Nevin Manimala

Thorax. 2021 Jun 21:thoraxjnl-2020-215600. doi: 10.1136/thoraxjnl-2020-215600. Online ahead of print.

ABSTRACT

INTRODUCTION: Observational studies suggested lung function is inversely associated with cardiovascular disease (CVD) although these studies could be confounded. We conducted a two sample Mendelian randomisation study using summary statistics from genome-wide association studies (GWAS) to clarify the role of lung function in CVD and its risk factors, and conversely the role of CVD in lung function.

METHODS: We obtained genetic instruments for forced expiratory volume in 1 s (FEV₁: 260) and forced vital capacity (FVC: 320) from publicly available UK Biobank summary statistics (n=421 986) and applied to GWAS summary statistics for coronary artery disease (CAD) (n=184 305), stroke (n=446 696), atrial fibrillation (n=1 030 836) and heart failure (n=977 320) and cardiovascular risk factors. Inverse variance weighting was used to assess the impact of lung function on these outcomes, with various sensitivity analyses. Bidirectional Mendelian randomisation was used to assess reverse causation.

RESULTS: FEV₁ and FVC were inversely associated with CAD (OR per SD increase, 0.72 (95% CI 0.63 to 0.82) and 0.70 (95%CI 0.62 to 0.78)), overall stroke (0.87 (95%CI 0.77 to 0.97), 0.90 (95% CI 0.82 to 1.00)) and some stroke subtypes. FEV₁ and FVC were inversely associated with type 2 diabetes and systolic blood pressure. Sensitivity analyses produced similar findings although the association with CAD was attenuated after adjusting for height (eg, OR for 1SD FEV₁0.95 (0.75 to 1.19), but not for stroke or type 2 diabetes. There was no strong evidence for reverse causation.

CONCLUSION: Higher lung function likely protect against CAD and stroke.

PMID:34155093 | DOI:10.1136/thoraxjnl-2020-215600

J Clin Pathol. 2021 Jun 21:jclinpath-2021-207595. doi: 10.1136/jclinpath-2021-207595. Online ahead of print.

ABSTRACT

AIMS: Novel prognostic markers are warranted for gastrointestinal stromal tumours. Caveolin-1 is a multifunctional protein that proved to be associated with outcome in multiple tumour types. Aim of this study was to investigate Caveolin-1 expression and prognostic efficacy in a series of gastrointestinal stromal tumours.

METHODS: Caveolin-1 expression was assessed by immunohistochemistry in a retrospective series of 66 gastrointestinal stromal tumours representative of the different molecular subtypes. Correlations with clinical, histopathological and molecular features were investigated. Statistical analyses were performed as appropriate.

RESULTS: Thirty-five cases out of 66 (53.0%) expressed Caveolin-1. Presence of Caveolin-1 expression correlated with favourable histopathologic and clinical traits, including a lower mitotic count (p=0.003) and lower relapse rate (p=0.005). Caveolin-1 expression also resulted associated with the presence of PDGFRA mutations (p=0.010). Outcome analyses showed a favourable prognostic significance of Caveolin-1 expression in terms of relapse-free survival (HR=0.14; 95% CI=0.03 to 0.63) and overall survival (HR=0.29; 95% CI=0.11 to 0.74), even after adjusting for the mutational subgroup (relapse-free survival: HR=0.14, 95% CI=0.04 to 0.44; overall survival: HR=0.29, 95% CI=0.11 to 0.51) and imatinib treatment (relapse-free survival: HR=0.14, 95% CI=0.02 to 0.81; overall survival: HR=0.29, 95% CI=0.17 to 0.48).

CONCLUSION: Caveolin-1 represents a novel prognostic marker in gastrointestinal stromal tumours. Further studies are warranted to validate these results and to explore the mechanisms linking Caveolin-1 expression with the PDGFRA oncogenic pathway.

PMID:34155091 | DOI:10.1136/jclinpath-2021-207595

BMJ Open. 2021 Jun 21;11(6):e047416. doi: 10.1136/bmjopen-2020-047416.

ABSTRACT

INTRODUCTION: The heterogeneity in people with borderline personality disorder (BPD) and the range of specialised psychotherapies means that people with certain BPD characteristics might benefit more or less from different types of psychotherapy. Identifying moderating characteristics of individuals is a key to refine and tailor standard treatments so they match the specificities of the individual participant. The objective of this is to improve the quality of care and the individual outcomes. We will do so by performing three systematic reviews with meta-analyses of individual participant data (IPD). The aim of these reviews is to investigate potential predictors and moderating patient characteristics on treatment outcomes for patients with BPD.

