Generality of the Basic Inverse‐Variance Method

2021 ◽  
pp. 349-357
2020 ◽  
Author(s):  
Emre Yekedüz ◽  
Elif Berna Köksoy ◽  
Hakan Akbulut ◽  
Yüksel Ürün ◽  
Güngör Utkan

Aim: Using circulating tumor DNA (ctDNA) instead of historical clinicopathological factors to select patients for adjuvant chemotherapy (ACT) may reduce inappropriate therapy. Material & methods: MEDLINE was searched on March 31, 2020. Studies, including data related to the prognostic value of ctDNA in the colon cancer patients after surgery and after ACT, were included. The generic inverse-variance method with a random-effects model was used for meta-analysis. Results: Four studies were included for this meta-analysis. ctDNA-positive colon cancer patients after surgery and ACT had a significantly increased risk of recurrence compared with ctDNA-negative patients. Conclusions: ctDNA is an independent prognostic factor, and this meta-analysis is a significant step for using ctDNA instead of historical prognostic factors in the adjuvant setting.


2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Shaoyu Zhu ◽  
N Patrik Brodin ◽  
Madhur K Garg ◽  
Patrick A LaSala ◽  
Wolfgang A Tomé

ABSTRACT BACKGROUND Intracranial arteriovenous malformation (AVM) is a congenital lesion that can potentially lead to devastating consequences if not treated. Many institutional cohort studies have reported on the outcomes after radiosurgery and factors associated with successful obliteration in the last few decades. OBJECTIVE To quantitatively assess the dose-response relationship and risk factors associated with AVM obliteration using a systematic review and meta-analysis approach. METHODS Data were extracted from reports published within the last 20 yr. The dose-response fit for obliteration as a function of marginal dose was performed using inverse-variance weighting. Risk factors for AVM obliteration were assessed by combining odds ratios from individual studies using inverse-variance weighting. RESULTS The logistic model fit showed a clear association between higher marginal dose and higher rates of obliteration. There appeared to be a difference in the steepness in dose-response when comparing studies with patients treated using Gamma Knife radiosurgery (Elekta), compared to linear accelerators (LINACs), and when stratifying studies based on the size of treated AVMs. In the risk-factor analysis, AVM obliteration rate decreases with larger AVM volume or AVM diameter, higher AVM score or Spetzler-Martin (SM) grade, and prior embolization, and increases with compact AVM nidus. No statistically significant associations were found between obliteration rate and age, sex, prior hemorrhage, prior aneurysm, and location eloquence. CONCLUSION A marginal dose above 18 Gy was generally associated with AVM obliteration rates greater than 60%, although lesion size, AVM score, SM grade, prior embolization, and nidus compactness all have significant impact on AVM obliteration rate.


2020 ◽  
pp. 1-9
Author(s):  
Andrea Raballo ◽  
Michele Poletti ◽  
Antonio Preti

Abstract Background The clinical high-risk (CHR) for psychosis paradigm is changing psychiatric practice. However, a widespread confounder, i.e. baseline exposure to antipsychotics (AP) in CHR samples, is systematically overlooked. Such exposure might mitigate the initial clinical presentation, increase the heterogeneity within CHR populations, and confound the evaluation of transition to psychosis at follow-up. This is the first meta-analysis examining the prevalence and the prognostic impact on transition to psychosis of ongoing AP treatment at baseline in CHR cohorts. Methods Major databases were searched for articles published until 20 April 2020. The variance-stabilizing Freeman-Tukey double arcsine transformation was used to estimate prevalence. The binary outcome of transition to psychosis by group was estimated with risk ratio (RR) and the inverse variance method was used for pooling. Results Fourteen studies were eligible for qualitative synthesis, including 1588 CHR individuals. Out of the pooled CHR sample, 370 individuals (i.e. 23.3%) were already exposed to AP at the time of CHR status ascription. Transition toward full-blown psychosis at follow-up intervened in 112 (29%; 95% CI 24–34%) of the AP-exposed CHR as compared to 235 (16%; 14–19%) of the AP-naïve CHR participants. AP-exposed CHR had higher RR of transition to psychosis (RR = 1.47; 95% CI 1.18–1.83; z = 3.48; p = 0.0005), without influence by age, gender ratio, overall sample size, duration of the follow-up, or quality of the studies. Conclusions Baseline AP exposure in CHR samples is substantial and is associated with a higher imminent risk of transition to psychosis. Therefore, such exposure should be regarded as a non-negligible red flag for clinical risk management.


2021 ◽  
Vol 8 (1) ◽  
pp. e000648
Author(s):  
Gilles Jadd Hoilat ◽  
Mohamad Fekredeen Ayas ◽  
Judie Noemie Hoilat ◽  
Ahmed Abu-Zaid ◽  
Ceren Durer ◽  
...  

