A Simplified Score to Quantify Comorbidity in COPD

Importance

Comorbidities are common in COPD, but quantifying their burden is difficult. Currently there is a COPD-specific comorbidity index to predict mortality and another to predict general quality of life. We sought to develop and validate a COPD-specific comorbidity score that reflects comorbidity burden on patient-centered outcomes.

Materials and Methods

Using the COPDGene study (GOLD II-IV COPD), we developed comorbidity scores to describe patient-centered outcomes employing three techniques: 1) simple count, 2) weighted score, and 3) weighted score based upon statistical selection procedure. We tested associations, area under the Curve (AUC) and calibration statistics to validate scores internally with outcomes of respiratory disease-specific quality of life (St. George''s Respiratory Questionnaire, SGRQ), six minute walk distance (6MWD), modified Medical Research Council (mMRC) dyspnea score and exacerbation risk, ultimately choosing one score for external validation in SPIROMICS.

Results

Associations between comorbidities and all outcomes were comparable across the three scores. All scores added predictive ability to models including age, gender, race, current smoking status, pack-years smoked and FEV₁ (p<0.001 for all comparisons). Area under the curve (AUC) was similar between all three scores across outcomes: SGRQ (range 0·7624–0·7676), MMRC (0·7590–0·7644), 6MWD (0·7531–0·7560) and exacerbation risk (0·6831–0·6919). Because of similar performance, the comorbidity count was used for external validation. In the SPIROMICS cohort, the comorbidity count performed well to predict SGRQ (AUC 0·7891), MMRC (AUC 0·7611), 6MWD (AUC 0·7086), and exacerbation risk (AUC 0·7341).

Conclusions

Quantifying comorbidity provides a more thorough understanding of the risk for patient-centered outcomes in COPD. A comorbidity count performs well to quantify comorbidity in a diverse population with COPD.     

Severity Assessment of Lower Respiratory Tract Infection in Malawi: Derivation of a Novel Index (SWAT-Bp) Which Outperforms CRB-65

Objective

To assess the validity of CRB-65 (Confusion, Respiratory rate >30 breaths/min, BP<90/60 mmHg, age >65 years) as a pneumonia severity index in a Malawian hospital population, and determine whether an alternative score has greater accuracy in this setting.

Design

Forty three variables were prospectively recorded during the first 48 hours of admission in all patients admitted to Queen Elizabeth Central Hospital, Malawi, for management of lower respiratory tract infection over a two month period (N = 240). Calculation of sensitivity and specificity for CRB-65 in predicting mortality was followed by multivariate modeling to create a score with superior performance in this population.

Results

Median age 37, HIV prevalence 79.9%, overall mortality 18.3%. CRB-65 predicted mortality poorly, indicated by the area under the ROC curve of 0.649. Independent predictors of death were: Male sex, “S” (AOR 2.6); Wasting, “W” (AOR 6.6); non-ambulatory, “A” (AOR 2.5); Temp >38°C or <35°C, “T” (AOR 3.2); BP<100/60, “Bp” (AOR 3.7). Combining these factors to form a severity index (SWAT-Bp) predicted mortality with high sensitivity and specificity (AUC: 0.867). Mortality for scores 0–5 was 0%, 3.3%, 7.4%, 29.2%, 61.5% and 87.5% respectively. A score ≥3 was 84% sensitive and 77% specific for mortality prediction, with a negative predictive value of 95.8%.

Conclusion

CRB-65 performs poorly in this population. The SWAT-Bp score can accurately stratify patients; ≤2 indicates non-severe infection (mortality 4.4%) and ≥3 severe illness (mortality 45%).     

Prevalence,concentration, and prognostic importance of proteinuria in patients with malignancies

Protein was found significantly more frequently in single urine samples from 504 patients with malignancy (290; 58%) than in 529 controls (119; 22%) (p<0·001). Median protein concentration was greater (p<0·001) in patients with neoplasia (0·14 g/l) than in controls (0·07 g/l). Actuarial analysis showed a median survival of 4·5 months in patients with proteinuria compared with 10 months in those without (p<0·001). The association between proteinuria and shorter survival was statistically significant for patients with gut tumours, lung tumours, and tumours at other sites analysed as a group. Patients with myeloma or urinary tract tumours were not studied.In many patients with malignancy the presence of proteinuria may be associated with a substantially reduced survival time.     

