bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for mortality of adult patients with COVID-19 hospitalised in an emerging country: a cohort study
Authors: Cueto-Manzano Alfonso M , Espinel-Bermúdez María C , Hernández-González Sandra O , Rojas-Campos Enrique , Nava-Zavala Arnulfo H , Fuentes-Orozco Clotilde , Balderas-Peña Luz Ma A , González-Ojeda Alejandro , Cortes-Sanabria Laura , Mireles-Ramírez Mario A. , Ramírez-Márquez José J , Martínez-Gutiérrez Porfirio E , Ávila-Morán Maribel , De-Dios-Pérez Ramón I , Acosta-Ramírez Carlos , Hernández-García Hugo R
Published: July 2021

Objective

To describe mortality of in-hospital patients with COVID-19 and compare risk factors between survivors and non-survivors.

Design

Prospective cohort of adult inpatients.

Setting

Tertiary healthcare teaching hospital in Guadalajara, Mexico.

Participants

All patients with confirmed COVID-19 hospitalised from 25 March to 7 September 2020 were included. End of study: 7 November 2020.

Primary outcome measures

Patient survival analysed by the Kaplan-Meier method and comparison of factors by the log-rank test. Mortality risk factors analysed by multivariate Cox’s proportional-hazard model.

Results

One thousand ten patients included: 386 (38%) died, 618 (61%) alive at discharge and six (0.6%) remained hospitalised. There was predominance of men (63%) and high frequency of overweight–obesity (71%); hypertension (54%); diabetes (40%); and lung (9%), cardiovascular (8%) and kidney diseases (11%); all of them significantly more frequent in non-survivors. Overweight–obesity was not different between groups, but severity of disease (Manchester Triage System and quick Sequential Organ Failure Assessment) was significantly worse in non-survivors, who were also significantly older (65 vs 45 years, respectively) and had haematological, biochemical, coagulation and inflammatory biomarkers more altered than survivors. Mortality predictors were invasive mechanical ventilation (IMV; OR 3.31, p<0.0001), admission to intensive care unit (ICU; OR 2.18, p<0.0001), age (OR 1.02, p<0.0001), Manchester Triage System (urgent OR 1.44, p=0.02; immediate/very urgent OR 2.02, p=0.004), baseline C reactive protein (CRP; OR 1.002, p=0.009) and antecedent of kidney disease (OR 1.58, p=0.04)

Conclusions

Mortality in hospitalised patients with COVID-19 in this emerging country centre seemed to be higher than in developed countries. Patients displayed a high frequency of risk factors for poor outcome, but the need for IMV, ICU admission, older age, more severe disease at admission, antecedent of kidney disease and higher CRP levels significantly predicted mortality.
Clinical trial transparency and data sharing among biopharmaceutical companies and the role of company size, location and product type: a cross-sectional descriptive analysis
Authors: Axson Sydney A , Mello Michelle M , Lincow Deborah , Yang Catherine , Gross Cary P , Ross Joseph S , Miller Jennifer
Published: July 2021

Objectives

To examine company characteristics associated with better transparency and to apply a tool used to measure and improve clinical trial transparency among large companies and drugs, to smaller companies and biologics.

Design

Cross-sectional descriptive analysis.

Setting and participants

Novel drugs and biologics Food and Drug Administration (FDA) approved in 2016 and 2017 and their company sponsors.

Main outcome measures

Using established Good Pharma Scorecard (GPS) measures, companies and products were evaluated on their clinical trial registration, results dissemination and FDA Amendments Act (FDAAA) implementation; companies were ranked using these measures and a multicomponent data sharing measure. Associations between company transparency scores with company size (large vs non-large), location (US vs non-US) and sponsored product type (drug vs biologic) were also examined.

Results

26% of products (16/62) had publicly available results for all clinical trials supporting their FDA approval and 67% (39/58) had public results for trials in patients by 6 months after their FDA approval; 58% (32/55) were FDAAA compliant. Large companies were significantly more transparent than non-large companies (overall median transparency score of 95% (IQR 91–100) vs 59% (IQR 41–70), p<0.001), attributable to higher FDAAA compliance (median of 100% (IQR 88–100) vs 57% (0–100), p=0.01) and better data sharing (median of 100% (IQR 80–100) vs 20% (IQR 20–40), p<0.01). No significant differences were observed by company location or product type.

Conclusions

It was feasible to apply the GPS transparency measures and ranking tool to non-large companies and biologics. Large companies are significantly more transparent than non-large companies, driven by better data sharing procedures and implementation of FDAAA trial reporting requirements. Greater research transparency is needed, particularly among non-large companies, to maximise the benefits of research for patient care and scientific innovation.
Prevalence of electronegative electroretinograms in a healthy adult cohort
Authors: Jiang Xiaofan , Bhatti Taha , Tariq Ambreen , Williams Katie M , Chow Isabelle , Dar Talib , Webster Andrew R , Hysi Pirro G , Hammond Christopher J , Mahroo Omar A
Published: July 2021

Objective

An electronegative electroretinogram (ERG) can indicate important ocular or systemic disease. This study explored the prevalence of electronegative responses to dark-adapted stimuli in a largely healthy cohort.

Methods and Analysis

211 participants recruited from the TwinsUK cohort underwent ERG testing incorporating international standard (International Society for Clinical Electrophysiology of Vision (ISCEV)) protocols and additional stimuli. Responses were recorded using conductive fibre electrodes, following pupil dilation and 20 min dark adaptation. Responses analysed were to the ISCEV standard and strong flashes (3.0 and 10 cd/m2s), and to additional white flashes (0.67–67 cd/m2s). A-wave and b-wave amplitudes were extracted; b:a ratios were calculated and proportions of eyes with ratios<1 were noted.

