ORCID Profile
0000-0003-0793-786X
Current Organisations
Monash University
,
Medical University of Vienna
,
University of Adelaide
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2019
Publisher: Wiley
Date: 20-08-2020
DOI: 10.1111/JCH.14009
Publisher: F1000 Research Ltd
Date: 08-06-2021
DOI: 10.12688/F1000RESEARCH.53034.1
Abstract: Background : Systematic reviews underpin clinical practice and policies that guide healthcare decisions. A core component of many systematic reviews is meta-analysis, which is a statistical synthesis of results across studies. Errors in the conduct and interpretation of meta-analysis can lead to incorrect conclusions regarding the benefits and harms of interventions and studies have shown that these errors are common. Enabling peer reviewers to better detect errors in meta-analysis through the use of a checklist provides an opportunity for these errors to be rectified before publication. To our knowledge, no such checklist exists. Objective : To develop and evaluate a checklist to detect errors in pairwise meta-analyses in systematic reviews of interventions. Methods : We will undertake a four-step process to develop the checklist. First, we will undertake a systematic review of studies that have evaluated errors in the conduct and interpretation of meta-analysis to generate a bank of items to consider for the checklist. Second, we will undertake a survey of systematic review methodologists and statisticians to seek their views on which items, of the bank of items generated in step 1, are most important to include in the checklist. Third, we will hold a virtual meeting to agree upon which items to include in the checklist. Fourth, before finalising the checklist, we will pilot with editors and peer reviewers of journals. Conclusion : The developed checklist is intended to help journal editors and peer reviewers identify errors in the application and interpretation of meta-analyses in systematic reviews. Fewer errors in the conduct and improved interpretation will lead to more accurate review findings and conclusions to inform clinical practice.
Publisher: Wiley
Date: 09-06-2023
DOI: 10.1002/JRSM.1646
Abstract: Interrupted time series (ITS) studies are frequently used to examine the impact of population‐level interventions or exposures. Systematic reviews with meta‐analyses including ITS designs may inform public health and policy decision‐making. Re‐analysis of ITS may be required for inclusion in meta‐analysis. While publications of ITS rarely provide raw data for re‐analysis, graphs are often included, from which time series data can be digitally extracted. However, the accuracy of effect estimates calculated from data digitally extracted from ITS graphs is currently unknown. Forty‐three ITS with available datasets and time series graphs were included. Time series data from each graph was extracted by four researchers using digital data extraction software. Data extraction errors were analysed. Segmented linear regression models were fitted to the extracted and provided datasets, from which estimates of immediate level and slope change (and associated statistics) were calculated and compared across the datasets. Although there were some data extraction errors of time points, primarily due to complications in the original graphs, they did not translate into important differences in estimates of interruption effects (and associated statistics). Using digital data extraction to obtain data from ITS graphs should be considered in reviews including ITS. Including these studies in meta‐analyses, even with slight inaccuracy, is likely to outweigh the loss of information from non‐inclusion.
Publisher: Medknow
Date: 2020
Publisher: Springer Science and Business Media LLC
Date: 08-05-2023
DOI: 10.1186/S12915-023-01606-1
Abstract: Aging in postmitotic tissues is associated with clonal expansion of somatic mitochondrial deletions, the origin of which is not well understood. Such deletions are often flanked by direct nucleotide repeats, but this alone does not fully explain their distribution. Here, we hypothesized that the close proximity of direct repeats on single-stranded mitochondrial DNA (mtDNA) might play a role in the formation of deletions. By analyzing human mtDNA deletions in the major arc of mtDNA, which is single-stranded during replication and is characterized by a high number of deletions, we found a non-uniform distribution with a “hot spot” where one deletion breakpoint occurred within the region of 6–9 kb and another within 13–16 kb of the mtDNA. This distribution was not explained by the presence of direct repeats, suggesting that other factors, such as the spatial proximity of these two regions, can be the cause. In silico analyses revealed that the single-stranded major arc may be organized as a large-scale hairpin-like loop with a center close to 11 kb and contacting regions between 6–9 kb and 13–16 kb, which