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1.
J Endocr Soc ; 8(11): bvae156, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39416426

RESUMO

Context: Body composition and glucose metabolism change with aging. Whether different levels of body-mass-index (BMI) are needed to define diabetes risk across the adult lifespan is unknown. Objective: This work aimed to investigate whether BMI similarly reflects relative fat mass (FM) and diabetes risk across age groups. Methods: Participants without diabetes from the Baltimore Longitudinal Study of Aging (973 men, 1073 women), stratified by age (<50, 50-59, 60-69, ≥70 years) and categorized by either World Health Organization (WHO)-defined BMI categories (for normal weight, overweight or obesity) or BMI quartiles. The primary exposure was BMI. The primary outcome was diabetes incidence. The relationship of BMI to dual-energy x-ray absorptiometry-derived FM was also investigated in older vs younger participants. Results: The median (range) follow-up time was 7.1 years (range, 0-29.0 years). Within WHO-defined BMI categories, different age groups demonstrated significantly different FM percentage, FM/lean mass, and waist circumference (P < .05). WHO-defined BMI categories for overweight and obesity were generally related to higher diabetes risk compared to normal weight in all ages except 50 to 59 years. When BMI was categorized by quartiles, diabetes incidence increased dramatically beginning in quartile 2 (23-25 kg/m2) in older groups. BMI cutoffs with equivalent diabetes incidence rate as BMI 25 kg/m2 and 30.0 kg/m2 in individuals younger than 50 years were 22.7 kg/m2 and 25.2 kg/m2 for ages 50 to 59 years; 22.8 kg/m2 and 25.0 kg/m2 for ages 60 to 69 years; and 23.2 kg/m2 and 25.8 kg/m2 for ages 70 years and older, respectively. Conclusion: WHO-defined BMI categories do not reflect similar diabetes risk across the lifespan. Diabetes incidence is greater at lower levels of BMI in older adults and may lead to underestimation of diabetes risk with aging, particularly among those traditionally classified as normal-weight individuals.

2.
Neurosurgery ; 95(2): 297-304, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38376157

RESUMO

BACKGROUND AND OBJECTIVES: Severe traumatic brain injury (sTBI) represents a diffuse, heterogeneous disease where therapeutic targets for optimizing clinical outcome remain unclear. Mean pressure reactivity index (PRx) values have demonstrated associations with clinical outcome in sTBI. However, the retrospective derivation of a mean value diminishes its bedside significance. We evaluated PRx temporal profiles for patients with sTBI and identified time thresholds suggesting optimal neuroprognostication. METHODS: Patients with sTBI and continuous bolt intracranial pressure monitoring were identified. Outcomes were dichotomized by disposition status ("good outcome" was denoted by home and acute rehabilitation). PRx values were obtained every minute by taking moving correlation coefficients of intracranial pressures and mean arterial pressures. Average PRx trajectories for good and poor outcome groups were calculated by extending the last daily averaged PRx value to day 18. Each patient also had smoothed PRx trajectories that were used to generate "candidate features." These "candidate features" included daily average PRx's, cumulative first-order changes in PRx and cumulative second-order changes in PRx. Changes in sensitivity over time for predicting poor outcome was then evaluated by generating penalized logistic regression models that were derived from the "candidate features" and maximized specificity. RESULTS: Among 33 patients with sTBI, 18 patients achieved good outcome and 15 patients had poor outcome. Average PRx trajectories for the good and poor outcome groups started on day 6 and consistently diverged at day 9. When targeting a specificity >83.3%, an 85% maximum sensitivity for determining poor outcome was achieved at hospital day 6. Subsequent days of PRx monitoring showed diminishing sensitivities. CONCLUSION: Our findings suggest that in a population of sTBI, PRx sensitivities for predicting poor outcome was maximized at hospital day 6. Additional study is warranted to validate this model in larger populations.


Assuntos
Lesões Encefálicas Traumáticas , Pressão Intracraniana , Humanos , Lesões Encefálicas Traumáticas/fisiopatologia , Lesões Encefálicas Traumáticas/diagnóstico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Pressão Intracraniana/fisiologia , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem , Idoso , Prognóstico
3.
Mil Med ; 189(9-10): e1890-e1902, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38345098