Results

Mean (SD) age was 62.4 (11.4) years (median, 64.3; range 23–86 years). 93% were female. Mean (SD) b:a ratios for right and left eyes, respectively, were 1.86 (0.33) and 1.81 (0.29) for the standard flash, and 1.62 (0.25) and 1.58 (0.23) for the stronger flash; average b:a ratio was lower for the stronger flash (p<0.0001). No waveforms were electronegative. For additional flashes, b:a ratio decreased with increasing flash strength. No electronegative waveforms were seen except in three eyes (0.7%) for the strongest flash; in some cases, drift in the waveform may have artefactually reduced the b:a ratio.

Conclusion

For standard dark-adapted stimuli, no participants had electronegative waveforms. The findings support the notion that electronegative waveforms (in response to standard flash strengths) are unusual, and should prompt further investigation.
Increasing the use of multimodal analgesia during adult surgery in a tertiary academic anaesthesia department
Authors: Olmos Andrea V , Steen Sasha , Boscardin Christy K , Chang Joyce M , Manahan Genevieve , Little Anthony R , Lee Man-Cheung , Liu Linda L
Published: July 2021

Objective

Multimodal analgesia pathways have been shown to reduce opioid use and side effects in surgical patients. A quality improvement initiative was implemented to increase the use of multimodal analgesia in adult patients presenting for general anaesthesia at an academic tertiary care centre. The aim of this study was to increase adoption of a perioperative multimodal analgesia protocol across a broad population of surgical patients. The use of multimodal analgesia was tracked as a process metric. Our primary outcome was opioid use normalised to oral morphine equivalents (OME) intraoperatively, in the postanaesthesia care unit (PACU), and 48 hours postoperatively. Pain scores and use of antiemetics were measured as balancing metrics.

Methods

We conducted a quality improvement study of a multimodal analgesia protocol implemented for adult (≥18 and≤70) non-transplant patients undergoing general anaesthesia (≥180 min). Components of multimodal analgesia were defined as (1) preoperative analgesic medication (acetaminophen, celecoxib, diclofenac, gabapentin), (2) regional anaesthesia (peripheral nerve block or catheter, epidural catheter or spinal) or (3) intraoperative analgesic medication (ketamine, ketorolac, lidocaine infusion, magnesium, acetaminophen, dexamethasone ≥8 mg, dexmedetomidine). We compared opioid use, pain scores and antiemetic use for patients 1 year before (baseline group—1 July 2018 to 30 June 2019) and 1 year after (implementation group—1 July 2019 to 30 June 2020) project implementation.

Results

Use of multimodal analgesia improved from 53.9% in the baseline group to 67.5% in the implementation group (p<0.001). There was no significant difference in intraoperative OME use before and after implementation (β0=44.0, β2=0.52, p=0.875). OME decreased after the project implementation in the PACU (β0=34.4, β2=−3.88, p<0.001) and 48 hours postoperatively (β0=184.9, β2=−22.59, p<0.001), while pain scores during those time points were similar.

Conclusion

A perioperative pragmatic multimodal analgesic intervention was associated with reduced OME use in the PACU and 48 hours postoperatively.
Incidence of bleeding in patients on different anticoagulants and antiplatelet therapies undergoing thoracentesis
Authors: Aljundi Lamia , Chaar Abdelkader , Boshara Peter , Shiari Aryan , Gennaoui George , Noori Zaid , Girard Cristine , Szpunar Suzan , Franco-Elizondo Rene
Published: July 2021

Introduction

Thoracentesis is one of the most commonly performed procedures in the inpatient setting. Although coagulation profile is usually evaluated prior to thoracentesis, bleeding is a rare complication, occurring in less than 1% of the cases. Several society guidelines recommend holding antiplatelet medications and anticoagulants prior to thoracentesis. Clinical practice guidelines also recommend correcting international normalised ratios of more than two and platelet counts <50 X10∧9/L.

Methods

This is a retrospective descriptive study that included 292 patients who underwent thoracentesis in the inpatient setting at Ascension St John Hospital in Detroit, Michigan, USA from 2016 to 2018. We identified patients who had uncorrected risk for bleeding and collected data about their demographics, comorbidities, use of antiplatelet or anticoagulants and procedural details including complications. We looked for any postprocedural bleeding events to study their relation to the already established bleeding risk.

Results

Two hundred and ninety-two thoracenteses were performed, 95.5% (n=279) were performed by interventional radiology. Majority of patients were at risk of bleeding 83% (n=242). No bleeding events occurred. Medications that were not held prior to thoracentesis included: clopidogrel 11% (n=32), novel anticoagulants 8.2% (n=24) and unfractionated heparin 50% (n=146). Use of ultrasound guidance decreased the amount of haemoglobin decline from 1 to 2 g/L (p=0.029). Seventeen patients suffered pneumothorax, eight of which required intervention.

Discussion

Our study suggests that performing thoracentesis without correction of underlying coagulopathy may be safe. This may prevent consequences of holding essential medications and reduce the amount of blood products administered to patients in need of thoracentesis.
Patterns of endogenous and exogenous ovarian hormone modulation on recovery metrics across the menstrual cycle
Authors: Sims Stacy T , Ware Laura , Capodilupo Emily R
Published: July 2021

Introduction

As the number of female athletes competing rises globally, training methodologies should reflect sex differences across critical metrics of adaptation to training. Surrogate markers of the autonomic nervous system (ANS) used for monitoring training load are heart rate variability (HRV) and resting heart rate (RHR). The aim was to investigate ovarian hormone effects on standard recovery metrics (HRV, RHR, respiratory rate (RR) and sleep duration) across a large population of female athletes.