would explain the high deletion activity in this contact zone. The direct repeats located within the contact zone, such as the well-known common repeat with a first arm at 8470–8482 bp (base pair) and a second arm at 13,447–13,459 bp, are three times more likely to cause deletions compared to direct repeats located outside of the contact zone. A comparison of age- and disease-associated deletions demonstrated that the contact zone plays a crucial role in explaining the age-associated deletions, emphasizing its importance in the rate of healthy aging. Overall, we provide topological insights into the mechanism of age-associated deletion formation in human mtDNA, which could be used to predict somatic deletion burden and maximum lifespan in different human haplogroups and mammalian species.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2019
Publisher: Cold Spring Harbor Laboratory
Date: 15-04-2019
DOI: 10.1101/603282
Abstract: Aging in postmitotic tissues is associated with clonal expansion of somatic mitochondrial deletions, the origin of which is not well understood. Deletions in mitochondrial DNA (mtDNA) are often flanked by direct nucleotide repeats, but this alone does not fully explain their distribution. Here, we hypothesized that the close proximity of direct repeats on single-stranded DNA might play a role in the formation of deletions. By analyzing human mtDNA deletions in the major arc of mtDNA, which is single-stranded during replication and is characterized by a high number of deletions, we found a non-uniform distribution with a "hot spot" where one deletion breakpoint occurred within the region of 6-9kb and another within 13-16kb of the mtDNA. This distribution was not explained by the presence of direct repeats, suggesting that other factors, such as the spatial proximity of these two regions can be the cause. In silico analyses revealed that the single-stranded major arc may be organized as a large-scale hairpin-like loop with a center close to 11kb and contacting regions between 6-9 kb and 13-16 kb, which would explain the high deletion activity in this contact zone. The direct repeats located within the contact zone, such as the well-known common repeat with a first arm at 8470-8482 bp and a second arm at 13447-13459 bp, are three times more likely to cause deletions compared to direct repeats located outside of the contact zone. An analysis of age- and disease-associated deletions demonstrated that the contact zone plays a crucial role in explaining the age-associated deletions, emphasizing its importance in the rate of healthy aging. Overall, we provide topological insights into the mechanism of age-associated deletion formation in human mtDNA, which could be used to predict somatic deletion burden and maximum lifespan in different human haplogroups and mammalian species.
Publisher: Elsevier BV
Date: 11-2015
Publisher: BMJ
Date: 22-11-2022
Abstract: To examine changes in completeness of reporting and frequency of sharing data, analytical code, and other review materials in systematic reviews over time and factors associated with these changes. Cross sectional meta-research study. Random s le of 300 systematic reviews with meta-analysis of aggregate data on the effects of a health, social, behavioural, or educational intervention. Reviews were indexed in PubMed, Science Citation Index, Social Sciences Citation Index, Scopus, and Education Collection in November 2020. The extent of complete reporting and the frequency of sharing review materials in the systematic reviews indexed in 2020 were compared with 110 systematic reviews indexed in February 2014. Associations between completeness of reporting and various factors (eg, self-reported use of reporting guidelines, journal policies on data sharing) were examined by calculating risk ratios and 95% confidence intervals. Several items were reported suboptimally among 300 systematic reviews from 2020, such as a registration record for the review (n=113 38%), a full search strategy for at least one database (n=214 71%), methods used to assess risk of bias (n=185 62%), methods used to prepare data for meta-analysis (n=101 34%), and source of funding for the review (n=215 72%). Only a few items not already reported at a high frequency in 2014 were reported more frequently in 2020. No evidence indicated that reviews using a reporting guideline were more completely reported than reviews not using a guideline. Reviews published in 2020 in journals that mandated either data sharing or inclusion of data availability statements were more likely to share their review materials (eg, data, code files) than reviews in journals without such mandates (16/87 (18%) v 4/213 (2%)). Incomplete reporting of several recommended items for systematic reviews persists, even in reviews that claim to have followed a reporting guideline. Journal policies on data sharing might encourage sharing of review materials.
