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Biventricular pacemaker therapy improves exercise capacity in patients with non-obstructive hypertrophic cardiomyopathy via augmented diastolic filling on exercise.
No full textAIMS
Treatment options for patients with non-obstructive hypertrophic cardiomyopathy (HCM) are limited. We sought to determine whether biventricular (BiV) pacing improves exercise capacity in HCM patients, and whether this is via augmented diastolic filling.
METHODS AND RESULTS
Thirty-one patients with symptomatic non-obstructive HCM were enrolled. Following device implantation, patients underwent detailed assessment of exercise diastolic filling using radionuclide ventriculography in BiV and sham pacing modes. Patients then entered an 8-month crossover study of BiV and sham pacing in random order, to assess the effect on exercise capacity [peak oxygen consumption (VO )]. Patients were grouped on pre-specified analysis according to whether left ventricular end-diastolic volume increased (+LVEDV) or was unchanged/decreased (-LVEDV) with exercise at baseline. Twenty-nine patients (20 male, mean age 55 years) completed the study. There were 14 +LVEDV patients and 15 -LVEDV patients. Baseline peak VO was lower in -LVEDV patients vs. +LVEDV patients (16.2 ± 0.9 vs. 19.9 ± 1.1 mL/kg/min, P = 0.04). BiV pacing significantly increased exercise ΔLVEDV (P = 0.004) and Δstroke volume (P = 0.008) in -LVEDV patients, but not in +LVEDV patients. Left ventricular ejection fraction and end-systolic elastance did not increase with BiV pacing in either group. This translated into significantly greater improvements in exercise capacity (peak VO + 1.4 mL/kg/min, P = 0.03) and quality of life scores (P = 0.02) in -LVEDV patients during the crossover study. There was no effect on left ventricular mechanical dyssynchrony in either group.
CONCLUSION
Symptomatic patients with non-obstructive HCM may benefit from BiV pacing via augmentation of diastolic filling on exercise rather than contractile improvement. This may be due to relief of diastolic ventricular interaction.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov NCT00504647
Care providers' and patients' attitudes toward using electronic-patient reported outcomes to support patients with traumatic brain injury: a qualitative study (PRiORiTy).
No full text: To (a) identify residual symptoms and deficits resulting from a traumatic brain injury (TBI) and impact on patients' and their families' quality of life; (b) explore views and experience of care providers, researchers, patients, and carers of using PROMs; and (c) explore their attitudes toward reporting symptoms and impacts on an electronic platform.
METHODS
Qualitative semi-structured interviews with people with TBI and their carers; health-care professionals, researchers, and third sector staff members working with people with TBI.
RESULTS
Symptoms and long-term impacts of TBI included cognitive problems, difficulties functioning, anxiety, and depression. PROMs were seen as improving knowledge of residual symptoms and their impact post-TBI but not always accurately reflecting patients' residual problems. Challenges to completing PROMs were cognitive impairment and lack of insight into condition. Perceived advantages of an electronic platform included easy data collection; flexibility; improving workflow; and the ability to send/ receive feedback and reminders easily. Suggested features of an electronic platform included simple layout, lay language, short questions, few items on the screen, and capability to send/receive feedback and additional information.
CONCLUSION
There is a demand for reporting symptoms and their impact electronically, providing the layout is kept simple and feedback from clinicians is provided
Importance and Evidence of Extent of Resection in Glioblastoma.
No full textMaximal safe resection is an essential part of the multidisciplinary care of patients with glioblastoma. A growing body of data shows that gross total resection is an independent prognostic factor associated with improved clinical outcome. The relationship between extent of glioblastoma (GB) resection and clinical benefit depends critically on the balance between cytoreduction and avoiding neurologic morbidity. The definition of the extent of tumor resection, how this is best measured pre- and postoperatively, and its relation to volume of residual tumor is still discussed. We review the literature supporting extent of resection in GB, highlighting the importance of a standardized definition and measurement of extent of resection to allow greater collaboration in research projects and trials. Recent developments in neurosurgical techniques and technologies focused on maximizing extent of resection and safety are discussed
Unique expansion of IL-21+ Tfh and Tph cells under control of ICOS identifies Sjögren's syndrome with ectopic germinal centres and MALT lymphoma.