Methods

A retrospective study analysed 362 852 days of data representing 13 535 menstrual cycles (MC) from 4594 respondents (natural MC n=3870, BC n=455, progestin-only n=269) for relationships and/or differences between endogenous and exogenous ovarian hormones on ANS.

Results

HRV and return to baseline (recovery) decreased as resting HR and RR increased (p<0.001) from the early follicular to the late luteal phase of the MC. Patterning was paradoxical across phases for users of combined hormonal contraception (BC) as compared with the patterning of the MC. HRV and recovery start elevated and drop off quickly during the withdrawal bleed, rising through the active pill weeks (p<0.001). Progestin-only users had similar patterning as the MC. The relationship between normalised recovery and previous day strain is modulated by birth control type. BC exhibited steeper declines in recovery with additional strain-normalised recovery decreases by an additional 0.0055±0.00135 (p<0.001) per unit of strain; with no significant difference between MC and progestin-only (p=0.19).

Conclusion

The patterning of ANS modulation from ovarian hormones is significantly different between naturally cycling women and those on BC, with the patterning dependent on the type of contraception used.
Full recovery of contraction late after acute myocardial infarction: determinants and early predictors
Authors: Lancellotti P , Albert A , Berthe C , Piérard L A
Published: July 2021

OBJECTIVES

To assess the relative value of electrocardiographic, echocardiographic, angiographic, and in-hospital therapeutic indices for predicting late functional recovery after acute myocardial infarction, and to determine the variables associated with absence of recovery, partial recovery, and full recovery.

DESIGN

Prospective observational follow up study.

SETTING

Teaching hospital.

PATIENTS

74 consecutive patients with a first uncomplicated acute myocardial infarct.

INTERVENTIONS

Dobutamine–atropine stress echocardiography was performed mean (SD) 5 (2) days after the acute event. Quantitative angiography was available in all patients before hospital discharge. A follow up resting echocardiogram was obtained 12 (2) months later.

RESULTS

Functional recovery (partial, n = 18; full, n = 27) was observed in 45 of the 74 patients. Recovery was associated with earlier thrombolytic treatment (p = 0.008), earlier peak concentration of creatine kinase (p = 0.009), greater contractile reserve (p = 0.0001), non-Q wave acute myocardial infarction (p = 0.002), and more frequent elective angioplasty of the infarct related vessel (p = 0.0004). Three independent variables were selected stepwise from multivariate analysis for predicting late recovery: contractile reserve (χ2 = 24.2, p < 0.0001); non-Q wave infarction (χ2 = 15.7, p = 0.0001); and the time from symptom onset to thrombolysis (χ2 = 4.94, p = 0.026). Three independent variables predicted full recovery: contractile reserve (χ2 = 17.2, p = 0.0001); non-Q wave infarction (χ2 = 10.1, p = 0.0016); and elective angioplasty of the infarct related artery (χ2 = 4.53, p = 0.033). Only contractile reserve (χ2 = 17.0, p < 0.001) was selected from the multivariate analysis for its ability to distinguish between partial recovery and absence of recovery.

CONCLUSIONS

Late recovery of contraction relates to earlier treatment, which is associated with lower infarct size unmasked by a non-Q wave event and the presence of contractile reserve. Elective coronary angioplasty of the infarct related artery before hospital discharge is associated with full recovery.
A cardiac prevention and rehabilitation programme for all patients at first presentation with coronary artery disease
Authors: Fox K F , Nuttall M , Wood D A , Wright M , Arora B , Dawson E , Devane P , Stock K , Sutcliffe S J , Brown K
Published: July 2021

OBJECTIVE

To develop and test a cardiac prevention and rehabilitation programme for achieving sustained lifestyle, risk factor, and therapeutic targets in patients presenting for the first time with exertional angina, acute coronary syndromes, or coronary revascularisation.

DESIGN

A descriptive study.

SETTING

A hospital based 12 week outpatient programme.

INTERVENTIONS

A multiprofessional family based programme of lifestyle and risk factor modification.

MAIN OUTCOME MEASURES

Non-smoking status, body mass index, blood pressure, plasma cholesterol, use of prophylactic drugs.

RESULTS

158 patients (82% of 194 possible cases) were recruited over 15 months, with 72% completing the programme. Targets for achieving non-smoking status, blood pressure < 140/90 mm Hg, and total cholesterol < 4.8 mmol/l were achieved in 92%, 73%, and 62%, respectively, and the proportion on aspirin, β blockers, and lipid lowering treatment was 95%, 58%, and 64% on referral back to general practice for continuing care.

CONCLUSIONS

A comprehensive cardiac prevention and rehabilitation programme can be offered to all patients presenting for the first time with coronary heart disease, including those with exertional angina who are normally managed in primary care. Lifestyle, risk factor, and therapeutic targets can be successfully achieved in most patients with such a hospital based programme.
Left ventricular dysfunction, natriuretic peptides, and mortality in an urban population
Authors: McDonagh T A , Cunningham A D , Morrison C E , McMurray J J V , Ford I , Morton J J , Dargie H J
Published: July 2021

OBJECTIVE

To report the mortality of left ventricular systolic dysfunction (LVD), assessed objectively by echocardiography, and its association with natriuretic peptide hormones in a random sample of 1640 men and women aged 25–74 years from a geographical, urban population.

METHODS

Left ventricular function was measured by echocardiography in 1640 attendees studied in 1992–3. LVD was defined as a left ventricular ejection fraction (LVEF) ⩽ 30%. Plasma concentrations of N-terminal atrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP) were measured by standard radioimmunoassays. Mortality was documented at four years.

