Nevin Manimala

PLoS One. 2022 Apr 21;17(4):e0263977. doi: 10.1371/journal.pone.0263977. eCollection 2022.

ABSTRACT

The results of a simulation-based evaluation of several policies for vaccine rollout are reported, particularly focusing on the effects of delaying the second dose of two-dose vaccines. In the presence of limited vaccine supply, the specific policy choice is a pressing issue for several countries worldwide, and the adopted course of action will affect the extension or easing of non-pharmaceutical interventions in the next months. We employ a suitably generalised, age-structure, stochastic SEIR (Susceptible → Exposed → Infectious → Removed) epidemic model that can accommodate quantitative descriptions of the major effects resulting from distinct vaccination strategies. The different rates of social contacts among distinct age-groups (as well as some other model parameters) are informed by a recent survey conducted in Greece, but the conclusions are much more widely applicable. The results are summarised and evaluated in terms of the total number of deaths and infections as well as life years lost. The optimal strategy is found to be one based on fully vaccinating the elderly/at risk as quickly as possible, while extending the time-interval between the two vaccine doses to 12 weeks for all individuals below 75 years old, in agreement with epidemic theory which suggests targeting a combination of susceptibility and infectivity. This policy, which is similar to the approaches adopted in the UK and in Canada, is found to be effective in reducing deaths and life years lost in the period while vaccination is still being carried out.

PMID:35446847 | DOI:10.1371/journal.pone.0263977

PLoS Comput Biol. 2022 Apr 21;18(4):e1010033. doi: 10.1371/journal.pcbi.1010033. eCollection 2022 Apr.

NO ABSTRACT

PMID:35446846 | DOI:10.1371/journal.pcbi.1010033

PLoS Comput Biol. 2022 Apr 21;18(4):e1010066. doi: 10.1371/journal.pcbi.1010066. Online ahead of print.

ABSTRACT

Machine learning-based classification approaches are widely used to predict host phenotypes from microbiome data. Classifiers are typically employed by considering operational taxonomic units or relative abundance profiles as input features. Such types of data are intrinsically sparse, which opens the opportunity to make predictions from the presence/absence rather than the relative abundance of microbial taxa. This also poses the question whether it is the presence rather than the abundance of particular taxa to be relevant for discrimination purposes, an aspect that has been so far overlooked in the literature. In this paper, we aim at filling this gap by performing a meta-analysis on 4,128 publicly available metagenomes associated with multiple case-control studies. At species-level taxonomic resolution, we show that it is the presence rather than the relative abundance of specific microbial taxa to be important when building classification models. Such findings are robust to the choice of the classifier and confirmed by statistical tests applied to identifying differentially abundant/present taxa. Results are further confirmed at coarser taxonomic resolutions and validated on 4,026 additional 16S rRNA samples coming from 30 public case-control studies.

PMID:35446845 | DOI:10.1371/journal.pcbi.1010066

PLoS One. 2022 Apr 21;17(4):e0252736. doi: 10.1371/journal.pone.0252736. eCollection 2022.

ABSTRACT

BACKGROUND: The correct estimation of fibre orientations is a crucial step for reconstructing human brain tracts. Bayesian Estimation of Diffusion Parameters Obtained using Sampling Techniques (bedpostx) is able to estimate several fibre orientations and their diffusion parameters per voxel using Markov Chain Monte Carlo (MCMC) in a whole brain diffusion MRI data, and it is capable of running on GPUs, achieving speed-up of over 100 times compared to CPUs. However, few studies have looked at whether the results from the CPU and GPU algorithms differ. In this study, we compared CPU and GPU bedpostx outputs by running multiple trials of both algorithms on the same whole brain diffusion data and compared each distribution of output using Kolmogorov-Smirnov tests.

RESULTS: We show that distributions of fibre fraction parameters and principal diffusion direction angles from bedpostx and bedpostx_gpu display few statistically significant differences in shape and are localized sparsely throughout the whole brain. Average output differences are small in magnitude compared to underlying uncertainty.

CONCLUSIONS: Despite small amount of differences in output between CPU and GPU bedpostx algorithms, results are comparable given the difference in operation order and library usage between CPU and GPU bedpostx.

PMID:35446840 | DOI:10.1371/journal.pone.0252736

Ann Hematol. 2022 Apr 20. doi: 10.1007/s00277-022-04840-9. Online ahead of print.

