25-hydroxyvitamin D is lower in deprived groups, but is not associated with carotid intima media thickness or plaques: results from pSoBid

Objective: The association of the circulating serum vitamin D metabolite 25-hydroxyvitamin D (25OHD) with atherosclerotic burden is unclear, with previous studies reporting disparate results. <p/>Method: Psychological, social and biological determinants of ill health (pSoBid) is a study of participants aged 35–64 years from Glasgow who live at extremes of the socioeconomic spectrum. Vitamin D deficiency was defined as 25OHD < 25nmol/L, as per convention. Cross-sectional associations between circulating 25OHD concentrations and a range of socioeconomic, lifestyle, and biochemistry factors, as well as carotid intima media thickness (cIMT) and plaque presence were assessed in 625 participants. <p/>Results: Geometric mean levels of circulating 25OHD were higher among the least deprived (45.6 nmol/L, 1-SD range 24.4–85.5) versus most deprived (34.2 nmol/L, 1-SD range 16.9–69.2; p < 0.0001). In the least deprived group 15% were “deficient” in circulating 25OHD versus 30.8% in the most deprived (χ2p < 0.0001). Log 25OHD was 27% lower among smokers (p < 0.0001), 20% higher among the physically active versus inactive (p = 0.01), 2% lower per 1 kg/m2 increase in body mass index (BMI) (p < 0.0001), and showed expected seasonal variation (χ2p < 0.0001). Log 25OHD was 13% lower in the most versus least deprived independent of the aforementioned lifestyle confounding factors (p = 0.03). One unit increase in log 25OHD was not associated with atherosclerotic burden in univariable models; cIMT (effect estimate 0.000 mm [95% CI −0.011, 0.012]); plaque presence (OR 0.88 [0.75, 1.03]), or in multivariable models. <p/>Conclusion: There is no strong association of 25OHD with cIMT or plaque presence, despite strong evidence 25OHD associates with lifestyle factors and socioeconomic deprivation

Proportion and characteristics of secondary progressive multiple sclerosis in five European registries using objective classifiers

Background: To assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing-remitting MS (RRMS) and SPMS and may identify situations where SPMS is under reported.Materials and methods: Data were obtained for 61,900 MS patients from MS registries in the Czech Republic, Denmark, Germany, Sweden, and the United Kingdom (UK), including date of birth, sex, SP conversion year, visits with an Expanded Disability Status Scale (EDSS) score, MS onset and diagnosis date, relapses, and disease-modifying treatment (DMT) use. We included RRMS or SPMS patients with at least one visit between January 2017 and December 2019 if ≥ 18 years of age. We applied three objective methods: A set of SPMS clinical trial inclusion criteria ("EXPAND criteria") modified for a real-world evidence setting, a modified version of the MSBase algorithm, and a decision tree-based algorithm recently published.Results: The clinically assigned proportion of SPMS varied from 8.7% (Czechia) to 34.3% (UK). Objective classifiers estimated the proportion of SPMS from 15.1% (Germany by the EXPAND criteria) to 58.0% (UK by the decision tree method). Due to different requirements of number of EDSS scores, classifiers varied in the proportion they were able to classify; from 18% (UK by the MSBase algorithm) to 100% (the decision tree algorithm for all registries). Objectively classified SPMS patients were older, converted to SPMS later, had higher EDSS at index date and higher EDSS at conversion. More objectively classified SPMS were on DMTs compared to the clinically assigned.Conclusion: SPMS appears to be systematically underdiagnosed in MS registries. Reclassified patients were more commonly on DMTs.</p

Factors associated with outcome and duration of therapy in outpatient parenteral antibiotic therapy (OPAT) patients with skin and soft-tissue infections

This study was designed to identify factors associated with adverse outcomes and increased duration of parenteral therapy in patients with skin and soft-tissue infections (SSTIs) managed with outpatient parenteral antibiotic therapy (OPAT). A retrospective cohort study interrogating variables recorded prospectively in an electronic OPAT patient database was performed. 'OPAT failure' was defined as hospitalisation following initiation of OPAT, or adverse event or progression of infection necessitating a change in antibiotic therapy. Variables associated with failure or increased duration of therapy were identified via univariate and multiple logistic regression analyses. In total, 963 first patient episodes of OPAT-treated SSTIs were observed; 84% were treated with daily ceftriaxone and 15% with teicoplanin (three daily loading doses then three times per week). Progression of infection was observed in 2.8% of cases, inpatient management was required in 6% and significant adverse events occurred in 7.1%. Overall OPAT success was 87.1%. Female sex, diabetes and treatment with teicoplanin were independently associated with OPAT failure. A significant reduction in duration of OPAT therapy was observed over time. A longer duration of intravenous therapy was associated with meticillin-resistant Staphylococcus aureus (MRSA), older age, vascular disease, a diagnosis of bursitis, and treatment with teicoplanin. Non-inpatient referrals, management via a nurse-led patient group direction, and treatment with ceftriaxone were associated with reduced duration of OPAT. For selected patients with SSTIs, OPAT was generally safe and effective, but specific patient groups were identified with more complex management pathways and poorer outcomes