RESULTS

The four year all cause mortality rate in the whole cohort was 4.9% (80 deaths). It was 21% (nine deaths) in those with an LVEF ⩽ 30% and 4% in those whose LVEF was > 30% (p < 0.001). The median (interquartile range) BNP concentration in those who died was 16.9 pg/ml (8.8–27) and 7.8 pg/ml (3.4–13) in survivors (p < 0.0001). Similarly, N-ANP had a median concentration of 2.35 ng/ml (1.32–3.36) in those with a fatal outcome and 1.27 ng/ml (0.9–2.0) in those alive at four years (p < 0.0001). Subjects with an LVEF ⩽ 40% also had a significant mortality rate of 17% if they also had a BNP concentration ⩾ 17.9 pg/ml compared with 6.8% if their BNP was below this concentration (p = 0.013). Multivariate analysis revealed the independent predictors of four year all cause mortality to be increasing age (p < 0.001), a BNP concentration ⩾ 17.9 pg/ml (p = 0.006), the presence of ischaemic heart disease (p = 0.03), and male sex (p = 0.04).

CONCLUSIONS

LVD is associated with a considerable mortality rate in this population. BNP also independently predicts outcome. In addition to its role as a diagnostic aid in chronic heart failure and LVD, it provides prognostic information and clarifies the meaning of a given degree of LVD.
Response of the QT interval to mental and physical stress in types LQT1 and LQT2 of the long QT syndrome
Authors: Paavonen K J , Swan H , Piippo K , Hokkanen L , Laitinen P , Viitasalo M , Toivonen L , Kontula K
Published: July 2021

OBJECTIVE

To study and compare the effects of mental and physical stress on long QT syndrome (LQTS) patients.

DESIGN

Case–control study.

MAIN OUTCOME MEASURES

QT intervals were measured from lead V3. Serum potassium and plasma catecholamine concentrations were also monitored.

PATIENTS

16 patients with type 1 LQTS (LQT1), 14 with type 2 LQTS (LQT2), both groups asymptomatic, and 14 healthy control subjects.

INTERVENTIONS

Three types of mental stress tests and a submaximal exercise stress test.

RESULTS

Heart rate responses to mental stress and exercise were similar in all groups. During mental stress, the mean QT interval shortened to a similar extent in controls (–29 ms), LQT1 patients (–34 ms), and LQT2 patients (–30 ms). During exercise, the corresponding QT adaptation to exercise stress was more pronounced (p < 0.01) in healthy controls (–47 ms) than in LQT1 (–38 ms) or LQT2 patients (–38 ms). During exercise changes in serum potassium concentrations were correlated to changes in QT intervals in controls, but not in LQTS patients. LQT1 and LQT2 patients did not differ in serum potassium, catecholamine or heart rate responses to mental or physical stress.

CONCLUSIONS

QT adaptation to mental and exercise stress in healthy people and in patients with LQTS is different. In healthy people QT adaptation is more sensitive to physical than to mental stress while no such diverging pattern was seen in asymptomatic LQTS patients.
Outlet strut fracture of Björk-Shiley convexo concave heart valves: the UK cohort study
Authors: Omar R Z , Morton L S , Halliday D A , Danns E M , Beirne M T , Blot W J , Taylor K M
Published: July 2021

OBJECTIVE

To investigate the risk of outlet strut fracture (OSF) in Björk-Shiley convexo concave (BSCC) valves in relation to patients' clinical and valve characteristics.

DESIGN

A cohort of 2977 patients with 3325 valves with a follow up of 18 years.

SETTING

38 cardiac implantation centres in the UK.

RESULTS

56 OSF events were reported with 43 occurring in mitral and 13 in aortic valves. The overall OSF rate was 0.17%/year. No dominant clinical factor of risk was found, but multiple regression analysis identified age, body surface area, valve size, shop order fracture rate, and manufacturing period as risk factors for OSF. A 4% (95% confidence interval (CI) 2% to 6%) decrease in the risk of OSF was observed for each advancing year of age and a fivefold (95% CI 2 to 13) increase in risk for a 0.5 m2 increase in body surface area. The association between the risk of OSF and valve size was not constant over time. Excess risks among 31 mm and 33 mm sizes (mainly mitral valves) decreased over time while that for 23 mm (almost all aortic valves) increased. The risk of OSF increased by 40% (95% CI 20% to 50%) for a unit increase in the fracture rate of other valves in the same batch. For valves manufactured during 1981 to 1984 the risk of OSF was 4 (95% CI 2 to 12) times greater than for valves manufactured before 1981.

CONCLUSIONS

The OSF rates for 60° BSCC valves observed in the UK are the highest among all monitored populations. The changing patterns of mitral and aortic valve OSF rates over time observed in this study have not been identified previously and highlight the need for continued monitoring of patients with the BSCC valve.
A simple benchmark for evaluating quality of care of patients following acute myocardial infarction
Authors: Dorsch M F , Lawrance R A , Sapsford R J , Oldham J , Greenwood D C , Jackson B M , Morrell C , Ball S G , Robinson M B , Hall A S
Published: July 2021

OBJECTIVE

To develop a simple risk model as a basis for evaluating care of patients admitted with acute myocardial infarction.

METHODS

From coronary care registers, biochemistry records and hospital management systems, 2153 consecutive patients with confirmed acute myocardial infarction were identified. With 30 day all cause mortality as the end point, a multivariable logistic regression model of risk was constructed and validated in independent patient cohorts. The areas under receiver operating characteristic curves were calculated as an assessment of sensitivity and specificity. The model was reapplied to a number of commonly studied subgroups for further assessment of robustness.