ABSTRACT

The optimal induction chemotherapy regimens for young adult patients with newly diagnosed acute myeloid leukemia (AML) are not well-defined since the lack of direct comparisons between emerging treatments. Network meta-analysis (NMA) is a statistical tool to integrate direct and indirect evidence to evaluate the effect of multiple interventions. Thus, we conducted an NMA to systematically assess the efficacy and safety of different inductions for these patients. PubMed, Embase, Cochrane Library, and Web of Science were searched from establishment to 2020-03-11. Randomized controlled trials (RCTs) using different inductions were included. We deemed 11 trials eligible, including 11 inductions with 5052 participants. Relative risk (RR) and 95% confidence intervals (CIs) were calculated. In terms of complete remission (CR) rate, DAC ranked highest and was significantly higher than IA (RR = 1.27, 95% CI (1.09-1.48)) and DA (RR = 1.28, 95% CI (1.13-1.46)) (p < 0.05). The ranking of DA + Pioglitazone was second only to that of DAC, followed by HAA. For early mortality, HAD, HAA, and DA + GO were significantly higher than DA/IA (p < 0.05). DAC and DA + Pioglitazone showed similar early mortality compared to DA/IA (p > 0.05). Regarding incidence of early grade 3-4 infection, no significant differences between interventions were observed. To conclude, among the included 11 induction regimens, DAC was potentially the top choice for young adult patients with newly diagnosed AML, with highest CR rate, low early mortality, and incidence of early infection. DA + Pioglitazone and HAA also showed a superiority over the others to achieve higher CR rate, while caution should be kept in mind due to the higher early mortality of HAA.

PMID:35445843 | DOI:10.1007/s00277-022-04840-9

Rheumatol Int. 2022 Apr 21. doi: 10.1007/s00296-022-05128-x. Online ahead of print.

ABSTRACT

The management of acute gout in the hospital setting may be challenging since most patients are elderly with multiple unstable comorbidities. However, there are no prospective clinical trials for hospitalized patients with gout to guide optimal management. Evidence indicates that steroids or adrenocorticotropic hormone (ACTH) may be effective and safe therapeutic options for these patients. This study aimed at directly comparing the efficacy and safety of ACTH vs betamethasone for the treatment of gout in hospitalized patients. This is the first prospective clinical trial for hospitalized patients with gout. We designed a randomized, open label study to assess the efficacy and safety of a single intramuscular injection of either ACTH or betamethasone in hospitalized patients with acute gout. Primary efficacy endpoints were the change in intensity of pain as recorded using a Visual Analogue Scale (VAS) at baseline compared to 24 h (ΔVAS24h), and 48 h. Moreover, we assessed safety and effects on the hypothalamic-pituitary-adrenal (HPA) axis, glucose and lipid homeostasis, bone metabolism, electrolytes and renal function. 38 patients were recruited. Both treatments were highly effective. The mean ± SE ΔVAS24h and ΔVAS48h for ACTH was 4.48 ± 0.29 and 5.58 ± 0.26, respectively. The mean ± SE ΔVAS24h and ΔVAS48h for betamethasone was 4.67 ± 0.32 and 5.67 ± 0.28, respectively. Direct comparison between the two groups at 24 h and 48 h did not show statistically significant differences. Both treatments were well tolerated and safe. The effects on all metabolic parameters were mostly minimal and transient for both treatments. However, ACTH may affect less the HPA axis and bone metabolism compared to betamethasone, thus leading to the conclusion that. ACTH and betamethasone are effective and safe for the management of acute gout in hospitalized patients but that ACTH may associate with less disturbance of the HPA axis and bone metabolism. Our data support the use of both drugs as first line treatments for hospitalized patients with gout.Clinical trial registration: ClinicalTrials.gov NCT04306653.

PMID:35445840 | DOI:10.1007/s00296-022-05128-x

Eur Radiol. 2022 Apr 21. doi: 10.1007/s00330-022-08746-y. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare the diagnostic performance of scapholunate gap (SLG) measurements acquired with dart throwing (DT), radio-ulnar deviation (RUD), and clenching fist (CF) maneuvers on 4D CT for the identification of scapholunate instability.

METHODS: In this prospective study, 47 patients with suspected scapholunate interosseous ligament (SLIL) tears were evaluated from March 2015 to March 2020 with semiautomatic quantitative analysis on 4D CT. Five parameters (median, maximal value, range, and coefficient of variation) for SLG, lunocapitate angle (LCA), and radioscaphoid angle (RSA) obtained during DT maneuver were evaluated in patients with and without SLIL tears. CT arthrography was used as the gold standard for the SLIL status. The SLG values obtained were also compared with those obtained during CF and RUD maneuvers.

RESULTS: Significant differences in all SLG- and LCA-derived parameters are found between patients with and without SLIL tears with DT (p < 0.003). The best diagnostic performance for the diagnosis of SLIL tears was obtained with median and maximal SLG values (sensitivity and specificity of 86-89% and 95%) and with maximal and range LCA values (sensitivity and specificity of 86% and 74%). No significant differences were observed for RSA values (p > 0.275). The SLG range obtained with DT maneuver was the only dynamic parameter statistically different between patients with partial and complete torn SLIL (p = 0.037).

CONCLUSION: 4D CT of the wrist during DT showed a similar performance than RUD and a better performance than CF for the differentiation between patients with and without SLIL tears.

KEY POINTS: • Four-dimensional computed tomography can dynamically assess scapholunate instability. • The best results for differentiating between patients with and without SLIL tears were obtained with SLG median and maximal values. • The dart throwing and radio-ulnar deviation maneuvers yielded the best results for the dynamic evaluation of scapholunate instability.

PMID:35445824 | DOI:10.1007/s00330-022-08746-y

Int Urogynecol J. 2022 Apr 21. doi: 10.1007/s00192-022-05195-5. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: To determine whether delayed administration of CXCL12 alters anorectal manometric pressures and histology in rats following anal sphincterotomy compared to primary surgical repair alone.