Blindness and Glaucoma: A Multicenter Data Review from 7 Academic Eye Clinics

PurposeTo evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities.MethodsThis multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder (‘controls’). Blindness was defined as visual acuity≤0.05 and/or visual field loss to less than 10°.ResultsUnilateral and bilateral blindness were respectively 11.0% and 1.6% at the beginning, and 15.5% and 3.6% at the end of the observation period (7.5±5.5 years, range:1–25 years); conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14% in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP was found to be protective (p<0.05).ConclusionsIn this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved; it could be predicted by high initial MD, high initial IOP, and old age.     

Malformations of Central Nervous System and Softness of Local Water Supplies

The mean annual prevalence at birth of congenital malformations of the central nervous system for the three years 1964-6 in 48 local authority areas in South Wales was negatively correlated (r = -0·402, P<0·01) with estimates of the mean total hardness of the related water supplies.The mean annual perinatal mortality rate from anencephalus for the five years 1963-7 in 58 county boroughs in England and Wales was also negatively correlated with estimates of the mean total hardness (r = -0·220, P>0·05) and calcium content (r = -0·289, P<0·05) of the related water supplies.It is concluded that the relationship between these associations may well be secondary. Analytical epidemiological studies of the association are called for.     

Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell’s Viper Bites with Coagulopathy

Background

Russell’s viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell’s viper envenoming.

Methodology/Principal Findings

In a prospective cohort of 146 patients with Russell’s viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT), activated partial thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39y (16–82y) and 111 were male. The median peak INR was 6.8 (interquartile range[IQR]:3.7 to >13), associated with low fibrinogen [median,<0.01g/L;IQR:<0.01–0.9g/L), low factor V levels [median,<5%;IQR:<5–4%], low factor VIII levels [median,40%;IQR:12–79%] and low factor X levels [median,48%;IQR:29–67%]. There were smaller reductions in factors II, IX and VII over time. All factors recovered over 48h post-antivenom. The median INR remained >3 at 6h post-antivenom but had reduced to <2, by 24h. The aPTT had also returned to close to normal (<50sec) at 24h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02) and aPTT (r = 0.19, p = 0.03) were correlated (non-parametric Spearman analysis).

Conclusions

Russell’s viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48h. Severity of clotting abnormalities was associated with venom concentrations.     

Obesity-Hypoventilation Syndrome: Increased Risk of Death over Sleep Apnea Syndrome

AimTo study whether mortality and cardiovascular morbidity differ in non-invasive ventilation (NIV)-treated patients with severe obesity-hypoventilation syndrome (OHS) as compared with CPAP-treated patients with obstructive sleep apnea syndrome (OSAS), and to identify independent predictors of mortality in OHS.ResultsThree hundred and thirty subjects (110 patients with OHS and 220 patients with OSAS) were studied. Mean follow-up time was 7±4 years. The five year mortality rates were 15.5% in OHS cohort and 4.5% in OSAS cohort (p< 0.05). Patients with OHS had a 2-fold increase (OR 2; 95% CI: 1.11–3.60) in the risk of mortality and 1.86 fold (OR 1.86; 95% CI: 1.14–3.04) increased risk of having a cardiovascular event. Diabetes, baseline diurnal SaO₂ < 83%, EPAP < 7 cmH2O after titration and adherence to NIV < 4 hours independently predicted mortality in OHS.ConclusionMortality of severe OHS is high and substantially worse than that of OSAS. Severe OHS should be considered a systemic disease that encompasses respiratory, metabolic and cardiovascular components that require a multimodal therapeutic approach.     

Evaluation of 18F-PSMA-1007 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy

PurposeProstate-specific membrane antigen (PSMA) ligands targeting has shown promising results in staging of prostate cancer (PCa). The aim of present study was to evaluate the value of ¹⁸F-PSMA-1007 PET/CT in PCa patients with biochemical recurrence.Methods71 patients with PCa after radical prostatectomy (RP) were included in the present study. Median prostate-specific antigen (PSA) level was 1.27 ng/mL (range 0.01–67.40 ng/mL, n = 69). All patients underwent whole-body PET/CT imaging after injection of 333±38 MBq ¹⁸F-PSMA-1007. The distribution of PSMA-positive lesions was assessed. The influence of PSA level, androgen deprivation therapy and primary Gleason score on PSMA-positive finding and uptake of ¹⁸F-PSMA-1007 were evaluated.Results56 (79%) patients showed at least one pathological finding on ¹⁸F-PSMA-1007 PET/CT. The rates of positive scans were 50%, 80%, 100%, 100% among patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL, respectively. The median Gleason score was 8 (range 7–10), and higher Gleason score (≤7 vs. ≥8) leads to higher detection rates (58.3% (14/24) vs. 88.9% (32/36), P = 0.006). The median SUVmax of positive findings in patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL were 4.51, 4.27, 11.50 and 14.08, respectively. The median SUVmax in patients with PSA level >2.0 ng/mL was significantly higher than that in patients with PSA ≤2.0 ng/mL (14.08 vs. 6.13, P<0.001).Conclusion¹⁸F-PSMA-1007 PET/CT demonstrated a high detection rate for patients with a raised PSA level after radical prostatectomy even in patients with extremely low PSA level (eg. PSA level ≤0.5 ng/mL), which was essential for further clinical management for PCa patients.     