RESULTS

A three variable model was developed based on age, heart rate, and systolic blood pressure on admission. This produced an individual probability of death by 30 days (P30) where P30 = 1/(1 + exp(−L30)) and L30 = −5.624 + (0.085 × age) + (0.014 × heart rate) − (0.022 × systolic blood pressure). The areas under the receiver operating characteristic curves for the reference and test cohorts were 0.79 (95% CI 0.76 to 0.82) and 0.76 (95% CI 0.72 to 0.79), respectively. To aid application of the model to routine clinical audit, a normogram relating observed mortality and sample size to the likelihood of a significant deviation from the expected 30 day mortality rate was constructed.

CONCLUSIONS

This risk model is simple, reproducible, and permits quality of care of acute myocardial infarction patients to be reliably evaluated both within and between centres.
Acute and chronic effects of surgical thromboendarterectomy on exercise capacity and ventilatory efficiency in patients with chronic thromboembolic pulmonary hypertension
Authors: Iwase T , Nagaya N , Ando M , Satoh T , Sakamaki F , Kyotani S , Takaki H , Goto Y , Ohkita Y , Uematsu M , Nakanishi N , Miyatake K
Published: July 2021

OBJECTIVE

To assess acute and chronic effects of surgical thromboendarterectomy on exercise capacity and ventilatory efficiency in patients with chronic thromboembolic pulmonary hypertension (CTEPH).

DESIGN

Cardiopulmonary exercise testing was performed in 20 patients with CTEPH before thromboendarterectomy (baseline), one month after (early phase), and four months after (late phase). Peak oxygen uptake (peakV˙o2) and the ventilatory response to carbon dioxide production (V˙e-V˙co2slope) were measured for assessment of exercise capacity and ventilatory efficiency. Right heart catheterisation was performed in all patients before and one month after surgery.

RESULTS

Baseline peakV˙o2decreased andV˙e-V˙co2slope increased along with the increase in pulmonary vascular resistance in patients with CTEPH. After thromboendarterectomy, theV˙e-V˙co2slope decreased greatly from baseline to the early phase (mean (SD), 50 (9) to 37 (7), p < 0.05) and reached a steady level thereafter. In contrast, a continued increase in peak V˙o2was noted from the early to the late phase (16.9 (4.1) to 21.1 (5.0) ml/kg/min, p < 0.05). The decrease in theV˙e-V˙co2slope from baseline to the early phase, but not the increase in peakV˙o2, correlated strongly with the decrease in pulmonary vascular resistance after surgery (r = 0.75, p < 0.01).

CONCLUSIONS

Thromboendarterectomy may cause an immediate improvement in ventilatory efficiency, possibly through its beneficial haemodynamic effects. In contrast, exercise capacity may continue to improve towards the late phase, reflecting peripheral adaptation to exercise.
Comparison of formulae for heart rate correction of QT interval in exercise ECGs from healthy children
Authors: Benatar A , Decraene T
Published: July 2021

OBJECTIVE

To investigate the differences in four formulae for heart rate correction of the QT interval in serial ECG recordings in healthy children undergoing a graded exercise test.

SUBJECTS

54 healthy children, median age 9.9 years (range 5.05–14.9 years), subjected to graded physical exercise (on a bicycle ergometer or treadmill) until heart rate reached > 85% of expected maximum for age.

DESIGN

ECG was recorded at baseline, at maximum exercise, and at one, two, four, and six minutes after exercise. For each stage, a 12 lead digital ECG was obtained and printed. In each ECG, QT and RR interval were measured (lead II), heart rate was calculated, and QTc values were obtained using the Bazett, Hodges, Fridericia, and Framingham formulae. A pairedttest was used for comparison of QTc, QT, and RR interval at rest and peak exercise, and analysis of variance for all parameters for different stages for each formula.

RESULTS

From peak exercise to two minutes recovery there was a delay in QT lengthening compared with RR lengthening, accounting for differences observed with the formulae after peak exercise. At peak exercise, the Bazett and Hodges formulae led to prolongation of QTc intervals (p < 0.001), while the Fridericia and Framingham formulae led to shortening of QTc intervals (p < 0.001) until four minutes of recovery. The Bazett QTc shortened significantly at one minute after peak exercise.

CONCLUSIONS

The practical meaning of QT interval measurements depends on the correction formula used. In studies investigating repolarisation changes (for example, in the long QT syndromes, congenital heart defects, or in the evaluation of new drugs), the use of an ad hoc selected heart rate correction formula may bias the results in either direction. The Fridericia and Framingham QTc values at one minute recovery from exercise may be useful in the assessment of long QT syndromes.
Expression and correlation analysis of Skp2 and CBX7 in cervical cancer
Authors: Maimaitirexiati Gulikezi , Tian Ping , Maimaiti Hatimihan , Ding Lu , Ma Cailing , Li Yuting , Wang Jing , Yan Qi , Li Rong
Published: July 2021

Aims

S-phase kinase-associated protein 2 (Skp2) oncoprotein is overexpressed in a variety of cancer tissues and promotes the malignant development of cancer. The expression levels of chromobox homolog 7 (CBX7) protein are varied among different types of cancer tissues, but its role in cervical cancer is not clear. We aimed to examine the expression and clinical significance of Skp2 and CBX7 proteins as well as their correlations in cervical cancer.

Methods

Immunohistochemistry was used to detect the expression of Skp2 and CBX7 proteins in the cancerous tissues and adjacent tissues of 64 patients with cervical cancer. Relevant clinicopathological data of these patients were collected, compared and analysed for the correlations.

