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Nevin Manimala Statistics

Sodium-glucose cotransporter protein-2 inhibitors and glucagon-like peptide-1 receptor agonists versus thiazolidinediones for non-alcoholic fatty liver disease: A network meta-analysis

Acta Diabetol. 2022 Jan 6. doi: 10.1007/s00592-021-01830-7. Online ahead of print.

ABSTRACT

AIMS: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disorders worldwide. Some hypoglycemic drugs can improve NAFLD. However, it is unclear which of these types of hypoglycemic drugs are more effective for NAFLD. Therefore, we conducted a network meta-analysis to determine the effect of thiazolidinediones (TZDs), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists on NAFLD patients.

METHODS: A literature search of PubMed, EMBASE, the Cochrane Library, and Medline was conducted, and the literature from database inception up to April 30, 2021 was obtained. Liver function tests, lipid profiles, body mass index (BMI) and glycemic parameters were obtained from randomized controlled trials. Weighted mean differences (WMDs), relative risks and 95% confidence intervals (CIs) were calculated for continuous outcomes, and the I2 statistic was used to evaluate the heterogeneity of the studies.

RESULTS: In total, 22 trials, including 1361 patients, were selected. In direct meta-analysis, GLP-1 receptor agonists were superior to TZDs in decreasing alanine aminotransferase (WMD, -0.40, 95% CI: -0.60 to -0.20), γ-glutamyl transferase (WMD, -5.00, 95% CI: -6.47 to -3.53), BMI (WMD, -4.10, 95%CI: -6.55 to -1.65) and triglycerides (WMD, – 0.50, 95% CI: -0.68 to -0.32). Based on Bayesian network meta-analysis, the effect of SGLT-2 inhibitors on weight loss was superior to that of TZDs (WMD, -1.80, 95%CI: -3.30 to -0.41).

CONCLUSIONS: GLP-1 receptor agonists and SGLT-2 inhibitors improved liver enzymes, BMI, blood lipid, blood glucose and insulin resistance in NAFLD patients.

PMID:34988690 | DOI:10.1007/s00592-021-01830-7

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Impact of sacrocolpopexy for the management of pelvic organ prolapse on voiding dysfunction and uroflowmetry parameters: a prospective cohort study

Arch Gynecol Obstet. 2022 Jan 6. doi: 10.1007/s00404-021-06369-0. Online ahead of print.

ABSTRACT

PURPOSE: Voiding difficulties in the context of pelvic organ prolapse are often neglected or underestimated. To date, there are heterogeneous data available on the outcome of a surgical correction of pelvic organ prolapse and the impact on concomitant voiding dysfunction. The primary aim of this study was to evaluate whether laparoscopic sacrocolpopexy would resolve preoperative voiding dysfunction and the impact on objective uroflowmetry parameters.

METHODS: Data from 103 women undergoing sacrocolpopexy for prolapse stage ≥ II with concurrent objective and/or subjective voiding dysfunction were prospectively evaluated. All women underwent full urogynecological examination, and completed a validated questionnaire pre- and postoperatively. Objective uroflowmetry parameters and subjective outcome data regarding voiding functions were compared pre- and postoperatively.

RESULTS: All points of the POP-Q system improved significantly pre- to postoperatively (p < 0.001). Preoperatively, 42 of 103 women showed a postvoid residual ≥ 100 ml, whereas only six women had a relevant postvoid residual postoperatively. In total, the postoperative postvoid residual in all women decreased significantly (p < 0.001). Voiding time decreased significantly postoperatively (p < 0.001) with no significant change in the voided volume (p = 0.352). The maximum flow rate increased postoperatively, reaching no statistically significant change (p = 0.132). Subjective outcome measurements (weak or prolonged stream, incomplete bladder emptying, and straining to void) improved significantly (p < 0.001 for all the questions).

CONCLUSION: Our prospective study demonstrates that sacrocolpopexy to correct pelvic organ prolapse can successfully resolve voiding dysfunction, as both objective and subjective parameters improved significantly after surgery.