Therapeutic drug monitoring of eculizumab: Rationale for an individualized dosing schedule

The annual cost of eculizumab maintenance therapy in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic–uremic syndrome (aHUS) exceeds $300,000 per patient. A better understanding of eculizumab pharmacokinetics and subsequent individual dose adjustment could reduce this cost. We measured the trough eculizumab concentration in 9 patients with maintenance therapy (aHUS, n = 7; PNH, n = 2) and determined: 1) the intra- and inter-individual variability; 2) the influence of weight on eculizumab pharmacokinetics; and 3) the rate of elimination of eculizumab following discontinuation. A one-compartment model was developed to describe the pharmacokinetics of eculizumab and predicted complement activity by body weight. Trough eculizumab concentrations were >50 µg/mL in 9/9, >100 µg/mL in 8/9, and >300 µg/mL in 5/9 of patients. Intra-individual variability was low but eculizumab concentrations, closely correlated with patient weight (R² = 0.66, p = 0.034), varied broadly (55 ± 12 to 733 ± 164 µg/mL). Pharmacokinetic modeling showed that the elimination half-life varied greatly, with an increase from 7.8 d in a patient weighing 100 kg to 19.5 d in a 40 kg patient. We predicted that infusions of 1200 mg could be spaced every 4 or 6 weeks in patients weighing <90 and <70 kg, respectively. In this pilot study, the current recommended use of a fixed eculizumab dose for maintenance therapy is associated with excessively high trough concentrations in many patients. Further prospective larger studies are now required to support an individualized schedule adjusted for patient weight and based on the observed trough serum eculizumab concentration.     

Correlation of Perfusion MRI and 18F-FDG PET Imaging Biomarkers for Monitoring Regorafenib Therapy in Experimental Colon Carcinomas with Immunohistochemical Validation

ObjectivesTo investigate a multimodal, multiparametric perfusion MRI / ¹⁸F-fluoro-deoxyglucose-(¹⁸F-FDG)-PET imaging protocol for monitoring regorafenib therapy effects on experimental colorectal adenocarcinomas in rats with immunohistochemical validation.ResultsRegorafenib significantly (p<0.01) suppressed PF (81.1±7.5 to 50.6±16.0 mL/100mL/min), PV (12.1±3.6 to 7.5±1.6%) and PS (13.6±3.2 to 7.9±2.3 mL/100mL/min) as well as TTB (3.4±0.6 to 1.9±1.1) between baseline and day 7. Immunohistochemistry revealed significantly (p<0.03) lower tumor microvascular density (CD-31, 7.0±2.4 vs. 16.1±5.9) and tumor cell proliferation (Ki-67, 434.0 ± 62.9 vs. 663.0 ± 98.3) in the therapy group. Perfusion MRI parameters ΔPF, ΔPV and ΔPS showed strong and significant (r = 0.67-0.78; p<0.01) correlations to the PET parameter ΔTTB and significant correlations (r = 0.57-0.67; p<0.03) to immunohistochemical Ki-67 as well as to CD-31-stainings (r = 0.49-0.55; p<0.05).ConclusionsA multimodal, multiparametric perfusion MRI/PET imaging protocol allowed for non-invasive monitoring of regorafenib therapy effects on experimental colorectal adenocarcinomas in vivo with significant correlations between perfusion MRI parameters and ¹⁸F-FDG-PET validated by immunohistochemistry.     

Estimation of Newborn Risk for Child or Adolescent Obesity: Lessons from Longitudinal Birth Cohorts

Objectives

Prevention of obesity should start as early as possible after birth. We aimed to build clinically useful equations estimating the risk of later obesity in newborns, as a first step towards focused early prevention against the global obesity epidemic.