Results

The expression of Skp2 protein in cervical cancer (87.5%) was higher than that in paracancerous tissues (14.1%), and the expression was positively correlated with clinical stage, malignant degree, lymphatic metastasis, vascular invasion and interstitial invasion. The expression of CBX7 protein in cervical cancer (48.4%) was lower than that in paracancerous tissues (96.8%), and the expression was negatively correlated with clinical stage, malignant degree, interstitial invasion, vascular invasion and lymphatic metastasis. The expression of Skp2 protein and CBX7 protein in cervical cancer tissues and adjacent tissues was negatively correlated. The expression of Skp2 and CBX7 proteins was closely related to the clinicopathological features of cervical cancer.

Conclusions

CBX7 may play the role of a tumour suppressor gene in cervical cancer and provide reference value for the diagnosis and new targeted treatment of cervical cancer.
CD137 and PD-L1 targeting with immunovirotherapy induces a potent and durable antitumor immune response in glioblastoma models
Authors: Puigdelloses Montserrat , Garcia-Moure Marc , Labiano Sara , Laspidea Virginia , Gonzalez-Huarriz Marisol , Zalacain Marta , Marrodan Lucia , Martinez-Velez Naiara , De la Nava Daniel , Ausejo Iker , Hervás-Stubbs Sandra , Herrador Guillermo , Chen ZhiHong , Hambardzumyan Dolores , Patino Garcia Ana , Jiang Hong , Gomez-Manzano Candelaria , Fueyo Juan , Gállego Pérez-Larraya Jaime , Alonso Marta
Published: July 2021

Background

Glioblastoma (GBM) is a devastating primary brain tumor with a highly immunosuppressive tumor microenvironment, and treatment with oncolytic viruses (OVs) has emerged as a promising strategy for these tumors. Our group constructed a new OV named Delta-24-ACT, which was based on the Delta-24-RGD platform armed with 4-1BB ligand (4-1BBL). In this study, we evaluated the antitumor effect of Delta-24-ACT alone or in combination with an immune checkpoint inhibitor (ICI) in preclinical models of glioma.

Methods

The in vitro effect of Delta-24-ACT was characterized through analyses of its infectivity, replication and cytotoxicity by flow cytometry, immunofluorescence (IF) and MTS assays, respectively. The antitumor effect and therapeutic mechanism were evaluated in vivo using several immunocompetent murine glioma models. The tumor microenvironment was studied by flow cytometry, immunohistochemistry and IF.

Results

Delta-24-ACT was able to infect and exert a cytotoxic effect on murine and human glioma cell lines. Moreover, Delta-24-ACT expressed functional 4-1BBL that was able to costimulate T lymphocytes in vitro and in vivo. Delta-24-ACT elicited a more potent antitumor effect in GBM murine models than Delta-24-RGD, as demonstrated by significant increases in median survival and the percentage of long-term survivors. Furthermore, Delta-24-ACT modulated the tumor microenvironment, which led to lymphocyte infiltration and alteration of their immune phenotype, as characterized by increases in the expression of Programmed Death 1 (PD-1) on T cells and Programmed Death-ligand 1 (PD-L1) on different myeloid cell populations. Because Delta-24-ACT did not induce an immune memory response in long-term survivors, as indicated by rechallenge experiments, we combined Delta-24-ACT with an anti-PD-L1 antibody. In GL261 tumor-bearing mice, this combination showed superior efficacy compared with either monotherapy. Specifically, this combination not only increased the median survival but also generated immune memory, which allowed long-term survival and thus tumor rejection on rechallenge.

Conclusions

In summary, our data demonstrated the efficacy of Delta-24-ACT combined with a PD-L1 inhibitor in murine glioma models. Moreover, the data underscore the potential to combine local immunovirotherapy with ICIs as an effective therapy for poorly infiltrated tumors.
Translating Cultural Safety to the UK
Authors: Lokugamage Amali U , Rix Elizabeth(Liz) , Fleming Tania , Khetan Tanvi , Meredith Alice , Hastie Carolyn Ruth
Published: July 2021

Disproportional morbidity and mortality experienced by ethnic minorities in the UK have been highlighted by the COVID-19 pandemic. The ‘Black Lives Matter’ movement has exposed structural racism’s contribution to these health inequities. ‘Cultural Safety’, an antiracist, decolonising and educational innovation originating in New Zealand, has been adopted in Australia. Cultural Safety aims to dismantle barriers faced by colonised Indigenous peoples in mainstream healthcare by addressing systemic racism.

This paper explores what it means to be ‘culturally safe’. The ways in which New Zealand and Australia are incorporating Cultural Safety into educating healthcare professionals and in day-to-day practice in medicine are highlighted. We consider the ‘nuts and bolts’ of translating Cultural Safety into the UK to reduce racism within healthcare. Listening to the voices of black, Asian and minority ethnic National Health Service (NHS) consumers, education in reflexivity, both personal and organisational within the NHS are key. By listening to Indigenous colonised peoples, the ex-Empire may find solutions to health inequity. A decolonising feedback loop is required; however, we should take care not to culturally appropriate this valuable reverse innovation.
Occupation and subcategories of asthma: a population-based incident case–control study
Authors: Jaakkola Maritta S , Lajunen Taina K , Heibati Behzad , Wang Ying-Chuan , Lai Ching-Huang , Jaakkola Jouni J K
Published: July 2021

Background

We hypothesised that occupational exposures differently affect subtypes of adult-onset asthma.

Objective

We investigated potential relations between occupation and three subtypes of adult asthma, namely atopic asthma, non-atopic asthma and asthma–COPD overlap syndrome (ACOS).

Methods

This is a population-based case–control study of incident asthma among working-age adults living in Pirkanmaa Hospital District in Southern Finland. The determinant of interest was occupation at the time of diagnosis of asthma or the job that the subject had quit due to respiratory symptoms. Asthma was divided into three mutually exclusive subtypes on the basis of any positive IgE antibody (atopic and non-atopic asthma) and presence of persistent airways obstruction in spirometry (ACOS). We applied unconditional logistic regression analysis to estimate adjusted OR (aOR), taking into account gender, age and smoking.