RESUMO

INTRODUCTION: Musculoskeletal (MSK) injury is an inherent risk for military personnel that can potentially impact job performance, productivity, and military readiness. Evidence is needed to show the efficacy of nonpharmacological, self-managed therapies to reduce MSK symptoms at common injury sites that are feasible for use during expeditionary operations and home stations. This systematic review and meta-analysis identified, summarized, and synthesized available evidence from randomized and non-randomized trials on the effectiveness of self-managed, home-use therapies to improve pain, muscle strength, and physical performance in military personnel with MSK injuries, when compared to controls. METHODS: The electronic databases of MEDLINE ALL Ovid, Embase.com, Cochrane Library, Scopus, Clinicaltrial.gov, and CINAHL Complete via EBSCO were systematically searched for relevant reports published in English. Utilizing the Covidence platform and consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, multiple reviewers, using pre-determined data fields, screened for eligibility, assessed risk of bias (RoB), and performed data extraction. Evaluation of treatment effectiveness was determined using multilevel mixed-effects meta-analysis. RESULTS: The database and register search yielded 1,643 reports that were screened for eligibility. After screening of titles/abstracts and full texts, 21 reports were identified for evidence synthesis. Of these, two reports were excluded and two described the same study, resulting in a final list of 18 studies (19 reports). For quality assessment, the overall RoB for the 18 studies was categorized as 33.3% low risk, 55.6% with some concerns, and 11.1% high risk. Across the five domains of bias, 70% of the reports were classified as low risk. This systematic review found that the differences in interventions, outcome measures, and design between the studies were associated with a substantial degree of heterogeneity (I2 = 60.74%), with a small overall improvement in outcomes of the interventions relative to their specific control (standard mean difference 0.28; 95% CI, 0.12 to 0.45). There were varying degrees of heterogeneity for individual body regions. This was due, in part, to a small number of studies per bodily location and differences in the study designs. For the neck/shoulder, heterogeneity was moderate, with the clearest positive effect being for physical performance outcomes via other medical devices. For the back, there was substantial heterogeneity between studies, with modest evidence that pain was favorably improved by other medical devices and exercise interventions. For the leg, one study showed a clear large effect for other medical devices (shockwave treatment) on pain with substantial heterogeneity. The best evidence for positive effects was for the knee, with mainly negligible heterogeneity and some benefits from bracing, electrotherapy, and exercise. CONCLUSION: Evidence showed small beneficial effects in pain, strength, and physical performance by individual body regions for some interventions, compared to controls. The best evidence for a positive effect was for the knee. The findings suggest that some benefit may be obtained by including several treatments during deployment in austere environments and prolonged casualty care scenarios of military personnel with MSK injuries. Further research is warranted to better assess the potential benefits of using these treatments during deployments in austere environments as part of an individualized, multimodal approach for MSK injuries.


Assuntos
Militares , Músculo Esquelético , Doenças Musculoesqueléticas , Humanos , Doenças Musculoesqueléticas/terapia , Sistema Musculoesquelético/lesões , Músculo Esquelético/lesões
4.
Neurocrit Care ; 40(2): 689-697, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37610640

RESUMO

BACKGROUND: Continuous infusion ketamine has demonstrated efficacy in the management of refractory seizures yet does not suppress respiratory drive like other continuous infusion anesthetics (CIAs) used for this indication. The aim of this study is to describe the safety and efficacy of ketamine infusions in patients with refractory seizure without intubation. METHODS: We analyzed a retrospective cohort of adult patients who were not intubated at the time of initiation of a ketamine infusion for refractory seizures. Seizure onset was determined to be the first clinical seizure or nonconvulsive seizure reported on electroencephalography (EEG) or the start time of EEG for patients with seizures at EEG initiation. Responders were defined as patients with resolution of seizures within 24 h of initiation without the need for intubation or an additional CIA. RESULTS: A total of 28 patients were analyzed (median age 62 years, 64.3% female, 82.1% African American, 82.1% with structural seizure etiology, and 85.7% focal seizures). Of patients, 78.5% received an initial bolus averaging 0.9 mg/kg, and the majority (89.3%) were initiated on an infusion at 10 µg/kg/minute; median duration was 39.8 h. Maximum infusion rates were 10 µg/kg/minute in 16 patients, 20 µg/kg/minute in seven patients, and 30 µg/kg/minute in five patients. Of patients, 71.4% were assessed to be ketamine responders; six of the eight nonresponders required intubation and an additional CIA. Responders were 80% more likely to have received ketamine 5 or more hours earlier than nonresponders. Hypotension (systolic blood pressure < 90 mmHg) occurred in 31.8% of patients receiving only ketamine, which did not correlate with duration or maximum dose of ketamine; hypertension (systolic blood pressure > 180 mmHg) occurred in 39.3%. CONCLUSIONS: Ketamine represents a safe and effective treatment option for refractory seizures and has potential to reduce morbidity associated with intubation in a carefully selected patient population. Early initiation may increase the likelihood of success.


