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1.
EBioMedicine ; 74: 103727, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34871961

RESUMO

BACKGROUND: Pulmonary tuberculosis (TB) is one of the most deadly pathogens on earth. However, the majority of people have resistance to active disease. Further, some individuals, termed resisters (RSTRs), do not develop traditional latent tuberculosis (LTBI). The RSTR phenotype is important for understanding pathogenesis and preventing TB. The host genetic underpinnings of RSTR are largely understudied. METHODS: In a cohort of 908 Ugandan subjects with genome-wide data on single nucleotide polymorphisms, we assessed the heritability of the RSTR phenotype and other TB phenotypes using restricted maximum likelihood estimation (REML). We then used a subset of 263 RSTR and LTBI subjects with high quality phenotyping and long-term follow-up to identify DNA variants genome-wide associated with the RSTR phenotype relative to LTBI subjects in a case-control GWAS design and annotated and enriched these variants to better understand their role in TB pathogenesis. RESULTS: The heritability of the TB outcomes was very high, at 55% for TB vs. LTBI and 50.4% for RSTR vs. LTBI among HIV- subjects, controlling for age and sex. We identified 27 loci associated with the RSTR phenotype (P<5e-05) and our annotation and enrichment analyses suggest an important regulatory role for many of them. INTERPRETATION: The heritability results show that the genetic contribution to variation in TB outcomes is very high and our GWAS results highlight variants that may play an important role in resistance to infection as well as TB pathogenesis as a whole.

2.
Policy Polit Nurs Pract ; : 15271544211063828, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34873980

RESUMO

Widely acknowledged is the disproportionate number of COVID-19 cases among nursing home residents. This observational study examined the relationship between accreditation status and COVID-19 case rates in states where the numbers and proportions of Joint Commission accredited facilities made such comparisons possible (Illinois (IL), Florida (FL), and Massachusetts (MA)). COVID-19 data were accessed from the Centers for Medicare & Medicaid Services (CMS) Nursing Home Compare Public Use File, which included retrospective COVID-19 data submitted by nursing homes to the Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network. The outcome variable was the total number of nursing home-identified COVID-19 cases from June 2020 to January 2021. Joint Commission accreditation status was the independent variable. Mediating factors included state, and county-level case rates. Increases in the county rate had a significant association with higher nursing home COVID-19 case rates (p < .001). After adjusting for county case rates, no differences were observed in the mean group case rates for accredited and nonaccredited nursing homes. However, comparing predicted case rates to actual case rates revealed that accredited nursing homes were more closely aligned with their predicted rates. Performance of the nonaccredited nursing homes was more variable and had proportionally more outliers compared to accredited nursing homes. Community prevalence of COVID-19 is the strongest predictor of nursing home cases. While accreditation status did not have an impact on overall mean group performance, nonaccredited nursing homes had greater variation in performance and a higher proportion of negative outliers. Accreditation was associated with more consistent performance during the COVID-19 pandemic, despite being located in counties with a higher prevalence of COVID-19.

3.
J Med Entomol ; 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34908136

RESUMO

Integrated tick management (ITM) is a comprehensive strategy used to reduce presence of ticks and their associated pathogens. Such strategies typically employ a combination of host and non-host targeted treatments which often include fipronil-based, rodent-targeted bait boxes. Bait boxes target small-bodied rodents, specifically white-footed mice (Peromyscus leucopus Rafinesque) that not only play a crucial role in the blacklegged tick (Ixodes scapularis Say (Ixodida: Ixodidae)) life cycle, but also in the transmission of numerous pathogens, primarily Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner (Spirochaetales: Spirochaetaceae), the causal agent of Lyme disease. This study aimed to determine the effect of bait box deployment configuration on tick burden reduction while also further exploring bait consumption and P. leucopus abundances as measures of bait box usage and effectiveness. Boxes were deployed on nine properties within each of six neighborhoods (n = 54) in two different configurations: grid and perimeter. Multiple factors were analyzed as potential predictors for reduction in tick burdens using a backward stepwise selection procedure. Results confirmed the perimeter configuration was a more effective deployment strategy. In addition, overall P. leucopus abundance was a significant predictor of tick burden reduction while bait consumption was not. These findings not only further support the recommended perimeter deployment configuration but provide insight into effective utilization in areas of high P. leucopus abundance. The identification of this significant relationship, in addition to configuration, can be utilized by vector control professionals and homeowners to make informed decisions on bait box placement to make sustained impacts on the I. scapularis vector and associated pathogens within an ITM framework.