Validation of magnetic resonance myocardial perfusion imaging with fractional flow reserve for the detection of significant coronary heart disease

Background— Magnetic resonance myocardial perfusion imaging (MRMPI) has a number of advantages over the other noninvasive tests used to detect reversible myocardial ischemia. The majority of previous studies have generally used quantitative coronary angiography as the gold standard to assess the accuracy of MRMPI; however, only an approximate relationship exists between stenosis severity and functional significance. Pressure wire–derived fractional flow reserve (FFR) values &#60;0.75 correlate closely with objective evidence of reversible ischemia. Accordingly, we have compared MRMPI with FFR. Methods and Results— One hundred three patients referred for investigation of suspected angina underwent MRMPI with a 1.5-T scanner. The stress agent was intravenous adenosine (140 µg · kg&lt;sup&gt;–1&lt;/sup&gt; · min&lt;sup&gt;–1&lt;/sup&gt;), and the first-pass bolus contained 0.1 mmol/kg gadolinium. In the following week, coronary angiography with pressure wire studies was performed. FFR was recorded in all patent major epicardial coronary arteries, with a value &#60;0.75 denoting significant stenosis. MRMPI scans, analyzed by 2 blinded observers, identified perfusion defects in 121 of 300 coronary artery segments (40%), of which 110 had an FFR &#60;0.75. We also found that 168 of 179 normally perfused segments had an FFR ≥0.75. The sensitivity and specificity of MRMPI for the detection of functionally significant coronary heart disease were 91% and 94%, respectively, with positive and negative predictive values of 91% and 94%. Conclusion— MRMPI can detect functionally significant coronary heart disease with excellent sensitivity, specificity, and positive and negative predictive values compared with FFR

Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: The RETAIN study

Aims To demonstrate non-inferiority of ranibizumab treat-and-extend (T&E) with/without laser to ranibizumab pro re nata (PRN) for best-corrected visual acuity (BCVA) in patients with diabetic macular oedema (DMO).Methods A 24-month single-masked study with patients randomised 1:1:1 to T&E+laser (n= 121), T&E (n= 128) or PRN (control; n= 123). All patients received monthly injections until BCVA stabilisation. The investigator decided on re-treatment in the PRN and treatment-interval adaptations in the T&E groups based on loss of BCVA stability due to DMO activity. Likewise, laser treatment was at investigator's discretion. Collectively, these features reflect a real-life scenario. Endpoints included mean average change in BCVA from baseline to months 1-12 (primary), mean BCVA change from baseline to months 12 and 24, treatment exposure and safety profile.Results Both T&E regimens were non-inferior to PRN based on mean average BCVA change from baseline to months 1-12 (T&E+laser: +5.9 and T&E: +6.1 vs PRN: +6.2 letters; both p= 2 months over 24 months. Safety profile was consistent with that described in the product information.Conclusions T&E is a feasible treatment option for patients with DMO, with a potential to reduce treatment burden. Slightly more injections were required versus PRN, likely due to the specifics of the T&E regimen applied here

Feasibility/eligibility of T-wave alternans testing in patients with heart failure: should we rethink our current modus operandi?: reply

We appreciate the interest of Dr Madias in our study regarding microvolt T-wave alternans testing. He addresses the important issue of eligibility for MTWA testing and identifies several recent studies where a large proportion of unselected patients have been ineligible for MTWA testing. However, Dr Madias suggests that implantable cardioverter-defibrillators (ICDs) may be recommended for certain patients including those ineligible for MTWA testing and proposes that MTWA testing may have a role in specific settings. There is no evidence to support any role for MTWA in the contemporary risk stratification of patients with heart failure. At present the use of MTWA testing can be justified for research purposes only. Patients should not be exposed to a test that has never been shown to be of any clinical value. An ICD should only be considered in patients fulfilling the evidence-based criteria laid out in guidelines

Microvolt T-wave alternans (MTWA) testing in 'real world' heart failure (HF): a study of prevalence and incremental prognostic value