Methods

We analyzed the lifetime Northern Finland Birth Cohort 1986 (NFBC1986) (N = 4,032) to draw predictive equations for childhood and adolescent obesity from traditional risk factors (parental BMI, birth weight, maternal gestational weight gain, behaviour and social indicators), and a genetic score built from 39 BMI/obesity-associated polymorphisms. We performed validation analyses in a retrospective cohort of 1,503 Italian children and in a prospective cohort of 1,032 U.S. children.

Results

In the NFBC1986, the cumulative accuracy of traditional risk factors predicting childhood obesity, adolescent obesity, and childhood obesity persistent into adolescence was good: AUROC = 0·78[0·74–0.82], 0·75[0·71–0·79] and 0·85[0·80–0·90] respectively (all p<0·001). Adding the genetic score produced discrimination improvements ≤1%. The NFBC1986 equation for childhood obesity remained acceptably accurate when applied to the Italian and the U.S. cohort (AUROC = 0·70[0·63–0·77] and 0·73[0·67–0·80] respectively) and the two additional equations for childhood obesity newly drawn from the Italian and the U.S. datasets showed good accuracy in respective cohorts (AUROC = 0·74[0·69–0·79] and 0·79[0·73–0·84]) (all p<0·001). The three equations for childhood obesity were converted into simple Excel risk calculators for potential clinical use.

Conclusion

This study provides the first example of handy tools for predicting childhood obesity in newborns by means of easily recorded information, while it shows that currently known genetic variants have very little usefulness for such prediction.     

Early Hepatic Dysfunction Is Associated with a Worse Outcome in Patients Presenting with Acute Respiratory Distress Syndrome: A Post-Hoc Analysis of the ACURASYS and PROSEVA Studies

Introduction

Bilirubin is well-recognized marker of hepatic dysfunction in intensive care unit (ICU) patients. Multiple organ failure often complicates acute respiratory distress syndrome (ARDS) evolution and is associated with high mortality. The effect of early hepatic dysfunction on ARDS mortality has been poorly investigated. We evaluated the incidence and the prognostic significance of increased serum bilirubin levels in the initial phase of ARDS.

Methods

The data of 805 patients with ARDS were retrospectively analysed. This population was extracted from two recent multicenter, prospective and randomised trials. Patients presenting with ARDS with a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen < 150 mmHg measured with a PEEP ≥ 5 cm of water were included. The total serum bilirubin was measured at inclusion and at days 2, 4, 7 and 14. The primary objective was to analyse the bilirubin at inclusion according to the 90-day mortality rate.

Results

The 90-day mortality rate was 33.8% (n = 272). The non-survivors were older, had higher Sepsis-related Organ Failure Assessment (SOFA) score and were more likely to have a medical diagnosis on admission than the survivors. At inclusion, the SOFA score without the liver score (10.3±2.9 vs. 9.0±3.0, p<0.0001) and the serum bilirubin levels (36.1±57.0 vs. 20.5±31.5 μmol/L, p<0.0001) were significantly higher in the non-survivors than in the survivors. Age, the hepatic SOFA score, the coagulation SOFA score, the arterial pH level, and the plateau pressure were independently associated with 90-day mortality in patients with ARDS.

Conclusion

Bilirubin used as a surrogate marker of hepatic dysfunction and measured early in the course of ARDS was associated with the 90-day mortality rate.     

Impact of COVID-19 outbreak on hospital admissions and outcome of acute coronary syndromes in a single high-volume centre in southeastern Europe

BackgroundAs coronavirus disease 2019 (COVID-19) has reached pandemic status, authors from the most severely affected countries have reported reduced rates of hospital admissions for patients with acute coronary syndrome (ACS).AimThe aim of the present study was to investigate the influence of the COVID-19 outbreak on hospital admissions and outcomes in ACS patients in a single high-volume centre in southeastern Europe.MethodsThis retrospective observational study aimed to investigate the number of hospital admissions for ACS, clinical findings at admission, length of hospitalisation, major complications and in-hospital mortality during the COVID-19 outbreak and to compare the data with the same parameters during an equivalent time frame in 2019. For the ST-elevated myocardial infarction (STEMI) subgroup of patients, changes in ischaemic times were analysed as well.ResultsThere was a significant reduction of 44.3% in the number of patients admitted for ACS during the COVID-19 outbreak when compared with the same period in 2019 (151 vs 271; 95% confidence interval 38.4–50.2, p < 0.01) with a higher mortality rate (13.2% vs 7.2%, p = 0.03). In 2020, patients with non-ST-elevated myocardial infarction presented more often with acute heart failure (3.3% vs 0.7%, p = 0.04). During the COVID-19 outbreak, we observed increases in the total ischaemic time (303 ± 163.4 vs 200.8 ± 156.8 min, p < 0.05) and door-to-balloon time (69.2 ± 58.4 vs 50.5 ± 31.3 min, p < 0.01) in STEMI patients.ConclusionsThese findings should increase the awareness of morbidity and mortality related to missed or delayed treatment of ACS among the public and the healthcare services.     

