Tag: statistics

Sci Rep. 2022 Oct 10;12(1):16953. doi: 10.1038/s41598-022-20452-9.

ABSTRACT

Musculoskeletal disorders (MSDs) are highly prevalent, burdensome, and putatively associated with an altered human resting muscle tone (HRMT). Osteopathic manipulative treatment (OMT) is commonly and effectively applied to treat MSDs and reputedly influences the HRMT. Arguably, OMT may modulate alterations in HRMT underlying MSDs. However, there is sparse evidence even for the effect of OMT on HRMT in healthy subjects. A 3 × 3 factorial randomised trial was performed to investigate the effect of myofascial release (MRT), muscle energy (MET), and soft tissue techniques (STT) on the HRMT of the corrugator supercilii (CS), superficial masseter (SM), and upper trapezius muscles (UT) in healthy subjects in Hamburg, Germany. Participants were randomised into three groups (1:1:1 allocation ratio) receiving treatment, according to different muscle-technique pairings, over the course of three sessions with one-week washout periods. We assessed the effect of osteopathic techniques on muscle tone (F), biomechanical (S, D), and viscoelastic properties (R, C) from baseline to follow-up (primary objective) and tested if specific muscle-technique pairs modulate the effect pre- to post-intervention (secondary objective) using the MyotonPRO (at rest). Ancillary, we investigate if these putative effects may differ between the sexes. Data were analysed using descriptive (mean, standard deviation, and quantiles) and inductive statistics (Bayesian ANOVA). 59 healthy participants were randomised into three groups and two subjects dropped out from one group (n = 20; n = 20; n = 19-2). The CS produced frequent measurement errors and was excluded from analysis. OMT significantly changed F (-0.163 [0.060]; p = 0.008), S (-3.060 [1.563]; p = 0.048), R (0.594 [0.141]; p < 0.001), and C (0.038 [0.017]; p = 0.028) but not D (0.011 [0.017]; p = 0.527). The effect was not significantly modulated by muscle-technique pairings (p > 0.05). Subgroup analysis revealed a significant sex-specific difference for F from baseline to follow-up. No adverse events were reported. OMT modified the HRMT in healthy subjects which may inform future research on MSDs. In detail, MRT, MET, and STT reduced the muscle tone (F), decreased biomechanical (S not D), and increased viscoelastic properties (R and C) of the SM and UT (CS was not measurable). However, the effect on HRMT was not modulated by muscle-technique interaction and showed sex-specific differences only for F.Trial registration German Clinical Trial Register (DRKS00020393).

PMID:36217012 | DOI:10.1038/s41598-022-20452-9

Nat Neurosci. 2022 Oct 10. doi: 10.1038/s41593-022-01165-8. Online ahead of print.

ABSTRACT

Voluntary movement requires communication from cortex to the spinal cord, where a dedicated pool of motor units (MUs) activates each muscle. The canonical description of MU function rests upon two foundational tenets. First, cortex cannot control MUs independently but supplies each pool with a common drive. Second, MUs are recruited in a rigid fashion that largely accords with Henneman’s size principle. Although this paradigm has considerable empirical support, a direct test requires simultaneous observations of many MUs across diverse force profiles. In this study, we developed an isometric task that allowed stable MU recordings, in a rhesus macaque, even during rapidly changing forces. Patterns of MU activity were surprisingly behavior-dependent and could be accurately described only by assuming multiple drives. Consistent with flexible descending control, microstimulation of neighboring cortical sites recruited different MUs. Furthermore, the cortical population response displayed sufficient degrees of freedom to potentially exert fine-grained control. Thus, MU activity is flexibly controlled to meet task demands, and cortex may contribute to this ability.

PMID:36216998 | DOI:10.1038/s41593-022-01165-8

Bone Marrow Transplant. 2022 Oct 10. doi: 10.1038/s41409-022-01839-8. Online ahead of print.

