Nevin Manimala

Eur J Cancer Prev. 2021 Jun 25. doi: 10.1097/CEJ.0000000000000703. Online ahead of print.

ABSTRACT

BACKGROUND: Prior epidemiologic studies on the association between diabetes and gastric cancer risk provided inconclusive findings, while traditional, aggregate data meta-analyses were characterized by high between-study heterogeneity.

OBJECTIVE: To investigate the association between type 2 diabetes and gastric cancer using data from the ‘Stomach Cancer Pooling (StoP) Project’, an international consortium of more than 30 case-control and nested case-control studies, which is large and provides harmonized definition of participants’ characteristics across individual studies. The data have the potential to minimize between-study heterogeneity and provide greater statistical power for subgroup analysis.

METHODS: We included 5592 gastric cancer cases and 12 477 controls from 14 studies from Europe, Asia, North America, and South America in a two-stage individual-participant data meta-analysis. Random-effect models were used to estimate summary odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) by pooling study-specific ORs.

RESULTS: We did not find an overall association between diabetes and gastric cancer (pooled OR = 1.01, 95% CI, 0.94-1.07). However, the risk of cardia gastric cancer was significantly higher among individuals with type 2 diabetes (OR = 1.16, 95% CI, 1.02-1.33). There was no association between diabetes and gastric cancer risk in strata of Helicobacter pylori infection serostatus, age, sex, BMI, smoking status, alcohol consumption, fruit/vegetable intake, gastric cancer histologic type, and source of controls.

CONCLUSION: This study provides additional evidence that diabetes is unrelated to gastric cancer overall but may be associated with excess cardia gastric cancer risk.

PMID:34183534 | DOI:10.1097/CEJ.0000000000000703

Clin J Pain. 2021 Jun 29. doi: 10.1097/AJP.0000000000000955. Online ahead of print.

ABSTRACT

OBJECTIVE: Musculoskeletal pain is a significant contributor to the global disease burden. Management of musculoskeletal pain where a neuropathic component is present can be challenging. This study evaluated the internal structure of the PROMIS® pain quality scales, explored the prevalence of neuropathic and nociceptive pain, and identified health demographics and behaviours related to musculoskeletal pain presentations.

METHODS: Patients presenting to the Victoria University Osteopathy Clinic (Melbourne, Australia) were invited to complete a health demographics and behaviours questionnaire, and the PROMIS neuropathic (NeuroPQ) and nociceptive (NociPQ) pain quality scales, before their initial consultation. Descriptive, inferential and correlation statistics were used to evaluate the PROMIS scales, health demographics and behaviours. Mokken scale analysis was used to evaluate the internal structure and dimensionality of the NeuroPQ and NociPQ scales.

RESULTS: Three hundred and eighty-three (N=383) patients completed the measures. Mokken scaling suggested the PROMIS scales demonstrated acceptable internal structure and were unidimensional. Over 22% of patients demonstrated cut-off scores above 50, suggesting a substantive neuropathic pain component to their musculoskeletal presentation. Patients who reported cigarette smoking, not being born in Australia or not speaking English at home, demonstrated higher NeuroPQ scores. Females demonstrated significantly higher NociPQ scores than males. Pain intensity demonstrated small to medium correlations with NeuroPQ and NociPQ scores.

DISCUSSION: This study provides support for the use of the NeuroPQ and NociPQ scales in a musculoskeletal pain patient cohort. Associations with health demographics and behaviours were identified, and patients typically experienced a combination of neuropathic and nociceptive pain.

PMID:34183533 | DOI:10.1097/AJP.0000000000000955

Epidemiology. 2021 Jun 24. doi: 10.1097/EDE.0000000000001385. Online ahead of print.

ABSTRACT

Owing to the rapidly evolving coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, quick public health investigations of the relationships between behaviors and infection risk are essential. Recently the test-negative design (TND) was proposed to recruit and survey participants who are symptomatic and being tested for SARS-CoV-2 infection with the goal of evaluating associations between the survey responses (including behaviors and environment) and testing positive on the test. It was also proposed to recruit additional controls who are part of the general population as a baseline comparison group to evaluate risk factors specific to SARS-CoV-2 infection. In this study, we consider an alternative design where we recruit among all individuals, symptomatic and asymptomatic, being tested for the virus in addition to population controls. We define a regression parameter related to a prospective risk factor analysis and investigate its identifiability under the two study designs. We review the difference between the prospective risk factor parameter and the parameter targeted in the typical TND where only symptomatic and tested people are recruited. Using missing data directed acyclic graphs, we provide conditions and required data collection under which identifiability of the prospective risk factor parameter is possible and compare the benefits and limitations of the alternative study designs and target parameters. We propose a novel inverse probability weighting estimator and demonstrate the performance of this estimator through simulation study.

PMID:34183531 | DOI:10.1097/EDE.0000000000001385

Epidemiology. 2021 Jun 25. doi: 10.1097/EDE.0000000000001373. Online ahead of print.