METHODS AND ANALYSIS: We performed comprehensive searches in 22 databases and trial registries up to October 6th 2020. These will be updated with a top-up search up until June 2021. Our primary meta-analytic method will be the one-stage random-effects approach. To identify predictors, we will use the one-stage model that accounts for interaction between covariates and treatment allocation. Heterogeneity in case-mix will be assessed with a membership model based on a multinomial logistic regression where study membership is the outcome. A random-effects meta-analysis is chosen to account for expected levels of heterogeneity.

ETHICS AND DISSEMINATION: The statistical analyses will be conducted on anonymised data that have already been approved by the respective ethical committees that originally assessed the included trials. The three IPD reviews will be published in high-impact factor journals and their results will be presented at international conferences and national seminars.

PROSPERO REGISTRATION NUMBER: CRD42021210688.

PMID:34155077 | DOI:10.1136/bmjopen-2020-047416

BMJ Open. 2021 Jun 21;11(6):e046545. doi: 10.1136/bmjopen-2020-046545.

ABSTRACT

OBJECTIVE: To examine the social determinants of influenza and pertussis vaccine uptake among pregnant women in England.

DESIGN: Nationwide population-based cohort study.

SETTING: The study used anonymised primary care data from the Clinical Practice Research Datalink and linked Hospital Episode Statistics secondary care data.

PARTICIPANTS: Pregnant women eligible for pertussis (2012-2015, n=68 090) or influenza (2010/2011-2015/2016, n=152 132) vaccination in England.

MAIN OUTCOME MEASURES: Influenza and pertussis vaccine uptake.

RESULTS: Vaccine uptake was 67.3% for pertussis and 39.1% for influenza. Uptake of both vaccines varied by region, with the lowest uptakes in London and the North East. Lower vaccine uptake was associated with greater deprivation: almost 10% lower in the most deprived quintiles compared with the least deprived for influenza (34.5% vs 44.0%), and almost 20% lower for pertussis (57.7% vs 76.0%). Lower uptake for both vaccines was also associated with non-white ethnicity (lowest among women of black ethnicity), maternal age under 20 years and a greater number of children in the household. The associations between all social factors and vaccine uptake were broadly unchanged in fully adjusted models, suggesting the social determinants of uptake were largely independent of one another. Among 3111 women vaccinated against pertussis in their first eligible pregnancy and pregnant again, 1234 (40%) were not vaccinated in their second eligible pregnancy.

CONCLUSIONS: Targeting promotional campaigns to pregnant women who are younger, of non-white ethnicity, with more children, living in areas of greater deprivation or the London or North East regions, has potential to reduce vaccine-preventable disease among infants and pregnant women, and to reduce health inequalities. Vaccination promotion needs to be sustained across successive pregnancies. Further research is needed into whether the effectiveness of vaccine promotion strategies may vary according to social factors.

PMID:34155074 | DOI:10.1136/bmjopen-2020-046545

BMJ Open. 2021 Jun 21;11(6):e045741. doi: 10.1136/bmjopen-2020-045741.

ABSTRACT

INTRODUCTION: We will evaluate the feasibility of a randomised controlled trial to estimate the effectiveness and cost-effectiveness of a rehabilitation intervention on pain, function and health-related quality of life following neck dissection (ND) after head and neck cancer (HNC).

METHODS AND ANALYSIS: This is a pragmatic, multicentred, feasibility study. Participants are randomised to usual care (control) or usual care plus an individualised, rehabilitation programme (Getting Recovery Right After Neck Dissection, GRRAND intervention). Adults aged over 18 with HNC for whom ND is part of their care will be recruited from specialist clinics. Participants are randomised in 1:1 ratio using a web-based service. The target sample size is 60 participants. Usual care will be received by all participants during their postoperative inpatient stay consisting standard National Health Service care supplemented with a booklet advising on postoperative self-management strategies. The GRRAND intervention programme consists of usual care plus up to six individual physiotherapy sessions including neck and shoulder range of motion (ROM) and progressive resistance exercises, advice and education. Between sessions participants will be advised to complete a home exercise programme. The primary outcome is to determine recruitment and retention rates from study participants across sites. Outcomes will be measured at 6 and 12 months. Participants and physiotherapists will be invited to an optional qualitative interview at the completion of their involvement in the study. The target qualitative sample size is 15 participants and 12 physiotherapists. Interviews aim to further investigate the feasibility and acceptability of the intervention and to determine wider experiences of the study design and intervention from patient and physiotherapist perspectives.

ETHICS AND DISSEMINATION: Ethical approval was given on 29 October 2019 (National Research Ethics Committee Number: 19/SC/0457). Results will be reported at conferences and in peer-reviewed publications.

TRIAL REGISTRATION NUMBER: ISRCTN11979997.

STATUS: Trial recruitment is ongoing and is expected to be completed by 30 August 2021.

