The usefulness of confusion, urea, respiratory rate, and shock index or adjusted shock index criteria in predicting combined mortality and/or ICU admission compared to CURB-65 in community-acquired pneumonia

Peer reviewedPublisher PD

Determinants of Length of Stay Following Total Anterior Circulatory Stroke

Identification of factors that determine length of stay (LOS) in total anterior circulatory stroke (TACS) has potential for targeted intervention to reduce the associated health care burden. This study aimed to determine which factors predict LOS following either ischaemic or haemorrhagic TACS. The study sample population was drawn from the Norfolk and Norwich Stroke and Transient Ischemic Attack (TIA) Register (1996 – 2012), a prospective registry. 2965 patients admitted with TACS verified by a stroke specialist team were included. Primary analysis identified predictors of length of stay (LOS) in either haemorrhagic or ischaemic TACS. Secondary analyses identified predictors of LOS in patients who were discharged alive or who died during admission separately. Moderate (p=0.014) to severe disability (p=0.015) and history of congestive heart failure (p=0.027) in the primary analysis and pre-stroke residence in a care facility among patients who survived to discharge (p=0.013) were associated with a shorter length of stay. Factors associated with increased length of stay included presence of neurological lateralisation in the primary analysis (p=0.004) and amongst patients who died (p=0.003 and p=0.014 for ischaemic and haemorrhagic stroke, respectively). Patients with advanced age (≥85 years) with haemorrhagic stroke had longer LOS regardless of mortality outcome. Patients with low pre-morbid disability (modified Rankin score ≤2 who died following haemorrhagic TACS also had longer LOS. Our study found predictors of LOS following TACS include neurological lateralisation, pre-stroke disability status, congestive heart failure, pre-morbid residence and age. The identification of such factors would assist in resource allocation and discharge planning

Efficacy of implantable haemodynamic monitoring in heart failure across ranges of ejection fraction: a systematic review and meta-analysis

Aims: We conducted a meta-analysis of randomised controlled trials (RCTs) of implantable haemodynamic monitoring (IHM)-guided care. Methods: PubMed and Ovid MEDLINE were searched for RCTs of IHM in patients with heart failure (HF). Outcomes were examined in total (first and recurrent) event analyses. Results: Five trials comparing IHM-guided care with standard care alone were identified and included 2710 patients across ejection fraction (EF) ranges. Data were available for 628 patients (23.2%) with heart failure with preserved ejection fraction (HFpEF) (EF ≥50%) and 2023 patients (74.6%) with heart failure with a reduced ejection fraction (HFrEF) (EF <50%). Chronicle, CardioMEMS and HeartPOD IHMs were used. In all patients, regardless of EF, IHM-guided care reduced total HF hospitalisations (HR 0.74, 95% CI 0.66 to 0.82) and total worsening HF events (HR 0.74, 95% CI 0.66 to 0.84). In patients with HFrEF, IHM-guided care reduced total worsening HF events (HR 0.75, 95% CI 0.66 to 0.86). The effect of IHM-guided care on total worsening HF events in patients with HFpEF was uncertain (fixed-effect model: HR 0.72, 95% CI 0.59 to 0.88; random-effects model: HR 0.60, 95% CI 0.32 to 1.14). IHM-guided care did not reduce mortality (HR 0.92, 95% CI 0.71 to 1.20). IHM-guided care reduced all-cause mortality and total worsening HF events (HR 0.80, 95% CI 0.72 to 0.88). Conclusions: In patients with HF across all EFs, IHM-guided care reduced total HF hospitalisations and worsening HF events. This benefit was consistent in patients with HFrEF but not consistent in HFpEF. Further trials with pre-specified analyses of patients with an EF of ≥50% are required. PROSPERO registration number: CRD42021253905

Association analysis of a highly polymorphic CAG Repeat in the human potassium channel gene KCNN3 and migraine susceptibility

BACKGROUND: Migraine is a polygenic multifactorial disease, possessing environmental and genetic causative factors with multiple involved genes. Mutations in various ion channel genes are responsible for a number of neurological disorders. KCNN3 is a neuronal small conductance calcium-activated potassium channel gene that contains two polyglutamine tracts, encoded by polymorphic CAG repeats in the gene. This gene plays a critical role in determining the firing pattern of neurons and acts to regulate intracellular calcium channels. METHODS: The present association study tested whether length variations in the second (more 3') polymorphic CAG repeat in exon 1 of the KCNN3 gene, are involved in susceptibility to migraine with and without aura (MA and MO). In total 423 DNA samples from unrelated individuals, of which 202 consisted of migraine patients and 221 non-migraine controls, were genotyped and analysed using a fluorescence labelled primer set on an ABI310 Genetic Analyzer. Allele frequencies were calculated from observed genotype counts for the KCNN3 polymorphism. Analysis was performed using standard contingency table analysis, incorporating the chi-squared test of independence and CLUMP analysis. RESULTS: Overall, there was no convincing evidence that KCNN3 CAG lengths differ between Caucasian migraineurs and controls, with no significant difference in the allelic length distribution of CAG repeats between the population groups (P = 0.090). Also the MA and MO subtypes did not differ significantly between control allelic distributions (P > 0.05). The prevalence of the long CAG repeat (>19 repeats) did not reach statistical significance in migraineurs (P = 0.15), nor was there a significant difference between the MA and MO subgroups observed compared to controls (P = 0.46 and P = 0.09, respectively), or between MA vs MO (P = 0.40). CONCLUSION: This association study provides no evidence that length variations of the second polyglutamine array in the N-terminus of the KCNN3 channel exert an effect in the pathogenesis of migraine