PMID:34988660 | DOI:10.1007/s00404-021-06369-0

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Interpretable generative deep learning: an illustration with single cell gene expression data

Hum Genet. 2022 Jan 6. doi: 10.1007/s00439-021-02417-6. Online ahead of print.

ABSTRACT

Deep generative models can learn the underlying structure, such as pathways or gene programs, from omics data. We provide an introduction as well as an overview of such techniques, specifically illustrating their use with single-cell gene expression data. For example, the low dimensional latent representations offered by various approaches, such as variational auto-encoders, are useful to get a better understanding of the relations between observed gene expressions and experimental factors or phenotypes. Furthermore, by providing a generative model for the latent and observed variables, deep generative models can generate synthetic observations, which allow us to assess the uncertainty in the learned representations. While deep generative models are useful to learn the structure of high-dimensional omics data by efficiently capturing non-linear dependencies between genes, they are sometimes difficult to interpret due to their neural network building blocks. More precisely, to understand the relationship between learned latent variables and observed variables, e.g., gene transcript abundances and external phenotypes, is difficult. Therefore, we also illustrate current approaches that allow us to infer the relationship between learned latent variables and observed variables as well as external phenotypes. Thereby, we render deep learning approaches more interpretable. In an application with single-cell gene expression data, we demonstrate the utility of the discussed methods.

PMID:34988661 | DOI:10.1007/s00439-021-02417-6

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Association between gene polymorphism and adverse effects in cancer patients receiving docetaxel treatment: a meta-analysis

Cancer Chemother Pharmacol. 2022 Jan 6. doi: 10.1007/s00280-021-04374-3. Online ahead of print.

ABSTRACT

PURPOSE: Large interindividual variability in the pharmacokinetic properties of docetaxel has been reported, with the clearance of docetaxel varying nearly six fold, in which pharmacogenetics of docetaxel may play an essential role in addition to physiological factors. The association between the gene polymorphism and risk of adverse clinical effects in docetaxel treated patients has been examined in several studies, but their conclusions are, to some extent, controversial. To clarify the role of gene polymorphism in the clinical outcomes of docetaxel treatment, a meta-analysis was performed in the present study.

METHODS: Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were employed to evaluate the impact of gene polymorphisms of CYP3A4, CYP3A5 and ABCB1. Four studies with 485 subjects were included in this study. Fixed or random-effects model was chosen according to heterogeneity to conduct the meta-analysis. Publication bias was evaluated by fail-safe numbers.

RESULTS: Significant association was identified between the ABCB1 C3435T (rs1045642) polymorphism and risk of short-term recurrent hematological toxicity (TT vs. CC + TC OR = 2.91, 95% CI 1.30-6.52, P = 0.009; TT vs. CC OR = 4.23, 95% CI 1.69-10.57 P = 0.002). The association of the ABCB1 G2677T/A (rs2032582) polymorphism with risk of fluid retention was statistically significant (T(A)/T(A) vs. GG + GT(A) OR = 2.08, 95% CI 1.16-3.73, P = 0.01). No statistically significant association between the CYP3A5 A6986G (rs776746) polymorphism and adverse effects was observed in this study. Due to the limitations of included literature, we did not conduct meta-analysis on CYP3A4 gene polymorphism and adverse effects.

CONCLUSION: An association between the ABCB1 C3435T (rs1045642), ABCB1 G2677T/A (rs2032582) polymorphism and risk of adverse effects of docetaxel was found by our meta-analysis. Namely, the TT homozygotes of the ABCB1 C3435T polymorphism may be associated with the risk of hematological toxicity. ABCB1 G2677T T(A)/T(A) genotype may be associated with the fluid retention.

TRAIL REGISTRATION: PROSPERO 2020 CRD42020203132.