5.
J Clin Oncol ; : JCO2100941, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34928708

RESUMO

PURPOSE: We previously reported that enzalutamide improved overall survival when added to standard of care in metastatic, hormone-sensitive prostate cancer. Here, we report its effects on aspects of health-related quality of life (HRQL). METHODS: HRQL was assessed with the European Organisation for Research and Treatment of Cancer core quality-of-life questionnaire and QLM-PR25 at weeks 0, 4, 12, and then every 12 weeks until progression. Scores from week 4 to 156 were analyzed with repeated measures modeling to calculate group means and differences. Deterioration-free survival was from random assignment until the earliest of death, clinical progression, discontinuation of study treatment, or a worsening of 10 points or more from baseline in fatigue, physical function, cognitive function, or overall health and quality of life (OHQL). HRQL scores range from 0 (lowest possible) to 100 (highest possible). RESULTS: HRQL was assessed in 1,042 of 1,125 participants (93%). Differences in means favored control over enzalutamide for fatigue (5.2, 95% CI, 3.6 to 6.9; P < .001), cognitive function (4.0, 95% CI, 2.5 to 5.5; P < .001), and physical function (2.6, 95% CI, 1.3 to 3.9; P < .001), but not OHQL (1.2, 95% CI, -0.2 to 2.7; P = .1). Deterioration-free survival rates at 3 years, and log-rank P values comparing the whole distributions, favored enzalutamide over control for OHQL (31% v 17%; P < .0001), cognitive function (31% v 20%; P = .001), and physical function (31% v 22%; P < .001), but not fatigue (24% v 18%; P = .16). The effects of enzalutamide on HRQL were independent of baseline characteristics. CONCLUSION: Enzalutamide was associated with worsening of self-reported fatigue, cognitive function, and physical function, but not OHQL. Enzalutamide was associated with improved deterioration-free survival for OHQL, physical function, and cognitive function because delays in disease progression outweighed early deteriorations in these aspects of HRQL.

6.
Hum Genomics ; 15(1): 70, 2021 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-34903281

RESUMO

The genetic basis of phenotypic variation across populations has not been well explained for most traits. Several factors may cause disparities, from variation in environments to divergent population genetic structure. We hypothesized that a population-level polygenic risk score (PRS) can explain phenotypic variation among geographic populations based solely on risk allele frequencies. We applied a population-specific PRS (psPRS) to 26 populations from the 1000 Genomes to four phenotypes: lactase persistence (LP), melanoma, multiple sclerosis (MS) and height. Our models assumed additive genetic architecture among the polymorphisms in the psPRSs, as is convention. Linear psPRSs explained a significant proportion of trait variance ranging from 0.32 for height in men to 0.88 for melanoma. The best models for LP and height were linear, while those for melanoma and MS were nonlinear. As not all variants in a PRS may confer similar, or even any, risk among diverse populations, we also filtered out SNPs to assess whether variance explained was improved using psPRSs with fewer SNPs. Variance explained usually improved with fewer SNPs in the psPRS and was as high as 0.99 for height in men using only 548 of the initial 4208 SNPs. That reducing SNPs improves psPRSs performance may indicate that missing heritability is partially due to complex architecture that does not mandate additivity, undiscovered variants or spurious associations in the databases. We demonstrated that PRS-based analyses can be used across diverse populations and phenotypes for population prediction and that these comparisons can identify the universal risk variants.