Alcohol consumption in Dundee primigravidas and its effects on outcome of pregnancy

In a population based cohort study information on the consumption of alcohol was obtained from 95% of the 952 consecutive primigravidas who lived in the Dundee district and attended for antenatal care between May 1985 and April 1986. Before realising that they were pregnant more than 90% drank alcohol and 53% were cigarette smokers. During the first four months of pregnancy, however, the proportion of women drinking and smoking fell to 56% and 44%, respectively. Alcohol consumption of more than 120 g absolute alcohol/week (12 or more standard drinks) during pregnancy was related to shorter gestational age (-2·6 weeks), smaller head circumference (-18 mm), shorter (-21 mm) and lighter (-499 g) babies, and lower Apgar scores at five minutes (-0·4, all p<0·01). After adjustment for the effect of smoking, social class, mother''s size, and other confounding factors, however, an alcohol intake of more than 120 g/week was significantly related only to shorter gestational age (-2·0 weeks, p<0·001) and lower Apgar score at five minutes (-0·2, p<0·05). Alcohol intake in the region of 100-119 g/week was significantly related to smaller head circumference (-12 mm, p<0·05). Analysis by type of beverage consumed suggested that beer rather than wine or spirits was associated with a poorer outcome.As there was no detectable effect on pregnancy of alcohol consumption below 100 g/week, it is suggested that health education should be directed towards mothers who drink more than this amount.     

Mortality Patterns and Site Heterogeneity of Severe Malaria in African Children

Background

In this study we aimed to assess site heterogeneity of early, intermediate, and late mortality prediction in children with severe Plasmodium falciparum malaria in sub-Saharan Africa.

Methods

Medical records of 26,036 children admitted with severe Plasmodium falciparum malaria in six hospital research centers between December 2000 to May 2005 were analyzed. Demographic, clinical and laboratory data of children who died within 24 hours (early), between 24 and 47 hours (intermediate) and thereafter (48 hours or later, late mortality) were compared between groups and survivors.

Results

Overall mortality was 4·3% (N = 1,129). Median time to death varied across sites (P<0·001), ranging from 8h (3h–52h) in Lambaréné to 40h (10h–100h) in Kilifi. Fifty-eight percent of deaths occurred within 24 hours and intermediate and late mortality rate were 19% and 23%, respectively. Combining all sites, deep breathing, prostration and hypoglycemia were independent predictors for early, intermediate and late mortality (P<0·01). Site specific independent predictors for early death included prostration, coma and deep breathing at all sites (P<0·001). Site specific independent predictors for intermediate and late death largely varied between sites (P<0·001) and included between 1 and 7 different clinical and laboratory variables.

Conclusion

Site heterogeneity for mortality prediction is evident in African children with severe malaria. Prediction for early mortality has the highest consistency between sites.     

Heart rate increase and inappropriate sinus tachycardia after cryoballoon pulmonary vein isolation for atrial fibrillation

BackgroundCryoballoon pulmonary vein isolation (PVI) is a common therapy for atrial fibrillation (AF). While moderately increased sinus rhythm heart rate (HR) after PVI has been observed, inappropriate sinus tachycardia (IST) is a rare phenomenon. We aimed to investigate the prevalence and natural history of an abnormal sinus HR response after cryoballoon PVI.MethodsWe included 169/646 (26.2%) patients with AF undergoing PVI with available Holter recordings before and 3, 6 and 12 months after the procedure. Patients with AF on Holter monitoring were excluded. Mean HR increase ≥ 20 bpm or an IST-like pattern (mean HR > 90 bpm or > 80 bpm when beta-blocking agents were used) following PVI was categorised as abnormal sinus HR response.ResultsFollowing PVI, mean HR ± standard deviation increased in the entire group from 63.5 ± 8.4 to 69.1 ± 9.9 bpm at 3 months (p < 0.001), and to 71.9 ± 9.4 bpm at 6 months (p < 0.001). At 12 months, mean HR was 71.2 ± 10.1 bpm (p < 0.001). Only 7/169 patients (4.1%) met criteria for abnormal sinus HR response: mean HR was 61.9 ± 10.6 bpm (pre-ablation), 84.6 ± 9.8 bpm (3 months), 80.1 ± 6.5 bpm (6 months) and 76.3 ± 10.1 bpm (12 months). Even at 12 months, mean HR was significantly different from that pre-ablation in this group (p = 0.033). However, in patients meeting IST-like pattern criteria, mean HR at 12 months was no longer significantly different from that pre-ablation.ConclusionFew patients had an abnormal sinus HR response after PVI. Peak HR was observed 3 months after PVI, but HR was still significantly increased 12 months post-ablation compared with pre-ablation. An IST-like pattern was rarely observed. In these patients, HR decreased to pre-ablation values within a year.     