Publisher: American Society of Interventional Pain Physicians
Date: 14-01-2017
Abstract: Background: Vitamin-D deficiency may possibly be related to chronic low back pain (CLBP). Objective: The study is aimed to assess the impact of vitamin-D supplementation on pain intensity, functional disability, and vitamin-D levels in patients with CLBP. Study Design: Single arm open-label study. Setting: Outpatient pain clinic of a tertiary care hospital. Methods: Sixty-eight eligible patients (CLBP for ≥ 3 months, pain score ≥ 50 on visual analogue scale (VAS) and plasma 25-Hydroxyvitamin D3 levels 30 ng/mL) were enrolled. Patients were supplemented with 60,000 IU of oral vitamin-D3 given every week for 8 weeks. Efficacy parameters included pain intensity and functional disability measured by VAS and modified Oswestry disability questionnaire (MODQ) scores at baseline, 2, 3, and 6 months post-supplementation. Plasma 25(OH) D3 levels were measured at baseline and 8 weeks. Results: Baseline mean (SD) vitamin-D levels were 12.8 (5.73) ng/mL and increased to 36.07 (12.51) post supplementation (P 0.01). Forty-five (66%) patients attained normal levels ( 29 ng/mL) post supplementation. Significant reduction in VAS was observed at 2, 3, and 6 months [61 (19), 45 (19), 36 (18)] as compared to 81 (19) at baseline (P ≤ 0.001 at all-time intervals). A significant improvement in the functional ability was also observed at 2, 3, and 6 months [36 (12), 31 (13), and 26 (10)] as compared to baseline 45 (16) (P ≤ 0.001 at all-time intervals). Conclusion: Vitamin-D supplementation in deficient CLBP patients may lead to improvement in pain intensity and functional ability apart from normalization of the levels. Future controlled clinical trials are required to confirm the hypothesis. Key words: Vitamin D, deficiency, screening, low back pain, chronic, supplementation
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/697404
Abstract: Aim . To pool the data currently available to determine the association between calcium channel blockers (CCBs) and risk of Parkinson’s disease (PD). Methods . Literature search in PubMed, EBSCO, and Cochrane library was undertaken through March 2014, looking for observational studies evaluating the association between CCBs use and PD. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using random-effects model. Subgroup analyses, sensitivity Analysis, and cumulative meta-analysis were also performed. Results . Six studies were included in our meta-analysis according to the selection criteria, including three cohort studies and three case-control studies involving 27,67,990 subjects including 11,941 PD cases. We found CCBs use was associated with significant decreased risk of PD, compared with not using CCBs (random effects model pooled RR, 0.81 (95% CI, 0.69–0.95)) a significant heterogeneity was found between studies ( P = 0.031 I 2 54.6%). Both the classes of CCB, that is, dihydropyridine calcium channel blockers (DiCCB) (0.80 (95% CI, 0.65–0.98) P = 0.032 ) and non-DiCCB (0.70 (95% CI, 0.53–0.92) P = 0.013 ), were found to be reducing the risk of PD. Conclusion . In our analysis, we found that CCBs use was associated with a Significantly decreased risk of PD compared with non-CCB use.
Publisher: Wiley
Date: 08-05-2014
Publisher: Elsevier BV
Date: 06-2020
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.VHRI.2016.05.002
Abstract: In an attempt to reduce costs of clinical trials and increase recruitments, pharmaceutical companies have been shifting their trials to offshore locations in Asia, Africa, the Middle East, Eastern Europe, and Latin America. Hence, methods for conducting clinical trials need to be adapted to the varying languages, cultures, ethnicities, and socioeconomic groups of these regions. This is of prime importance in the collection of patient-reported outcome (PRO) data. To ensure correct capturing of PRO data from multiregional sites, it is important that the tools for data collection are adapted to the respective cultures, and the data collected have the same interpretation across cultures (cross-cultural equivalence). This article deals with challenges involved in the adaptation of PRO measures to various cultures, especially of those used for multiregional trials being conducted in the developing world.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.JCLINEPI.2021.11.016
Abstract: To investigate how often review authors encounter multiple results from included studies that are eligible for inclusion in a particular meta-analysis, and how often methods to select results are specified. MEDLINE and Epistemonikos were searched (January 2018-June 2019) to identify systematic reviews with meta-analysis of the association between food/diet and health-related outcomes. A random s le of these reviews was selected, and for the first presented (index) meta-analysis, rules used to select effect estimates to include in this meta-analysis were extracted from the reviews and their protocols. All effect estimates from the primary studies that were eligible for inclusion in the index meta-analyses were extracted (e.g., when a study report presented effect estimates for blood pressure at 3 weeks and 6 weeks, both unadjusted and adjusted for covariates, and all were eligible for inclusion in a meta-analysis of the effect of red meat consumption on blood pressure, we extracted all estimates, and classified the study as having "multiplicity of results"). Forty-two systematic reviews with 325 studies (104 randomized, 221 non-randomized) were included 14 reviews had a protocol. In 29% of review protocols and 69% of reviews, authors specified at least one decision rule to select effect estimates when multiple were available. In 68% of studies included in the index meta-analyses, there was at least one type of multiplicity of results. Authors of systematic reviews of nutrition studies should anticipate encountering multiplicity of results in the included primary studies. Specification of methods to handle multiplicity when designing reviews is therefore recommended.
