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Nevin Manimala Statistics

A comparison of statistical methods to predict the residual lifetime risk

Eur J Epidemiol. 2022 Jan 3. doi: 10.1007/s10654-021-00815-8. Online ahead of print.

ABSTRACT

Lifetime risk measures the cumulative risk for developing a disease over one’s lifespan. Modeling the lifetime risk must account for left truncation, the competing risk of death, and inference at a fixed age. In addition, statistical methods to predict the lifetime risk should account for covariate-outcome associations that change with age. In this paper, we review and compare statistical methods to predict the lifetime risk. We first consider a generalized linear model for the lifetime risk using pseudo-observations of the Aalen-Johansen estimator at a fixed age, allowing for left truncation. We also consider modeling the subdistribution hazard with Fine-Gray and Royston-Parmar flexible parametric models in left truncated data with time-covariate interactions, and using these models to predict lifetime risk. In simulation studies, we found the pseudo-observation approach had the least bias, particularly in settings with crossing or converging cumulative incidence curves. We illustrate our method by modeling the lifetime risk of atrial fibrillation in the Framingham Heart Study. We provide technical guidance to replicate all analyses in R.

PMID:34978669 | DOI:10.1007/s10654-021-00815-8

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Nevin Manimala Statistics

Association of milk intake with hay fever, asthma, and lung function: a Mendelian randomization analysis

Eur J Epidemiol. 2022 Jan 3. doi: 10.1007/s10654-021-00826-5. Online ahead of print.

ABSTRACT

BACKGROUND: Previous observational studies have indicated a protective effect of drinking milk on asthma and allergy. In Mendelian Randomization, one or more genetic variants are used as unbiased markers of exposure to examine causal effects. We examined the causal effect of milk intake on hay fever, asthma, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by using the lactase rs4988235 genotype associated with milk intake.

METHODS: We performed a Mendelian Randomization study including 363,961 participants from the UK Biobank.

RESULTS: Observational analyses showed that self-reported milk-drinkers vs. non-milk drinkers had an increased risk of hay fever: odds ratio (OR) = 1.36 (95% CI 1.32, 1.40, p < 0.001), asthma: OR = 1.33 (95% CI 1.38, 1.29, p < 0.001), yet a higher FEV1: β = 0.022 (SE = 0.004, p < 0.001) and FVC: β = 0.026 (SE = 0.005, p < 0.001). In contrast, genetically determined milk-drinking vs. not drinking milk was associated with a lower risk of hay fever: OR = 0.791 (95% CI 0.636, 0.982, p = 0.033), and asthma: OR = 0.587 (95% CI 0.442, 0.779, p = 0.001), and lower FEV1: β = – 0.154 (standard error, SE = 0.034, p < 0.001) liter, and FVC: β = – 0.223 (SE = 0.034, p < 0.001) liter in univariable MR analyses. These results were supported by multivariable Mendelian randomization analyses although not statistically significant.

CONCLUSIONS: As opposed to observational results, genetic association findings indicate that drinking milk has a protective effect on hay fever and asthma but may also have a negative effect on lung function. The results should be confirmed in other studies before any recommendations can be made.

PMID:34978666 | DOI:10.1007/s10654-021-00826-5

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Nevin Manimala Statistics

Are NOACs as safe and efficient as VKA regarding thromboembolic prophylaxis and major bleeding in patients with surgical bioprosthesis and atrial fibrillation within 3 months of surgery?

Interact Cardiovasc Thorac Surg. 2022 Jan 3:ivab363. doi: 10.1093/icvts/ivab363. Online ahead of print.