What is The Utility of Electrophysiological Study in Elderly Patients with Syncope and Heart Disease?

BackgroundSyncope in elderly patients with heart disease is a growing problem. Its aetiological diagnosis is often difficult. We intended to investigate the value of the electrophysiological study (EPS) in old patients with syncope and heart disease.MethodsEPS was performed in 182 consecutive patients with syncope and heart disease, among whom 62 patients were ≥75 years old and 120 patients <75.ResultsLeft ventricular ejection fraction was 43.9±11.7% in patients ≥75 and 41.1±12.6% in patients <75. During EPS, induced sustained ventricular arrhythmias were as frequent in both groups (27.4% in patients ≥75 versus 27.5% in patients <75, p=0.99) whereas AV conduction abnormalities were more frequent in older patients (37.1% in patients ≥75 versus 18.3% in patients<75, p<0.005). Syncope remained unexplained in 35.5% of patients ≥75 and in 51.7% of patients <75 (p<0.04). ICD was more likely to be implanted in younger patients than in patients ≥75 years (37.5% vs 21% respectively, p<0.009). During a mean follow-up period of 3.3±3 years, the 4-year-survival rate was 66.9±6.8 % in patients ≥75 and 75.9±6.2 % in patients <75 years. The main cause of death was heart failure in both groups. The factors related to a worse outcome in a multivariate analysis were low LVEF and higher age.ConclusionComplete EPS allows the identification of treatable causes in a high proportion of elderly patients with syncope and heart disease. Yet, the prognosis of these patients is mainly related to LVEF and age.     

General Practice Observed: The Distress of Dying

A simple method of recording the distress of dying patients is described. Significant differences occurred between deaths at home and in hospital for three factors. Patients dying at home were (a) more likely to be fully alert shortly before death (P < 0·05); (b) less likely to be suffering from vomiting, incontinence, or bedsores (P < 0·001); and (c) less likely to have unrelieved physical distress (P < 0·05). No significant differences occurred in the distress of patients dying in general-practitioner compared with other hospitals, though the numbers compared were small and a larger study might prove useful.     

Correlation of exhaled breath temperature with bronchial blood flow in asthma

In asthma elevated rates of exhaled breath temperature changes (Δe°T) and bronchial blood flow (Q_aw) may be due to increased vascularity of the airway mucosa as a result of inflammation.We investigated the relationship of Δe°T with Q_aw and airway inflammation as assessed by exhaled nitric oxide (NO). We also studied the anti-inflammatory and vasoactive effects of inhaled corticosteroid and β₂-agonist.Δe°T was confirmed to be elevated (7.27 ± 0.6 Δ°C/s) in 19 asthmatic subjects (mean age ± SEM, 40 ± 6 yr; 6 male, FEV₁ 74 ± 6 % predicted) compared to 16 normal volunteers (4.23 ± 0.41 Δ°C/s, p < 0.01) (30 ± 2 yr) and was significantly increased after salbutamol inhalation in normal subjects (7.8 ± 0.6 Δ°C/ s, p < 0.05) but not in asthmatic patients. Q_aw, measured using an acetylene dilution method was also elevated in patients with asthma compared to normal subjects (49.47 ± 2.06 and 31.56 ± 1.6 μl/ml/min p < 0.01) and correlated with exhaled NO (r = 0.57, p < 0.05) and Δe°T (r = 0.525, p < 0.05). In asthma patients, Q_aw was reduced 30 minutes after the inhalation of budesonide 400 μg (21.0 ± 2.3 μl/ml/min, p < 0.05) but was not affected by salbutamol.Δe°T correlates with Q_aw and exhaled NO in asthmatic patients and therefore may reflect airway inflammation, as confirmed by the rapid response to steroids.