No full textOBJECTIVES
To explore the relevance of T-follicular-helper (Tfh) and pathogenic peripheral-helper T-cells (Tph) in promoting ectopic lymphoid structures (ELS) and B-cell mucosa-associated lymphoid tissue (MALT) lymphomas (MALT-L) in Sjögren's syndrome (SS) patients.
METHODS
Salivary gland (SG) biopsies with matched peripheral blood were collected from four centres across the European Union. Transcriptomic (microarray and quantitative PCR) analysis, FACS T-cell immunophenotyping with intracellular cytokine detection, multicolor immune-fluorescence microscopy and hybridisation were performed to characterise lesional and circulating Tfh and Tph-cells. SG-organ cultures were used to investigate functionally the blockade of T-cell costimulatory pathways on key proinflammatory cytokine production.
RESULTS
Transcriptomic analysis in SG identified Tfh-signature, interleukin-21 (IL-21) and the inducible T-cell co-stimulator (ICOS) costimulatory pathway as the most upregulated genes in ELS+SS patients, with parotid MALT-L displaying a 400-folds increase in IL-21 mRNA. Peripheral CD4CXC-motif chemokine receptor 5 (CXCR5)programmed cell death protein 1 (PD1)ICOS Tfh-like cells were significantly expanded in ELS+SS patients, were the main producers of IL-21, and closely correlated with circulating IgG and reduced complement C4. In the SG, lesional CD4CD45ROICOSPD1 cells selectively infiltrated ELS+ tissues and were aberrantly expanded in parotid MALT-L. In ELS+SG and MALT-L parotids, conventional CXCR5CD4PD1ICOSFoxp3 Tfh-cells and a uniquely expanded population of CXCR5CD4PD1ICOSFoxp3 Tph-cells displayed frequent IL-21/interferon-γ double-production but poor IL-17 expression. Finally, ICOS blockade in SG-organ cultures significantly reduced the production of IL-21 and inflammatory cytokines IL-6, IL-8 and tumour necrosis factor-α (TNF-α).
CONCLUSIONS
Overall, these findings highlight Tfh and Tph-cells, IL-21 and the ICOS costimulatory pathway as key pathogenic players in SS immunopathology and exploitable therapeutic targets in SS
Peri-operative Outcomes and Survival Following Palliative Gastrectomy for Gastric Cancer: a Systematic Review and Meta-analysis.
No full textBACKGROUND
Many patients with gastric cancer present with late stage disease. Palliative gastrectomy remains a contentious intervention aiming to debulk tumour and prevent or treat complications such as gastric outlet obstruction, perforation and bleeding.
METHODS
We conducted a systematic review of the literature for all papers describing palliative resections for gastric cancer and reporting peri-operative or survival outcomes. Data from peri-operative and survival outcomes were meta-analysed using random effects modelling. Survival data from patients undergoing palliative resections, non-resective surgery and palliative chemotherapy were also combined. This study was registered with the PROSPERO database (CRD42019159136).
RESULTS
One hundred and twenty-eight papers which included 58,675 patients contributed data. At 1 year, there was a significantly improved survival in patients who underwent palliative gastrectomy when compared to non-resectional surgery and no treatment. At 2 years following treatment, palliative gastrectomy was associated with significantly improved survival compared to chemotherapy only; however, there was no significant improvement in survival compared to patients who underwent non-resectional surgery after 1 year. Palliative resections were associated with higher rates of overall complications versus non-resectional surgery (OR 2.14; 95% CI, 1.34, 3.46; p < 0.001). However, palliative resections were associated with similar peri-operative mortality rates to non-resectional surgery.
CONCLUSION
Palliative gastrectomy is associated with a small improvement in survival at 1 year when compared to non-resectional surgery and chemotherapy. However, at 2 and 3 years following treatment, survival benefits are less clear. Any survival benefits come at the expense of increased major and overall complications
Portosystemic shunts versus endoscopic intervention with or without medical treatment for prevention of rebleeding in people with cirrhosis.