PMID:34988655 | DOI:10.1007/s00280-021-04374-3

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The predictive validity and outcome of ICD-10 and DSM-5 short-lived psychotic disorders: a review and meta-analysis

Eur Arch Psychiatry Clin Neurosci. 2022 Jan 6. doi: 10.1007/s00406-021-01356-7. Online ahead of print.

ABSTRACT

The ICD-10 Classification of Mental and Behavioural Disorders introduced the category of ‘acute and transient psychotic disorders’ (ATPDs) encompassing polymorphic, schizophrenic and predominantly delusional subtypes, and the forthcoming ICD-11 revision has restricted it to polymorphic psychotic disorder, while the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) listed ‘brief psychotic disorder’ (BPD). To assess the predictive validity and outcome of ATPDs and BPD, relevant papers in English, French and German were searched in PubMed and Web of Science. Where possible meta-analysis of prognostic validators (diagnostic stability, course, outcome and response to treatment) was conducted. Fifty studies published between January 1993 and July 2019 were found. The clinical and functional outcome of ATPDs proved better than in schizophrenia and related disorders, but mortality risk is high, particularly suicide, and treatment trials provide little evidence. Meta-analysis of 25 studies (13,507 cases) revealed that 55% (95% CI 49-62) do not change diagnosis, 25% (95% CI 20-31) converted into schizophrenia and related disorders, and 12% (95% CI 7-16) into affective disorders on average over 6.3 years. Subgroup meta-analysis estimated prospective consistency of polymorphic psychotic disorder (55%; 95% CI 52-58) significantly greater than that of the ATPD subtypes with schizophrenic (OR 1.7; 95% CI 1.4-2.0) and predominantly delusional (OR 1.3; 95% CI 1.1-1.5) symptoms. Moreover, the diagnostic stability of BPD (13 studies; 294 cases) was 45% (95% CI 32-50) over a mean 4.2 years. Although these findings indicate that short-lived psychotic disorders have little predictive validity, significant differences among the ATPD subtypes support the revised ICD-11 ATPD category.

PMID:34988647 | DOI:10.1007/s00406-021-01356-7

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Red blood cell fatty acids and age-related macular degeneration in postmenopausal women

Eur J Nutr. 2022 Jan 6. doi: 10.1007/s00394-021-02746-2. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the relationship between red blood cell (RBC) polyunsaturated fatty acid (PUFA) levels, and dietary PUFA and fish intake, with prevalent and incident age-related macular degeneration (AMD) in a US cohort of postmenopausal women.

METHODS: This analysis included 1456 postmenopausal women from the Women’s Health Initiative (WHI) Clinical Trials. RBC PUFAs were measured from fasting serum samples collected at WHI baseline. Dietary PUFAs and fish intake were assessed via food frequency questionnaires at baseline. There were 240 women who had prevalent AMD and 138 who self-reported AMD development over 9.5 years. Adjusted odds ratios and 95% confidence intervals were estimated for prevalent AMD by RBC PUFA levels, dietary PUFA intake, and frequency of fish consumption. Adjusted hazard ratios and 95% confidence intervals were estimated for incident AMD. A p-for-trend was estimated for continuous measures of dietary PUFA and fish intake.

RESULTS: No significant association was found between prevalent or incident AMD and RBC docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), EPA, DHA, alpha-linolenic acid (ALA), linoleic acid (LA), or arachidonic acid (AA). A positive association was found between dietary intake of AA and odds of prevalent AMD (p-for-trend for continuous AA intake = 0.02) and between intake of LA/ALA and incident AMD (p-for-trend for continuous ratio of LA/ALA intake = 0.03). No statistically significant associations were found between AMD and dietary intake of PUFAs or fish.

CONCLUSIONS: RBC PUFAs were not associated with AMD in this cohort. Overall, dietary analyses of PUFAs supported this, excepting dietary AA intake and intake of LA in proportion to ALA of which there were trends of increased risk.