7.
Elife ; 102021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34812141

RESUMO

Adaptations of the lower back to bipedalism are frequently discussed but infrequently demonstrated in early fossil hominins. Newly discovered lumbar vertebrae contribute to a near-complete lower back of Malapa Hominin 2 (MH2), offering additional insights into posture and locomotion in Australopithecus sediba. We show that MH2 possessed a lower back consistent with lumbar lordosis and other adaptations to bipedalism, including an increase in the width of intervertebral articular facets from the upper to lower lumbar column ('pyramidal configuration'). These results contrast with some recent work on lordosis in fossil hominins, where MH2 was argued to demonstrate no appreciable lordosis ('hypolordosis') similar to Neandertals. Our three-dimensional geometric morphometric (3D GM) analyses show that MH2's nearly complete middle lumbar vertebra is human-like in overall shape but its vertebral body is somewhat intermediate in shape between modern humans and great apes. Additionally, it bears long, cranially and ventrally oriented costal (transverse) processes, implying powerful trunk musculature. We interpret this combination of features to indicate that A. sediba used its lower back in both bipedal and arboreal positional behaviors, as previously suggested based on multiple lines of evidence from other parts of the skeleton and reconstructed paleobiology of A. sediba.

8.
Pathogens ; 10(11)2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34832643

RESUMO

Tuberculosis (TB) remains a major public health threat globally, especially in sub-Saharan Africa. Both human and Mycobacterium tuberculosis (MTBC) genetic variation affect TB outcomes, but few studies have examined if and how the two genomes interact to affect disease. We hypothesize that long-term coexistence between human genomes and MTBC lineages modulates disease to affect its severity. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which we identified three MTBC lineages, of which one, L4.6-Uganda, is clearly derived and hence recent. We quantified TB severity using the Bandim TBscore and examined the interaction between MTBC lineage and human single-nucleotide polymorphisms (SNPs) genome-wide, in two independent cohorts of TB cases (n = 149 and n = 127). We found a significant interaction between an SNP in PPIAP2 and the Uganda lineage (combined p = 4 × 10-8). PPIAP2 is a pseudogene that is highly expressed in immune cells. Pathway and eQTL analyses indicated potential roles between coevolving SNPs and cellular replication and metabolism as well as platelet aggregation and coagulation. This finding provides further evidence that host-pathogen interactions affect clinical presentation differently than host and pathogen genetic variation independently, and that human-MTBC coevolution is likely to explain patterns of disease severity.

9.
Neurology ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34706975

RESUMO

OBJECTIVE: People with epilepsy, one-third of whom in the US are on Medicaid, experience a wide range of chronic and physical comorbidities that influence their care and outcomes. In this study, we examine the burden and racial/ethnic disparities of chronic and acute conditions, injuries, and symptoms in a large and diverse group of people with epilepsy on Medicaid. METHODS: Using 5 years of Medicaid claims data we identified adult people with epilepsy and used all available claims and diagnoses to identify each person's Clinical Classification Codes groups diagnosed during the study period. Using association rule mining we identified the top combinations of conditions and stratified these by race/ethnicity to identify potential prevalence disparities. Additionally, we examined the top combinations of conditions in high utilizers - that is individuals in the top quartile of hospitalizations and emergency department visits. RESULTS: Among 81,963 patients the most common conditions were: anxiety and mood disorders (46.5%), hypertension (36.9%), back problems (35.2%), developmental disorders (31.6%), and headache (29.5%). When examining combinations of conditions, anxiety and mood disorders continued to have an outsized prevalence - appearing in nearly every combination. There were notable disparities in disease burden, with American Indians and Alaskan Natives having a substantially higher prevalence of developmental disabilities, while Black individuals had a higher prevalence of hypertension. These disparities persisted to the higher-order combinations that included these conditions. High utilizers had a much higher disease burden, with 75.8% having an anxiety or mood disorder, as well as a higher burden of injuries. SIGNIFICANCE: This study shows a high prevalence of psychiatric and physical conditions and identifies racial and ethnic disparities affecting people with epilepsy. Targeting interventions to consider the comorbidities, race and ethnicity has potential to improve clinical care and reduce disparities.