ABSTRACT

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: ‘Are NOACs as safe and efficient as vitamin K antagonist regarding thromboembolic prophylaxis and major bleeding in patients with surgical bioprosthesis and atrial fibrillation within 3 months of surgery?’ Altogether more than 324 papers were found using the reported search, of which 6 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The RIVER and ENAVLE trials showed non-inferiority of rivaroxaban (regarding mean time free from composite of death, major cardiovascular events or major bleeding at 12 months) and edoxaban (composite of death, clinical thromboembolic events or asymptomatic intracardiac thrombosis; and major bleeding) when compared with vitamin K antagonist. These studies include a low number of patients within 3 months of index surgery and overall low statistical power regarding this particular subgroup of patients. Data derived from lower evidence studies are compatible with the aforementioned findings. The available evidence suggests that non-vitamin K antagonist anticoagulants are as safe and as efficient as vitamin K antagonist regarding thromboembolic prophylaxis and bleeding event rates in patients with surgical bioprosthesis and atrial fibrillation within 3 months of bioprosthesis implantation. However, this evidence is derived from a limited number of studies with important methodological limitations. Expanding non-vitamin K antagonist anticoagulant recommendation to the early postoperative period warrants more confirmatory research.

PMID:34977926 | DOI:10.1093/icvts/ivab363

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Nevin Manimala Statistics

Improvement in colorectal cancer outcomes over time is limited to patients with left-sided disease

J Cancer Res Clin Oncol. 2022 Jan 3. doi: 10.1007/s00432-021-03868-0. Online ahead of print.

ABSTRACT

PURPOSE: Incidence and mortality of colorectal cancer (CRC) declined over the last decades. However, survival depends on the primary tumor location. It is unknown if all progress in outcomes vary depending on left-sided (LCRC) versus right-sided (RCC) colorectal cancer. We compare incidence and mortality rates over time according to the primary tumor location.

METHODS: Data from the Austrian National Cancer Registry spanning from 1983 to 2018 were used to calculate annual incidence and mortality rates and survival stratified by primary tumor localization and stage. Joinpoint regression with linear regression models were used on different subgroups to identify significant changes of incidence- and mortality slopes.

RESULTS: A total of 168,260 (incidence dataset) and 87,355 cases (mortality dataset) were identified. Survival of disseminated RCC was worse compared to LCRC (HR 1.14; CI 1.106-1.169). Total and LCRC incidence and mortality rates declined steadily over time, whereas the rates of RCC did not. Incidence of disseminated RCC declined significantly less (slope – 0.07; CI – 0.086; – 0.055) than in LCRC (slope – 0.159; CI – 0.183; – 0.136); mortality rate of RCC was unchanged over time. Incidence and mortality of localized RCC remained unchanged over time, whereas both rates declined independently of stage in LCRC.

CONCLUSION: Colorectal cancer outcomes during the last 35 years have preferentially improved in LCRC but not in RCC, indicating that the progress made is limited to LCRC. It is necessary to define RCC as a distinct form of CRC and to focus on specific strategies for its early detection and treatment.

PMID:34977964 | DOI:10.1007/s00432-021-03868-0

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Nevin Manimala Statistics

Spin Statistics for Triplet-Triplet Annihilation Upconversion: Exchange Coupling, Intermolecular Orientation, and Reverse Intersystem Crossing

JACS Au. 2021 Oct 13;1(12):2188-2201. doi: 10.1021/jacsau.1c00322. eCollection 2021 Dec 27.

ABSTRACT

Triplet-triplet annihilation upconversion (TTA-UC) has great potential to significantly improve the light harvesting capabilities of photovoltaic cells and is also sought after for biomedical applications. Many factors combine to influence the overall efficiency of TTA-UC, the most fundamental of which is the spin statistical factor, η, that gives the probability that a bright singlet state is formed from a pair of annihilating triplet states. The value of η is also critical in determining the contribution of TTA to the overall efficiency of organic light-emitting diodes. Using solid rubrene as a model system, we reiterate why experimentally measured magnetic field effects prove that annihilating triplets first form weakly exchange-coupled triplet-pair states. This is contrary to conventional discussions of TTA-UC that implicitly assume strong exchange coupling, and we show that it has profound implications for the spin statistical factor η. For example, variations in intermolecular orientation tune η from to through spin mixing of the triplet-pair wave functions. Because the fate of spin-1 triplet-pair states is particularly crucial in determining η, we investigate it in rubrene using pump-push-probe spectroscopy and find additional evidence for the recently reported high-level reverse intersystem crossing channel. We incorporate all of these factors into an updated model framework with which to understand the spin statistics of TTA-UC and use it to rationalize the differences in reported values of η among different common annihilator systems. We suggest that harnessing high-level reverse intersystem crossing channels in new annihilator molecules may be a highly promising strategy to exceed any spin statistical limit.