ABSTRACT

BACKGROUND: Integrating results from multiple samples is often desirable, but privacy restrictions may preclude full data pooling, and most datasets do not include fully harmonized variable sets. We propose a simulation-based method leveraging partial information across datasets to guide creation of synthetic data, based on explicit assumptions about the underlying causal structure, that permits pooled analyses that adjust for all desired confounders in the context of privacy restrictions.

METHODS: This proof-of-concept project uses data from the Health and Retirement Study (HRS) and Atherosclerosis Risk in Communities (ARIC) study. We specified an estimand of interest and a directed acyclic graph (DAG) summarizing the presumed causal structure for the effect of glycated hemoglobin (HbA1c) on cognitive change. We derived publicly reportable statistics to describe the joint distribution of each variable in our DAG. These summary estimates were used as data-generating rules to create synthetic datasets. After pooling, we imputed missing covariates in the synthetic datasets and used the synthetic data to estimate the pooled effect of HbA1c on cognitive change, adjusting for all desired covariates.

RESULTS: Distributions of covariates, as well as model coefficients and associated standard errors for our model estimating the effect of HbA1c on cognitive change were similar across cohort-specific original and pre-imputation synthetic data. The estimate from the pooled synthetic incorporates control for confounders measured in either original dataset.

DISCUSSION: Our approach has advantages over meta-analysis or individual-level pooling/data harmonization when privacy concerns preclude data sharing and key confounders are not uniformly measured across datasets.

PMID:34183527 | DOI:10.1097/EDE.0000000000001373

Ann Surg. 2021 Jun 25. doi: 10.1097/SLA.0000000000005028. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine the hypothesis that survival in esophageal cancer increases with more removed lymph nodes during esophagectomy up to a plateau, after which it levels out or even decreases with further lymphadenectomy.

SUMMARY BACKGROUND DATA: There is uncertainty regarding the ideal extent of lymphadenectomy during esophagectomy to optimize long-term survival in esophageal cancer.

METHODS: This population-based cohort study included almost every patient who underwent esophagectomy for esophageal cancer in Sweden or Finland in 2000-2016 with follow-up through 2019. Degree of lymphadenectomy, divided into deciles, was analyzed in relation to all-cause 5-year mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for all established prognostic factors.

RESULTS: Among 2,306 patients, the 2nd (4-8 nodes), 7th (21-24 nodes) and 8th decile (25-30 nodes) of lymphadenectomy showed the lowest all-cause 5-year mortality compared to the 1st decile (HR = 0.77, 95% CI 0.61-0.97, HR = 0.76, 95% CI 0.59-0.99, and HR = 0.73, 95% CI 0.57-0.93, respectively). In stratified analyses, the survival benefit was greatest in decile 7 for patients with pathological T-stage T3/T4 (HR = 0.56, 95% CI 0.40-0.78), although it was statistically improved in all deciles except decile 10. For patients without neoadjuvant chemotherapy, survival was greatest in decile 7 (HR = 0.60, 95% CI 0.41-0.86), although survival was also statistically significantly improved in deciles 2, 6, and 8.

CONCLUSION: Survival in esophageal cancer was not improved by extensive lymphadenectomy, but resection of a moderate number (20-30) of nodes was prognostically beneficial for patients with advanced T-stages (T3/T4) and those not receiving neoadjuvant therapy.

PMID:34183514 | DOI:10.1097/SLA.0000000000005028

Indian Pediatr. 2021 Jun 28:S097475591600350. Online ahead of print.

ABSTRACT

Systematic reviews involve the application of scientific methods to reduce bias in review of literature. The key components of a systematic review are a well-defined research question, comprehensive literature search to identify all studies that potentially address the question, systematic assembly of the studies that answer the question, critical appraisal of the methodological quality of the included studies, data extraction and analysis (with and without statistics), and considerations towards applicability of the evidence generated in a systematic review. These key features can be remembered as six ‘A’; Ask, Access, Assimilate, Appraise, Analyze and Apply. Meta-analysis is a statistical tool that provides pooled estimates of effect from the data extracted from individual studies in the systematic review. The graphical output of meta-analysis is a forest plot which provides information on individual studies and the pooled effect. Systematic reviews of literature can be undertaken for all types of questions, and all types of study designs. This article highlights the key features of systematic reviews, and is designed to help readers understand and interpret them. It can also help to serve as a beginner’s guide for both users and producers of systematic reviews and to appreciate some of its methodological issues.

PMID:34183469

Indian Pediatr. 2021 Jun 28:S097475591600346. Online ahead of print.

ABSTRACT

OBJECTIVE: To study the anti-seizure drug levels and associated factors in children with breakthrough seizures.

METHODS: This cross-sectional study was conducted at a public hospital between November 2017 to April 2019, included 145 children with epilepsy aged 2 to 12 years presenting with breakthrough seizure. Anti-seizure drug levels were measured, and the levels were categorized as within, below, and above the reference range.