Assuntos
Ketamina , Estado Epiléptico , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Ketamina/efeitos adversos , Estado Epiléptico/tratamento farmacológico , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Intubação
5.
Mil Med ; 189(Suppl 1): 31-38, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37956329

RESUMO

INTRODUCTION: Military nurses comprise the largest percentage of military health care providers. In the current military health care system, they have two roles: (1) Patient care in military treatment facilities (MTFs) and (2) patient care during combat operations. Although in MTFs, the military nurse's roles are similar to those of their civilian counterpart, their roles are unique and varied in the combat operational environment. These combined roles lead to questions regarding readiness training to ensure that nurses are proficient in both MTFs and combat operational settings where treatment requirements may differ. The purpose of this paper is to (1) present the current state of educational readiness programs to maintain a ready medical force that entail formal teaching programs, military-civilian partnerships, and joint exercises of combat simulations, and (2) identify gaps as presented in an evidence-based practice educational panel. METHODS: On March 11, 2022, TriService Nursing Research Program hosted the virtual First Military Evidence-Based Practice Summit from the Uniformed Services University of the Health Sciences in Bethesda, MD. As part of the summit, an evidence-based practice education panel discussed the availability of current evidence-driven military medical readiness programs and identified gaps in the integration of military readiness for nursing personnel into the Defense Health Agency and Armed Services. RESULTS: The panel participants discussed the separate requirements for training within the MTFs and in combat operational settings. The available training programs identified by the panel were primarily those developed in local MTF settings to meet local needs. Although these programs support the MTFs' peacetime mission, competing roles, limited time, and limited funds contributed to limited preparation of nursing personnel in skills associated with combat-related injuries and illnesses. Prolonged casualty care has become an important focus for the Department of Defense as greater considerations are directed to wartime operations in austere expeditionary environments. Although there is some training available that is specific for prolonged casualty care, the focus has been the adaptation of combat casualty care during contingency operations. A keynote here was the concept that combat casualty care training must include both development of individual skills and integration of the team since maximal care can be achieved only when the individual and the team operate as a unit. A key point was the utility of central repositories for storing information related to training a ready medical force at individual and unit levels and that these repositories could also be used to collect and facilitate the accession of current evidence-based information. DISCUSSION: Optimal patient care at all levels of the military health system requires training that maximizes individual and unit skills specific to the environment at an MTF or in a combat operational setting. Training must be designed to incorporate evidence-driven knowledge in all military settings with guidance that is specific to the environment. CONCLUSION: Enhanced communication of evidence-based training and knowledge is an important component of maintaining a ready medical force for broader medical support of combat contingency operations.


Assuntos
Medicina , Medicina Militar , Militares , Humanos , Prática Clínica Baseada em Evidências , Medicina Militar/educação
6.
Mil Med ; 189(Suppl 1): 51-56, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37956330

RESUMO

INTRODUCTION: The incidence of perioperative pressure injuries (PPIs) at a military medical treatment facility (MTF) increased from three PPI events in 2018 to five PPI events in the first half of 2019. The purpose of this quality improvement initiative was to determine whether an evidence-based PPI prevention program introduced during the second half of 2019 reduced pressure injuries compared to the previous 1.5 years that followed the standard of care for perioperative patient positioning. METHODS: We used a multidisciplinary quality improvement PPI prevention approach that included education, Scott Triggers® patient risk assessment, application of a five-layer silicone dressing to at-risk surgical position sites, and feedback via multidisciplinary postoperative rounding. RESULTS: There was an observed decrease in the rate of PPIs from 0.62 to 0.00 per 1,000 patient surgeries during the 26-month period that this protocol was implemented. CONCLUSION: This project was conducted at a major MTF using a multidisciplinary PPI prevention approach that may be of value in reducing PPIs in other settings. This approach seems worthy of further investigation and may be applicable to other military MTFs and in deployed settings.


Assuntos
Militares , Úlcera por Pressão , Humanos , Úlcera por Pressão/prevenção & controle , Melhoria de Qualidade , Medição de Risco/métodos , Incidência
7.
Front Oncol ; 13: 1174831, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37637062

RESUMO

Introduction: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC), increasing lifetime risk of CRC by up to 70%. Despite this higher lifetime risk, disease penetrance in LS patients is highly variable and most LS patients undergoing CRC surveillance will not develop CRC. Therefore, biomarkers that can correctly and consistently predict CRC risk in LS patients are needed to both optimize LS patient surveillance and help identify better prevention strategies that reduce risk of CRC development in the subset of high-risk LS patients. Methods: Normal-appearing colorectal tissue biopsies were obtained during repeat surveillance colonoscopies of LS patients with and without a history of CRC, healthy controls (HC), and patients with a history of sporadic CRC. Biopsies were cultured in an ex-vivo explant system and their supernatants were assayed via multiplexed ELISA to profile the local immune signaling microenvironment. High quality cytokines were identified using the rxCOV fidelity metric. These cytokines were used to perform elastic-net penalized logistic regression-based biomarker selection by computing a new measure - overall selection probability - that quantifies the ability of each marker to discriminate between patient cohorts being compared. Results: Our study demonstrated that cytokine based local immune microenvironment profiling was reproducible over repeat visits and sensitive to patient LS-status and CRC history. Furthermore, we identified sets of cytokines whose differential expression was predictive of LS-status in patients when compared to sporadic CRC patients and in identifying those LS patients with or without a history of CRC. Enrichment analysis based on these biomarkers revealed an LS and CRC status dependent constitutive inflammatory state of the normal appearing colonic mucosa. Discussion: This prospective pilot study demonstrated that immune profiling of normal appearing colonic mucosa discriminates LS patients with a prior history of CRC from those without it, as well as patients with a history of sporadic CRC from HC. Importantly, it suggests the existence of immune signatures specific to LS-status and CRC history. We anticipate that our findings have the potential to assess CRC risk in individuals with LS and help in preemptively mitigating it by optimizing surveillance and identifying candidate prevention targets. Further studies are required to validate our findings in an independent cohort of LS patients over multiple visits.