BackgroundHepatic encephalopathy (HE) is defined as brain dysfunction that occurs because of acute liver failure or liver cirrhosis and is associated with significant morbidity and mortality. Lactulose is the standard of care till this date; however, polyethylene glycol (PEG) has gained the attention of multiple investigators.MethodsWe screened five databases namely PubMed, Scopus, Web of Science, Cochrane Library and Embase from inception to 10 February 2021. Dichotomous and continuous data were analysed using the Mantel-Haenszel and inverse variance methods, respectively, which yielded a meta-analysis comparing PEG versus lactulose in the treatment of HE.ResultsFour trials with 229 patients were included. Compared with lactulose, the pooled effect size demonstrated a significantly lower average HE Scoring Algorithm (HESA) Score at 24 hours (Mean difference (MD)=−0.68, 95% CI (−1.05 to –0.31), p<0.001), a higher proportion of patients with reduction of HESA Score by ≥1 grade at 24 hours (risk ratio (RR)=1.40, 95% CI (1.17 to 1.67), p<0.001), a higher proportion of patients with a HESA Score of grade 0 at 24 hours (RR=4.33, 95% CI (2.27 to 8.28), p<0.0010) and a shorter time to resolution of HE group (MD=−1.45, 95% CI (−1.72 to –1.18), p<0.001) in favour of patients treated with PEG.ConclusionPEG leads to a higher drop in the HESA Score and thus leads to a faster resolution of HE compared with lactulose.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danyang Tian ◽  
Linjing Zhang ◽  
Zhenhuang Zhuang ◽  
Tao Huang ◽  
Dongsheng Fan

AbstractObservational studies have shown that several risk factors are associated with cardioembolic stroke. However, whether such associations reflect causality remains unknown. We aimed to determine whether established and provisional cardioembolic risk factors are causally associated with cardioembolic stroke. Genetic instruments for atrial fibrillation (AF), myocardial infarction (MI), electrocardiogram (ECG) indices and N-terminal pro-brain natriuretic peptide (NT-pro BNP) were obtained from large genetic consortiums. Summarized data of ischemic stroke and its subtypes were extracted from the MEGASTROKE consortium. Causal estimates were calculated by applying inverse-variance weighted analysis, weighted median analysis, simple median analysis and Mendelian randomization (MR)-Egger regression. Genetically predicted AF was significantly associated with higher odds of ischemic stroke (odds ratio (OR): 1.20, 95% confidence intervals (CI): 1.16–1.24, P = 6.53 × 10–30) and cardioembolic stroke (OR: 1.95, 95% CI: 1.85–2.06, P = 8.81 × 10–125). Suggestive associations were found between genetically determined resting heart rate and higher odds of ischemic stroke (OR: 1.01, 95% CI: 1.00–1.02, P = 0.005), large-artery atherosclerotic stroke (OR: 1.02, 95% CI: 1.00–1.04, P = 0.026) and cardioembolic stroke (OR: 1.02, 95% CI: 1.00–1.04, P = 0.028). There was no causal association of P‐wave terminal force in the precordial lead V1 (PTFVI), P-wave duration (PWD), NT-pro BNP or PR interval with ischemic stroke or any subtype.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lars Harbaum ◽  
Jan K. Hennigs ◽  
Marcel Simon ◽  
Tim Oqueka ◽  
Henrik Watz ◽  
...  

Abstract Background Observational studies on the general population have suggested that airflow obstruction associates with left ventricular (LV) filling. To limit the influence of environmental risk factors/exposures, we used a Mendelian randomisation (MR) approach based on common genetic variations and tested whether a causative relation between airflow obstruction and LV filling can be detected. Methods We used summary statistics from large genome-wide association studies (GWAS) on the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) measured by spirometry and the LV end-diastolic volume (LVEDV) as assessed by cardiac magnetic resonance imaging. The primary MR was based on an inverse variance weighted regression. Various complementary MR methods and subsets of the instrument variables were used to assess the plausibility of the findings. Results We obtained consistent evidence in our primary MR analysis and subsequent sensitivity analyses that reducing airflow obstruction leads to increased inflow to the LV (odds ratio [OR] from inverse variance weighted regression 1.05, 95% confidence interval [CI] 1.01–1.09, P = 0.0172). Sensitivity analyses indicated a certain extent of negative horizontal pleiotropy and the estimate from biased-corrected MR-Egger was adjusted upward (OR 1.2, 95% CI 1.09–1.31, P < 0.001). Prioritisation of single genetic variants revealed rs995758, rs2070600 and rs7733410 as major contributors to the MR result. Conclusion Our findings indicate a causal relationship between airflow obstruction and LV filling in the general population providing genetic context to observational associations. The results suggest that targeting (even subclinical) airflow obstruction can lead to direct cardiac improvements, demonstrated by an increase in LVEDV. Functional annotation of single genetic variants contributing most to the causal effect estimate could help to prioritise biological underpinnings.


Sign in / Sign up

Export Citation Format

Share Document