10.
Cancers (Basel) ; 13(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638382

RESUMO

PURPOSE: Hypoxia has been linked to radioresistance. Strategies to safely dose escalate dominant intraprostatic lesions have shown promising results, but further dose escalation to overcome the effects of hypoxia require a novel approach to constrain the dose in normal tissue.to safe levels. In this study, we demonstrate a biologically targeted radiotherapy (BiRT) approach that can utilise multiparametric magnetic resonance imaging (mpMRI) to target hypoxia for favourable treatment outcomes. METHODS: mpMRI-derived tumour biology maps, developed via a radiogenomics study, were used to generate individualised, hypoxia-targeting prostate IMRT plans using an ultra- hypofractionation schedule. The spatial distribution of mpMRI textural features associated with hypoxia-related genetic profiles was used as a surrogate of tumour hypoxia. The effectiveness of the proposed approach was assessed by quantifying the potential benefit of a general focal boost approach on tumour control probability, and also by comparing the dose to organs at risk (OARs) with hypoxia-guided focal dose escalation (DE) plans generated for five patients. RESULTS: Applying an appropriately guided focal boost can greatly mitigate the impact of hypoxia. Statistically significant reductions in rectal and bladder dose were observed for hypoxia-targeting, biologically optimised plans compared to isoeffective focal DE plans. CONCLUSION: Results of this study suggest the use of mpMRI for voxel-level targeting of hypoxia, along with biological optimisation, can provide a mechanism for guiding focal DE that is considerably more efficient than application of a general, dose-based optimisation, focal boost.

11.
Lancet ; 398(10305): 1075-1090, 2021 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-34370973

RESUMO

The management of prostate cancer continues to evolve rapidly, with substantial advances being made in understanding the genomic landscape and biology underpinning both primary and metastatic prostate cancer. Similarly, the emergence of more sensitive imaging methods has improved diagnostic and staging accuracy and refined surveillance strategies. These advances have introduced personalised therapeutics to clinical practice, with treatments targeting genomic alterations in DNA repair pathways now clinically validated. An important shift in the therapeutic framework for metastatic disease has taken place, with metastatic-directed therapies being evaluated for oligometastatic disease, aggressive management of the primary lesion shown to benefit patients with low-volume metastatic disease, and with several novel androgen pathway inhibitors significantly improving survival when used as a first-line therapy for metastatic disease. Research into the molecular characterisation of localised, recurrent, and progressive disease will undoubtedly have an impact on clinical management. Similarly, emerging research into novel therapeutics, such as targeted radioisotopes and immunotherapy, holds much promise for improving the lives of patients with prostate cancer.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Gerenciamento Clínico , Genômica/tendências , Imunoterapia/tendências , Neoplasias da Próstata/tratamento farmacológico , Humanos , Imageamento por Ressonância Magnética , Masculino , Gradação de Tumores , Neoplasias da Próstata/fisiopatologia
12.
Res Sq ; 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34341784

RESUMO

We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection ( ACE2, TMPRSS2, DPP4 , and LY6E ). We analyzed novel data from 2,012 ethnically diverse Africans and 15,997 individuals of European and African ancestry with electronic health records, and integrated with global data from the 1000GP. At ACE2 , we identified 41 non-synonymous variants that were rare in most populations, several of which impact protein function. However, three non-synonymous variants were common among Central African hunter-gatherers from Cameroon and are on haplotypes that exhibit signatures of positive selection. We identify strong signatures of selection impacting variation at regulatory regions influencing ACE2 expression in multiple African populations. At TMPRSS2 , we identified 13 amino acid changes that are adaptive and specific to the human lineage. Genetic variants that are targets of natural selection are associated with clinical phenotypes common in patients with COVID-19.