8.
J Neurol Sci ; 450: 120691, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37267816

RESUMO

BACKGROUND: Pressure reactivity index (PRx) utilizes moving correlation coefficients from intracranial pressure (ICP) and mean arterial pressures to evaluate cerebral autoregulation. We evaluated patients with poor-grade subarachnoid hemorrhage (SAH), identified their PRx trajectories over time, and identified threshold time points where PRx could be used for neuroprognostication. METHODS: Patients with poor-grade SAH were identified and received continuous bolt ICP measurements. Dichotomized outcomes were based on ninety-day modified Rankin scores and disposition. Smoothed PRx trajectories for each patient were created to generate "candidate features" that looked at daily average PRx, cumulative first-order changes in PRx, and cumulative second-order changes in PRx. "Candidate features" were then used to perform penalized logistic regression analysis using poor outcome as the dependent variable. Penalized logistic regression models that maximized specificity for poor outcome were generated over several time periods and evaluated how sensitivities changed over time. RESULTS: 16 patients with poor-grade SAH were evaluated. Average PRx trajectories for the good (PRx < 0.25) and poor outcome groups (PRx > 0.5) started diverging at post-ictus day 8. When targeting specificities ≥88% for poor outcome, sensitivities for poor outcome consistently increased to >70% starting at post-ictus days 12-14 with a maximum sensitivity of 75% occurring at day 18. CONCLUSIONS: Our results suggest that by using PRx trends, early neuroprognostication in patients with SAH and poor clinical exams may start becoming apparent at post-ictus day 8 and reach adequate sensitivities by post-ictus days 12-14. Further study is required to validate this in larger poor-grade SAH populations.


Assuntos
Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Humanos , Estudos Retrospectivos , Pressão Sanguínea/fisiologia , Modelos Logísticos , Pressão Intracraniana/fisiologia , Circulação Cerebrovascular/fisiologia
9.
medRxiv ; 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36945451

RESUMO

Introduction: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC), increasing lifetime risk of CRC by up to 70%. Despite this higher lifetime risk, disease penetrance in LS patients is highly variable and most LS patients undergoing CRC surveillance will not develop CRC. Therefore, biomarkers that can correctly and consistently predict CRC risk in LS patients are needed to both optimize LS patient surveillance and help identify better prevention strategies that reduce risk of CRC development in the subset of high-risk LS patients. Methods: Normal-appearing colorectal tissue biopsies were obtained during repeat surveillance colonoscopies of LS patients with and without a history of CRC, healthy controls (HC), and patients with a history of sporadic CRC. Biopsies were cultured in an ex-vivo explant system and their supernatants were assayed via multiplexed ELISA to profile the local immune signaling microenvironment. High quality cytokine signatures were identified using rx COV fidelity metric. These signatures were used to perform biomarker selection by computing their selection probability based on penalized logistic regression. Results: Our study demonstrated that cytokine based local immune microenvironment profiling was reproducible over repeat visits and sensitive to patient LS-status and CRC history. Furthermore, we identified sets of biomarkers whose differential expression was predictive of LS-status in patients when compared to sporadic CRC patients and in identifying those LS patients with or without a history of CRC. Enrichment analysis based on these biomarkers revealed an LS and CRC status dependent constitutive inflammatory state of the normal appearing colonic mucosa. Discussion: This prospective pilot study demonstrated that immune profiling of normal appearing colonic mucosa discriminates LS patients with a prior history of CRC from those without it, as well as patients with a history of sporadic CRC from HC. Importantly, it suggests existence of immune signatures specific to LS-status and CRC history. We anticipate that our findings have the potential to assess CRC risk in individuals with LS and help in preemptively mitigating it by optimizing surveillance and identifying candidate prevention targets. Further studies are required to validate our findings in an independent cohort of LS patients over multiple visits.