PMID:34988653 | DOI:10.1007/s00394-021-02746-2

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Nevin Manimala Statistics

Advantages of skin closure with subcuticular suture for liver resection on postoperative and cosmetic outcomes: a propensity matched analysis

Langenbecks Arch Surg. 2022 Jan 6. doi: 10.1007/s00423-021-02388-2. Online ahead of print.

ABSTRACT

PURPOSE: The effects of subcuticular sutures on postoperative and cosmetic outcomes in patients who underwent liver resection have not been well studied. Here, we investigated the advantages of subcuticular suture compared to skin stapler regarding open liver resection.

METHODS: We assessed 342 patients who underwent liver resection at Nara Medical University between 2008 and 2015. They were divided into two groups: subcuticular suture and staple groups. Baseline characteristics and perioperative outcomes were retrospectively compared using one-to-one propensity score matching analysis.

RESULTS: In this period, 179 patients underwent skin closure with subcuticular sutures and 163 patients underwent skin closure with staples. After propensity matching, 85 pairs of cases were matched. The incidence of wound infection was similar in the two groups (3.5% in the subcuticular suture group and 9.4% in the staple group; p = 0.119). The length of hospital stay was significantly shorter in the subcuticular suture group than in the staple group (10 days vs 15 days; p < 0.001). In addition, the rate of patients who were discharged within 7 days after surgery was statistically higher in the subcuticular group (21.1% vs 3.5%, p = 0.001). Hypertrophic scar 6 months after surgery was significantly less frequent in the subcuticular group (9.4% vs 25.9%, p = 0.010).

CONCLUSION: Subcuticular sutures might be advantageous for liver surgery reducing length of hospital stay and proportion of hypertrophic scar.

PMID:34988640 | DOI:10.1007/s00423-021-02388-2

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What happens to the gluteus medius in young and middle-aged patients with hip dysplasia?

Int Orthop. 2022 Jan 6. doi: 10.1007/s00264-021-05271-3. Online ahead of print.

ABSTRACT

BACKGROUND: Much research has focused on quantifying the bony characteristics of patients with developmental dysplasia of the hip (DDH). Far less attention, however, has been paid to muscle abnormalities around the hip such as those in the gluteus medius (GM).

METHODS: We retrospectively examined clinical and imaging data, such as the age of onset and computed tomography (CT) findings, in 108 consecutive hips. Subjects for the control group were selected from our radiology database. Two readers independently evaluated the length (LGM), cross-sectional area (CSA), width (WGM), and thickness (TGM) of the GM and arm of GM (AGM) and angle of the GM activation (AOA) and bony parameters including the acetabulum-head index (AHI), lateral central edge angle (LCEA), acetabular index (AI), femoral offset (FO), and height of the rotation centre of femoral head (HCFH) among all cases using the imaging data.

RESULTS: The patient group included 108 hips. The AGM, LGM, CSA, and TGM were lower in the DDH patients, while AOA was higher. However, there was no significant difference in the WGM between the two groups. Multiple linear regression analysis showed that AGM and AOA were independent factors affecting LCEA. The following regression equation was used: Y(LCEA) = 5.377 * X1 (AGM) – 0.310 * X2 (AOA) – 11.331. The mechanical characteristics of the GM and many bony parameters were significantly correlated (the AGM and AHI, LCEA, AI, FO, but not HCFH; AOA and AHI, LCEA, AI, but not FO or HCFH). The CSA was positively correlated with only HCFH. The rest were not statistical significance linear correlation. The multivariate regression results showed that the age of onset was positively correlated with AGM (r = 0.467). The regression equation used was Y = 9.0 * X (age of onset) – 11.4.

CONCLUSION: We found difference in the morphological and mechanical characteristics of the GM between hips with DDH and hips of normal morphology. Of note, the mechanical characteristics of the GM were influenced by bony parameters in patients with DDH.