METHODS: Adult female rats were divided into three groups: A, a control group that did not undergo surgery; B, anal sphincterotomy with primary surgical repair; C, anal sphincterotomy with primary surgical repair and intra-sphincteric injection of CXCL12 at 6 weeks post-injury. All rats underwent anal manometry measurements at baseline and at 6 and 12 weeks post-injury. Histologic analysis of the anal sphincters was also performed.

RESULTS: At baseline and 6 weeks, there were no statistically significant differences among D, T_max and P∆ of Groups A, B and C. At 12-week manometry, the total duration of contractions on anal manometry was significantly less in Group C compared to Groups A and B (3.65, 5.5, 5.3 p < 0.01) as was time to peak of contraction at 12 weeks (1.6, 2.1, 3.1, p < 0.01); however, group C had a significantly higher P∆ at 12 weeks compared to Groups A and B (2.25, 1.4, 0.34, p < 0.01). There were no statistically significant differences in the ratio of muscle to collagen at the site of injury; however, muscle fibers were significantly smaller in group C and less per bundle than the other groups.

CONCLUSIONS: Administration of chemokine therapy at 6 weeks post-repair using CXCL12 enhanced the magnitude of anal sphincter contractions in a rat model of anal sphincter injury but decreased overall duration of contraction. Increased anal sphincter contraction magnitude was not explained by histologic differences in explanted specimens.

PMID:35445812 | DOI:10.1007/s00192-022-05195-5

Int Urogynecol J. 2022 Apr 21. doi: 10.1007/s00192-022-05100-0. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: Translabial ultrasound is currently regarded as one of the most promising modalities in the evaluation of female pelvic organ prolapse. However, abnormal bladder descent on pelvic floor ultrasound has not been established among Chinese women. This study aimed to establish optimal cutoffs for defining bladder prolapse among Chinese women using translabial ultrasound.

METHODS: In this prospective multicenter study, 674 women with symptoms of lower urinary tract dysfunction and/or pelvic floor dysfunction were finally included and underwent interview, Pelvic Organ Prolapse Quantification (POP-Q) examinations and 4D translabial ultrasound. The receiver-operating characteristic (ROC) statistic was used to assess accuracy and define the optimal cutoffs.

RESULTS: The mean patient age was 42.6 (range, 19-82) years. Multivariable analysis showed that both POP-Q assessment and translabial ultrasound findings for anterior compartment were significantly associated with prolapse symptoms. The ROC statistics suggested an optimal cutoff value of 10 mm below the symphysis pubis of bladder position on Valsalva for predicting prolapse symptoms, with an area under the curve (AUC) of 0.73. Compared to translabial ultrasound, POP-Q stage showed similar accuracy for predicting prolapse symptoms (AUC: 0.74; P = 0.79), with an optimal cutoff of POP-Q stage ≥ 2.

CONCLUSIONS: This study proposed that the descent of the bladder to ≥ 10 mm below the symphysis pubis on Valsalva should be proposed as an optimal cutoff value for defining abnormal bladder prolapse on translabial ultrasound among the Chinese population. These cutoff values are nearly identical to those previously established in mainly Caucasian women.

PMID:35445811 | DOI:10.1007/s00192-022-05100-0

Int Urogynecol J. 2022 Apr 21. doi: 10.1007/s00192-022-05206-5. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: Obstructive sleep apnea syndrome is associated with urological symptoms, including overactive bladder (OAB). This study aims to determine whether combined tolterodine and CPAP therapies are more effective for patients with OSAS than CPAP treatment only.

METHODS: Women who underwent polysomnography test and were diagnosed with moderate-to-severe OSAS with apnea-hypopnea index (AHI) were included in the study. Data were collected on AHI, OAB awareness-8-item tool (OAB-V8), incontinence questionnaire-urinary incontinence short form (ICIQ-UI-SF), total daily urine volume (DUV), and the Benefit, satisfaction with treatment and willingness (BSW) tool. Eligible patients were randomized to receive either CPAP treatment only or combined CPAP and tolterodine treatment for 3 months.

RESULTS: Among 103 participants, a total of 60 were included. Patients in both treatment arms showed significant improvements in OAB-V8, ICIQ-UI-SF, and total DUV compared to their baseline. The mean OAB-V8 was 15.7 at baseline and 5.6 at 3 months for the combined treatment arm and 16.6 and 7.6 at 3 months for the CPAP group only (mean baseline-adjusted between-group difference -1.1 [95% CI, -12.3 to -7.4]; p < 0.001). The improvement in the mean ICIQ-UI-SF was also statistically more significant in the combined therapy group than in the CPAP only arm (mean baseline-adjusted between-group difference -3.27 [95% CI, -4.6 to -1.59]; p < 0.001). No statistical significance was found in the improvement of total DUV between the groups.

CONCLUSIONS: In this study, combined use of tolterodine with CPAP provides beneficial effects to CPAP treatment only regarding OAB symptoms. Further research is required to confirm these findings in a large cohort.

PMID:35445808 | DOI:10.1007/s00192-022-05206-5