trials that recruited patients with mild-moderate disease severities only, as compared to trials where patients with severe disease were allowed (188.6 vs 78.6 deaths per 1000 patient/years, IRR 0.30-0.59, p < 0.0001). No statistical difference was seen between trials permitting and excluding low-dose prednisolone use. LRTIs were found to be commoner in trials allowing low dose prednisolone use compared with those that did not (227.1 vs 63.4 infections per 1000 patient/years. IRR 2.56-5.13, p < 0.0001), and were less frequent in trials excluding patients with severe disease (153.9 vs 257.8 infections per 1000 patient/years, IRR 0.45-0.81, p = 0.0003). Acute exacerbations occurred less frequently in trials excluding severe disease (28.2 vs 122.9 exacerbations per 1000 patient/years, IRR 0.11-0.55, p < 0.0001). There was no difference between groups in rates of IPF progression. CONCLUSION: Mortality is heterogeneous and dependent on entry criteria. Infection rates were high, both with and without immunosuppression, and were higher in severe disease. Consideration should be given to alternative outcomes to mortality in future IPF trials if severe disease is excluded.
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Fibrosis Pulmonar Idiopática/mortalidad , Inmunosupresores/efectos adversos , Anciano , Progresión de la Enfermedad , Humanos , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Infecciones del Sistema Respiratorio/inducido químicamente , Resultado del TratamientoRESUMEN
The benefits of specialist geriatric assessment in acute medical units are debated and it is unclear if there is a reduction in readmission rates for older patients with specialist geriatric care compared to general acute medical care. We examined readmission rates for 2414 older patients who had been discharged from the acute medical unit at the Norfolk and Norwich University Hospital, either by acute medicine or older people's medicine (OPM), both of which teams were consultant-led. We found no significant difference in readmission rates between patients discharged by the acute medical team as compared to the OPM team. This finding was robust to a variety of sensitivity analyses, including different lengths of stay, or readmissions at different time intervals. Hence, acute medical teams may be able to achieve similar levels of quality care for older patients to specialist geriatric teams.
RESUMEN
To conduct a meta-analysis of published data of the effectiveness of drug treatment in giant cell arteritis (GCA) to provide evidence to support the optimal use of glucocorticoids (GCs) and adjunct therapy. MEDLINE, CENTRAL and EMBASE searches were used to identify randomised control trials on the treatment of GCA. Studies included were trials in which: (1) the participants were classified as having GCA by the 1990 ACR criteria or biopsy proven disease; (2) parallel-group randomised control of at least 16 weeks duration had been conducted with at least 20 participants; (3) the design included either alternative adjunct immunosuppressant regimens, alternative GCs dosing or routes of administration; and (4) outcome data was included on either relapse rates or rates of infection. One thousand eight hundred thirty-six articles were retrieved, of which only 37 met the primary inclusion criteria. Sixteen of these studies reported some information about the GCs or adjuvant regimen used. Only ten studies were of sufficient quality to be included in the meta-analysis. Together these comprised 638 participants of which 72 % were female. Three studies compared various GCs regimens, with two comparing IV GCs, the latter showing a marginal benefit with respect to relapse (risk ratio (RR) = 0.78, 95 % CI = 0.54 to 1.12) but a greater risk of infection (RR = 1.58, 95 % CI = 0.90 to 2.78). Another three used methotrexate as an adjunctive agent and showed marginal benefit with respect to relapse (RR = 0.85, 95 % CI = 0.66 to 1.11). The remaining four trials compared prednisolone to dapsone, infliximab, adalimumab and hydroxychloroquine, respectively. There are various clinical trials of varying quality. The results from this meta-analysis show that the use of adjunct agents is not associated with improved outcome.
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Arteritis de Células Gigantes/tratamiento farmacológico , Terapia de Inmunosupresión/métodos , Inmunosupresores/administración & dosificación , Prednisolona/administración & dosificación , Adalimumab , Antiinflamatorios/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Dapsona/administración & dosificación , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Infliximab , Masculino , Metotrexato/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Inducción de Remisión , Resultado del Tratamiento , Vasculitis/tratamiento farmacológicoRESUMEN
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.
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Inhibidores de 5-alfa-Reductasa/efectos adversos , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Azaesteroides/efectos adversos , Azaesteroides/uso terapéutico , Enfermedades Cardiovasculares/inducido químicamente , Método Doble Ciego , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Dutasterida , Humanos , Masculino , Enfermedades de la Próstata/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , RiesgoRESUMEN
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.