13.
Oncogene ; 40(40): 5963-5969, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34376808

RESUMO

The primary cause of gastric cancer is chronic infection with Helicobacter pylori (H. pylori), particularly the high-risk genotype cagA, and risk modification by human genetic variants. We studied 94 variants in 54 genes for association with gastric cancer, including rs2302615 in ornithine decarboxylase (ODC1), which may affect response to chemoprevention with the ODC inhibitor, eflornithine (difluoromethylornithine; DFMO). Our population-based, case-control study included 1366 individuals (664 gastric cancer cases and 702 controls) from Western Honduras, a high incidence region of Latin America. CagA seropositivity was strongly associated with cancer (OR = 3.6; 95% CI: 2.6, 5.1). The ODC1 variant rs2302615 was associated with gastric cancer (OR = 1.36; p = 0.018) in a model adjusted for age, sex, and CagA serostatus. Two additional single nucleotide polymorphisms (SNPs) in CASP1 (rs530537) and TLR4 (rs1927914) genes were also associated with gastric cancer in univariate models as well as models adjusted for age, sex, and CagA serostatus. The ODC1 SNP association with gastric cancer was stronger in individuals who carried the TT genotype at the associating TLR4 polymorphism, rs1927914 (OR = 1.77; p = 1.85 × 10-3). In conclusion, the ODC1 variant, rs2302615, is associated with gastric cancer and supports chemoprevention trials with DFMO, particularly in individuals homozygous for the T allele at rs1927914.

14.
Mil Med ; 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34424328

RESUMO

INTRODUCTION: Sleep disorders' are highly prevalent among U.S. active duty service members (ADSMs) and present well-documented challenges to military health, safety, and performance. In addition to increased need for sleep medicine services, a major barrier to effective sleep management has been a lack of alignment among patients, health providers, and economic-decision-makers. To address this gap in knowledge, the purpose of the present study was to engage diverse stakeholders vested in improving sleep disorders' management in the military. MATERIALS AND METHODS: We elicited feedback from ADSMs with sleep disorders (five focus group discussion, n = 26) and primary care managers (PCMs) (11 individual semi-structured interview) in two military treatment facilities (MTFs) in the National Capitol Region, in addition to national level military and civilian administrative stakeholders (11 individual semi-structured interview) about their experiences with sleep disorders' management in U.S. MTFs, including facilitators and barriers for reaching a definitive sleep diagnosis, convenience and effectiveness of sleep treatments, and key desired outcomes from interventions designed to address effectively sleep disorders in the U.S. military health care system (MHS). Recordings from focus groups and semi-structured interviews were transcribed verbatim and analyzed using QSR International's NVivo 12 software using inductive thematic analysis. The study was approved by Walter Reed National Military Medical Center Department of Research Programs. RESULTS: Active duty service members with sleep disorders often fail to recognize their need for professional sleep management. Whereas PCMs identified themselves as first-line providers for sleep disorders in the military, patients lacked confidence that PCMs can make accurate diagnoses and deliver effective sleep treatments. Active duty service members cited needs for expeditious treatment, educational support and care coordination, and support for obtaining sleep treatments during deployment. Challenges that PCMs identified for effective management include insufficient time during routine care visits, delays in scheduling testing procedures, and limited number of sleep specialists. Primary care managers suggested offering evidence-based telehealth tools and enhanced care coordination between PCMs and specialists; standardized medical education, materials, and tools; patient preparation before appointments; self-administered patient education; and including behavioral sleep specialists as part of the sleep management team. For administrative stakeholders, key outcomes of enhanced sleep management included (1) improved resource allocation and cost savings, and (2) improved ADSM safety, productivity, and combat effectiveness. CONCLUSION: Current military sleep management practices are neither satisfactory nor maximally effective. Our findings suggest that solving the military sleep problem will require sustained effort and ongoing collaboration from ADSM patients, providers, and health systems leaders. Important potential roles for telehealth and technology were identified. Future research should seek to enhance implementation of sleep management best practices to improve outcomes for patients, providers, MHS, and the military as a whole.

15.
BMC Cancer ; 21(1): 846, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294073

RESUMO

BACKGROUND: Prostate cancer is caused by genomic aberrations in normal epithelial cells, however clinical translation of findings from analyses of cancer cells alone has been very limited. A deeper understanding of the tumour microenvironment is needed to identify the key drivers of disease progression and reveal novel therapeutic opportunities. RESULTS: In this study, the experimental enrichment of selected cell-types, the development of a Bayesian inference model for continuous differential transcript abundance, and multiplex immunohistochemistry permitted us to define the transcriptional landscape of the prostate cancer microenvironment along the disease progression axis. An important role of monocytes and macrophages in prostate cancer progression and disease recurrence was uncovered, supported by both transcriptional landscape findings and by differential tissue composition analyses. These findings were corroborated and validated by spatial analyses at the single-cell level using multiplex immunohistochemistry. CONCLUSIONS: This study advances our knowledge concerning the role of monocyte-derived recruitment in primary prostate cancer, and supports their key role in disease progression, patient survival and prostate microenvironment immune modulation.