10.
Mil Med ; 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36807977

RESUMO

INTRODUCTION: The high prevalence of patellofemoral pain in military service members results in strength loss, pain, and functional limitations during required physical performance tasks. Knee pain is often the limiting factor during high-intensity exercise for strengthening and functional improvement, thus limiting certain therapies. Blood flow restriction (BFR) improves muscle strength when combined with resistance or aerobic exercise and may serve as a possible alternative to high-intensity training during recovery. In our previous work, we showed that Neuromuscular electrical stimulation (NMES) improves pain, strength, and function in patellofemoral pain syndrome (PFPS), which led us to ask whether the addition of BFR to NMES would result in further improvements. This randomized controlled trial compared knee and hip muscle strength, pain, and physical performance of service members with PFPS who received BFR-NMES (80% limb occlusion pressure [LOP]) or BFR-NMES set at 20 mmHg (active control/sham) over 9 weeks. METHODS: This randomized controlled trial randomly assigned 84 service members with PFPS to one of the two intervention groups. In-clinic BFR-NMES was performed two times per week, while at-home NMES with exercise and at-home exercise alone were performed on alternating days and omitted on in-clinic days. The outcome measures included strength testing of knee extensor/flexor and hip posterolateral stabilizers, 30-second chair stand, forward step-down, timed stair climb, and 6-minute walk. RESULTS: Improvement was observed in knee extensor (treated limb, P < .001) and hip strength (treated hip, P = .007) but not flexor over 9 weeks of treatment; however, there was no difference between high BFR (80% LOP) and BFR-sham. Physical performance and pain measures showed similar improvements over time with no differences between groups. In analyzing the relationship between the number of BFR-NMES sessions and the primary outcomes, we found significant relationships with improvements in treated knee extensor strength (0.87 kg/session, P < .0001), treated hip strength (0.23 kg/session, P = .04), and pain (-0.11/session, P < .0001). A similar set of relationships was observed for the time of NMES usage for treated knee extensor strength (0.02/min, P < .0001) and pain (-0.002/min, P = .002). CONCLUSION: NMES strength training offers moderate improvements in strength, pain, and performance; however, BFR did not provide an additive effect to NMES plus exercise. Improvements were positively related to the number of BFR-NMES treatments and NMES usage.

11.
Sci Rep ; 13(1): 88, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596931

RESUMO

Immunoassay based bioanalytical measurements are widely used in a variety of biomedical research and clinical settings. In these settings they are assumed to faithfully represent the experimental conditions being tested and the sample groups being compared. Although significant technical advances have been made in improving sensitivity and quality of the measurements, currently no metrics exist that objectively quantify the fidelity of the measured analytes with respect to noise associated with the specific assay. Here we introduce ratio of cross-coefficient-of-variation (rxCOV), a fidelity metric for objectively assessing immunoassay analyte measurement quality when comparing its differential expression between different sample groups or experimental conditions. We derive the metric from first principles and establish its feasibility and applicability using simulated and experimental data. We show that rxCOV assesses fidelity independent of statistical significance, and importantly, identifies when latter is meaningful. We also discuss its importance in the context of averaging experimental replicates for increasing signal to noise ratio. Finally, we demonstrate its application in a Lynch Syndrome case study. We conclude by discussing its applicability to multiplexed immunoassays, other biosensing assays, and to paired and unpaired data. We anticipate rxCOV to be adopted as a simple and easy-to-use fidelity metric for performing robust and reproducible biomedical research.


Assuntos
Imunoensaio , Imunoensaio/métodos , Razão Sinal-Ruído
12.
Mil Med ; 188(1-2): 12-19, 2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34510214

RESUMO

INTRODUCTION: Low back pain (LBP) is a major cause of visits to ambulatory care, missed duty time, and disability discharge. The subacute phase of LBP presents an opportune time to prevent chronicity and lessen recurrence. The goal of this randomized controlled trial (RCT) was to determine the relative effectiveness of neuromuscular electrical stimulation (NMES) training and a progressive exercise program (PEP) on improving physical performance, pain, and torso strength in U.S. service members with subacute LBP, compared to standard primary care management (PCM) alone. METHODS: This is an Institutional Review Board-approved protocol for an RCT conducted with active duty military personnel (n = 128) at Fort Campbell, Kentucky, between April 2018 and March 2020. Participants were randomized to receive NMES (n = 43), PEP (n = 42), or PCM (n = 43) for 9 weeks. Outcome measures of physical performance (sit-ups, push-ups, walking, and torso endurance), torso muscle strength (flexion and extension), and pain were assessed at baseline and after 3, 6, and 9 weeks. Analysis was intent-to-treat using linear mixed effects models. A sensitivity analysis was performed to address the protocol deviations that occurred in response to coronavirus disease 2019 pandemic, which required rescheduling 17 in-person study visits to home assessments at 9-week testing. RESULTS: Evidence was found for group differences in physical performance for sit-ups and push-ups, with NMES showing greater improvement than PCM. The two groups showed similar improvements in torso muscle strength, although the NMES groups may show better improvement during early treatment. No group differences in pain levels were observed during the intervention, and all groups improved during the course of the study period. The amount of NMES muscle stimulation was directly related to the level of improvement, which was not the case for the hours reported for PEP exercise. CONCLUSION: In an active duty population with subacute LBP, integrating NMES strength training into the rehabilitation therapy may offer a modest benefit for increasing sit-ups and push-ups and improving torso strength.