RESULTS: Children with epilepsy receiving sodium valproate, phenytoin and carbamazepine were 111 (73%), 31 (20.4%) and 10 (6.6%), respectively, of which 7 were receiving multiple anti-seizure drugs. Drug levels below the reference range were found in 64 (44.1%), within the reference range in 70 (48.3%), and the above reference range in 11 (7.6%) children.

CONCLUSION: Nearly half the children with breakthrough seizures had sub-therapeutic levels, especially those on phenytoin therapy. Drug levels in below therapeutic range do not predict the occurrence of breakthrough seizures.

PMID:34183465

Proc Natl Acad Sci U S A. 2021 Jul 6;118(27):e2105873118. doi: 10.1073/pnas.2105873118.

ABSTRACT

Weighing technology was invented around 3000 BCE between Mesopotamia and Egypt and became widely adopted in Western Eurasia within ∼2,000 y. For the first time in history, merchants could rely on an objective frame of reference to quantify economic value. The subsequent emergence of different weight systems goes hand in hand with the formation of a continental market. However, we still do not know how the technological transmission happened and why different weight systems emerged along the way. Here, we show that the diffusion of weighing technology can be explained as the result of merchants’ interaction and the emergence of primary weight systems as the outcome of the random propagation of error constrained by market self-regulation. We found that the statistical errors of early units between Mesopotamia and Europe overlap significantly. Our experiment with replica weights gives error figures that are consistent with the archaeological sample. We used these figures to develop a model simulating the formation of primary weight systems based on the random propagation of error over time from a single original unit. The simulation is consistent with the observed distribution of weight units. We demonstrate that the creation of the earliest weight systems is not consistent with a substantial intervention of political authorities. Our results urge a revaluation of the role of individual commercial initiatives in the formation of the first integrated market in Western Eurasia.

PMID:34183401 | DOI:10.1073/pnas.2105873118

Cancer Discov. 2021 Jun 28:candisc.1647.2020. doi: 10.1158/2159-8290.CD-20-1647. Online ahead of print.

ABSTRACT

AURORA aims to study the processes of relapse in metastatic breast cancer (MBC) by performing multi-omics profiling on paired primary tumors and early-course metastases. Among 381 patients (primary tumor and metastasis pairs: 252 TGS, 152 RNA-Seq, 67 SNP Arrays), we found a driver role for GATA1 and MEN1 somatic mutations. Metastases were enriched in ESR1, PTEN, CDH1, PIK3CA and RB1 mutations; MDM4, MYC amplifications; ARID1A deletions. An increase in clonality was observed in driver genes like ERBB2 and RB1. Intrinsic subtype switching occurred in 36% of cases. Luminal A/B to HER2-Enriched switching was associated with TP53 and/or PIK3CA mutations. Metastases had lower immune score and increased immune permissive cells. High TMB correlated to shorter time to relapse in HR+/HER2- cancers. ESCAT tier I/II alterations were detected in 51% of patients and matched therapy was used in 7%. Integration of multi-omics analyses in clinical practice could impact treatment strategies in MBC.

PMID:34183353 | DOI:10.1158/2159-8290.CD-20-1647

BMJ Open. 2021 Jun 28;11(6):e052312. doi: 10.1136/bmjopen-2021-052312.

ABSTRACT

INTRODUCTION: Major depressive disorder (MDD) in people with advanced life-limiting illnesses can have significant impact on the quality-of-life of those affected. The management of MDD in the palliative care setting can be challenging as typical antidepressants may not work in time nor be tolerated due to coexisting organ dysfunctions, symptom burden and frailty. Parenteral ketamine was found to exhibit effective and rapid-onset antidepressant effect even against treatment-resistant depression in the psychiatric population. However, there is currently neither feasibility study nor available prospective study available to inform of the safety, tolerability and efficacy of such for MDD in the palliative setting.

METHODS AND ANALYSIS: This is an open-labelled, single arm, phase II pilot feasibility study involving adult patients with advanced life-limiting illnesses and MDD across four palliative care services in Australia. It has an individual dose-titration design (0.1-0.4 mg/kg) with weekly treatments of subcutaneous ketamine infusion over 2 hours. The primary outcome is feasibility. The secondary outcomes are related to the safety, tolerability and antidepressant efficacy of ketamine, participants’ satisfaction in relation to the trial process and the reasons for not completing the study at various stages. The feasibility data will be reported using descriptive statistics. Meanwhile, side effects, tolerability and efficacy data will be analysed using change of assessment scores from baseline.

ETHICS AND DISSEMINATION: Ethics approval was acquired (South Western Sydney Local Health District: HREC/18/LPOOL/466). The results of this study will be submitted for publication in peer-reviewed journals and presented at relevant conferences.

TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry Number: ACTRN12618001586202; Pre-results.

PMID:34183351 | DOI:10.1136/bmjopen-2021-052312