No full textBACKGROUND
People with liver cirrhosis who have had one episode of variceal bleeding are at risk for repeated episodes of bleeding. Endoscopic intervention and portosystemic shunts are used to prevent further bleeding, but there is no consensus as to which approach is preferable.
OBJECTIVES
To compare the benefits and harms of shunts (surgical shunts (total shunt (TS), distal splenorenal shunt (DSRS), or transjugular intrahepatic portosystemic shunt (TIPS)) versus endoscopic intervention (endoscopic sclerotherapy or banding, or both) with or without medical treatment (non-selective beta blockers or nitrates, or both) for prevention of variceal rebleeding in people with liver cirrhosis.
SEARCH METHODS
We searched the CHBG Controlled Trials Register; CENTRAL, in the Cochrane Library; MEDLINE Ovid; Embase Ovid; LILACS (Bireme); Science Citation Index - Expanded (Web of Science); and Conference Proceedings Citation Index - Science (Web of Science); as well as conference proceedings and the references of trials identified until 22 June 2020. We contacted study investigators and industry researchers.
SELECTION CRITERIA
Randomised clinical trials comparing shunts versus endoscopic interventions with or without medical treatment in people with cirrhosis who had recovered from a variceal haemorrhage.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. When possible, we collected data to allow intention-to-treat analysis. For each outcome, we estimated a meta-analysed estimate of treatment effect across trials (risk ratio for binary outcomes). We used random-effects model meta-analysis as our main analysis and as a means of presenting results. We reported differences in means for continuous outcomes without a meta-analytic estimate due to high variability in their assessment among all trials. We assessed the certainty of evidence using GRADE.
MAIN RESULTS
We identified 27 randomised trials with 1828 participants. Three trials assessed TSs, five assessed DSRSs, and 19 trials assessed TIPSs. The endoscopic intervention was sclerotherapy in 16 trials, band ligation in eight trials, and a combination of band ligation and either sclerotherapy or glue injection in three trials. In eight trials, endoscopy was combined with beta blockers (in one trial plus isosorbide mononitrate). We judged all trials to be at high risk of bias. We assessed the certainty of evidence for all the outcome review results as very low (i.e. the true effects of the results are likely to be substantially different from the results of estimated effects). The very low evidence grading is due to the overall high risk of bias for all trials, and to imprecision and publication bias for some outcomes. Therefore, we are very uncertain whether portosystemic shunts versus endoscopy interventions with or without medical treatment have effects on all-cause mortality (RR 0.99, 95% CI 0.86 to 1.13; 1828 participants; 27 trials), on rebleeding (RR 0.40, 95% CI 0.33 to 0.50; 1769 participants; 26 trials), on mortality due to rebleeding (RR 0.51, 95% CI 0.34 to 0.76; 1779 participants; 26 trials), and on occurrence of hepatic encephalopathy, both acute (RR 1.60, 95% CI 1.33 to 1.92; 1649 participants; 24 trials) and chronic (RR 2.51, 95% CI 1.38 to 4.55; 956 participants; 13 trials). No data were available regarding health-related quality of life. Analysing each modality of portosystemic shunts individually (i.e. TS, DSRS, and TIPS) versus endoscopic interventions with or without medical treatment, we are very uncertain if each type of shunt has effect on all-cause mortality: TS, RR 0.46, 95% CI 0.19 to 1.13; 164 participants; 3 trials; DSRS, RR 0.93, 95% CI 0.65 to 1.33; 352 participants; 4 trials; and TIPS, RR 1.10, 95% CI 0.92 to 1.31; 1312 participants; 19 trial; on rebleeding: TS, RR 0.28, 95% CI 0.14 to 0.56; 127 participants; 2 trials; DSRS, RR 0.26, 95% CI 0.11 