Publisher: Cold Spring Harbor Laboratory
Date: 18-04-2022
DOI: 10.1101/2022.04.11.22273688
Abstract: Objectives: To examine changes in completeness of reporting and frequency of sharing data, analytic code and other review materials in systematic reviews (SRs) over time and factors associated with these changes. Design: Cross-sectional meta-research study. S le: A random s le of 300 SRs with meta-analysis of aggregate data on the effects of a health, social, behavioural or educational intervention, which were indexed in PubMed, Science Citation Index, Social Sciences Citation Index, Scopus and Education Collection in November 2020. Analysis/Outcomes: The extent of complete reporting and frequency of sharing review materials in these reviews were compared with 110 SRs indexed in February 2014. Associations between completeness of reporting and various factors (e.g. self-reported use of reporting guidelines, journal's data sharing policies) were examined by calculating risk ratios (RR) and 95% confidence intervals (CI). Results: Several items were reported sub-optimally among 300 SRs from 2020, such as a registration record for the review (38%), a full search strategy for at least one database (71%), methods used to assess risk of bias (62%), methods used to prepare data for meta-analysis (34%), and funding source for the review (72%). Only a few items not already reported at a high frequency in 2014 were reported more frequently in 2020. There was no evidence that reviews using a reporting guideline were more completely reported than reviews not using a guideline. Reviews published in 2020 in journals that mandated either data sharing or inclusion of Data Availability Statements were more likely to share their review materials (e.g. data, code files) (18% vs 2%). Conclusion: Incomplete reporting of several recommended items for systematic reviews persists, even in reviews that claim to have followed a reporting guideline. Data sharing policies of journals potentially encourage sharing of review materials.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2019
Publisher: BMJ
Date: 04-06-2021
DOI: 10.1136/BMJEBM-2021-111675
Abstract: To assess the methodological and reporting quality of systematic reviews (SRs) that informed recommendations in the recent American and European hypertension guidelines. Meta-epidemiological study. We identified SRs that were cited for class I recommendations based on Level of Evidence-A in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) and the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) hypertension guidelines. Methodological and reporting quality of the SRs was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) checklist and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, respectively. A total of 40 SRs was included in the analysis (28 from 2017 ACC/AHA 22 from 2018 ESC/ESH and 10 were included in both). Based on the AMSTAR-2 assessment, only 7.5% SRs were found to be of high methodological quality, 47.5% were of moderate, each 22.5% were of low and critically low quality. Based on the PRISMA checklist assessment, a mean of 24 items (SD (2.76) were reported appropriately, and only five SRs reported all 27 items appropriately. Methodological and reporting quality of SRs were found to vary considerably. Lack of information on the funding source of included studies, use of a protocol, integration of risk of bias assessments while interpreting findings and reporting of excluded studies were major methodological deficiencies.
Publisher: Cold Spring Harbor Laboratory
Date: 15-09-2022
DOI: 10.1101/2022.09.12.22279878
Abstract: Interrupted Time Series (ITS) studies are frequently used to examine the impact of population-level interventions or exposures. Systematic reviews with meta-analyses including ITS designs may inform public health and policy decision-making. Re-analysis of ITS may be required for inclusion in meta-analysis. While publications of ITS rarely provide raw data for re-analysis, graphs are often included, from which time series data can be digitally extracted. However, the accuracy of effect estimates calculated from data digitally extracted from ITS graphs is currently unknown. Forty-three ITS with available datasets and time series graphs were included. Time series data from each graph was extracted by four researchers using digital data extraction software. Data extraction errors were analysed. Segmented linear regression models were fitted to the extracted and provided datasets, from which estimates of immediate level and slope change (and associated statistics) were calculated and compared across the datasets. Although there were some data extraction errors of time points, primarily due to complications in the original graphs, they did not translate into important differences in estimates of interruption effects (and associated statistics). Using digital data extraction to obtain data from ITS graphs should be considered in reviews including ITS. Including these studies in meta-analyses, even with slight inaccuracy, is likely to outweigh the loss of information from non-inclusion.
Location: India
No related grants have been discovered for Raju Kanukula.