Prevalent and incident anemia in PARADIGM-HF and the effect of sacubitril/valsartan

Background: Anemia is common in patients with heart failure with reduced ejection fraction and is associated with poor clinical outcomes. Renin-angiotensin system blockers lower hemoglobin and may induce anemia. Objectives: The authors investigated whether concomitant neprilysin inhibition might ameliorate this effect of renin-angiotensin system blockers in PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure). Methods: Anemia was defined as hemoglobin <120 g/L in women and <130 g/L in men at screening. The authors investigated the effect of randomized treatment on clinical outcomes according to anemia status, change in hemoglobin from baseline, and the incidence of anemia. Results: Of 8,239 participants with a baseline hemoglobin measurement, 1,677 (20.4%) were anemic. Patients with anemia had a more severe heart failure profile, worse kidney function, greater neurohormonal derangement, and worse clinical outcomes. Sacubitril/valsartan, compared with enalapril, decreased the risk of cardiovascular death or heart failure hospitalization similarly in patients with (HR: 0.84; 95% CI: 0.71-1.00) and without anemia (HR: 0.78 [95% CI: 0.71-0.87]; P value for interaction = 0.478). Between baseline and 12 months, hemoglobin decreased by 1.5 g/L (95% CI: 1.2-1.7 g/L) with sacubitril/valsartan compared with 2.3 g/L (95% CI: 2.0-2.6 g/L) with enalapril: mean difference 0.8 g/L (95% CI: 0.5-1.2 g/L; P < 0.001). Patients assigned to sacubitril/valsartan were less likely to develop anemia at 12 months (321 of 2,806 [11.4%]) compared with patients randomized to enalapril (440 of 2,824 [15.6%]) (odds ratio [OR]: 0.70 [95% CI: 0.60-0.81]; P < 0.001). These findings were similar in PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) (sacubitril/valsartan vs valsartan). There was biomarker evidence of increased iron utilization with sacubitril/valsartan. Conclusions: Irrespective of anemia status, sacubitril/valsartan compared with enalapril, decreased mortality and hospitalization. Hemoglobin decreased less with sacubitril/valsartan and the incidence of new anemia was lower with sacubitril/valsartan. (This study will evaluate the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure [PARADIGM-HF] trial; NCT01035255)

Effect of sacubitril/valsartan on investigator-reported ventricular arrhythmias in PARADIGM-HF

Background: Sudden death is a leading cause of mortality in HFrEF. In PARADIGM-HF, sacubitril/valsartan reduced the incidence of sudden death. The purpose of this post hoc study was to analyze the effect of sacubitril/valsartan, compared to enalapril, on the incidence of ventricular arrhythmias. Methods: Adverse event reports related to ventricular arrhythmias were examined in PARADIGM-HF. The effect of randomized treatment on two arrhythmia outcomes was analyzed: ventricular arrhythmias and the composite of a ventricular arrhythmia, ICD shock or resuscitated cardiac arrest. The risk of death related to a ventricular arrhythmia was examined in time-updated models. The interaction between heart failure aetiology, or baseline ICD/CRT-D use, and the effect of sacubitril/valsartan was analyzed. Results: Of the 8399 participants, 333 (4.0%) reported a ventricular arrhythmia and 372 (4.4%) the composite arrhythmia outcome. Ventricular arrhythmias were associated with higher mortality. Compared with enalapril, sacubitril/valsartan reduced the risk of a ventricular arrhythmia [HR 0.76 (0.62–0.95); p = 0.015] and the composite arrhythmia outcome [HR 0.79 (0.65–0.97); p = 0.025]. The treatment effect was maintained after adjustment and accounting for the competing risk of death. Baseline ICD/CRT-D use did not modify effect of sacubitril/valsartan, but aetiology did: HR in patients with an ischaemic aetiology 0.93 (0.71–1.21) versus 0.53 (0.37–0.78) in those without an ischaemic aetiology (p for interaction = 0.020). Conclusions: Sacubitril/valsartan reduced the incidence of investigator-reported ventricular arrhythmias in patients with HFrEF. This effect may have been greater in patients with a non-ischaemic aetiology

Effect of dapagliflozin on anaemia in DAPA-HF

Background: Anaemia is common in heart failure and associated with worse outcomes. We examined the effect of dapagliflozin on correction of anaemia in patients with heart failure and reduced ejection fraction (HFrEF) in DAPA‐HF. We also analyzed the effect of dapagliflozin on outcomes, according to anaemia status at baseline. Methods: Anaemia was defined at baseline as a haematocrit <39% in men and <36% in women. Resolution of anaemia was defined as two consecutive haematocrit measurements above these thresholds at any time during follow‐up. The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death.. Findings: Of the 4744 patients randomized in DAPA‐HF, 4691 had a haematocrit available at baseline, of which 1032 were anaemic (22.0%). The rate of the primary outcome was higher in patients with anaemia (16.1 per 100 person‐years) compared with those without (12.9 per 100 person‐years). Anaemia was corrected in 62.2% of patients in the dapagliflozin group, compared with 41.1% of patients in the placebo group. The effect of dapagliflozin on the primary outcome was consistent in anaemic compared with non‐anaemic patients (HR 0.68 [95%CI 0.52‐0.88] versus 0.76 [0.65‐0.89]; P‐interaction=0.44). Similar findings were observed for cardiovascular death, HF hospitalization, and all‐cause mortality. Patients with resolution of anaemia had better outcomes than those in which anaemia persisted. Conclusion: Patients with anaemia had worse outcomes in DAPA‐HF. Dapagliflozin corrected anaemia more often than placebo and improved outcomes, irrespective of anaemia status at baseline