to 0.65; 330 participants; 5 trials; and TIPS, RR 0.44, 95% CI 0.36 to 0.55; 1312 participants; 19 trials; on mortality due to rebleeding: TS, RR 0.25, 95% CI 0.06 to 0.96; 164 participants; 3 trials; DSRS, RR 0.31, 95% CI 0.13 to 0.74; 352 participants; 5 trials; and TIPS, RR 0.65, 95% CI 0.40 to 1.04; 1263 participants; 18 trials; on acute hepatic encephalopathy: TS, RR 1.66, 95% CI 0.70 to 3.92; 115 participants; 2 trials; DSRS, RR 1.70, 95% CI 0.94 to 3.08; 287 participants; 4 trials, TIPS, RR 1.61, 95% CI 1.29 to 1.99; 1247 participants; 18 trials; and chronic hepatic encephalopathy: TS, Fisher's exact test P = 0.11; 69 participants; 1 trial; DSRS, RR 4.87, 95% CI 1.46 to 16.23; 170 participants; 2 trials; and TIPS, RR 1.88, 95% CI 0.93 to 3.80; 717 participants; 10 trials. The proportion of participants with shunt occlusion or dysfunction was overall 37% (95% CI 33% to 40%). It was 3% (95% CI 0.8% to 10%) following TS, 7% (95% CI 3% to 13%) following DSRS, and 47.1% (95% CI 43% to 51%) following TIPS. Shunt dysfunction in trials utilising polytetrafluoroethylene-covered stents was 17% (95% CI 11% to 24%). Length of inpatient hospital stay and cost were not comparable across trials. Funding was unclear in 16 trials; 11 trials were funded by government, local hospitals, or universities.
AUTHORS' CONCLUSIONS
Evidence on whether portosystemic shunts versus endoscopy interventions with or without medical treatment in people with cirrhosis and previous hypertensive portal bleeding have little or no effect on all-cause mortality is very uncertain. Evidence on whether portosystemic shunts may reduce bleeding and mortality due to bleeding while increasing hepatic encephalopathy is also very uncertain. We need properly conducted trials to assess effects of these interventions not only on assessed outcomes, but also on quality of life, costs, and length of hospital stay
Rare CNVs provide novel insights into the molecular basis of GH and IGF-1 insensitivity.
No full textObjective
Copy number variation (CNV) has been associated with idiopathic short stature, small for gestational age and Silver-Russell syndrome (SRS). It has not been extensively investigated in growth hormone insensitivity (GHI; short stature, IGF-1 deficiency and normal/high GH) or previously in IGF-1 insensitivity (short stature, high/normal GH and IGF-1).
Design and methods
Array comparative genomic hybridisation was performed with ~60 000 probe oligonucleotide array in GHI (n = 53) and IGF-1 insensitivity (n = 10) subjects. Published literature, mouse models, DECIPHER CNV tracks, growth associated GWAS loci and pathway enrichment analyses were used to identify key biological pathways/novel candidate growth genes within the CNV regions.
Results
Both cohorts were enriched for class 3-5 CNVs (7/53 (13%) GHI and 3/10 (30%) IGF-1 insensitivity patients). Interestingly, 6/10 (60%) CNV subjects had diagnostic/associated clinical features of SRS. 5/10 subjects (50%) had CNVs previously reported in suspected SRS: 1q21 (n = 2), 12q14 (n = 1) deletions and Xp22 (n = 1), Xq26 (n = 1) duplications. A novel 15q11 deletion, previously associated with growth failure but not SRS/GHI was identified. Bioinformatic analysis identified 45 novel candidate growth genes, 15 being associated with growth in GWAS. The WNT canonical pathway was enriched in the GHI cohort and CLOCK was identified as an upstream regulator in the IGF-1 insensitivity cohorts.
Conclusions
Our cohort was enriched for low frequency CNVs. Our study emphasises the importance of CNV testing in GHI and IGF-1 insensitivity patients, particularly GHI subjects with SRS features. Functional experimental evidence is now required to validate the novel candidate growth genes, interactions and biological pathways identified
The Electronic Health Record in Ophthalmology: Usability Evaluation Tools for Health Care Professionals.
