Citations

Objective Implantable cardioverter defibrillators (ICD), cardiac resynchronisation therapy pacemakers (CRT-P) and the combination therapy (CRT-D) have been shown to reduce all-cause mortality compared with medical therapy alone in patients with heart failure and reduced EF. Our aim was to synthesise data from major randomised controlled trials to estimate the comparative mortality effects of these devices and how these vary according to patients’ characteristics. Methods Data from 13 randomised trials (12 638 patients) were provided by medical technology companies. Individual patient data were synthesised using network meta-analysis. Results Unadjusted analyses found CRT-D to be the most effective treatment (reduction in rate of death vs medical therapy: 42% (95% credible interval: 32–50%), followed by ICD (29% (20–37%)) and CRT-P (28% (15–40%)). CRT-D reduced mortality compared with CRT-P (19% (1–33%)) and ICD (18% (7–28%)). QRS duration, left bundle branch block (LBBB) morphology, age and gender were included as predictors of benefit in the final adjusted model. In this model, CRT-D reduced mortality in all subgroups (range: 53% (34–66%) to 28% (−1% to 49%)). Patients with QRS duration ≥150 ms, LBBB morphology and female gender benefited more from CRT-P and CRT-D. Men and those <60 years benefited more from ICD. Conclusions These data provide estimates for the mortality benefits of device therapy conditional upon multiple patient characteristics. They can be used to estimate an individual patient's expected relative benefit and thus inform shared decision making. Clinical guidelines should discuss age and gender as predictors of device benefits.

Older adults are more susceptible to muscle loss during bed rest, but exercise effectively reverses these detrimental effects.

Abstract Background Previous studies comparing early laparoscopic cholecystectomy (ELC) with delayed laparoscopic cholecystectomy (DLC) for acute cholecystitis were incomplete. A meta-analysis was undertaken to compare the cost-effectiveness, quality of life, safety and effectiveness of ELC versus DLC. Methods PubMed, Embase, the Cochrane Library and Web of Science were searched for randomized clinical trials (RCTs) that compared ELC (performed within 7 days of symptom onset) with DLC (undertaken at least 1 week after symptoms had subsided) for acute cholecystitis. Results Sixteen studies reporting on 15 RCTs comprising 1625 patients were included. Compared with DLC, ELC was associated with lower hospital costs, fewer work days lost (mean difference (MD) –11·07 (95 per cent c.i. –16·21 to −5·94) days; P &lt; 0·001), higher patient satisfaction and quality of life, lower risk of wound infection (relative risk 0·65, 95 per cent c.i. 0·47 to 0·91; P = 0·01) and shorter hospital stay (MD −3·38 (−4·23 to −2·52) days; P &lt; 0·001), but a longer duration of operation (MD 11·12 (4·57 to 17·67) min; P &lt; 0·001). There were no significant differences between the two groups in mortality, bile duct injury, bile leakage, conversion to open cholecystectomy or overall complications. Conclusion For patients with acute cholecystitis, ELC appears as safe and effective as DLC. ELC might be associated with lower hospital costs, fewer work days lost, and greater patient satisfaction.

Abstract To establish a useful laboratory protocol to investigate possible cases of fatal anaphylaxis, we measured mast-cell-derived tryptase levels and allergen-specific immunoglobulin E (IgE) antibody levels in sera obtained prior to or within 24 h after death from 19 anaphylaxis victims. Elevated serum tryptase levels (range = 12 ng/mL to 150 μg/mL) were found in nine of nine Hymenoptera sting fatalities, six of eight food-induced fatalities, and two of two reactions to diagnostic/therapeutic agents. Tryptase levels were normal (&lt;10 ng/mL) in 57 sequential sera obtained postmortem from six control patients. Tryptase could not be measured by pleural or pericardial fluids for technical reasons. Serum IgE antibodies were elevated in five of the nine Hymenoptera sting fatalities and in eight of the eight fatal food reactions; assays were unavailable for the two diagnostic/therapeutic agents. If elevated, the victim's serum IgE antibodies to food could be used to identify allergens in uneaten portions of foods consumed shortly before the anaphylactic event. IgE antibodies were moderately stable during storage in a variety of anticoagulants at room temperature for up to 11 weeks. Elevated mast-cell-derived tryptase levels in postmortem sera reflect antemortem mast cell activation and may be used as a marker for fatal anaphylaxis. If assays are available for IgE antibodies to relevant allergens, such assays provide evidence for antemortem sensitization; these assays may be modified to identify allergens in foods consumed by victims of food-induced anaphylaxis.