PMID:34155073 | DOI:10.1136/bmjopen-2020-045741

BMJ Open. 2021 Jun 21;11(6):e042302. doi: 10.1136/bmjopen-2020-042302.

ABSTRACT

INTRODUCTION: Daily multidisciplinary rounds (DMRs) consist of systematic patient-centred discussions aiming to establish joint therapeutic goals for the next 24 hours of intensive care unit (ICU) care. The aim of the present study protocol is to evaluate whether an intervention consisting of guided DMRs, supported by a remote specialist and audit/feedback on care performance will reduce ICU length of stay compared with a control group.

METHODS AND ANALYSIS: A multicentre, controlled, cluster-randomised superiority trial including 30 ICUs in Brazil (15 intervention and 15 control), from August 2019 to June 2021. In a parallel assignment, ICUs are randomised to a complex-intervention composed by daily rounds carried out through Tele-ICU by a remote ICU physician; development of local quality indicators dashboards coupled with monthly meetings with local leadership; and dissemination of evidence-based clinical protocols versus usual care. Primary outcome is ICU length of stay. Secondary outcomes include classification of the unit according to the profiles defined by the standardised resource use and the standardised mortality rate, hospital mortality, incidence of healthcare-associated infections, ventilator-free days at 28 days, patient-days receiving oral or enteral feeding, patient-days under light sedation or alert and calm, rate of patients under normoxaemia. All adult patients admitted after the beginning of the study in each participant ICU will be enrolled. Inclusion criteria (clusters): public Brazilian ICUs with a minimum of 8 ICU beds interested/committed to participating in the study. Exclusion criteria (clusters): units with fully established DMRs by an intensivist, specialised or step-down units.

ETHICS AND DISSEMINATION: The study protocol was approved by the institutional review board (IRB) of the coordinator centre, and by IRBs of each enrolled hospital/ICU. Statistical analysis protocol is being prepared for submission before the end of patient’s enrolment. Results will be disseminated through conferences, peer-reviewed journals and to each participating unit.

TRIAL REGISTRATION NUMBER: NCT03920501; Pre-results.

PMID:34155070 | DOI:10.1136/bmjopen-2020-042302

Cancer Epidemiol Biomarkers Prev. 2021 Jun 21:cebp.0016.2021. doi: 10.1158/1055-9965.EPI-21-0016. Online ahead of print.

ABSTRACT

BACKGROUND: Tobacco or human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCC) represent different clinical and epidemiological entities. This study investigated the prevalence of HPV-positive and HPV-negative OPSCC in a reference cancer hospital in Brazil and its association with clinical and demographic data, as well as its impact on overall survival.

METHODS: HPV infection was determined by p16-immunohistochemistry (p16-IHC) in pre-treatment FFPE samples from all OPSCC patients diagnosed at Barretos Cancer Hospital between 2008 and 2018. The prevalence of HPV-positive cases and its temporal trend was assessed, and the association of clinical and demographic data with HPV infection and the impact on patient overall survival was evaluated.

RESULTS: A total of 797 OPSCC patients were included in the study. The prevalence of HPV-associated tumors in the period was 20.6% (95% CI: 49.3-54.4) with a significant trend for increase of HPV-positive cases over the years (APC = 12.87). In a multivariate analysis, the variables gender, level of education, smoking, tumor sub-location, region of Brazil and tumor staging had a significant impact in HPV positivity and a greater overall survival (OS) was observed in HPV-positive patients (5-year OS: 47.9% versus 22.0%; p-value = 0.0001).

CONCLUSIONS: This study represents the largest cohort of Brazilian OPSCC patients characterized according to HPV status. We report significant differences in demographics and clinical presentation according to HPV status, and an increasing trend in prevalence for HPV-induced tumors.

IMPACT: These findings can potentially contribute to a better stratification and management of patients as well as assist in prevention strategies.

PMID:34155066 | DOI:10.1158/1055-9965.EPI-21-0016

Eur Urol Oncol. 2021 Jun 18:S2588-9311(21)00116-4. doi: 10.1016/j.euo.2021.06.001. Online ahead of print.

ABSTRACT

BACKGROUND: Discordant findings between multiparametric magnetic resonance imaging (mpMRI) and transrectal image-guided biopsies of the prostate (TRUS-P) may result in inadequate risk stratification of localized prostate cancer.

OBJECTIVE: To assess transperineal image-guided biopsies of the index target (TPER-IT) in terms of disease reclassification and treatment recommendations.