No full textINTRODUCTION
The adoption of the electronic health record (EHR) has grown rapidly in ophthalmology. However, despite its potential advantages, its implementation has often led to dissatisfaction amongst health care professionals (HCP). This can be addressed using a user centred design (UCD) which is based on the philosophy that 'the final product should suit the users, rather than making the users suit the product'. There is often no agreed best practice on the role of HCPs in the UCD process. In this paper, we describe practical qualitative methodologies that can be used by HCPs in the design, implementation and evaluation of ophthalmology EHRs.
METHODS
A review of current qualitative usability methodologies was conducted by practising ophthalmologists who are also qualified health informaticians.
RESULTS
We identified several qualitative methodologies that could be used for EHR evaluation. These include: 1 Tools for user centred design: shadowing and autoethnography, semi-structured interviews and questionnaires 2 Tools for summative testing: card sort and reverse card sort, retrospective think aloud protocol, wireframing, screenshot testing and heat maps CONCLUSION: High-yield, low-fidelity tools can be used to engage HCPs with the process of ophthalmology EHR design, implementation and evaluation. These methods can be used by HCPs without the requirement for prior training in usability science, and by clinical centres without significant technical requirements
Validation of subscales of the Severe Asthma Questionnaire (SAQ) using exploratory factor analysis (EFA).
No full textBACKGROUND
The Severe Asthma Questionnaire (SAQ) is a health related quality of life (HRQoL) questionnaire validated for use in severe asthma. It is scored using the mean value of 16 items (SAQ score) in addition to a single item global rating of HRQoL (SAQ-global). The aim was to validate clinically relevant subscales using exploratory factor analysis (EFA).
METHODS
The SAQ was completed, along with measures of asthma control and EQ5D-5L by patients attending six UK severe asthma centres. Clinical data were included in the analysis. EFA using principal axis factoring and oblimin rotation was used to achieve simple structure of data.
RESULTS
460 patients with severe asthma participated, 65% women, mean age 51 (16-83) years. A three factor solution achieved best fit and showed that the SAQ items formed three distinct but inter-correlated groups of items where items were grouped in a way that was consistent with item content. The three subscales were differentially associated with clinically relevant variables (lung function and mood). Males and females interpreted the question of night disturbance in different ways.
CONCLUSIONS
This paper provides a template for best practice in the use of EFA when validating HRQoL subscales. The SAQ can be scored as three subscales with content reflecting three different constructs people with severe asthma use when making judgements about their lives. The subscale 'My Life' assesses the impact of severe asthma on different life activities, 'My Mind' assesses the perceived emotional impact and 'My Body' the impact of extra-pulmonary symptoms and side effects
Prevalence of Chronic Obstructive Pulmonary Disease and its Associated Factors in Nepal: Findings from a Community-based Household Survey.
No full textBackground
Despite chronic obstructive pulmonary disease (COPD) being the commonest non-communicable disease in Nepal, there is limited research evidence estimating the spirometry-based burden of COPD. This study aims to estimate the prevalence of COPD and its correlates through a community-based survey in Pokhara Metropolitan City, a semi-urban area of Western Nepal.
Methods
A cross-sectional household survey was conducted among 1459 adults ≥40 years. COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as a post-bronchodilator ratio of forced expiratory volume in 1st second (FEV) to forced vital capacity (FVC) <0.70 with the presence of symptoms. COPD was also defined by the lower limit of normal (LLN) threshold - FEV/FVC < LLN cut-off values with the presence of symptoms. Study participants were interviewed about sociodemographic and behavioural characteristics and respiratory symptoms. Descriptive statistics and logistic regression analysis were applied.
Results
Spirometry reports were acceptable in 1438 participants. The mean age of the participants was 55 (±10) years, and, 54% were female. The prevalence of GOLD-defined COPD was 8.5% (95% CI: 7.1-10.0) and based on the LLN threshold of 5.4% (95% CI: 4.2-6.6). The multivariate logistic regression showed that increasing age, low body mass index, illiterate, current or former smoker, and biomass fuel smoke increased the odds of COPD in both the definitions.
Conclusion
COPD is highly prevalent at community level and often underdiagnosed. Strategies aiming at early diagnosis and treatment of COPD, especially for the elderly, illiterate, and reducing exposure to smoking and biomass fuel smoke and childhood lung infection could be effective