ABSTRACT

Donor lymphocyte infusion (DLI) is a treatment option to prevent or treat relapse after allogeneic hematopoietic cell transplantation (HCT). We here report data for 173 patients who received one or multiple DLIs after haploidentical-HCT with post-transplant cyclophosphamide (PTCY) at 47 EBMT centers from 2009 to 2018. Indication for DLI was: prophylactic for 59(34.3%), preemptive for 20(11.6%), and therapeutic for 93(54.1%). For the prophylactic group, the median number of DLIs was 1 (IQR:1-2.5) with a median first dose of 0.1 × 10⁶ CD3+ T cell/kg, for the preemptive 2 (IQR:1-3) with 0.5 × 10⁶ CD3+ T cell/kg, for the therapeutic 1 (IQR:1-3) with 1 × 10⁶CD3+ Tcell/kg, respectively. OS after first DLI was 61% (46-75%) for prophylactic, 40% (19-61%) for preemptive, and 22% (13-31%) for therapeutic. CI of II-IV aGVHD and cGVHD was 17%(7-27%) and 53% (40-67%) for the prophylactic, 20% (2-38%) and 21% (3-39%) for the preemptive, 17% (9-24%) and 24% (15-33%) for the therapeutic group, respectively. Our data show great variability in the indications and modalities of DLI across responding EBMT centers. Survival rates remain relatively low in patients with active disease. While the cumulative incidence of aGVHD appears acceptable, we showed a high incidence proportion of cGVHD in the prophylactic group, compared with preemptive and therapeutic DLI. These data should be investigated further in prospective clinical trials.

PMID:36216975 | DOI:10.1038/s41409-022-01839-8

Nat Med. 2022 Oct 10. doi: 10.1038/s41591-022-01970-5. Online ahead of print.

ABSTRACT

Previous research suggests a protective effect of vegetable consumption against chronic disease, but the quality of evidence underlying those findings remains uncertain. We applied a Bayesian meta-regression tool to estimate the mean risk function and quantify the quality of evidence for associations between vegetable consumption and ischemic heart disease (IHD), ischemic stroke, hemorrhagic stroke, type 2 diabetes and esophageal cancer. Increasing from no vegetable consumption to the theoretical minimum risk exposure level (306-372 g daily) was associated with a 23.2% decline (95% uncertainty interval, including between-study heterogeneity: 16.4-29.4) in ischemic stroke risk; a 22.9% (13.6-31.3) decline in IHD risk; a 15.9% (1.7-28.1) decline in hemorrhagic stroke risk; a 28.5% (-0.02-51.4) decline in esophageal cancer risk; and a 26.1% (-3.6-48.3) decline in type 2 diabetes risk. We found statistically significant protective effects of vegetable consumption for ischemic stroke (three stars), IHD (two stars), hemorrhagic stroke (two stars) and esophageal cancer (two stars). Including between-study heterogeneity, we did not detect a significant association with type 2 diabetes, corresponding to a one-star rating. Although current evidence supports increased efforts and policies to promote vegetable consumption, remaining uncertainties suggest the need for continued research.

PMID:36216936 | DOI:10.1038/s41591-022-01970-5

Aesthetic Plast Surg. 2022 Oct 10. doi: 10.1007/s00266-022-03131-y. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this study was to assess the effect of different grades of dermatochalasis (DC) and upper eyelid blepharoplasty (UEB) surgery on corneal epithelial thickness (CET), objectively using anterior segment-optical coherence tomography (AS-OCT) measurements.

METHODS: 90 eyes of patients with DC were divided into three groups according to the severity of the DC. Forty-one eyes of age and sex-matched patients without DC were randomly selected as the control group. The study did not include patients with more than 2 D of spherical refractive error and more than 1.5 D of astigmatism, a history of previous eyelid surgery, ocular surface disease, contact lens use, and ophthalmic eye drop use. CET measurements of all the patients were performed with an AS-OCT (RTVue-XR, Optovue Inc., USA).