PMID:34977890 | PMC:PMC8715495 | DOI:10.1021/jacsau.1c00322

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Nevin Manimala Statistics

Cohort Profile: The COVID-19 in Pregnancy in Scotland (COPS) dynamic cohort of pregnant women to assess effects of viral and vaccine exposures on pregnancy

Int J Epidemiol. 2022 Jan 3:dyab243. doi: 10.1093/ije/dyab243. Online ahead of print.

NO ABSTRACT

PMID:34977922 | DOI:10.1093/ije/dyab243

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Nevin Manimala Statistics

Capturing the transcription factor interactome in response to sub-lethal insecticide exposure

Curr Res Insect Sci. 2021;1:None. doi: 10.1016/j.cris.2021.100018.

ABSTRACT

The increasing levels of pesticide resistance in agricultural pests and disease vectors represents a threat to both food security and global health. As insecticide resistance intensity strengthens and spreads, the likelihood of a pest encountering a sub-lethal dose of pesticide dramatically increases. Here, we apply dynamic Bayesian networks to a transcriptome time-course generated using sub-lethal pyrethroid exposure on a highly resistant Anopheles coluzzii population. The model accounts for circadian rhythm and ageing effects allowing high confidence identification of transcription factors with key roles in pesticide response. The associations generated by this model show high concordance with lab-based validation and identifies 44 transcription factors putatively regulating insecticide-responsive transcripts. We identify six key regulators, with each displaying differing enrichment terms, demonstrating the complexity of pesticide response. The considerable overlap of resistance mechanisms in agricultural pests and disease vectors strongly suggests that these findings are relevant in a wide variety of pest species.

PMID:34977825 | PMC:PMC8702396 | DOI:10.1016/j.cris.2021.100018

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Nevin Manimala Statistics

Abnormal Femoral Anteversion Is Associated With the Development of Hip Osteoarthritis: A Systematic Review and Meta-Analysis

Arthrosc Sports Med Rehabil. 2021 Sep 2;3(6):e2047-e2058. doi: 10.1016/j.asmr.2021.07.029. eCollection 2021 Dec.

ABSTRACT

PURPOSE: To perform a systematic review and meta-analysis of literature and to evaluate the relationship between abnormal femoral version and the development of hip osteoarthritis (OA).

METHODS: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, evaluating Level I and II studies. Included studies had to provide granular femoral version (FV) information. The severity of OA was ranked on the Kellgren-Lawrence (KL) scale. Excel version 1808 (Microsoft, Redmond, WA) was used to perform a student t test statistical analyses.

RESULTS: Our review identified 19 qualifying studies-5 Level I and 14 Level II with 1,756 patients. Patients with FV above normal range (>14°) had greater KL scores than patients with normal range FV (mean ± standard deviation; 3.37 ± 1.44 vs 2.05 ± 1.72, P < .05). Analysis of KL scores in patients with FV >24° (>1 standard deviation) versus patients with FV >14° but <24° also demonstrated a positive correlation between increasing FV and KL (4.00 ± 1.96 vs 2.34 ± 0). This was significant independent of the presence or absence of developmental dysplasia of the hip. Retroverted hips (FV<10°) in the present study showed variable OA results upon analysis.

CONCLUSIONS: The present review suggests that elevated FV may be a risk factor for more severe hip OA with or without the presence of concurrent dysplasia of the hip. The relative amount of increased anteversion appears positively correlated with severity of OA. Although femoral retroversion may impact hip mechanics, in this review it does not appear to strongly correlate with the development of OA.

LEVEL OF EVIDENCE: II: systematic review of Level I and II studies.

PMID:34977664 | PMC:PMC8689222 | DOI:10.1016/j.asmr.2021.07.029

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Nevin Manimala Statistics

Biomechanical Testing of Suture Anchor Versus Transosseous Tunnel Technique for Quadriceps Tendon Repair Yields Similar Outcomes: A Systematic Review

Arthrosc Sports Med Rehabil. 2021 Sep 30;3(6):e2059-e2066. doi: 10.1016/j.asmr.2021.08.013. eCollection 2021 Dec.