Assuntos
Perfilação da Expressão Gênica , Monócitos/metabolismo , Monócitos/patologia , Neoplasias da Próstata/genética , Transcriptoma , Microambiente Tumoral/genética , Biologia Computacional/métodos , Progressão da Doença , Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Imunofenotipagem , Estimativa de Kaplan-Meier , Masculino , Anotação de Sequência Molecular , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade
17.
medRxiv ; 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34230933

RESUMO

We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection (ACE2, TMPRSS2, DPP4, and LY6E). We analyzed novel data from 2,012 ethnically diverse Africans and 15,997 individuals of European and African ancestry with electronic health records, and integrated with global data from the 1000GP. At ACE2, we identified 41 non-synonymous variants that were rare in most populations, several of which impact protein function. However, three non-synonymous variants were common among Central African hunter-gatherers from Cameroon and are on haplotypes that exhibit signatures of positive selection. We identify strong signatures of selection impacting variation at regulatory regions influencing ACE2 expression in multiple African populations. At TMPRSS2, we identified 13 amino acid changes that are adaptive and specific to the human lineage. Genetic variants that are targets of natural selection are associated with clinical phenotypes common in patients with COVID-19.

18.
Am J Phys Anthropol ; 176(2): 283-294, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34227681

RESUMO

OBJECTIVES: One of the most contentious issues in paleoanthropology is the nature of the last common ancestor of humans and our closest living relatives, chimpanzees and bonobos (panins). The numerical composition of the vertebral column has featured prominently, with multiple models predicting distinct patterns of evolution and contexts from which bipedalism evolved. Here, we study total numbers of vertebrae from a large sample of hominoids to quantify variation in and patterns of regional and total numbers of vertebrae in hominoids. MATERIALS AND METHODS: We compile and study a large sample (N = 893) of hominoid vertebral formulae (numbers of cervical, thoracic, lumbar, sacral, caudal segments in each specimen) and analyze full vertebral formulae, total numbers of vertebrae, and super-regional numbers of vertebrae: presacral (cervical, thoracic, lumbar) vertebrae and sacrococcygeal vertebrae. We quantify within- and between-taxon variation using heterogeneity and similarity measures derived from population genetics. RESULTS: We find that humans are most similar to African apes in total and super-regional numbers of vertebrae. Additionally, our analyses demonstrate that selection for bipedalism reduced variation in numbers of vertebrae relative to other hominoids. DISCUSSION: The only proposed ancestral vertebral configuration for the last common ancestor of hominins and panins that is consistent with our results is the modal formula demonstrated by chimpanzees and bonobos (7 cervical-13 thoracic-4 lumbar-6 sacral-3 coccygeal). Hox gene expression boundaries suggest that a rostral shift in Hox10/Hox11-mediated complexes could produce the human modal formula from the proposal ancestral and panin modal formula.


Assuntos
Pan troglodytes , Coluna Vertebral , Animais , Antropologia Física , Antropometria , Evolução Biológica , Hominidae/anatomia & histologia , Hominidae/fisiologia , Humanos , Pan troglodytes/anatomia & histologia , Pan troglodytes/fisiologia , Coluna Vertebral/anatomia & histologia , Coluna Vertebral/fisiologia , Caminhada/fisiologia
19.
J Am Heart Assoc ; 10(15): e018373, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34325522