RESULTS: There were statistically significant differences in the CET of the superior, superonasal, superotemporal, inferotemporal, and temporal sectors between the DC and control groups (p = 0.001, p = 0.02, p = 0.03, p = 0.02, p = 0.04, respectively). While there were no differences in CET among the sectors of the control group, there was a difference in CET among some sectors of the DC group. When the DC group was subdivided by severity, there was no difference between subgroups for CET across all sectors both preoperatively and postoperatively. In the measurements made 6 months after UEB surgery, the CET in all sectors increased statistically significantly compared to those measured in the preoperative period.

CONCLUSION: This study revealed that DC reshaped the corneal epithelium and UEB surgery restored this remodeling 6 months after surgery.

LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID:36216918 | DOI:10.1007/s00266-022-03131-y

Aesthetic Plast Surg. 2022 Oct 10. doi: 10.1007/s00266-022-03130-z. Online ahead of print.

ABSTRACT

BACKGROUND: Breast augmentation is the most performed cosmetic surgery in the world. Although smooth round implants are widely used, the trend in breast morphology change after dual-plane augmentation with such implants remains unclear. In this study, we analyzed the issue with the support of 3D scanning technology, which may help provide an objective basis for the evaluation of postoperative outcomes and the determination of follow-up time points.

METHODS: Patients undergoing dual-plane augmentation with smooth round implants were prospectively included in this study. The variation trend of postoperative breast morphology was analyzed by measuring the specified linear distance, body surface distance, breast projection, nipple position and breast volume at different follow-up time points (1st month, post-1M; 3rd month, post-3M; 6th month, post-6M; 12th month, post-12M).

RESULTS: A total of 18 patients were included in this study. During the postoperative follow-up period, breast height prolonged while interval of the medial border gradually widened. Breast width was maintained without significant alterations from post-1M. The N-MBB lengthened with shortening of the N-LBB, meanwhile the N-IMF was prolonged by 0.6 cm. Breast volume was gradually reduced with the decrease in breast projection. The position of the nipple gradually shifted laterally, superiorly, and posteriorly after surgery. There was no statistically significant difference between the linear distance at post-3M and post-12M, while the surface distance, breast projection, nipple position and breast volume tended to be stable at post-6M.

CONCLUSIONS: After dual-plane augmentation with smooth round implants, the base contour of the breast shifted outwards and downwards, and stabilized after 3 months. The remaining breast morphological parameters reached a relative steady state by post-6M, which could be regarded as the time point for objective evaluation of postoperative effect.

LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID:36216919 | DOI:10.1007/s00266-022-03130-z

Nat Microbiol. 2022 Oct 10. doi: 10.1038/s41564-022-01238-1. Online ahead of print.

ABSTRACT

Characterizing the genetic diversity of pathogens within the host promises to greatly improve surveillance and reconstruction of transmission chains. For bacteria, it also informs our understanding of inter-strain competition and how this shapes the distribution of resistant and sensitive bacteria. Here we study the genetic diversity of Streptococcus pneumoniae within 468 infants and 145 of their mothers by deep sequencing whole pneumococcal populations from 3,761 longitudinal nasopharyngeal samples. We demonstrate that deep sequencing has unsurpassed sensitivity for detecting multiple colonization, doubling the rate at which highly invasive serotype 1 bacteria were detected in carriage compared with gold-standard methods. The greater resolution identified an elevated rate of transmission from mothers to their children in the first year of the child’s life. Comprehensive treatment data demonstrated that infants were at an elevated risk of both the acquisition and persistent colonization of a multidrug-resistant bacterium following antimicrobial treatment. Some alleles were enriched after antimicrobial treatment, suggesting that they aided persistence, but generally purifying selection dominated within-host evolution. Rates of co-colonization imply that in the absence of treatment, susceptible lineages outcompeted resistant lineages within the host. These results demonstrate the many benefits of deep sequencing for the genomic surveillance of bacterial pathogens.