Abstract The authors describe three cases (two blacks and one Latin American) of sudden death caused by late complications of Kawasaki disease (mucocutaneous lymph node syndrome). At autopsy each heart contained multiple coronary artery aneurysms with luminal stenosis caused by intimal hyperplasia and thrombi. Although virtually all fatal cases of Kawasaki disease occur within six months of the onset of symptoms, there have been other reported deaths up to 14 years after the acute illness. The coronary artery aneurysms of Kawasaki disease may persist and cause death years after the acute illness.

SummaryBackgroundTemporary faecal diversion is sometimes used for management of refractory perianal Crohn's disease (CD) with variable success.AimsTo perform a systematic review with meta‐analysis to evaluate the effectiveness, long‐term outcomes and factors associated with success of temporary faecal diversion for perianal CD.MethodsThrough a systematic literature review through 15 July 2015, we identified 16 cohort studies (556 patients) reporting outcomes after temporary faecal diversion. We estimated pooled rates [with 95% confidence interval (CI)] of early clinical response, attempted and successful restoration of bowel continuity after temporary faecal diversion (without symptomatic relapse), and rates of re‐diversion (in patients with attempted restoration) and proctectomy (with or without colectomy and end‐ileostomy). We identified factors associated with successful restoration of bowel continuity.ResultsOn meta‐analysis, 63.8% (95% CI: 54.1–72.5) of patients had early clinical response after faecal diversion for refractory perianal CD. Restoration of bowel continuity was attempted in 34.5% (95% CI: 27.0–42.8) of patients, and was successful in only 16.6% (95% CI: 11.8–22.9). Of those in whom restoration was attempted, 26.5% (95% CI: 14.1–44.2) required re‐diversion because of severe relapse. Overall, 41.6% (95% CI: 32.6–51.2) of patients required proctectomy after failure of temporary faecal diversion. There was no difference in the successful restoration of bowel continuity after temporary faecal diversion in the pre‐biological or biological era (13.7% vs. 17.6%, P = 0.60), in part due to selection bias. Absence of rectal involvement was the most consistent factor associated with restoration of bowel continuity.ConclusionsTemporary faecal diversion may improve symptoms in approximately two‐thirds of patients with refractory perianal Crohn's disease, but bowel restoration is successful in only 17% of patients.

AbstractIntroductionRapid eye movement (REM) sleep behavior disorder (RBD) in Parkinson's disease (PD) is associated with differences in clinical phenotype, including dementia, autonomic loss, and gait dysfunction. The pathological basis for this remains unclear.MethodsParkinson's disease subjects in a longitudinal clinicopathologic study were screened for probable RBD with the Mayo Sleep Questionnaire. After death, semiquantitative analyses were conducted for synuclein, amyloid, neurofibrillary tangles, and cerebrovascular lesions.ResultsForty cases had probable RBD (PD+RBD), and 41 did not (PD‐RBD). Despite similar age at death (∼80 y) and disease duration (∼14.5 y), PD+RBD had increased synuclein deposition in all regions examined, with nine of 10 regions significantly different. The Lewy body 10‐region total score (scale = 0‐40) was 29.5 in PD+RBD versus 24.5 in PD‐RBD (Cohen‐d effect size = 0.79, P = 0.002). Cerebrovascular lesion burden was slightly higher in PD‐RBD.ConclusionsAlthough overlap occurs between groups, PD patients with probable RBD may have greater density and range of synuclein pathology on autopsy. © 2015 International Parkinson and Movement Disorder Society

Summary Background Treatment of IBS and functional lower gastrointestinal disorders is still based predominantly on symptoms; biomarkers that reflect the mechanism or pathophysiology have been identified. Given the diverse mechanisms that result in the same clinical phenotype of IBS , it is hypothesised that identification of biomarkers may lead to individualisation of medical therapy. Aim To review the biomarkers that have been appraised in IBS . Methods A single author reviewed the published literature on biomarkers appraised in IBS . Results The current literature suggests that these biomarkers are insufficiently sensitive or specific to differentiate IBS from health or from other diseases causing similar symptoms, such as coeliac disease or inflammatory bowel disease. Most of the proposed biomarkers are not actionable, that is, they do not lead to an efficacious therapy based on the biological inference of the biomarker itself. However, among proposed biomarkers in IBS , some are actionable, as they specifically reflect a quantitative difference in a mediator of dysfunction or result in a quantifiable disturbance of function that can be specifically treated. Such biomarkers may potentially identify relevant subgroups that respond to specific therapy. The most promising actionable biomarkers are measurement of colonic transit (leading to treatments that reverse the abnormal transit) and measurements of bile acid diarrhoea to identify responders to bile acid sequestrants. Conclusions Therefore, although biomarkers are not ready for prime time as diagnostic tests in IBS , some biomarkers could identify subgroups of patients with IBS for inclusion in clinical trials that target specific dysfunctions. Such an approach may enhance treatment efficacy, and may ultimately help reduce costs in drug development and in the management of patients in clinical practice.