Background Ventricular arrhythmias contribute to the high risk of death in heart failure (HF) and can be treated with an implantable cardioverter-defibrillator (ICD). Microvolt T-wave alternans (MTWA) testing examines beat-to-beat fluctuations in the morphology of the T-wave. Alternans is believed to reflect dynamic instability of repolarisation and to be linked, mechanistically, to ventricular arrhythmias. Observational studies in highly selected populations have suggested that MTWA testing may identify individuals likely to benefit from a primary prevention ICD. The aims of this study were to evaluate the applicability of MTWA testing in an unselected cohort of patients recently hospitalised with HF and determine the prevalence and incremental prognostic value of an abnormal test.&lt;p&gt;&lt;/p&gt; Methods Consecutive admissions with confirmed HF (typical clinical findings and BNP&gt;100 pg/ml) were recruited in three hospitals from 1 December 2006 to 12 January 2009. Survivors were invited to attend 1-month post-discharge for MTWA testing (HearTWave II, Cambridge Heart).&lt;p&gt;&lt;/p&gt; Results 648 of 1003 patients recruited returned for MTWA testing (58% males, mean age 70.8 years). 318 patients (49%) were ineligible for MTWA testing due to atrial fibrillation (AF), pacemaker-dependency or inability to exercise. Of the 330 patients who underwent MTWA treadmill testing, 100 (30%) were positive, 78 (24%) were negative and 152 (46%) were indeterminate. Failure to achieve the target heart rate due to chronotropic incompetence, secondary to β-blocker therapy or physical limitations, accounted for 75% of indeterminate tests. 131 deaths occurred during a mean follow-up of 18 months. 23% of ineligible patients died vs 17% of eligible patients. 12%, 20% and 19% of patients with a positive, negative and indeterminate test, respectively, died (p=0.24). MTWA results were analysed in the accepted way of non-negative (positive and indeterminate) and negative, but there was still no difference in mortality between the groups (p=0.39). MTWA showed no incremental prognostic value in a multivariable mortality model. The independent predictors of mortality were: lower body mass index (HR 0.96 [95% CI 0.93 to 0.99], p=0.01), New York Heart Association class III–IV (1.72 [95% CI 1.2 to 2.47], p=0.003), previous myocardial infarction (1.68 [95% CI 1.18 to 2.4], p=0.004), elevated B-type natriuretic peptide concentration (1.36 [95% CI 1.12 to 1.65], p=0.002) and elevated troponin (1.57 [95% CI 1.04 to 2.37], p=0.03).&lt;p&gt;&lt;/p&gt; Conclusion MTWA treadmill-testing was not widely applicable in typical patients with HF and failed to predict mortality risk. At present MTWA cannot be endorsed as a tool for improving risk stratification in HF.&lt;p&gt;&lt;/p&gt

Cognitive behaviour therapy for violent men with antisocial personality disorder in the community: an exploratory randomized controlled trial

&lt;b&gt;BACKGROUND&lt;/b&gt; Little information exists on treatment effectiveness in antisocial personality disorder (ASPD). We investigated the feasibility and effectiveness of carrying out a randomized controlled trial of cognitive behaviour therapy (CBT) in men with ASPD who were aggressive.&lt;p&gt;&lt;/p&gt; &lt;b&gt;METHOD&lt;/b&gt; This was an exploratory two-centre, randomized controlled trial in a community setting. Fifty-two adult men with a diagnosis of ASPD, with acts of aggression in the 6 months prior to the study, were randomized to either treatment as usual (TAU) plus CBT, or usual treatment alone. Change over 12 months of follow-up was assessed in the occurrence of any act of aggression and also in terms of alcohol misuse, mental state, beliefs and social functioning.&lt;p&gt;&lt;/p&gt; &lt;b&gt;RESULTS&lt;/b&gt; The follow-up rate was 79%. At 12 months, both groups reported a decrease in the occurrence of any acts of verbal or physical aggression. Trends in the data, in favour of CBT, were noted for problematic drinking, social functioning and beliefs about others.&lt;p&gt;&lt;/p&gt; &lt;b&gt;CONCLUSIONS&lt;/b&gt; CBT did not improve outcomes more than usual treatment for men with ASPD who are aggressive and living in the community in this exploratory study. However, the data suggest that a larger study is required to fully assess the effectiveness of CBT in reducing aggression, alcohol misuse and improving social functioning and view of others. It is feasible to carry out a rigorous randomized controlled trial in this group.&lt;p&gt;&lt;/p&gt