PMID:34988620 | DOI:10.1007/s00264-021-05271-3

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Recurrence in traumatic anterior shoulder dislocations increases the prevalence of Hill-Sachs and Bankart lesions: a systematic review and meta-analysis

Knee Surg Sports Traumatol Arthrosc. 2022 Jan 6. doi: 10.1007/s00167-021-06847-7. Online ahead of print.

ABSTRACT

PURPOSE: The extent of shoulder instability and the indication for surgery may be determined by the prevalence or size of associated lesions. However, a varying prevalence is reported and the actual values are therefore unclear. In addition, it is unclear whether these lesions are present after the first dislocation and whether or not these lesions increase in size after recurrence. The aim of this systematic review was (1) to determine the prevalence of lesions associated with traumatic anterior shoulder dislocations, (2) to determine if the prevalence is higher following recurrent dislocations compared to first-time dislocations and (3) to determine if the prevalence is higher following complete dislocations compared to subluxations.

METHODS: PubMed, EMBASE, Cochrane and Web of Science were searched. Studies examining shoulders after traumatic anterior dislocations during arthroscopy or with MRI/MRA or CT published after 1999 were included. A total of 22 studies (1920 shoulders) were included.

RESULTS: The proportion of Hill-Sachs and Bankart lesions was higher in recurrent dislocations (85%; 66%) compared to first-time dislocations (71%; 59%) and this was statistically significant (P < 0.01; P = 0.05). No significant difference between recurrent and first-time dislocations was observed for SLAP lesions, rotator-cuff tears, bony Bankart lesions, HAGL lesions and ALPSA lesions. The proportion of Hill-Sachs lesions was significantly higher in complete dislocations (82%) compared to subluxations (54%; P < 0.01).

CONCLUSION: Higher proportions of Hill-Sachs and Bankart were observed in recurrent dislocations compared to first-time dislocations. No difference was observed for bony Bankart, HAGL, SLAP, rotator-cuff tear and ALPSA. Especially when a Hill-Sachs or Bankart is present after first-time dislocation, early surgical stabilization may need to be considered as other lesions may not be expected after recurrence and to limit lesion growth. However, results should be interpreted with caution due to substantial heterogeneity and large variance.

LEVEL OF EVIDENCE: IV.

PMID:34988633 | DOI:10.1007/s00167-021-06847-7

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Different FreeSurfer versions might generate different statistical outcomes in case-control comparison studies

Neuroradiology. 2022 Jan 6. doi: 10.1007/s00234-021-02862-0. Online ahead of print.

ABSTRACT

PURPOSE: Neuroimaging pipelines have long been known to generate mildly differing results depending on various factors, including software version. While considered generally acceptable and within the margin of reasonable error, little is known about their effect in common research scenarios such as inter-group comparisons between healthy controls and various pathological conditions. The aim of the presented study was to explore the differences in the inferences and statistical significances in a model situation comparing volumetric parameters between healthy controls and type 1 diabetes patients using various FreeSurfer versions.

METHODS: T1- and T2-weighted structural scans of healthy controls and type 1 diabetes patients were processed with FreeSurfer 5.3, FreeSurfer 5.3 HCP, FreeSurfer 6.0 and FreeSurfer 7.1, followed by inter-group statistical comparison using outputs of individual FreeSurfer versions.

RESULTS: Worryingly, FreeSurfer 5.3 detected both cortical and subcortical volume differences out of the preselected regions of interest, but newer versions such as FreeSurfer 5.3 HCP and FreeSurfer 6.0 reported only subcortical differences of lower magnitude and FreeSurfer 7.1 failed to find any statistically significant inter-group differences.

CONCLUSION: Since group averages of individual FreeSurfer versions closely matched, in keeping with previous literature, the main origin of this disparity seemed to lie in substantially higher within-group variability in the model pathological condition. Ergo, until validation in common research scenarios as case-control comparison studies is included into the development process of new software suites, confirmatory analyses utilising a similar software based on analogous, but not fully equivalent principles, might be considered as supplement to careful quality control.

PMID:34988592 | DOI:10.1007/s00234-021-02862-0