RESUMO

Background Previous studies of patients with nontraumatic subarachnoid hemorrhage (SAH) suggest better outcomes at hospitals with higher case and procedural volumes, but the shape of the volume-outcome curve has not been defined. We sought to establish minimum volume criteria for SAH and aneurysm obliteration procedures that could be used for comprehensive stroke center certification. Methods and Results Data from 8512 discharges in the National Inpatient Sample (NIS) from 2010 to 2011 were analyzed using logistic regression models to evaluate the association between clinical outcomes (in-hospital mortality and the NIS-SAH Outcome Measure [NIS-SOM]) and measures of hospital annual case volume (nontraumatic SAH discharges, coiling, and clipping procedures). Sensitivity and specificity analyses for the association of desirable outcomes with different volume thresholds were performed. During 8512 SAH hospitalizations, 28.7% of cases underwent clipping and 20.1% underwent coiling with rates of 21.2% for in-hospital mortality and 38.6% for poor outcome on the NIS-SOM. The mean (range) of SAH, coiling, and clipping annual case volumes were 30.9 (1-195), 8.7 (0-94), and 6.1 (0-69), respectively. Logistic regression demonstrated improved outcomes with increasing annual case volumes of SAH discharges and procedures for aneurysm obliteration, with attenuation of the benefit beyond 35 SAH cases/year. Analysis of sensitivity and specificity using different volume thresholds confirmed these results. Analysis of previously proposed volume thresholds, including those utilized as minimum standards for comprehensive stroke center certification, showed that hospitals with more than 35 SAH cases annually had consistently superior outcomes compared with hospitals with fewer cases, although some hospitals below this threshold had similar outcomes. The adjusted odds ratio demonstrating lower risk of poor outcomes with SAH annual case volume ≥35 compared with 20 to 34 was 0.82 for the NIS-SOM (95% CI, 0.71-094; P=0.0054) and 0.80 (95% CI, 0.68-0.93; P=0.0055) for in-hospital mortality. Conclusions Outcomes for patients with SAH improve with increasing hospital case volumes and procedure volumes, with consistently better outcomes for hospitals with more than 35 SAH cases per year.


Assuntos
Procedimentos Endovasculares/tendências , Hospitalização/tendências , Hospitais com Alto Volume de Atendimentos/tendências , Hospitais com Baixo Volume de Atendimentos/tendências , Procedimentos Neurocirúrgicos/tendências , Hemorragia Subaracnóidea/terapia , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Mortalidade Hospitalar/tendências , Humanos , Pacientes Internados , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/mortalidade , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
20.
BJU Int ; 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34273231

RESUMO

OBJECTIVE: To determine whether the addition of inhaled methoxyflurane to periprostatic infiltration of local anaesthetic (PILA) during transrectal ultrasonography-guided prostate biopsies (TRUSBs) improved pain and other aspects of the experience. PATIENTS AND METHODS: We conducted a multicentre, placebo-controlled, double-blind, randomized phase 3 trial, involving 420 men undergoing their first TRUSB. The intervention was PILA plus a patient-controlled device containing either 3 mL methoxyflurane, or 3 mL 0.9% saline plus one drop of methoxyflurane to preserve blinding. The primary outcome was the pain score (0-10) reported by the participant after 15 min. Secondary outcomes included ratings of other aspects of the biopsy experience, willingness to undergo future biopsies, urologists' ratings, biopsy completion, and adverse events. RESULTS: The mean (SE) pain scores 15 min after TRUSB were 2.51 (0.22) in those assigned methoxyflurane vs 2.82 (0.22) for placebo (difference 0.31, 95% confidence interval [CI] -0.75 to 0.14; P = 0.18). Methoxyflurane was associated with better scores for discomfort (difference -0.48, 95% CI -0.92 to -0.03; P = 0.035, adjusted [adj.] P = 0.076), whole experience (difference -0.50, 95% CI -0.92 to -0.08; P = 0.021, adj. P = 0.053), and willingness to undergo repeat biopsies (odds ratio 1.67, 95% CI 1.12-2.49; P = 0.01) than placebo. Methoxyflurane resulted in higher scores for drowsiness (difference +1.64, 95% CI 1.21-2.07; P < 0.001, adj. P < 0.001) and dizziness (difference +1.78, 95% CI 1.31-2.24; P < 0.001, adj. P < 0.001) than placebo. There was no significant difference in the number of ≥ grade 3 adverse events. CONCLUSIONS: We found no evidence that methoxyflurane improved pain scores at 15 min, however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.

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