Results

The following occupational groups showed significantly increased risk of atopic asthma: chemical industry workers (aOR 15.76, 95% CI 2.64 to 94.12), bakers and food processors (aOR 4.69, 95% CI 1.18 to 18.69), waiters (aOR 4.67, 95% CI 1.40 to 15.56) and those unemployed (aOR 3.06, 95% CI 1.52 to 6.17). The following occupations showed clearly increased risk of non-atopic asthma: metal workers (aOR 8.37, 95% CI 3.77 to 18.59) and farmers and other agricultural workers (aOR 2.36, 95% CI 1.10 to 5.06). Some occupational groups showed statistically significantly increased OR of ACOS: electrical and electronic production workers (aOR 30.6, 95% CI 6.10 to 153.35), fur and leather workers (aOR 16.41, 95% CI 1.25 to 215.85) and those retired (aOR 5.55, 95% CI 1.63 to 18.97).

Conclusions

Our results show that different occupations are associated with different subtypes of adult-onset asthma.
Paraproteinaemic neuropathy: MGUS and beyond
Authors: Carroll Antonia S , Lunn Michael P T
Published: July 2021

Paraproteinaemic neuropathies comprise a heterogeneous group of neuro-haematological conditions with some distinct neurological, haematological and systemic phenotypes. The spectrum of disease varies from mild to severe, indolent to rapidly progressive and from small fibre sensory involvement to dramatic sensorimotor deficits. The haematological association may be overlooked, resulting in delayed treatment, disability, impaired quality of life and increased mortality. However, the presence of an irrelevant benign paraprotein can sometimes lead to inappropriate treatment. In this review, we outline our practical approach to paraproteinaemic disorders, discuss the utility and limitations of diagnostic tests and the distinctive clinical phenotypes and touch on the complex multidisciplinary management approaches.
Dendritic cells in the mucosa of the human trachea are not regularly found in the first year of life
Authors: Tschernig T , Debertin A S , Paulsen F , Kleemann W J , Pabst R
Published: July 2021

BACKGROUND

Dendritic cells (DCs) in the mucosa of the respiratory tract might be involved in the early development of pulmonary allergy or tolerance. To date, little is known about when the first DCs occur in human airways.

METHODS

Specimens of the distal trachea from patients who had died from sudden death in the first year of life (n=29) and in older age groups (n=59) as well as from those who had died from respiratory tract infections in the first year of life (n=8) were examined by immunohistochemistry. Transmission electron microscopy was performed in additional samples from two adults.

RESULTS

In the sudden death subgroup DCs were absent in 76% of those who died in the first year of life but were present in 53 of the 59 older cases. All infants who had died of respiratory infectious diseases had DCs in the tracheal mucosa.

CONCLUSIONS

Mature DCs are not constitutively present in the human tracheobronchial mucosa in the first year of life, but their occurrence seems to be triggered by infectious stimuli. These data support the hypothesis that DCs play a crucial role in immunoregulation in early childhood.
Intracellular cytokine repertoire in different T cell subsets from patients with sarcoidosis
Authors: Möllers M , Aries S P , Drömann D , Mascher B , Braun J , Dalhoff K
Published: July 2021

BACKGROUND

Pulmonary sarcoidosis is characterised by a mononuclear alveolitis with a predominance of CD4+ T cells and macrophages. We determined the intracellular expression of interferon (IFN)γ, interleukin (IL)-2, tumour necrosis factor (TNF)α, IL-4, IL-5 and IL-10 in CD4+ and CD8+, naive and memory lymphocytes from blood and bronchoalveolar lavage (BAL) fluid using three colour flow cytometry.

METHODS

Eighteen untreated patients with pulmonary sarcoidosis were evaluated and stratified according to whether they had acute or chronic disease.

RESULTS

Significantly more T cells expressed Th1 than Th2 type cytokines in both BAL fluid and peripheral blood samples, regardless of clinical presentation. Significantly greater proportions of T cells secreted Th1 type cytokines in BAL fluid than in peripheral blood. Th1 type cytokines were more frequently expressed by peripheral and alveolar T cells in acute disease than in chronic disease. There were no significant differences between CD4+ and CD8+ T cells. Concerning naive and memory lymphocytes, significantly higher CD45RO:CD45RA ratios were found in BAL fluid than in blood, and increased expression of Th2 type cytokines was found in peripheral compared with alveolar memory T cells.

CONCLUSIONS

Our data support the immunopathogenetic concept of Th1/Th2 imbalance and compartmentalisation in pulmonary sarcoidosis and suggest that the cytokine patterns change during the course of disease. Expression of Th2 type cytokines in memory lymphocytes is decreased in the alveolar compartment compared with peripheral blood.
Asthma in preschool children: prevalence and risk factors
Authors: Haby M M , Peat J K , Marks G B , Woolcock A J , Leeder S R
Published: July 2021

BACKGROUND

The prevalence of asthma in children has increased in many countries over recent years. To plan effective interventions to reverse this trend we need a better understanding of the risk factors for asthma in early life. This study was undertaken to measure the prevalence of, and risk factors for, asthma in preschool children.

METHODS

Parents of children aged 3–5 years living in two cities (Lismore, n=383; Wagga Wagga, n=591) in New South Wales, Australia were surveyed by questionnaire to ascertain the presence of asthma and various proposed risk factors for asthma in their children. Recent asthma was defined as ever having been diagnosed with asthma andhaving cough or wheeze in the last 12 monthsand having used an asthma medication in the last 12 months. Atopy was measured by skin prick tests to six common allergens.