Assuntos
COVID-19 , Dor Lombar , Militares , Humanos , Dor Lombar/terapia , Tronco , Músculo Esquelético
13.
Int J Epidemiol ; 52(1): 71-86, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35726641

RESUMO

BACKGROUND: Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. METHODS: Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. RESULTS: In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. CONCLUSIONS: These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.


Assuntos
Fator de Crescimento Insulin-Like I , Neoplasias da Próstata , Masculino , Humanos , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Estudos Prospectivos , Análise da Randomização Mendeliana , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Fatores de Risco , Estudos de Casos e Controles
14.
Int J Cancer ; 151(7): 1033-1046, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35579976

RESUMO

Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet  = .0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.


Assuntos
Neoplasias da Próstata , Globulina de Ligação a Hormônio Sexual , Biomarcadores , Humanos , Masculino , Análise da Randomização Mendeliana , Próstata , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Fatores de Risco , Globulina de Ligação a Hormônio Sexual/análise , Testosterona
15.
J Neurointerv Surg ; 14(6): 623-627, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34433646

RESUMO

BACKGROUND: Mobile stroke units (MSUs) performance dependability and diagnostic yield of 16-slice, ultra-fast CT with auto-injection angiography (CTA) of the aortic arch/neck/circle of Willis has not been previously reported. METHODS: We performed a prospective observational study of the first-of-its kind MSU equipped with high resolution, 16-slice CT with multiphasic CTA. Field CT/CTA was performed on all suspected stroke patients regardless of symptom severity or resolution. Performance dependability, efficiency and diagnostic yield over 365 days was quantified. RESULTS: 1031 MSU emergency activations occurred; of these, 629 (61%) were disregarded with unrelated diagnoses, and 402 patients transported: 245 (61%) ischemic or hemorrhagic stroke, 17 (4%) transient ischemic attack, 140 (35%) other neurologic emergencies. Total time from non-contrast CT/CTA start to images ready for viewing was 4.0 (IQR 3.5-4.5) min. Hemorrhagic stroke totaled 24 (10%): aneurysmal subarachnoid hemorrhage 3, hemorrhagic infarct 1, and 20 intraparenchymal hemorrhages (median intracerebral hemorrhage score was 2 (IQR 1-3), 4 (20%) spot sign positive). In 221 patients with ischemic stroke, 73 (33%) received alteplase with 31.5% treated within 60 min of onset. CTA revealed large vessel occlusion in 66 patients (30%) of which 9 (14%) were extracranial; 27 (41%) underwent thrombectomy with onset to puncture time averaging 141±90 min (median 112 (IQR 90-139) min) with full emergency department (ED) bypass. No imaging needed to be repeated for image quality; all patients were triaged correctly with no inter-hospital transfer required. CONCLUSIONS: MSU use of advanced imaging including multiphasic head/neck CTA is feasible, offers high LVO yield and enables full ED bypass.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral Hemorrágico , Acidente Vascular Cerebral , Angiografia , Isquemia Encefálica/cirurgia , Angiografia Cerebral , Angiografia por Tomografia Computadorizada/métodos , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Tomografia Computadorizada por Raios X
16.
Mil Med ; 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34950952