DESIGN, SETTING, AND PARTICIPANTS: Cases referred for suspicion or treatment of localized prostate cancer were reviewed in a multidisciplinary setting, and discordance was characterized into three scenarios: type I-negative biopsies or International Society of Urological Pathology (ISUP) grade 1 cancer in Prostate Imaging Reporting and Data System (PI-RADS) ≥4 index target (IT); type II-negative biopsies or ISUP grade 1 cancer in anterior IT; and type III-<3 mm stretch of cancer in PI-RADS ≥3 IT. Discordant findings were characterized in 132/558 (23.7%) patients after TRUS-P. Of these patients, 102 received reassessment TPER-IT.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary objective was to report changes in treatment recommendations after TPER-IT. Therefore, cores obtained by primary TRUS-P and TPER-IT were analyzed in terms of cancer detection, ISUP grade, and Cambridge Prognostic Group classification using descriptive statistics.

RESULTS AND LIMITATIONS: TPER-IT biopsies that consisted of fewer cores than the initial TRUS-P (seven vs 14, p < 0.0001) resulted in more cancer tissue materials for analysis (56 vs 42.5 mm, p = 0.0003). As a result, 40% of patients initially considered for follow-up (12/30) and 49% for active surveillance (30/61) were reassigned after TPER-IT to surgery or intensity-modulated radiotherapy.

CONCLUSIONS: Nonconcordance between pathology and imaging was observed in a significant proportion of patients receiving TRUS-P. TPER-IT better informed the presence and grade of cancer, resulting in a significant impact on treatment recommendations. A multidisciplinary review of mpMRI and TRUS-P findings and reassessment TPER-IT in type I-II discordances is recommended.

PATIENT SUMMARY: In this report, patients with suspicious imaging of the prostate, but no or well-differentiated cancer on transrectal image-guided -biopsies, were offered transperineal image-guided biopsies for reassessment. We found that a large share of these had a more aggressive cancer than initially suspected. We conclude that discordant results warrant reassessment transperineal image-guided biopsies as these may impact disease risk classification and treatment recommendations.

PMID:34154979 | DOI:10.1016/j.euo.2021.06.001

Disabil Health J. 2021 May 15:101115. doi: 10.1016/j.dhjo.2021.101115. Online ahead of print.

ABSTRACT

BACKGROUND: Between 2008 and 2014, annual estimates of disability prevalence among U.S. adults varied somewhat across federal surveys that use a standardized measure of disability, but trends over-time were relatively stable and consistent. In 2014, however, estimates of disability from the Survey of Income and Program Participation (SIPP) increased markedly relative to previous years and were much higher than disability estimates from other federal surveys.

OBJECTIVE: To examine why disability prevalence among adults aged 40 and older substantially increased in the first wave of the 2014 SIPP Panel.

METHODS: We consider three factors that may have contributed to the rise in disability: data processing, context effects linked to question order, and sampling. To do so, we compare estimates with and without survey weights and imputed data, analyze supplemental disability-related data collected among SIPP participants, and employ decomposition analysis to assess what proportion of the increase in disability can be attributed to changes in sample composition.

RESULTS: We find evidence that differences in sample composition contributed to the observed rise in disability prevalence in SIPP between 2011 and 2014. There is less evidence that weighting and imputation or context effects played a role.

CONCLUSIONS: Previous studies emphasize differences in operationalization and conceptualization of disability as the major factor driving discrepancies in disability estimates. This study suggests that other factors related to survey design and administration may influence disability measurement. Such aspects of surveys, like question order and sampling, may be difficult to standardize, leading to meaningful cross-survey differences in disability estimates.

PMID:34154971 | DOI:10.1016/j.dhjo.2021.101115

Transpl Infect Dis. 2021 Jun 21:e13673. doi: 10.1111/tid.13673. Online ahead of print.

ABSTRACT

BACKGROUND: Infections post-liver transplantation are major drivers for morbidity and mortality. However, the impact of infections within 180 days post-liver transplantation on long-term survival is not clear.

METHODS: We present a retrospective cohort of 317 liver transplant patients for whom all infectious episodes were prospectively collected during a mean follow-up of 4.4 years.

RESULTS: 143/317 (45%) of patients suffered from any infectious episode during the first six months following liver transplantation. Patients with surgical site infections had a reduced survival compared to those with no infection (HR 0.33, 95% CI 0.172-0.636, p=0.001), whereas infections from other sources, including pneumonia, UTI, and line-related infections were not associated with increased mortality. Furthermore, even though the presence of any infection within 30 days or six months post-transplantation did not affect survival, more than a single infectious episode per patient was significantly associated with increased mortality (HR 1.70, CI 1.12- 2.60, p=0.013). In a multivariate analysis, the number of infectious episodes remained statistically significant (HR 1.58, 95% CI 1.03-2.43, p=0.035) upon adjustment for other major variables associated with comorbidities and infection risk.

CONCLUSIONS: Surgical site infections and the number of infectious episodes within 180 days post-liver transplantation are major determinants of long-term survival among these patients.

PMID:34153169 | DOI:10.1111/tid.13673