PMID:36216891 | DOI:10.1038/s41564-022-01238-1

Diabetologia. 2022 Oct 11. doi: 10.1007/s00125-022-05806-2. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: We examined the contribution of rare HNF1A variants to type 2 diabetes risk and age of diagnosis, and the extent to which their impact is affected by overall genetic susceptibility, across three ancestry groups.

METHODS: Using exome sequencing data of 160,615 individuals of the UK Biobank and 18,797 individuals of the BioMe Biobank, we identified 746 carriers of rare functional HNF1A variants (minor allele frequency ≤1%), of which 507 carry variants in the functional domains. We calculated polygenic risk scores (PRSs) based on genome-wide association study summary statistics for type 2 diabetes, and examined the association of HNF1A variants and PRS with risk of type 2 diabetes and age of diagnosis. We also tested whether the PRS affects the association between HNF1A variants and type 2 diabetes risk by including an interaction term.

RESULTS: Rare HNF1A variants that are predicted to impair protein function are associated with increased risk of type 2 diabetes in individuals of European ancestry (OR 1.46, p=0.049), particularly when the variants are located in the functional domains (OR 1.89, p=0.002). No association was observed for individuals of African ancestry (OR 1.10, p=0.60) or Hispanic-Latino ancestry (OR 1.00, p=1.00). Rare functional HNF1A variants were associated with an earlier age at diagnosis in the Hispanic-Latino population (β=-5.0 years, p=0.03), and this association was marginally more pronounced for variants in the functional domains (β=-5.59 years, p=0.03). No associations were observed for other ancestries (African ancestry β=-2.7 years, p=0.13; European ancestry β=-3.5 years, p=0.20). A higher PRS was associated with increased odds of type 2 diabetes in all ancestries (OR 1.61-2.11, p<10^-5) and an earlier age at diagnosis in individuals of African ancestry (β=-1.4 years, p=3.7 × 10^-6) and Hispanic-Latino ancestry (β=-2.4 years, p<2 × 10^-16). Furthermore, a higher PRS exacerbated the effect of the functional HNF1A variants on type 2 diabetes in the European ancestry population (p_interaction=0.037).

CONCLUSIONS/INTERPRETATION: We show that rare functional HNF1A variants, in particular those located in the functional domains, increase the risk of type 2 diabetes, at least among individuals of European ancestry. Their effect is even more pronounced in individuals with a high polygenic susceptibility. Our analyses highlight the importance of the location of functional variants within a gene and an individual’s overall polygenic susceptibility, and emphasise the need for more genetic data in non-European populations.

PMID:36216889 | DOI:10.1007/s00125-022-05806-2

Ann Intern Med. 2022 Oct 11. doi: 10.7326/M22-0835. Online ahead of print.

ABSTRACT

BACKGROUND: The effectiveness of screening for colorectal cancer (CRC) by sex and age in randomized trials is uncertain.

OBJECTIVE: To evaluate the 15-year effect of sigmoidoscopy screening on CRC incidence and mortality.

DESIGN: Pooled analysis of 4 large-scale randomized trials of sigmoidoscopy screening.

SETTING: Norway, the United States, the United Kingdom, and Italy.

PARTICIPANTS: Women and men aged 55 to 64 years at enrollment.

INTERVENTION: Sigmoidoscopy screening.

MEASUREMENTS: Primary end points were cumulative incidence rate ratio (IRR) and mortality rate ratio (MRR) and rate differences after 15 years of follow-up comparing screening versus usual care in intention-to-treat analyses. Stratified analyses were done by sex, cancer site, and age at screening.