RESUMO

INTRODUCTION: The purpose of this quality improvement project was to develop and evaluate the use of an electronic medication request dashboard to reduce the amount of time required for medication processing and decrease time lost to workflow interruptions during patient discharge. Delayed discharges are associated with increased health care costs and adverse patient outcomes. Processing of medication requests at discharge contributes to these delays and to workflow interruptions for nursing and pharmacy staff at the project site. Electronic dashboards have been successfully implemented in multiple medical settings to streamline patient processing and enhance communication. MATERIALS AND METHODS: The Human Protections Office at Carl R. Darnall Army Medical Center (Fort Hood, TX) reviewed and approved the project with a non-human research determination. A multi-disciplinary workgroup with representatives from nursing, pharmacy, and health information technology (HIT) was formed to develop the dashboard. Based on a logic flow diagram of the desired communication, HIT created a medication request form and status dashboard using SharePoint and Nintex workflows. The dashboard was implemented for a 30-day pilot on a 25-bed medical/surgical nursing unit. The time required for medication processing, the time from discharge order to patient exit, the number of phone calls between nursing and pharmacy, and the usability of the medication request process were measured before and after implementation. The results were analyzed with descriptive statistics and evaluated for statistical significance with a P value ≤.05. RESULTS: With implementation of the dashboard, the average medication processing time decreased from 125 minutes to 48 minutes (P < .0001), and the average patient discharge time decreased from 137 minutes to 117 minutes (P = .002). The usability score of the medication request process increased from 40 to 87 for nursing (P < .0001) and from 62 to 85 for pharmacy (P = .003). The total number of voice calls between nursing and pharmacy decreased from 1,115 to 434, while the total time on voice calls decreased from 33 hours and 50 minutes to 13 hours and 19 minutes (P < .0001). CONCLUSIONS: The electronic dashboard is an effective method to enhance interdisciplinary communication during patient discharge and significantly reduces medication processing times. However, despite the medication processing time decreasing by over an hour, the discharge time only decreased by 20 minutes. Additional investigation is needed to evaluate other contributors to delayed discharge. A key limitation of this study was the convenience sampling used over a 30-day pilot on a single unit. The process has since been adopted by the entire hospital, and additional analysis could better reveal the impact to the organization. This communication system shows high usability and reduces phone call interruptions for both nursing and pharmacy staff. Additionally, this technology could easily be applied to other communication pathways or request processes across military medicine.

17.
Am J Physiol Gastrointest Liver Physiol ; 320(3): G396-G410, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33355506

RESUMO

Poor translatability of animal disease models has hampered the development of new inflammatory bowel disorder (IBD) therapeutics. We describe a preclinical, ex vivo system using freshly obtained and well-characterized human colorectal tissue from patients with ulcerative colitis (UC) and healthy control (HC) participants to test potential therapeutics for efficacy and target engagement, using the JAK/STAT inhibitor tofacitinib (TOFA) as a model therapeutic. Colorectal biopsies from HC participants and patients with UC were cultured and stimulated with multiple mitogens ± TOFA. Soluble biomarkers were detected using a 29-analyte multiplex ELISA. Target engagement in CD3+CD4+ and CD3+CD8+ T-cells was determined by flow cytometry in peripheral blood mononuclear cells (PBMCs) and isolated mucosal mononuclear cells (MMCs) following the activation of STAT1/3 phosphorylation. Data were analyzed using linear mixed-effects modeling, t test, and analysis of variance. Biomarker selection was performed using penalized and Bayesian logistic regression modeling, with results visualized using uniform manifold approximation and projection. Under baseline conditions, 27 of 29 biomarkers from patients with UC were increased versus HC participants. Explant stimulation increased biomarker release magnitude, expanding the dynamic range for efficacy and target engagement studies. Logistic regression analyses identified the most representative UC baseline and stimulated biomarkers. TOFA inhibited biomarkers dependent on JAK/STAT signaling. STAT1/3 phosphorylation in T-cells revealed compartmental differences between PBMCs and MMCs. Immunogen stimulation increases biomarker release in similar patterns for HC participants and patients with UC, while enhancing the dynamic range for pharmacological effects. This work demonstrates the power of ex vivo human colorectal tissue as preclinical tools for evaluating target engagement and downstream effects of new IBD therapeutic agents.NEW & NOTEWORTHY Using colorectal biopsy material from healthy volunteers and patients with clinically defined IBD supports translational research by informing the evaluation of therapeutic efficacy and target engagement for the development of new therapeutic entities. Combining experimental readouts from intact and dissociated tissue enhances our understanding of the tissue-resident immune system that contribute to disease pathology. Bayesian logistic regression modeling is an effective tool for predicting ex vivo explant biomarker release patterns.


Assuntos
Colite Ulcerativa/metabolismo , Citocinas/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Linfócitos T/efeitos dos fármacos , Teorema de Bayes , Biomarcadores , Colite Ulcerativa/patologia , Citocinas/antagonistas & inibidores , Citocinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Janus Quinases/genética , Janus Quinases/metabolismo , Fator de Transcrição STAT1 , Fator de Transcrição STAT3 , Linfócitos T/metabolismo
18.
Mil Med ; 186(1-2): 27-32, 2021 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-33313889

RESUMO

During World War I, the 1918 influenza pandemic struck the fatigued combat troops serving on the Western Front. Medical treatment options were limited; thus, skilled military nursing care was the primary therapy and the best indicator of patient outcomes. This article examines the military nursing's role in the care of the soldiers during the 1918 flu pandemic and compares this to the 2019 coronavirus pandemic.