RESULTS

The prevalence of recent asthma was 22% in Lismore and 18% in Wagga Wagga. Factors which increased the risk of recent asthma were: atopy (odds ratio (OR) 2.35, 95% CI 1.49 to 3.72), having a parent with a history of asthma (OR 2.05, 95% CI 1.34 to 3.16), having had a serious respiratory infection in the first 2 years of life (OR 1.93, 95% CI 1.25 to 2.99), and a high dietary intake of polyunsaturated fats (OR 2.03, 95% CI 1.15 to 3.60). Breast feeding (OR 0.41, 95% CI 0.22 to 0.74) and having three or more older siblings (OR 0.16, 95% CI 0.04 to 0.71) decreased the risk of recent asthma.

CONCLUSIONS

Of the factors tested, those that have the greatest potential to be modified to reduce the risk of asthma are breast feeding and consumption of polyunsaturated fats.
Exogenous female sex steroid hormones and risk of asthma and asthma-like symptoms: a cross sectional study of the general population
Authors: Lange P , Parner J , Prescott E , Ulrik C Suppli , Vestbo J
Published: July 2021

BACKGROUND

Recent evidence suggests a role for hormonal factors in the aetiology of asthma.

METHODS

Data from a large study of women selected from the general population were used to relate treatment with oral hormonal contraceptives (OCP) and postmenopausal hormone replacement therapy (HRT) to the following asthma indicators: self-reported asthma, wheezing, cough at exertion, and use of medication for asthma. The study sample comprised 1536 premenopausal and 3016 postmenopausal women who participated in the third round of the Copenhagen City Heart Study in 1991–4. A total of 377 women were taking OCP (24.5% of premenopausal women) and 458 were on HRT (15.2% of postmenopausal women).

RESULTS

In premenopausal women 4.8% reported having asthma. The prevalence of self-reported asthma, wheeze, use of asthma medication, and cough at exertion was not significantly related to use of OCP. In postmenopausal women the prevalence of self-reported asthma was 6.2%. A weak but consistent association was observed between HRT and self-reported asthma (OR 1.42 (95% CI 0.95 to 2.12)), wheeze (OR 1.29 (95% CI 1.02 to 1.64)), cough at exertion (OR 1.34 (95% CI 1.01 to 1.77)), and use of asthma medication (OR 1.45 (95% CI 0.97 to 2.18)).

CONCLUSIONS

In this study of the general population no relationship was found between the use of OCP and asthma. Although an association was observed between HRT and asthma and asthma-like symptoms, this was relatively weak and it is concluded that there is no necessity to change present prescription practice.
Airway function at one year: association with premorbid airway function, wheezing, and maternal smoking
Authors: Dezateux C , Stocks J , Wade A M , Dundas I , Fletcher M E
Published: July 2021

BACKGROUND

Impaired growth and development of the respiratory system during fetal and early postnatal life may have important implications for lung development and later lung health. The aim of this study was to examine the association of diminished premorbid airway function, prior wheezing, and maternal smoking with airway function at 1 year of age.

METHODS

Respiratory function was measured at the end of the first year in 100 of 108 healthy term infants (93%) in whom similar measurements had been undertaken prior to any respiratory illness at 8 weeks. Physician diagnosed wheezing episodes were identified retrospectively from medical records.

RESULTS

At 1 year specific airway conductance during end expiration (sGawee; /s/kPa) was significantly diminished in those infants with prior wheezing (95% CI wheeze/no wheeze –0.76 to –0.14), mothers who smoked (95% CI smoke/no smoke –0.81 to –0.27), a family history of asthma (95% CI family history/no family history –0.62 to 0.00), or diminished premorbid sGawee (95% CI –0.13 to –0.43/s/kPa per unit reduction sGawee at 8 weeks). In a multivariate model only maternal smoking and diminished premorbid sGaweewere independently associated with diminished sGawee at 1 year.

CONCLUSIONS

Diminished airway function at the end of the first year appears to be mediated by impaired airway development during early life as well as by exposure to maternal smoking. These findings are consistent with the hypothesis that, at a population level, diminished premorbid airway function provides the link between wheezing lower respiratory illness and diminished airway function at 1 year. Maternal smoking remains an important and avoidable cause of impaired airway development and function in infancy.
Changing patterns of hospital admission for asthma, 1981–97
Authors: Morrison D S , McLoone P
Published: July 2021

BACKGROUND

Hospital admission rates for asthma have stopped rising in several countries. The aim of this study was to use linked hospital admission data to explore recent trends in asthma admissions in Scotland.

METHODS

Linked Scottish Morbidity Records (SMR1) for asthma (ICD-9 493 and ICD-10 J45–6) from 1981 to 1997 were used to describe rates of first admissions and readmissions by age and sex. As a measure of resource use, annual trends in bed days used were also explored by age and sex.

RESULTS

There were 160 039 hospital admissions for asthma by 82 421 individuals in Scotland during the study period. The overall hospital admission rate increased by 122% (from 106.7 to 236.7 per 100 000 population) but this varied by sex, age, and admission type. First admissions rose by 70% from 73.2 per 100 000 in 1986 to 124.8 per 100 000 in 1997 while readmissions fell. Children (<15 years) experienced a decline in overall admissions after 1992 due to falls in both new admissions and readmissions. By 1997 the ratio of female to male admissions was 0.57 in children, but 1.50 above 14 years of age. Mean lengths of stay fell from 10.7 days to 3.7 days between 1981 and 1997 and bed days used showed little change except for a decline after 1992 in children.

CONCLUSIONS

After a period of increasing hospitalisation for asthma in Scotland, rates of admission among children have begun to fall but among adults admissions continue to rise.