RESULTS: Analyses comprised 274 952 persons (50.7% women), 137 493 in the screening and 137 459 in the usual care group. Screening attendance was 58% to 84%. After 15 years, the rate difference for CRC incidence was 0.51 cases (95% CI, 0.40 to 0.63 cases) per 100 persons and the IRR was 0.79 (CI, 0.75 to 0.83). The rate difference for CRC mortality was 0.13 deaths (CI, 0.07 to 0.19 deaths) per 100 persons, and the MRR was 0.80 (CI, 0.72 to 0.88). Women had less benefit from screening than men for CRC incidence (IRR for women, 0.84 [CI, 0.77 to 0.91]; IRR for men, 0.75 [CI, 0.70 to 0.81]; P = 0.032 for difference) and mortality (MRR for women, 0.91 [CI, 0.77 to 1.17]; MRR for men, 0.73 [CI, 0.64 to 0.83]; P = 0.025 for difference). There was no statistically significant difference in screening effect between persons aged 55 to 59 years and those aged 60 to 64 years.

LIMITATION: Data from the U.K. trial were less granular because of privacy regulations.

CONCLUSION: This pooled analysis of all large randomized trials of sigmoidoscopy screening demonstrates a significant and sustained effect of sigmoidoscopy on CRC incidence and mortality for 15 years.

PRIMARY FUNDING SOURCE: Health Fund of South-East Norway.

PMID:36215714 | DOI:10.7326/M22-0835

Ann Intern Med. 2022 Oct 11. doi: 10.7326/M22-0760. Online ahead of print.

ABSTRACT

BACKGROUND: It is important to document the performance of rapid antigen tests (Ag-RDTs) in detecting SARS-CoV-2 variants.

OBJECTIVE: To compare the performance of Ag-RDTs in detecting the Delta (B.1.617.2) and Omicron (B.1.1.529) variants of SARS-CoV-2.

DESIGN: Secondary analysis of a prospective cohort study that enrolled participants between 18 October 2021 and 24 January 2022. Participants did Ag-RDTs and collected samples for reverse transcriptase polymerase chain reaction (RT-PCR) testing every 48 hours for 15 days.

SETTING: The parent study enrolled participants throughout the mainland United States through a digital platform. All participants self-collected anterior nasal swabs for rapid antigen testing and RT-PCR testing. All Ag-RDTs were completed at home, whereas nasal swabs for RT-PCR were shipped to a central laboratory.

PARTICIPANTS: Of 7349 participants enrolled in the parent study, 5779 asymptomatic persons who tested negative for SARS-CoV-2 on day 1 of the study were eligible for this substudy.

MEASUREMENTS: Sensitivity of Ag-RDTs on the same day as the first positive (index) RT-PCR result and 48 hours after the first positive RT-PCR result.

RESULTS: A total of 207 participants were positive on RT-PCR (58 Delta, 149 Omicron). Differences in sensitivity between variants were not statistically significant (same day: Delta, 15.5% [95% CI, 6.2% to 24.8%] vs. Omicron, 22.1% [CI, 15.5% to 28.8%]; at 48 hours: Delta, 44.8% [CI, 32.0% to 57.6%] vs. Omicron, 49.7% [CI, 41.6% to 57.6%]). Among 109 participants who had RT-PCR-positive results for 48 hours, rapid antigen sensitivity did not differ significantly between Delta- and Omicron-infected participants (48-hour sensitivity: Delta, 81.5% [CI, 66.8% to 96.1%] vs. Omicron, 78.0% [CI, 69.1% to 87.0%]). Only 7.2% of the 69 participants with RT-PCR-positive results for shorter than 48 hours tested positive by Ag-RDT within 1 week; those with Delta infections remained consistently negative on Ag-RDTs.

LIMITATION: A testing frequency of 48 hours does not allow a finer temporal resolution of the analysis of test performance, and the results of Ag-RDTs are based on self-report.

CONCLUSION: The performance of Ag-RDTs in persons infected with the SARS-CoV-2 Omicron variant is not inferior to that in persons with Delta infections. Serial testing improved the sensitivity of Ag-RDTs for both variants. The performance of rapid antigen testing varies on the basis of duration of RT-PCR positivity.

PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute of the National Institutes of Health.

PMID:36215709 | DOI:10.7326/M22-0760