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Neumonía/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/etiología , Administración por Inhalación , Adulto , Anciano , Estudios de Cohortes , Infecciones Comunitarias Adquiridas/complicaciones , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/mortalidad , Femenino , Glucocorticoides/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Neumonía/tratamiento farmacológico , Neumonía/mortalidad , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Fármacos del Sistema Respiratorio/administración & dosificación , Factores de RiesgoRESUMEN
A method is introduced to measure friction on small, free standing objects, specifically microfabricated silicon plates, based on atomic force microscopy (AFM). An AFM tip is brought into contact with the plate resting on a substrate. The substrate is displaced laterally and, provided the AFM tip does not slide over the plate, the twisting of the AFM cantilever is used to measure the friction of the underlying plate-substrate interface. The method can measure nano-Newton to micro-Newton forces (both friction and applied load) and provides a means to measure friction of macroscopic structures at low load.
RESUMEN
OBJECTIVES: Despite many interventions that have been tried, controversy remains regarding the efficacy of interventions for contrast-induced nephropathy (CIN), so we aimed to evaluate the best evidence from recent meta-analyses. METHODS: We searched MEDLINE, EMBASE and the Cochrane library for interventions which have been used for CIN. We included only the most recent meta-analysis of each intervention. We extracted data on the methodology, quality and results of each meta-analysis. We performed narrative synthesis and adjusted indirect comparison of interventions that were shown to be statistically significant compared with a placebo. RESULTS: We included 7 systematic reviews and meta-analyses involving 9 different interventions for CIN, with a total of 15 976 participants. A significantly decreased risk of CIN was reported in meta-analysis of the following interventions: N-acetylcysteine [odds ratio (OR) 0.65, 95% confidence interval (CI) 0.48-0.88, I(2)=64%], theophylline [relative risk (RR) 0.48, 95% CI 0.26-0.89, I(2)=44%], statins (RR 0.51, 95% CI 0.34-0.77, I(2)=0%) and sodium bicarbonate (RR 0.62, 95% CI 0.45-0.86, I(2)=49%). Furosemide was shown to increase the risk of CIN (RR 3.27, 95% CI 1.48-7.26, I(2)=0%). Other interventions such as renal replacement therapy, angiotensin-converting enzyme inhibitors, dopamine and fenoldapam failed to show any significant difference from the control group. CONCLUSION: Although there is some evidence to suggest that N-acetylcysteine, theophylline, sodium bicarbonate and statins may reduce incidence of CIN, limitations in the study quality and heterogeneity preclude any firm recommendations. ADVANCES IN KNOWLEDGE: N-acetylcysteine, theophylline, sodium bicarbonate and statins show some promise as potentially efficacious agents for preventing CIN, but more high-quality studies are needed before they can be recommended for use in routine practice.
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Acetilcisteína/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/epidemiología , Bicarbonato de Sodio/uso terapéutico , Teofilina/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Prevalencia , Medición de Riesgo , Resultado del TratamientoRESUMEN
Reasons for the rising annual incidence of esophageal adenocarcinoma (EAC) remain uncertain. Previous studies have given conflicting results, but some have suggested that drugs which relax the lower esophageal sphincter (LES) may increase the risk of EAC. This study is to determine systematically the risk of EAC associated with individual medications which relax the LES and compare risks with esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA). Relevant published studies were identified by systematic searching PubMed for case-control studies reporting on risk of EAC, ESCC or GCA with use of medications known to reduce LES pressure. Pooled odds ratios (ORs) were calculated for each malignancy. Data were analyzed from four case-control studies involving 9,412 participants. EAC was significantly associated with theophylline use (OR 1.55, 95% confidence interval [CI] 1.05-2.28; P= 0.03, I(2) = 0%) and anticholinergic medications (OR 1.66, 95% CI 1.13-2.44; P= 0.01, I(2) = 84%). This effect was not observed in cases of ESCC or GCA. Other drug groups including calcium channel modulators and nitrates did not increase the risk of EAC. An inverse relationship was observed between ESCC and nitrates and between GCA and benzodiazepines. The lack of increased EAC risk with many commonly used medications is reassuring. However, a significant correlation was found between EAC and the use of anticholinergics and theophyllines. This may reflect common causality between obstructive lung disease and EAC, and further studies to explore these relationships are warranted.