ABSTRACT

PURPOSE: To systematically review the literature to evaluate the biomechanical properties of the suture anchor (SA) versus transosseous tunnel (TO) techniques for quadriceps tendon (QT) repair.

METHODS: A systematic review was performed by searching PubMed, the Cochrane Library, and Embase using PRISMA guidelines to identify studies that evaluated the biomechanical properties of SA and TO techniques for repair of a ruptured QT. The search phrase used was “quadriceps tendon repair biomechanics”. Evaluated properties included ultimate load to failure (N), displacement (mm), stiffness (N/mm), and mode of failure.

RESULTS: Five studies met inclusion criteria, including a total of 72 specimens undergoing QT repair via the SA technique and 42 via the TO technique. Three of 4 studies found QTs repaired with SA to have significantly less elongation upon initial cyclic loading when compared to QTs repaired with the TO technique (P < .05). Three of 5 studies found QTs repaired with SA to have significantly less elongation upon final cyclic loading when compared to QTs repaired with the TO technique (P < .05). The pooled analysis from 4 studies reporting on initial displacement showed a statistically significant difference in favor of the SA group compared to the TO group (P = .03). The pooled analysis from studies reporting on secondary displacement and ultimate load to failure showed no significant difference between the SA and TO groups (P > .05). The most common mode of failure in both groups was suture slippage.

CONCLUSION: On the basis of the included cadaveric studies, QTs repaired via the SA technique have less initial displacement upon cyclic testing when compared to QTs repaired via the TO technique. However, final displacement and ultimate load to failure outcomes did not reveal differences between the two fixation strategies. Knot slippage remains a common failure method for both strategies.

PMID:34977665 | PMC:PMC8689238 | DOI:10.1016/j.asmr.2021.08.013

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Nevin Manimala Statistics

Three-Dimensional Magnetic Resonance Arthrography of Post-Arthroscopy Hip Instability Demonstrates Increased Effective Intracapsular Volume and Anterosuperior Capsular Changes

Arthrosc Sports Med Rehabil. 2021 Nov 28;3(6):e1999-e2006. doi: 10.1016/j.asmr.2021.09.022. eCollection 2021 Dec.

ABSTRACT

PURPOSE: To quantify the magnetic resonance arthrography (MRA) capsular morphologic findings associated with postarthroscopy hip instability.

METHODS: Among patients with clinically significant iatrogenic hip instability at a single center, patients with preindex and postindex surgery MRAs were identified. These MRAs were compared regarding effective intracapsular volume calculated by semi-automated 3-dimensional pixel intensity region segmentation, 2-dimensional anterior proximal intracapsular area in the femoral neck axial plane reconstruction, maximal anterior fluid pocket depth, capsule retraction distance, and capsular instability grade. Morphological measurements were conducted using Horos image processing software. Paired t-test, paired Wilcoxon signed rank test, and the McNemar test were used for identifying statistical significance.

RESULTS: In 42 patients, mean effective intracapsular volume was significantly greater in the postindex surgery MRAs (19.44 cm3 vs 17.26 cm3; P = .006). Proximal anterosuperior (12-3 o’clock) intracapsular area was also significantly greater after index surgery (2.84 cm2 vs 1.43 cm2; P < .001. Proximal anteroinferior (3-6 o’clock) intracapsular area (1.34 cm2 vs 0.97 cm2; P = .002), capsule deficiency grade (P < .001), anterior capsule retraction distance (4.83 mm vs 0.34 mm; P < .001), and maximum anterior fluid depth (8.33 mm vs 4.90 mm; P <.001) were also significantly increased after index surgery.

CONCLUSION: In comparison to the preoperative state, iatrogenic hip instability is associated with MRA findings that include increases in total effective intracapsular volume, proximal anterosuperior and anteroinferior intracapsular cross-sectional area, maximum proximal anterosuperior fluid depth, and capsule retraction distance.

LEVEL OF EVIDENCE: Level IV, diagnostic case series.

PMID:34977659 | PMC:PMC8689270 | DOI:10.1016/j.asmr.2021.09.022