Assuntos
Influenza Humana , Medicina Militar/história , Enfermagem Militar/história , Papel do Profissional de Enfermagem/história , COVID-19 , História do Século XX , Humanos , Militares/história , Pandemias , I Guerra Mundial
19.
Mil Med ; 186(5-6): 486-492, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33242071

RESUMO

INTRODUCTION: Knee injuries associated with intense physical training are one of the most frequent injuries associated with medical encounters for military members. The purpose of this study was to evaluate four approaches to physiotherapy rehabilitation and their effects on work efficiency in active duty military with a knee injury. The four groups included neuromuscular electrical stimulation (NMES), walking with a weighted vest (WALK), combined NMES/Walk, and standard physiotherapy rehabilitation. All groups received standard physiotherapy rehabilitation.We have previously reported that quadriceps muscle strength improved over 18 weeks in the study for the three interventions relative to standard rehabilitation alone. This report presents results from an examination of work efficiency as evaluated during a step test while measuring oxygen utilization. METHODS: A randomized controlled trial was conducted, with repeated outcome measures of work efficiency assessed at baseline, 3, 6, 12, and 18 weeks. The sample consisted of 67 active duty service members between the ages of 18 and 50 years with a knee injury. Participants were randomized to one of the four approaches to physiotherapy rehabilitation: (1) NMES was applied to the quadriceps muscle four times per week, for 30 minutes (15 minutes to each leg), consisting of 15 quadriceps muscle contractions per leg; (2) graduated strength walking using a weighted vest (WALK) was for 30 minutes, 3 to 4 days a week; (3) combined NMES with strength walking received both the NMES therapy and the weighted vest walking; and (4) standard physiotherapy consisted of progressive exercise with the number and type of sessions not controlled by the study. All four groups received the standard physiotherapy for a knee injury. The primary outcome was work efficiency, as measured by oxygen utilization during a 2-minute self-paced step test over 18 weeks. The primary analysis used repeated measures, linear mixed-effects models with a random effect for subject. RESULTS: Both the number of steps performed and gross work efficiency improved during the study for all three intervention groups. For gross work efficiency, standard rehabilitation improved 12%, WALK showed a 19% improvement, NMES increased by 24%, and the NMES/Walk group improved by 40%. CONCLUSIONS: All groups showed improved submaximal exercise efficiency based on oxygen utilization, with the intervention groups showing a greater improvement in work efficiency as compared to standard rehabilitation. Knee injuries can be problematic for active duty members because of reduced mobility leading to deconditioning and associated declines in work efficiency. Rehabilitative programs, including those described in this study, may minimize loss of work efficiency and fitness and promote a quicker recovery.


Assuntos
Terapia por Estimulação Elétrica , Traumatismos do Joelho , Militares , Adolescente , Adulto , Humanos , Pessoa de Meia-Idade , Força Muscular , Músculo Quadríceps , Adulto Jovem
20.
Am J Emerg Med ; 40: 162-165, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33143956

RESUMO

OBJECTIVES: There are limited non-invasive methods to assess lower extremity arterial injuries in the emergency department (ED) and pre-hospital setting. The ankle-brachial index (ABI) requires careful auscultation by Doppler, an approach made difficult in noisy environments. We sought to determine the agreement of the ABI measured using the pulse oximeter plethysmograph waveform (Pleth) with auscultation by Doppler in a controlled setting. A secondary outcome sought to examine the agreement of ABI by automated oscillometric sphygmomanometer (AOS) with Doppler. METHODS: We measured blood pressure in the right upper and lower extremities of healthy volunteers using: (1) Doppler and manual sphygmomanometer; (2) Pleth and manual sphygmomanometer; and (3) AOS. The Bland-Altman approach to assessing agreement between methods was used comparing mean differences between ABI pairs to their means for Doppler versus Pleth and Doppler versus AOS. The intraclass correlation coefficient (ICC) from mixed effects models examined intra- and inter-rater reliability. RESULTS: Among 100 participants with normal ABI the mean ABI (95%CI) were Doppler 1.11 (0.90-1.33), Pleth 1.10 (0.91-1.30), and AOS 1.10 (0.90-1.30). The ABI difference (95% CI for limits of agreement) were 0.01 (-0.20,0.18) for Doppler-Pleth and 0.02 (-0.26, 0.22) for Doppler-AOS. The ICC for the Doppler-Pleth comparison (ICC = 0.56, 95% CI 0.47-0.63) was greater than for the Doppler-AOS (ICC = 0.32, 95% CI 0.19-0.43). CONCLUSIONS: The ABI measured using the Pleth has a high level of agreement with measurement by Doppler. The AOS and Doppler have good agreement with greater measurement variability. Pleth and AOS may be reasonable alternatives to Doppler for ABI.


Assuntos
Índice Tornozelo-Braço/métodos , Serviço Hospitalar de Emergência , Oximetria , Pletismografia , Ultrassonografia Doppler , Adulto , Auscultação , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Masculino , Esfigmomanômetros
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